Epidemiological and Clinical Aspects of Cutaneous and Mucosal Leishmaniases in Portugal: Retrospective Analysis of Cases Diagnosed in Public Hospitals and Reported in the Literature between 2010 and 2020.

Leishmania infantum, a zoonotic vector-born parasite, is endemic in the Mediterranean region, presenting mostly as visceral (VL), but also as cutaneous (CL) and mucosal leishmaniasis (ML). This study aimed to describe the epidemiological and clinical aspects of the CL and ML cases diagnosed in mainland Portugal between 2010 and 2020. Collaboration was requested from every hospital of the Portuguese National Health System. Cases were screened through a search of diagnostic discharge codes or positive laboratory results for Leishmania infection. Simultaneously, a comprehensive literature search was performed. Descriptive statistics and hypothesis testing were performed using IBM® SPSS® Statistics. A total of 43 CL and 7 ML cases were identified, with a predominance of autochthonous cases (86%). In CL, immunosuppressed individuals constituted a significant proportion of patients (48%), and in this group, disseminated CL (22%) and simultaneous VL (54%) were common. In autochthonous cases, lesions, mostly papules/nodules (62%), were frequently observed on the head (48%). The approach to treatment was very heterogeneous. ML cases were all autochthonous, were diagnosed primarily in older immunosuppressed individuals, and were generally treated with liposomal amphotericin B. The findings suggest a need for enhanced surveillance and reporting, clinical awareness, and diagnostic capacity of these forms of leishmaniasis to mitigate underdiagnosis and improve patient outcomes. A holistic One Health approach is advocated to address the multifaceted challenges posed by leishmaniases in Portugal and beyond.

Diez años de experiencia con el primer biosimilar autorizado de hormona del crecimiento recombinante humana en la práctica clínica habitual / Ten years experience with the first approved biosimilar recombinant human growth hormone drug in normal clinical practice

INTRODUCCIÓN: La hormona de crecimiento humana recombinante biosimilar (rhGH) fue el primer medicamento autorizado por la Agencia Europea del Medicamento (EMA), en el año 2006, por la vía de registro biosimilar. Se aprobó su uso para el tratamiento del déficit de hormona de crecimiento, trastorno de crecimiento asociado al síndrome de Turner, trastorno de crecimiento asociado a insuficiencia renal crónica, síndrome de Prader-Willi, trastorno de crecimiento en niños/adolescentes nacidos pequeños para su edad gestacional y como terapia de sustitución en adultos con deficiencia pronunciada de hormona de crecimiento. MATERIALES Y MÉTODOS: Esta revisión se centra en las evidencias científicas publicadas en los últimos 10 años, incluyendo los ensayos clínicos utilizados para conseguir la aprobación por parte de la EMA y los estudios más relevantes que evalúan el medicamento en la práctica clínica habitual. RESULTADOS: La equivalencia entre este biosimilar de rhGH y su producto de referencia ha sido demostrada en los ensayos clínicos publicados por Romer et al. y López-Siguero et al. Asimismo, los estudios del fármaco realizados en condiciones de práctica clínica habitual confirman su eficacia y seguridad a largo plazo, así como la ausencia de impacto clínico al cambiar el producto original por el biosimilar. CONCLUSIÓN: Desde su aprobación, el número de pacientes que reciben esta medicación ha experimentado un continuo crecimiento. Los datos preliminares del estudio postautorización PATRO indican que la eficacia y seguridad del fármaco se correlaciona con la obtenida en los ensayos clínicos. No obstante, aún queda pendiente evaluar los resultados definitivos del estudio que aportarán información adicional sobre la eficacia y seguridad del fármaco a largo plazo

INTRODUCTION: Recombinant human growth hormone (rhGH) is the first biosimilar drug approved by the European Medicines Agency in 2006, using the biosimilar registration process. It was authorised for the treatment of growth hormone deficiency, and growth disorders associated with Turner's syndrome, chronic renal failure, Prader-Willi syndrome, and growth disorders in children/adolescents born small for gestational age, and replacement therapy in adults with pronounced growth hormone deficiency. MATERIALS AND METHODS: This review is focused on the scientific evidence published about this drug in the last ten years, including the clinical trials on which the approval of the regulatory authority is based, and the most relevant studies evaluating the clinical impact of the drug in clinical practice. RESULTS: The equivalence between biosimilar and original product has been confirmed in the clinical trials published by Romer et al. and López-Siguero et al. Furthermore, studies carried out in real-life conditions confirm its long-term efficacy and safety, as well as the absence of clinical impact by switching treatment from the original to the biosimilar product. CONCLUSION: The number of patients receiving this medication has continuously increased since its approval. Its equivalence with the original product has been verified. Preliminary data from the post-authorisation PATRO study confirm the efficacy and safety of the biosimilar product in comparison with data from clinical trials. However, final results must be evaluated at the end of the study, which will provide additional information about the long-term efficacy and safety of the biosimilar drug

[Ten years experience with the first approved biosimilar recombinant human growth hormone drug in normal clinical practice]. / Diez años de experiencia con el primer biosimilar autorizado de hormona del crecimiento recombinante humana en la práctica clínica habitual.

