Retrospective data analysis of animal poisoning events in Liguria.

Intentional poisoning represents a serious risk to domestic and wild animals, and it can be an environmental and human health issue as well . This paper is a retrospective study, which covers a decade, based on animal poisoning cases and poisoned baits that were submitted for diagnostic examinations to the Veterinary Medical Research Institute for Piedmont, Liguria and the Aosta Valley (IZS-PLVA) in Liguria region. All data were collected through a passive surveillance system introduced in Italy by a decree of the Ministry of Health in January 2009. 43.2% of the animal poisoning cases were confirmed by toxicological analysis, whereas toxic agents were detected in 31.1% of the baits. The most affected animal species were dogs and cats, followed by synanthropic birds,. Only 4% of the total poisoning events analysed involved wild animals and cases of livestock poisoning were minimal. An increased number of cases in January, March, April and August was noticed, but no seasonal trend was detected. The most affected areas were the ones with the highest level of urbanization and population density. The major cause of the poisonings and the most common substances detected in the examined baits were anticoagulants whereas cholinesterase inhibitors, organochlorine pesticides and carbamates were detected in a minor number of cases. This study raises concerns about deliberate animal poisoning in ligurian region and highlights the necessity to fight this phenomenon as it endangers animals, humans and environment.

Internalizing and externalizing symptoms and suicidal behaviour in young people: a systematic review and meta-analysis of longitudinal studies.

OBJECTIVE: To assess internalizing and externalizing symptoms as risk factors for suicidal behaviour and suicide among adolescents and young adults. METHOD: We conducted a systematic review of articles published until January 2017. We identified 26 883 potential papers; 1701 full-text articles were assessed for eligibility, of which 1479 were excluded because of methodological reasons. Diverse meta-analyses were performed for each group of symptoms. Odds ratios (ORs) and 95% confidence intervals (95% CI) or beta coefficients for categorical variables, and effect size (ES) were calculated for continuous variables. RESULTS: Finally, 41 studies were included, involving participants aged 12-26 years for a systematic review, and 24 articles were included for meta-analysis. The meta-analysis showed that youths with any internalizing (ES = 0.93) or externalizing symptoms (ES = 0.76 and OR = 2.59) were more likely to attempt suicide in future. This effect was also seen in depression symptoms (OR = 6.58 and ES = 1.00), legal problems (OR = 3.36), and anxiety (ES = 0.65). CONCLUSION: Reported internalizing and externalizing symptoms are predictors of suicide behaviour in young people; therefore, the detection and management of these symptoms in young populations could be a crucial strategy for preventing suicidality in this group.

Sexual orientation and suicidal behaviour in adolescents and young adults: systematic review and meta-analysis.

BackgroundResearch suggests that lesbian, gay and bisexual (LGB) adolescents have a higher risk of suicidal behaviours than their heterosexual peers, but little is known about specific risk factors.AimsTo assess sexual orientation as a risk factor for suicidal behaviours, and to identify other risk factors among LGB adolescents and young adults.MethodA systematic search was made of six databases up to June 2015, including a grey literature search. Population-based longitudinal studies considering non-clinical populations aged 12-26 years and assessing being LGB as a risk factor for suicidal behaviour compared with being heterosexual, or evaluating risk factors for suicidal behaviour within LGB populations, were included. Random effect models were used in meta-analysis.ResultsSexual orientation was significantly associated with suicide attempts in adolescents and youths (OR = 2.26, 95% CI 1.60-3.20). Gay or bisexual men were more likely to report suicide attempts compared with heterosexual men (OR = 2.21, 95% CI 1.21-4.04). Based on two studies, a non-significant positive association was found between depression and suicide attempts in LGB groups.ConclusionsSexual orientation is associated with a higher risk of suicide attempt in young people. Further research is needed to assess completed suicide, and specific risk factors affecting the LGB population.

Longitudinal association between self-injurious thoughts and behaviors and suicidal behavior in adolescents and young adults: A systematic review with meta-analysis.