INTRODUCTION: Recombinant human growth hormone (rhGH) is the first biosimilar drug approved by the European Medicines Agency in 2006, using the biosimilar registration process. It was authorised for the treatment of growth hormone deficiency, and growth disorders associated with Turner's syndrome, chronic renal failure, Prader-Willi syndrome, and growth disorders in children/adolescents born small for gestational age, and replacement therapy in adults with pronounced growth hormone deficiency. MATERIALS AND METHODS: This review is focused on the scientific evidence published about this drug in the last ten years, including the clinical trials on which the approval of the regulatory authority is based, and the most relevant studies evaluating the clinical impact of the drug in clinical practice. RESULTS: The equivalence between biosimilar and original product has been confirmed in the clinical trials published by Romer et al. and López-Siguero et al. Furthermore, studies carried out in real-life conditions confirm its long-term efficacy and safety, as well as the absence of clinical impact by switching treatment from the original to the biosimilar product. CONCLUSION: The number of patients receiving this medication has continuously increased since its approval. Its equivalence with the original product has been verified. Preliminary data from the post-authorisation PATRO study confirm the efficacy and safety of the biosimilar product in comparison with data from clinical trials. However, final results must be evaluated at the end of the study, which will provide additional information about the long-term efficacy and safety of the biosimilar drug.

A follow-up study to monitor adult height among Spanish children with growth hormone deficiency who received biosimilar human recombinant growth hormone (Omnitrope®) during a phase III clinical trial.

INTRODUCTION: An initial Phase III clinical trial has evaluated the efficacy and safety of biosimilar recombinant human growth hormone (rhGH; Omnitrope(®), Sandoz) in Spanish children with growth hormone deficiency (GHD). At the end of the study, those patients still growing were offered to remain on treatment (as in usual clinical practice), and continued to be monitored. The aim of this study was to determine the adult height achieved by the Spanish children who participated in the initial Phase III clinical trial, and to evaluate the long-term safety of rhGH treatment. METHODS: This study was a multicenter, observational, retrospective follow-up study of patients who participated in the Phase III clinical trial (70 patients recruited). Auxological parameters [including height, height velocity, and their associated height standard deviation scores (HSDS)] were obtained from 39 patients. Safety was assessed by recording any adverse events (AEs). RESULTS: In total, 27 men and 12 women provided auxological data. At the start of the follow-up study, the mean age of the patients was 12.5 ± 2.7 years, mean height was 144.8 ± 13.9 cm and mean HSDS was -1.16 ± 0.63. By the end of the follow-up period, mean height had increased to 163.1 ± 7.6 cm (n = 36; men 165.5 ± 7.8 cm, women 157.6 ± 3.2 cm) and mean HSDS also increased to -1.01 ± 0.59 (n = 36; men -1.07 ± 0.52, women -0.86 ± 0.72). In terms of safety, no treatment-related AEs were reported during the study. CONCLUSION: This cohort of Spanish patients with GHD showed a positive response to rhGH treatment, achieving adult height within the local normal ranges. In addition, rhGH treatment was well tolerated, with no new or additional safety concerns.

[Usefulness of electronic drug registers: Spanish register of patients treated with fingolimod (Gilenya ®)]. / Utilidad de los registros electronicos de medicamentos: registro español de pacientes tratados con fingolimod (Gilenya ®).

INTRODUCTION: This study outlines the design of an electronic register of patients with multiple sclerosis who began treatment with fingolimod in Spain. The system is intended to serve as a tool to monitor its utilisation in daily clinical practice and thus allow optimisation of the way it is used. AIMS: To establish the profile of patients with multiple sclerosis undergoing treatment with fingolimod and to determine the effectiveness and safety of this treatment in daily clinical practice. DEVELOPMENT: An observation-based, retrospective and prospective, multi-centre registry is set up, which will be active for five years. Forty neurologists working in Spain will participate in the project. Patients treated with fingolimod who fulfil the selection criteria will be included in the study. The effectiveness variables that will be evaluated are: disability measured by means of the Expanded Disability Status Scale, the rate of attacks, T1 gadolinium-enhancing lesions and new lesions in T2, and the percentage of patients who were free of activity and those who require concomitant treatments. The tolerability variables that will be evaluated are: the rate of patients who present events and adverse reactions, respectively, with a separate analysis of those presenting after the first dose or that are related to the fingolimod risk management plan and the treatment dropout rate. CONCLUSIONS: New pharmaceuticals that have only recently been commercialised require more information about their effectiveness and safety, beyond the controlled environment of a clinical trial. Initiatives involving electronic registries such as the Gilenya register are a solution that can respond to such needs by providing information in the shortest possible time about the most suitable management in order to be able to make the best and most efficient use of it.

TITLE: Utilidad de los registros electronicos de medicamentos: registro español de pacientes tratados con fingolimod (Gilenya ®).Introduccion. Se describe el diseño de un registro electronico de los pacientes con esclerosis multiple que inician tratamiento con fingolimod en España, que se plantea como una herramienta para monitorizar su manejo en la practica clinica habitual que permita optimizar su uso. Objetivos. Conocer el perfil de los pacientes con esclerosis multiple en tratamiento con fingolimod y determinar la efectividad y seguridad de este tratamiento en la practica clinica habitual. Desarrollo. Se establece un registro observacional, retrospectivo y prospectivo, multicentrico, que estara activo durante cinco años. Participaran 40 neurologos de España. Se incluiran pacientes tratados con fingolimod que cumplan los criterios de seleccion. Las variables de efectividad que se evaluaran son: la discapacidad medida mediante la escala ampliada del estado de discapacidad, la tasa de brotes, las lesiones captantes de gadolinio en secuencia T1 y las lesiones nuevas en secuencia T2, y el porcentaje de pacientes libres de actividad y aquellos que requieran tratamientos concomitantes. Las variables de seguridad que se evaluaran son: la tasa de pacientes que presenten acontecimientos y reacciones adversas, respectivamente, analizandose separadamente aquellos que se presenten tras la primera dosis o relacionados con el plan de manejo del riesgo de fingolimod, y la tasa de abandonos del tratamiento. Conclusiones. Los nuevos farmacos de reciente comercializacion requieren mayor informacion acerca de su efectividad y seguridad, mas alla del entorno controlado de un ensayo clinico. Las iniciativas de registros electronicos como el registro Gilenya son la solucion para dar respuesta a dicha necesidad, proporcionando informacion en el menor tiempo posible acerca del manejo mas adecuado para conseguir su uso mas optimo y eficiente posible.