BACKGROUND: Adolescents with previous self-injurious thoughts and behaviors (SITB) have over 2-fold risk of dying by suicide, higher than older ages. This meta-analysis aims to disentangle the association of each SITB with subsequent suicidal behavior in adolescence/young adulthood, the contribution of each SITB, and the proportion of suicide deaths with no previous suicide attempt. METHODS: We searched 6 databases until June 2015. INCLUSION CRITERIA: 1. Assessment of any previous SITB [a) suicidal thoughts and behaviors (ideation; threat/gesture; plan; attempt); b) non-suicidal thoughts and behaviors (thoughts; threat/gesture; self-injury); c) self-harm] as a risk factor of suicide attempt or suicide death; 2. Case-control or cohort studies; 3. Subjects aged 12-26y. Random effect models, metaregression analyses including mental health and environmental variables, and population attributable risks (PAR)s were estimated. RESULTS: From 23,682 potentially eligible articles, 29 were included in the meta-analysis (1,122,054 individuals). While 68% of all youth suicide deaths had no previous suicide attempt, suicide death was very strongly associated with any previous SITB (OR=22.53, 95%CI: 18.40-27.58). Suicide attempts were also associated with a history of previous SITB (OR=3.48, 95%CI: 2.71-4.43). There were no moderating effects for mental health and environmental features. The PAR of previous SITB to suicide attempts is 26%. LIMITATIONS: There is considerable heterogeneity between the available studies. Due to limitations in the original studies, an over-estimation of the proportion dying at their first attempt cannot be ruled out, since they might have missed unrecognized previous suicide attempts. CONCLUSIONS: Although more than two thirds of suicide deaths in adolescence/young adulthood have occurred with no previous suicidal behavior, previous SITBs have a much higher risk of dying by suicide than previously reported in this age group.

Exposure to violence, a risk for suicide in youths and young adults. A meta-analysis of longitudinal studies.

OBJECTIVE: To assess the association and magnitude of the effect of early exposure to different types of interpersonal violence (IPV) with suicide attempt and suicide death in youths and young adults. METHOD: We searched six databases until June 2015. Inclusion criteria were as follows: (1) assessment of any type of IPV as risk factor of suicide attempt or suicide: (i) child maltreatment [childhood physical, sexual, emotional abuse, neglect], (ii) bullying, (iii) dating violence, and (iv) community violence; (2) population-based case-control or cohort studies; and (3) subjects aged 12-26 years. Random models were used for meta-analyses (Reg: CRD42013005775). RESULTS: From 23 682 articles, 29 articles with 143 730 subjects for meta-analyses were included. For victims of any IPV, OR of subsequent suicide attempt was 1.99 (95% CI: 1.73-2.28); for child maltreatment, 2.25 (95% CI: 1.85-2.73); for bullying, 2.39 (95% CI: 1.89-3.01); for dating violence, 1.65 (95% CI: 1.40-1.94); and for community violence, 1.48 (95% CI: 1.16-1.87). Young victims of IPV had an OR of suicide death of 10.57 (95% CI: 4.46-25.07). CONCLUSION: Early exposure to IPV confers a risk of suicide attempts and particularly suicide death in youths and young adults. Future research should address the effectiveness of preventing and detecting early any type of IPV exposure in early ages.

Obesity, metabolic syndrome and Mediterranean diet: Impact on depression outcome.

OBJECTIVE: Obesity, metabolic syndrome (MetS) and low adherence to Mediterranean diet are frequent in major depression patients and have been separately related with prognosis. The aim of this study is to analyse their predictive power on major depression outcome, at 6 and 12 months. METHODS: 273 Major depressive patients completed the Beck Depression Inventory for depressive symptoms and the 14-item Mediterranean diet adherence score. MetS was diagnosed according to the International Diabetes Federation (IDF). RESULTS: At the baseline Mediterranean diet adherence was inversely associated with depressive symptoms (p=0.007). Depression response was more likely in those patients with normal weight (p=0.006) and not MetS (p=0.013) but it was not associated with Mediterranean diet adherence (p=0.625). Those patients with MetS and obesity were less likely to improve symptoms of depression than patients with obesity but not MetS. CONCLUSIONS: Obesity and MetS, but not low adherence to the Mediterranean diet at baseline, predicted a poor outcome of depression at 12 months. Our study suggests that MetS is the key factor that impacts negatively in depression prognosis, rather than obesity or diet. If this finding is confirmed, clinicians should be aware about MetS diagnosis and treatment in overweight depressed patients, especially if outcome is not being satisfactory enough.