Utilidad de los registros electrónicos de medicamentos: registro español de pacientes tratados con fingolimod (Gilenya (R)) / Usefulness of electronic drug registers: Spanish register of patients treated with fingolimod (Gilenya (R))

Introducción. Se describe el diseño de un registro electrónico de los pacientes con esclerosis múltiple que inician tratamiento con fingolimod en España, que se plantea como una herramienta para monitorizar su manejo en la práctica clínica habitual que permita optimizar su uso. Objetivos. Conocer el perfil de los pacientes con esclerosis múltiple en tratamiento con fingolimod y determinar la efectividad y seguridad de este tratamiento en la práctica clínica habitual. Desarrollo. Se establece un registro observacional, retrospectivo y prospectivo, multicéntrico, que estará activo durante cinco años. Participarán 40 neurólogos de España. Se incluirán pacientes tratados con fingolimod que cumplan los criterios de selección. Las variables de efectividad que se evaluarán son: la discapacidad medida mediante la escala ampliada del estado de discapacidad, la tasa de brotes, las lesiones captantes de gadolinio en secuencia T1 y las lesiones nuevas en secuencia T2, y el porcentaje de pacientes libres de actividad y aquéllos que requieran tratamientos concomitantes. Las variables de seguridad que se evaluarán son: la tasa de pacientes que presenten acontecimientos y reacciones adversas, respectivamente, analizándose separadamente aquellos que se presenten tras la primera dosis o relacionados con el plan de manejo del riesgo de fingolimod, y la tasa de abandonos del tratamiento. Conclusiones. Los nuevos fármacos de reciente comercialización requieren mayor información acerca de su efectividad y seguridad, más allá del entorno controlado de un ensayo clínico. Las iniciativas de registros electrónicos como el registro Gilenya son la solución para dar respuesta a dicha necesidad, proporcionando información en el menor tiempo posible acerca del manejo más adecuado para conseguir su uso más óptimo y eficiente posible (AU)

Introduction. This study outlines the design of an electronic register of patients with multiple sclerosis who began treatment with fingolimod in Spain. The system is intended to serve as a tool to monitor its utilisation in daily clinical practice and thus allow optimisation of the way it is used. Aims. To establish the profile of patients with multiple sclerosis undergoing treatment with fingolimod and to determine the effectiveness and safety of this treatment in daily clinical practice. Development. An observation-based, retrospective and prospective, multi-centre registry is set up, which will be active for five years. Forty neurologists working in Spain will participate in the project. Patients treated with fingolimod who fulfil the selection criteria will be included in the study. The effectiveness variables that will be evaluated are: disability measured by means of the Expanded Disability Status Scale, the rate of attacks, T1 gadolinium-enhancing lesions and new lesions in T2, and the percentage of patients who were free of activity and those who require concomitant treatments. The tolerability variables that will be evaluated are: the rate of patients who present events and adverse reactions, respectively, with a separate analysis of those presenting after the first dose or that are related to the fingolimod risk management plan and the treatment dropout rate. Conclusions. New pharmaceuticals that have only recently been commercialised require more information about their effectiveness and safety, beyond the controlled environment of a clinical trial. Initiatives involving electronic registries such as the Gilenya register are a solution that can respond to such needs by providing information in the shortest possible time about the most suitable management in order to be able to make the best and most efficient use of it (AU)

Situación de partida y abordaje asistencial de la migraña en las consultas de neurología de España. Estudio PRIMERA / Initial situation and approach to the care of migraine in neurology services in Spain. The PRIMERA study

Introducción. A pesar de la alta discapacidad que conlleva, muchos pacientes con migraña nunca han consultado por este motivo. El estudio de quienes acuden por primera vez a consulta es obligado como paso previo a plantear medidas de intervención específicas para este colectivo de pacientes. Objetivo. Conocer el perfil de los pacientes con migraña que acuden por primera vez a una consulta de neurología, así como las actitudes diagnósticas y terapéuticas adoptadas por los neurólogos con respecto a ellos. Pacientes y métodos. Estudio transversal y multicéntrico, realizado en consultas de neurología de todo el territorio nacional. Participaron 168 neurólogos que reclutaron un total de 851 pacientes (74,6% mujeres; edad media: 34,0 ± 10,7 años). La discapacidad se evaluó mediante el cuestionario específico para migraña (Headache Impact Test) y el cuestionario de discapacidad genérico (Sheehan Disability Scale). Resultados. El 66,5% de los pacientes consultó por consejo médico, el 33,5% restante lo hizo por iniciativa propia. Sólo el 55,9% tenía un diagnóstico previo de migraña. Los principales motivos de consulta fueron la ineficacia del tratamiento sintomático (25%) y el incremento en la frecuencia o intensidad de las crisis (23,4%). Aunque el 70,3% de los pacientes puntuaba alta discapacidad en el Headache Impact Test, sólo el 17,4% utilizaba tratamiento específico y únicamente el 13,3% tratamiento preventivo. Conclusiones. El estudio PRIMERA ratifica, una vez más, que la migraña es una entidad infradiagnosticada e infratratada en nuestro medio, por lo que siguen siendo precisas intervenciones de tipo educativo y formativo específicas para esta patología (AU)