Obesity reduces the pro-angiogenic potential of adipose tissue stem cell-derived extracellular vesicles (EVs) by impairing miR-126 content: impact on clinical applications.

BACKGROUND/OBJECTIVES: Soluble factors and cell-derived extracellular vesicles (EVs) are crucial tissue repair mediators in cell-based therapy. In the present study, we investigate the therapeutic impact of EVs released by adipose tissue-derived stem cells (ASCs) recovered from obese subjects' visceral and subcutaneous tissues. METHODS: ASCs were recovered from 10 obese (oASCs) and 6 non-obese (nASCs) participants and characterized. In selected experiments, nASCs and oASCs were cultured with palmitic acid (PA) or high glucose (HG), respectively. EVs from obese (oEVs) and non-obese (nEVs) subjects' visceral and subcutaneous ASCs were collected after ultracentrifugation and analyzed for their cargo: microRNA-126 (miR-126), vascular endothelial growth factor (VEGF), and matrix metalloproteinase 2 (MMP-2), and for their biological effects on endothelial cells (ECs). Western blotting analysis and loss- and gain-of function experiments were performed. RESULTS: oEVs show impaired angiogenic potential compared with nEVs. This effect depends on EV cargo: reduced content of VEGF, MMP-2 and, more importantly, miR-126. We demonstrate, using gain- and loss-of-function experiments, that this reduced miR-126 content leads to Spred1 upregulation and the inhibition of the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway in ECs. We also show that PA treatment of nASCs translates into the release of EVs that recapitulate oEV cargo. Moreover, HG treatment of oASCs further reduces miR-126 EV content and EV-mediated in vitro angiogenesis. Finally, impaired pro-angiogenic potential is also detected in EVs released from obese subcutaneous adipose tissue-derived ASCs. CONCLUSIONS: These results indicate that obesity impacts on EV pro-angiogenic potential and may raise concerns about the use of adipose tissue-derived EVs in cell-based therapy in the obese setting.

Lifestyle change recommendations in major depression: Do they work?

BACKGROUND: Modifying some lifestyle factors can be useful in depression, at least as an adjuvant treatment. Combining different lifestyle interventions seems to be an adequate strategy to increase their antidepressant efficacy according with preliminary studies, but this issue has not been enough investigated. METHODS: The present study is a randomized, double-blinded, multicentre, two arm-parallel clinical trials, with a 12 month follow-up. The sample consisted of 273 Primary Care patients. Four combined hygienic-dietary written recommendations were given to the patients about diet, exercise, light exposure and sleep hygiene. RESULTS: Both active and control interventions were associated with improvement on BDI (Beck Depression Inventory) scores. However, there were not statistically significant differences (7.0 vs. 7.6; p=0.594). LIMITATIONS: We were unable to monitor whether patients carry out recommendations. Intervention could be too difficult to accomplish for depressed patients without enough support and supervision. CONCLUSIONS: Just giving written lifestyle recommendations are not enough for depressive patients to benefit from them, so perhaps lifestyle change recommendations work or do not work on Depression depending on how they are presented to patients and on monitoring systems of their implementation.