Introduction. Despite the high degree of disability it entails, many patients with migraine have never visited their doctor for this reason. It is necessary to conduct a study to examine the characteristics of first-time visits as a step that must be carried out prior to establishing specific intervention measures for this group of patients. Aim. To determine the profile of the patients with migraine who visit a neurology service for the first time, together with the diagnostic and therapeutic attitudes that neurologists display towards them. Patients and methods. We conducted a cross-sectional, multi-centre study of neurology services across the country. The research included 168 neurologists who recruited 851 patients (74.6% females; mean age: 34.0 ± 10.7 years). Disability was assessed by means of the specific migraine questionnaire (Headache Impact Test) and the generic disability questionnaire (Sheehan Disability Scale). Results. A third (66.5%) of the patients went for consultation following their doctor’s advice, while the remaining 33.5% went on their own accord. Only 55.9% had been previously diagnosed with migraine. The main reasons for visiting were ineffective symptomatic treatment (25%) and an increase in the frequency or intensity of the attacks (23.4%). Although 70.3% of the patients had high disability scores on the Headache Impact Test, only 17.4% used specific treatment and only13.3% were on preventive treatment. Conclusions. The PRIMERA study confirms, once again, that migraine is an under-diagnosed and under-treated condition in our setting, which means that specific educational interventions and training are still required for this pathology (AU)

[Precipitating factors of migraine attacks in patients attended in neurology services. The FACTOR study]. / Factores precipitantes de crisis de migraña en pacientes atendidos en consultas de neurología. Estudio FACTOR.

INTRODUCTION: Patients with migraine often report factors or circumstances that precipitate or trigger their attacks. Yet few studies have been conducted to examine this matter. AIM: To explore the factors that precipitate migraine in our setting, as well is their possible relation with the intensity of the attacks or the overall repercussion of migraine. PATIENTS AND METHODS: An epidemiological, cross-sectional, multi-centre study was conducted in neurology consultation services. Sociodemographic and clinical data were collected and the precipitating factors were identified from a closed list. The specific migraine disability questionnaire -Headache Impact Test (HIT-6)- and the measurement of the number of lost workday equivalents were used in the study. RESULTS: Altogether 817 patients were recruited (72.5% females, mean age: 34.6 ± 10.3 years). A total of 70.5% of the patients had severe disability according to the HIT-6. The mean monthly number of lost workday equivalents was 2.1 ± 2.5. A total of 96.6% of the patients identified some precipitating factor for the attacks, the most commonly reported being hormonal (75.2%), stress (70.9%) and those related with disorders affecting sleep patterns (68.4%). CONCLUSIONS: The FACTOR study confirms that most patients with migraine identify some circumstance that precipitates their attacks. Controlling or avoiding these factors, whenever possible, must be part of the programme of education received by patients suffering from migraine.

Psychopathology, coronary heart disease and metabolic syndrome in schizophrenia spectrum patients with deficit versus non-deficit schizophrenia: findings from the CLAMORS study.

The objective of this study was to compare coronary heart disease (CHD) risk and metabolic syndrome (MS) prevalence in patients with deficit (DS) and non-deficit schizophrenia treated with antipsychotics. A total of 1452 antipsychotic-treated outpatients meeting criteria for schizophrenia, schizophreniform or schizoaffective disorder were included in this cross-sectional multicentre study. CHD risk was assessed by SCORE (10-year cardiovascular death) risk score, and metabolic syndrome was assessed according to NCEP-ATP III criteria. A total of 1452 patients (863 men, 60.9%), 40.7±12.2years (mean±SD) were included. DS was found in 404 patients (35.1%). Patients with DS were older, more frequently male and obese, more likely to be receiving sickness benefits, and had longer illness duration and fewer previous hospitalisations. Furthermore, DS patients had higher negative PANSS scores (56.3% vs. 40.6% of patients with PANSS-N>21). High/very high risk of fatal CHD according to SCORE function (≥3%) was significantly higher in DS [11.8% (95% CI: 8.8-15.5) vs. 6.0% (95% CI: 4.4-8.1), (p<0.05)]. Schizophrenia spectrum patients with DS were more obese and had a higher CHD risk than non-deficit patients.

Clinical differences between first and recurrent episodes in depressive patients.

BACKGROUND: Depressive disorder is one of the most common mental disorders in primary care. Depression is often a chronic disorder with recurrent episodes. Little is known about the differences in clinical profile between first and recurrent episodes. The aim of the study is to analyze the differences between clinical presentation of first and subsequent episodes of depressive disorders in primary care patients. METHOD: A cross-sectional epidemiologic study in primary care centers in Spain was designed. A total of 10,257 primary care patients having a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major depressive episode were analyzed. Clinical symptoms were measured using the Montgomery Asberg Depression Scale. Patient Health Questionnaire was used to assess somatic symptoms. RESULTS: There were 40.6% of patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for recurrent depression. Compared with those diagnosed of their first major depressive disorder, recurrent patients had greater rates and severity of depressive (t = -7.85, P < .001) and somatic symptoms (t = 5.64, P < .001). The severity of symptoms also increases with number of episodes (F = 40.2, P < .001, for depressive symptoms; F = 27.8, P < .001, for somatic symptoms). First-episode patients were more likely to experience reduced appetite (adjusted odds ratio, 1.2) and suicidal thoughts (adjusted odds ratio, 1.2). CONCLUSION: There are differences in the clinical profile of initial and recurrent episodes in primary care depressive patients. Each recurrent depressive episode seems to have a greater impact on symptoms and well-being. The identification of a specific depression symptom profile in first or recurrent episodes is needed to improve the long-term management of major depressive episode patients in primary care settings.

Healthy lifestyle habits and 10-year cardiovascular risk in schizophrenia spectrum disorders: an analysis of the impact of smoking tobacco in the CLAMORS schizophrenia cohort.

AIM: We analysed the impact of tobacco smoking over several healthy lifestyle habits along with the impact on 10-years cardiovascular event (CVE) risk in the CLAMORS schizophrenia cohort. METHODS: This analysis was performed within the scope of the CLAMORS study which included consecutive outpatients meeting DSM-IV criteria for schizophrenia spectrum disorder. Beside smoking history, data on usual healthy lifestyle habits included current exercise, saturated fat sparing diet, low-caloric diet, and daily dietary fibre, salt, caffeine and alcohol consumption were recorded. The 10-year CVE risk was calculated with Framingham function. RESULTS: 1704 patients (61.1% male), 18 to 74 years were examined. Prevalence of smoking was 54.54% (95% CI: 52.16%-56.90%) significantly higher than in age and sex matched general population subjects, 31.51% (31.49%-31.52%); OR=2.61 (2.37-2.87, p<0.0001). After controlling by confounders smokers showed a 10-year CVE risk excess versus non-smokers of 2.63 (2.16-3.09), p<0.001. Smoking cessation would reduce the likely of high/very high 10-year CVE risk (above 10%) by near 90% [OR=0.10 (0.06-0.18), p<0.0001]. Also, smokers were more likely to consume alcohol daily [4.13 (3.07-5.54), p<0.0001] and caffeine [3.39 (2.72-4.23), p<0.0001] than non-smoker patients with schizophrenia, and less likely to avoid daily consumption of salt [0.58 (0.43-0.78), p<0.0001], saturated fat [0.71 (0.56-0.91), p=0.006], high fibre diet [0.67 (0.53-0.84), p=0.001], or to follow a low-caloric diet [0.63 (0.48-0.81), p<0.0001]. Smokers also were less likely to do exercise habitually [0.62 (0.48-0.82, p=0.001]. CONCLUSION: Compared with the general population, patients with schizophrenia showed significant higher prevalence of smoking. Smokers who stop smoking would benefit by a near 90% reduction in the likely of 10-year cardiovascular event risk above 10%.

Prevalence of negative symptoms in outpatients with schizophrenia spectrum disorders treated with antipsychotics in routine clinical practice: findings from the CLAMORS study.

OBJECTIVE: To analyze the prevalence of negative symptoms in antipsychotic-treated outpatients with schizophrenia spectrum disorders. METHOD: A cross-sectional, retrospective multicenter study was carried out between May 2004 and April 2005 in 1,704 adult psychiatric outpatients meeting DSM-IV criteria for schizophrenia, schizophreniform, or schizoaffective disorder. We used 5 items of the Positive and Negative Syndrome Scale (PANSS) negative symptoms subscale to individually determine the presence of a negative symptom when the score on the item was > 3. Primary negative symptoms were considered present when patients fulfilled all of the following: > 3 score on the corresponding item; < 3 score on any positive item; no extrapyramidal symptoms; 40/45 years (men/women; symptoms 1,2,4); single/unmarried status (symptoms 2-4); unemployment (symptoms 3,4); higher score on the Clinical Global Impressions (CGI) scale and PANSS total score (symptoms 1-5); lower score on the PANSS positive symptoms subscale (symptoms 1,3); more than 52 weeks of treatment (symptoms 1-3,5); and high antipsychotic dose (symptom 2). CONCLUSIONS: The prevalence of negative symptoms in patients with schizophrenia spectrum disorders treated with antipsychotics in routine clinical practice not only is still considerably high but also seems to be related to poorer functioning, unemployment, greater severity, and less positive symptomatology and higher antipsychotic dose.

Effectiveness and tolerability of fixed-dose combination enalapril plus nitrendipine in hypertensive patients: results of the 3-month observational, post-marketing, multicentre, prospective CENIT study.