Sueño y depresión en una muestra de pacientes con dolor crónico / Sleep and depressive disorder in patients with chronic pain

Introducción: los trastornos del sueño y los trastornos afectivos (trastorno depresivo mayor y trastorno de ansiedad generalizada) son dos de las condiciones comórbidas más frecuentes en los pacientes con dolor crónico. Objetivo: el objetivo principal de este estudio es evaluar la calidad del sueño y la prevalencia del trastorno depresivo mayor y trastorno de ansiedad generalizada en pacientes con dolor crónico osteomuscular. Como objetivos secundarios se señalan: comparar la calidad del sueño y la evaluación del dolor en distintas variables y conocer los predictores de la calidad del sueño. Material y métodos: se diseñó un estudio descriptivo transversal realizado en la Unidad del Dolor del Servicio de Anestesiología y Reanimación del Hospital Son Llàtzer (Palma de Mallorca). Un total de 39 pacientes participaron en el estudio, todos ellos mayores de edad y con diagnóstico de dolor crónico tipo osteomuscular. La inclusión se realizó durante los meses de marzo, abril y mayo de 2013. Se excluyeron aquellos pacientes menores de 18 años, rechazaban participar en el estudio y/o presentaban un trastorno psiquiátrico grave (demencia psicosis, abuso de alcohol/drogas). Se utilizó un cuestionario de elaboración propia para recoger variables sociodemográficas, de estilo de vida y clínicas, una escala visual analógica para evaluar la intensidad del dolor, la entrevista Neuropsiquiátrica Internacional para determinar diagnóstico de trastorno depresivo mayor y trastorno de ansiedad generalizada, el Cuestionario de Pittsburgh para evaluar la calidad del sueño y la Escala de Depresión Montgomery-Asberg para evaluar la gravedad de la sintomatología depresiva. Resultados: la muestra refirió una mala calidad del sueño. El 69,2 % de la muestra presentaba un trastorno depresivo mayor y/o un 65,5 % un trastorno de ansiedad generalizada. No se encontraron diferencias estadísticamente significativas en la calidad del sueño entre los grupos tratados con opioides potentes y tratados con opioides menores/antiinflamatorios. Existen diferencias estadísticamente significativas en determinados ítems del Cuestionario de Pittsburgh: calidad subjetiva del sueño, eficiencia habitual, perturbaciones del sueño, disfunción durante el día y en la puntuación total del cuestionario, así como en la evaluación del dolor en el que los pacientes con depresión presentaban puntuaciones más elevadas respecto a los que no tenían depresión. Los predictores significantes de la calidad del sueño fueron la edad y la gravedad de la depresión. Conclusiones: estos resultados van en la línea de aquellas investigaciones que muestran que los pacientes con dolor crónico presentan pobre calidad de sueño, depresión y ansiedad. Se necesitan futuras investigaciones para evaluar estas variables, conocer la importancia de los factores implicados en esta condición médica y mejorar el manejo clínico y la calidad de vida de estos pacientes (AU)

Introduction: Sleep disturbances and affective disorders major depressive disorder and generalized anxiety disorder) are two comorbidities very frequents in patients with chronic pain. Objective: The main objective is to evaluate sleep quality and the prevalence of major depressive disorder and generalized anxiety disorder in patients with musculoskeletal chronic pain. As secondary objectives: To compare sleep quality and pain severity with different variables and to know the sleep quality predictors. Material and methods: Transversal descriptive study was made in the Pain Unit from Son Llàtzer Hospital (Palma de Mallorca, Spain). A total of 39 patients were included, all of them older than 18 years old and with musculoskeletal chronic pain. Inclusion was during March, April and May 2013. Excluded were patients younger than 18 years old, those who refuse to participate in the study or/and those who diagnosed with severe psychiatric disorder (dementia, psychosis, alcohol/drug abuse). Pain severity was assessed by a visual analogue scale, major depressive disorder and generalized anxiety disorder was assessed by the International Neuropsychiatric Interview, sleep quality was assessed by the Pittsburgh Questionnaire and depressive symptomatology was assessed by the Montgomery-Asberg Questionnaire. Results: Chronic pain patients related poor sleep quality. 69.2 % of patients had major depressive disorder and/or 65.5% had a generalized anxiety disorder. There are not statistical differences in quality of sleep between pharmacological groups (potens opioids vs. minor/antiinflamatories). There are statistical differences in some Pittsburgh Questionnaire items: subjective sleep quality, regular efficiency, dreams perturbances, daily dysfunction and total score, as well as, in pain severity: patients with depression had higher scores than patients without depression. The significant predictors of sleep quality were age and depression severity. Conclusions: These results are in accordance with other studies that show that chronic pain patients suffer poor sleep quality, depression and anxiety. Future researchers are necessary to evaluate these variables, to know the importance of these factors that play a role in this medical condition and to improve clinical management and quality of life of these patients (AU)

Comparative efficacy of two interventions to discontinue long-term benzodiazepine use: cluster randomised controlled trial in primary care.