BACKGROUND AND OBJECTIVE: Monotherapy with any class of antihypertensive drug effectively controls blood pressure (BP) in only about 50% of patients. Consequently, the majority of patients with hypertension require combined therapy with two or more medications. This study aimed to evaluate the effectiveness (systolic BP [SBP]/diastolic BP [DBP] control) and tolerability of the fixed-dose combination enalapril/nitrendipine 10 mg/20 mg administered as a single daily dose in hypertensive patients. METHODS: This was a post-authorization, multicentre, prospective, observational study conducted in primary care with a 3-month follow-up. Patients throughout Spain with uncontrolled hypertension (> or =140/90 mmHg for patients without diabetes mellitus, or > or =130/85 mmHg for patients with diabetes) on monotherapy or with any combination other than enalapril + nitrendipine, or who were unable to tolerate their previous antihypertensive therapy, were recruited. Change from previous to study treatment was according to usual clinical practice. BP was measured once after 5 minutes of rest in the sitting position. Therapeutic response was defined as follows: 'controlled' meant controlled BP (<140/90 mmHg for nondiabetic patients, or <130/85 mmHg for diabetic patients); 'response' meant controlled BP, or a decrease in SBP of > or =20 mmHg and in DBP of > or =10 mmHg. The main laboratory test parameters were documented at baseline and after 3 months. Patients aged >65 years, with diabetes, with isolated systolic hypertension (ISH; SBP > or =140 mmHg for patients without diabetes, SBP > or =130 mmHg for patients with diabetes) and who were obese (body mass index [BMI] > or =30 kg/m2) were analysed separately. RESULTS: Of 6537 patients included, 5010 and 6354 patients were assessed in effectiveness and tolerability analyses, respectively. In the tolerability analysis population, there were 3023 men (47.6%) and 3321 women (52.4%). The mean (+/- SD) age of the tolerability analysis group was 62.8 (+/- 10.7) years. A total of 71.1% of the patients presented at least one clinical cardiovascular risk factor other than hypertension, with the most frequent being dyslipidaemia (42.3%), obesity (29.2%) and diabetes (23.9%). After 3 months of treatment, SBP and DBP showed mean (+/- SD) decreases of 26.5 (+/- 14.4) mmHg and 14.9 (+/- 9.0) mmHg, respectively, and 73.0% of patients responded to treatment while 40.9% achieved BP control (70.8%/36.1% in 2658 patients aged >65 years; 61.7%/46.8% in 1521 patients with diabetes; 55.3%/44.2% in 731 patients with ISH; 72.0%/36.4% in 1762 obese patients). Adverse events were reported in 10.8% of patients (n = 689). During the follow-up period, ten patients died and seven patients had serious adverse events; in no case was a causal relationship attributed to the study product. CONCLUSIONS: The rate of SBP/DBP control achieved demonstrates the effectiveness of the fixed-dose enalapril/nitrendipine 10 mg/20 mg combination administered as a single daily dose in patients with essential hypertension not adequately controlled with monotherapy or with any combination other than enalapril + nitrendipine. The proportion and type of adverse events reported were as expected and have already been described for both components of the enalapril/nitrendipine 10 mg/20 mg combination. These results confirm the effectiveness of a strategy based on a fixed-dose enalapril/nitrendipine 10 mg/20 mg combination in reducing BP and achieving BP control goals.

Validation of the Barcelona Bipolar Eating Disorder Scale for bipolar patients with eating disturbances.

BACKGROUND: Eating disturbances are frequent in bipolar disorder and are associated with poor outcome. Our objective is to assess the psychometric properties of a specific scale for the evaluation of eating disturbances in bipolar patients. SAMPLING AND METHODS: Validation study of 2 groups with a 6-month follow-up (90 patients diagnosed with bipolar and eating disturbances and 40 healthy controls). RESULTS: The scale showed: (1) adequate feasibility (non- response <2.5%); (2) adequate reliability (Cronbach's alpha coefficients = 0.79 and 0.57 in groups A and B; intraclass correlation coefficient = 0.79 in group A); (3) adequate discriminant validity between patients and controls [AUC = 0.85; moderate correlations with the Bulimic Investigatory Test Edinburgh (r = 0.32-0.64); low correlations with the Barratt Impulsiveness Scale, Young Mania Rating Scale and Hamilton Depression Rating Scale 17 (r < 0.3)]; (4) adequate sensitivity to changes. CONCLUSIONS: The Barcelona Bipolar Eating Disorder Scale showed adequate psychometric properties to assess eating disturbances in bipolar patients in clinical practice and research.

A comparison of schizophrenia outpatients treated with antipsychotics with and without metabolic syndrome: findings from the CLAMORS study.

OBJECTIVE: To compare clinical, laboratory, lifestyle, and sociodemographic parameters and cardiac risk in antipsychotic-treated patients with and without metabolic syndrome (MS). METHODS: A multicenter cross-sectional study in which 117 psychiatrists recruited antipsychotic-treated outpatients meeting DSM-IV criteria for schizophrenia, schizophreniform or schizoaffective disorder. MS was diagnosed when 3 or more of the following criteria were met: waist circumference > 102 cm (men)/> 88 cm (women); serum triglycerides > or = 150 mg/dl; HDL cholesterol < 40 mg/dl (men)/< 50 mg/dl (women); blood pressure > or = 130/85 mmHg; fasting blood glucose > or = 110 mg/dl. The 10-year cardiovascular (CV) risk was assessed by the Systematic COronary Risk Evaluation (SCORE) function (CV mortality) and the Framingham function (any-CV-event). RESULTS: 1452 evaluable patients (863 men, 60.9%), aged 40.7+/-12.2 years and with a mean duration of illness of 15.5+/-10.8 years (mean+/-SD), were included. MS was present in 24.6% [23.6% (men), 27.2% (women); p=0.130]. Overall 10-year risks were 0.9+/-1.9 (SCORE) and 7.2+/-7.6 (Framingham). Coronary heart disease (CHD) 10-year risk was higher in MS patients: 6.6% vs 2.8% showed high/very-high CV mortality risk (SCORE > or = 3%), and 44.2% vs 12.9% high/very-high CV event risk (Framingham > or = 10%) (p<0.001). MS patients also had more psychopathology (PANSS) and greater severity (CGI). CONCLUSIONS: MS is highly prevalent in antipsychotic-treated patients and is associated with increased cardiovascular risk and psychopathology.