BACKGROUND: Benzodiazepines are extensively used in primary care, but their long-term use is associated with adverse health outcomes and dependence. AIMS: To analyse the efficacy of two structured interventions in primary care to enable patients to discontinue long-term benzodiazepine use. METHOD: A multicentre three-arm cluster randomised controlled trial was conducted, with randomisation at general practitioner level (trial registration ISRCTN13024375). A total of 532 patients taking benzodiazepines for at least 6 months participated. After all patients were included, general practitioners were randomly allocated (1:1:1) to usual care, a structured intervention with follow-up visits (SIF) or a structured intervention with written instructions (SIW). The primary end-point was the last month self-declared benzodiazepine discontinuation confirmed by prescription claims at 12 months. RESULTS: At 12 months, 76 of 168 (45%) patients in the SIW group and 86 of 191 (45%) in the SIF group had discontinued benzodiazepine use compared with 26 of 173 (15%) in the control group. After adjusting by cluster, the relative risks for benzodiazepine discontinuation were 3.01 (95% CI 2.03-4.46, P<0.0001) in the SIW and 3.00 (95% CI 2.04-4.40, P<0.0001) in the SIF group. The most frequently reported withdrawal symptoms were insomnia, anxiety and irritability. CONCLUSIONS: Both interventions led to significant reductions in long-term benzodiazepine use in patients without severe comorbidity. A structured intervention with a written individualised stepped-dose reduction is less time-consuming and as effective in primary care as a more complex intervention involving follow-up visits.

Stressful life events severity in patients with first and recurrent depressive episodes.

BACKGROUND: Stressful life events are associated with depression and their role in first onset and recurrences is a promising but controversial perspective of research. The objective is to analyze the role of number of previous episodes and life events exposure in a large sample of primary care depressive patients taking into account life events severity. METHOD: 10,257 patients with DSM-IV criteria for a current single or recurrent major depressive episode were recruited by 2,056 general practitioners in a cross-sectional epidemiological study. Patients answered the Montgomery-Asberg Depression Rating Scale, the Patient Health Questionnaire and the Social Readjustment Rating Scale (SRRS). Stressful life events were categorized into three levels of severity (severe, moderate and mild). All relevant confounding variables were analyzed: age, gender, depression severity, somatic symptoms severity and length of episode. RESULTS: We found a significant positive correlation with number of episodes and depression severity. There was no significant correlation of SRRS scores with age, gender and length of episode. ANOVA exploring life events severity with regard to number of episodes showed statistically differences in SRRS total score, moderate life events and mild life events (F = 15.14, p < 0.001) but not for severe life events. CONCLUSIONS: Prevention and treatment strategies for recurrent depression need to manage life stressful events during mild and long-term periods and not just in the initial recurrences of the disease.

A diabetic milieu promotes OCT4 and NANOG production in human visceral-derived adipose stem cells.