Concordance of standard and modified NCEP ATP III criteria for identification of metabolic syndrome in outpatients with schizophrenia treated with antipsychotics: a corollary from the CLAMORS study.

OBJECTIVE: To analyze the concordance between standard and modified NCEP-ATP-III criteria for identification of metabolic syndrome (MS) in outpatients with schizophrenia. METHOD: We used the sample from a cross-sectional study carried out to ascertain the prevalence of MS in schizophrenia. Kappa agreement and the symmetry Kendall's tau-b coefficients were calculated in a post-hoc analysis, a long with McNemar test and logistic regression models. RESULTS: The study enrolled 1,452 consecutive outpatients. MS was found in 24.6% (95%CI: 22.4%-26.8%) using the standard criteria and in 25.5% (23.2%-27.7%) using the modified criteria. Agreement was high; kappa 0.81 (p<0.0001) and tau-b 0.81 (p<0.0001), with a McNemar value of 0.2325. Kappa coefficients varied between 1.0 and 0.76 in subgroups according to sex, age-group, severity of disease, and duration of therapy. CONCLUSIONS: MS in outpatients with schizophrenia may be assessed by either the standard or the modified NCEP ATP III criteria without losing reliability.

Cardiovascular and metabolic risk in outpatients with schizophrenia treated with antipsychotics: results of the CLAMORS Study.

AIM: To assess the prevalence of Coronary Heart Disease (CHD) and Metabolic Syndrome (MS) in patients treated with antipsychotics. METHODS: Retrospective, cross-sectional, multicenter study in which 117 Spanish psychiatrists (the CLAMORS Study Collaborative Group) recruited consecutive outpatients meeting DSM-IV criteria for Schizophrenia, Schizophreniform or Schizoaffective Disorder, receiving antipsychotic treatment for at least 12 weeks. CHD risk was assessed by SCORE (10-year CV death) and Framingham (10-year all CHD events) function. MS was defined by at least 3 of the following components: waist circumference >102 (men)/>88 (women) cm; triglycerides > or =150 mg/dl; HDL-cholesterol <40 mg/dl (men)/<50 mg/dl (women); blood pressure > or =130/85; fasting glucose > or =110 mg/dl. RESULTS: 1452 evaluable patients (863 men, 60.9%), aged 40.7+/-12.2 years (mean+/-SD) were included. MS was present in 24.6% [23.6% (men), 27.2% (women); p=0.130)]. The overall 10-year risks were 0.9+/-1.9 (SCORE) and 7.2+/-7.6 (Framingham). 8% (95%CI: 6.5-9.5) and 22.1% (95%CI: 20.0-24.3) of patients showed a high/very high risk according to SCORE (> or =3%) and Framingham (> or =10%) function. Abdominal obesity and low HDL-cholesterol were more prevalent in women: 54.5% (95%CI: 50.2-58.9) versus 34.3% (95%CI: 31.0-37.7), and 46.1% (95%CI: 41.4) versus 28.5 (95%CI: 50.8), p<0.001 in both cases. Hypertension and hypertriglyceridemia were more prevalent in men: 59.0% (95%CI: 55.7-62.3) versus 46.0% (95%CI: 41.8-50.2), and 40.7% (95%CI: 37.2-44.2) versus 32.4 (95%CI: 28.3-36.5), p<0.01 in both cases. CONCLUSIONS: CHD risk and MS prevalences among patients with schizophrenia treated with antipsychotics were in the same range as the Spanish general population 10 to 15 years older.

Development and validation of the Migraine Screen Questionnaire (MS-Q).

AIM: To develop and evaluate the clinimetric properties of a new migraine screening questionnaire: the Migraine Screen Questionnaire (MS-Q). BACKGROUND: Migraine is a public health problem requiring screening programs and tools to ensure early detection. METHODS: A questionnaire was developed based on the criteria of the International Headache Society (IHS) and a review of the literature by a committee of experts. Stage I: The original version of the MS-Q was distributed by mail and completed by Pfizer employees and self-administered to neurological patients; all subjects were afterward evaluated by a neurologist who was blinded to the MS-Q results, to establish an independent IHS diagnosis. Stage II: A final version of the MS-Q was administered to neurological patients to confirm clinimetric properties. Logistic regression and receiver-operator characteristic curve statistical methods were used and the 95% confidence interval, sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values, were estimated. RESULTS: Of the 605 subjects recruited, 465 were evaluable (325 in stage I and 140 in stage II). Of the original 15 items, 5 conformed the final version of the MS-Q: frequency and intensity of headache; a duration of between 4 hours and 3 days; nausea; sensitivity to light/noise; and disability. A cutoff point of > or = 4 points showed a sensitivity of 0.93 (95% CI = 0.87 to 0.99), specificity of 0.81 (95% CI = 0.72 to 0.91), PPV of 0.83 (95% CI = 0.75 to 0.91), and NPV of 0.92 (95% CI = 0.85 to 0.99). Cronbach's alpha coefficient = 0.82. CONCLUSIONS: The MS-Q showed adequate validity and reliability, and it could be a good screening tool for application to clinical practice and research.

[Validation of the Spanish version of the SEAR (Self-Esteem And Relationship Questionnaire) for men with erectile dysfunction]. / Validación de la versión española del cuestionario SEAR (Self-Esteem And Relationship Questionnaire) para varones con disfunción eréctil.

BACKGROUND AND OBJECTIVE: The aim was to validate the Spanish version of the Self-Esteem and Relationship Questionnaire (SEAR), specific for patients with erectile dysfunction (ED), and based on the concept of self-esteem, for use in research and clinical practice in Spain. PATIENTS AND METHOD: Observational, prospective, multisite, study comparing patients with ED (IIEF questionnaire score < 26 points), with a score (3/4) 16 points in the Self-Esteem domain of the SEAR questionnaire and undergoing treatment with sildenafil (group A), and healthy control subjects without ED. Patients with ED were assessed at baseline and after 3 months' treatment. RESULTS: Among 586 evaluable subjects (504 patients with ED and 82 health subjects) the questionnaire showed: a) adequate feasibility with a percentage of patients without response < 5%; b) adequate reliability with Cronbach alpha coefficients for the total and all domains (Sexual-Relationship, Confidence, Self-Esteem, and Overall-Relationship), of SEAR questionnaire, respectively: 0.92, 0.89, 0.84, 0.75, and 0.82 un patients, and 0.86, 0.80, 0.73, 0.56 and 0.74 un healthy subjects; c) adequate discriminatory validity between patients and healthy subjects (Mann-Whitney test, p < 0.0001), and between patients with vaying degrees of ED (Kruskall-Wallis test, p < 0.05); d) adequate convergent/divergent validity (correlations > 0.5 with the IIEF questionnaire and r > 0.3 and < 0.5 with Mental Health domain score of SF-12 questionnaire); e) adequate construct validity, obtaining 2 domains: Sexual-Relationship, and Confidence, and f) adequate sensitivity to clinical changes (SES: 2.1/SRM: 1.5/SEM: 4.4/MID: 13.1). Mark scores were estimated. CONCLUSIONS: The Spanish version of the SEAR questionnaire showed adequate and similar psychometric properties to those shown with the original English version.

Validación de la versión española del cuestionario SEAR (Self-Esteem And Relationship Questionnaire) para varones con disfunción eréctil / Validation of the Spanish version of the SEAR (Self-Esteem And Relationship Questionnaire) for men with erectile dysfunction

Fundamento y objetivo: Validar la versión española del cuestionario específico para disfunción eréctil SEAR (Self-Esteem And Relationship Questionnaire), centrado en el concepto de autoestima, para su uso en la investigación y/o práctica clínica en España. Pacientes y método: Estudio observacional, prospectivo, multicéntrico y comparativo entre pacientes con disfunción eréctil (DE) ­puntuación inferior a 26 puntos en cuestionario IIEF (Índice Internacional de Función Eréctil)­ y con ¾ 16 puntos o menos en la dimensión Autoestima del cuestionario SEAR, en tratamiento con sildenafilo (grupo A), y sujetos controles sanos sin DE (grupo B). Se evaluó a los pacientes con DE en la visita basal y a los 3 meses de tratamiento. Resultados: El cuestionario mostró en 586 sujetos valorables (504 pacientes con DE y 82 sujetos sanos): a) adecuada factibilidad, con porcentaje de pacientes sin respuesta inferior al 5%; b) adecuada fiabilidad, con coeficientes alfa de Cronbach para SEAR total y dimensiones Relaciones sexuales, Autoconfianza, Autoestima y Relaciones en General, respectivamente de 0,92, 0,89, 0,84, 0,75 y 0,82 en los pacientes, y de 0,86, 0,80, 0,73, 0,56 y 0,74 en sujetos sanos; c) adecuada validez discriminante entre pacientes y sujetos sanos (prueba Mann-Whitney p 0,5 con cuestionario IIEF, y r 0,3 con escala Salud Mental del cuestionario SF-12); e) adecuada validez de constructo, encontrando las dimensiones Relaciones Sexuales y Autoconfianza, y f) adecuada sensibilidad para detectar cambios clínicos (tamaño del efecto estandarizado: 2,1; respuesta media estandarizada: 1,5; error estándar de medida: 4,4; diferencia mínimamente importante: 13,1). Se estimaron las puntuaciones de referencia. Conclusiones: La versión española del cuestionario SEAR mostró propiedades psicométricas adecuadas y similares a las de la versión original en inglés

Background and objective: The aim was to validate the Spanish version of the Self-Esteem and Relationship Questionnaire (SEAR), specific for patients with erectile dysfunction (ED), and based on the concept of self-esteem, for use in research and clinical practice in Spain. Patients and method: Observational, prospective, multisite, study comparing patients with ED (IIEF questionnaire score 0.5 with the IIEF questionnaire and r > 0.3 and < 0.5 with Mental Health domain score of SF-12 questionnaire); e) adequate construct validity, obtaining 2 domains: Sexual-Relationship, and Confidence, and f) adequate sensitivity to clinical changes (SES: 2.1/SRM: 1.5/SEM: 4.4/MID: 13.1). Mark scores were estimated. Conclusions: The Spanish version of the SEAR questionnaire showed adequate and similar psychometric properties to those shown with the original English version