AIMS/HYPOTHESIS: Successful outcomes have been obtained by exploiting adipose-derived stem cells (ASCs) in regenerative medicine. NADPH oxidase (NOX)-generated reactive oxygen species (ROS) are known to control stem cell self-renewal. Several high glucose (HG)-mediated effects depend on NOX-generated ROS. In this study, we investigated whether, and how mechanistically, HG concentrations control ASC fate in patients with diabetes. METHODS: ASCs from the visceral adipose tissue of non-diabetic (N-ASCs) and diabetic participants (D-ASCs), identified by surface markers, were counted and evaluated for ROS generation and stem cell properties. Their ability to release soluble factors was assessed by BioPlex analysis. To reproduce an in vitro diabetic glucose milieu, N-ASCs were cultured in HG (25 mmol/l) or normal glucose (NG) concentration (5 mmol/l), as control. ASC pluripotency was assessed by in vitro study. The p47(phox) NOX subunit, AKT and octamer-binding transcription factor 4 (OCT4; also known as POU5F1) were knocked down by small-interfering RNA technology. Stem-cell features were evaluated by sphere cluster formation. RESULTS: The ASC number was higher in diabetic patients than in non-diabetic controls. Production of OCT4 and NANOG, stem-cell-specific transcription factors, was upregulated in D-ASCs compared with N-ASCs. Moreover, we found that ROS production and AKT activation drove D-ASC, but not N-ASC, secretion. When N-ASCs were cultured in vitro in the presence of HG, they also expressed OCT4/NANOG and formed spheres. By knock-down of the p47(phox) NOX subunit, AKT and OCT4 we demonstrated that NOX-generated ROS and their downstream signals are crucial for HG-mediated ASC de-differentiation and proinflammatory cytokine production. CONCLUSIONS/INTERPRETATION: We herein provide a rationale for exploiting D-ASCs in regenerative medicine and/or exploiting HG preconditioning to increase ASCs ex vivo.

Intervención farmacéutica en la adherencia al tratamiento de pacientes con enfermedad renal crónica / Pharmaceutical intervention on the therapeutic adherence in patients with chronic renal disease

Objetivos. Evaluar el cumplimiento terapéutico global en pacientes con enfermedad renal crónica (ERC) estadio 3-5, y determinar si la intervención farmacéutica mejora el cumplimiento terapéutico. Material y métodos. Estudio prospectivo no controlado de intervención tipo antes y después (julio 2008-marzo 2009), realizado en la Unidad de Atención Farmacéutica. Pacientes mayores de 65 años con ERC 3-5, polimedicados y en tratamiento con eritropoyetina. Se utilizó el programa Infowin® para ofrecer información escrita a los pacientes, quienes firmaron consentimiento informado. Para valorar el cumplimiento terapéutico se aplicaron los cuestionarios Haynes-Sackett y Morisky-Green. Resultados. De 103 pacientes candidatos, se propuso participar a 94; aceptaron 53 (56,4%); mujeres, 60,4%; media de edad, 76,8±6,9 años. Causas de exclusión: negación a participar (19,5%); el paciente o el cuidador habitual no asistieron (70,7%); paciente institucionalizado (9,8%). Número medio de fármacos/paciente: 10,8±2,97. El 88,7% no presentó dificultades en tomar la medicación (Haynes-Sackett) y el 73,6% se consideró cumplidor (Morisky-Green). Al relacionar estos dos métodos, se objetivó diferencia entre ambos (p=0,036). Los pacientes con dificultad en tomar la medicación fueron menos cumplidores en un 45,6%. Se realizó por segunda vez el cuestionario Morisky-Green al 78,6% de los incumplidores, quienes presentaron un 45,5% más de cumplimiento, aumentándose el cumplimiento global a un 87,8% (p=0,00003). Se detectaron 52 problemas relacionados con la medicación (PRM). Conclusiones. El cumplimiento inicial de los pacientes con ERC 3-5 se considera notable. No obstante, tras la intervención farmacéutica, se observa una mejora en la adherencia a los tratamientos, con resultados estadísticamente significativos(AU)

Objectives. To assess the therapeutic adherence in patients with stage 3-5 chronic renal disease (CRD), and evaluate whether pharmaceutical intervention improves medication adherence. Material and methods. A prospective uncontrolled before-after study (July 2008-March 2009) was carried out in the Pharmaceutical Care Unit of a tertiary hospital. Polymedicated patients >65years with stage 3-5 CRD, and on treatment with erythropoietin. Infowin® program was used to provide written information during the interviews with patients, who signed the informed consent. The Haynes-Sackett and Morisky-Green questionnaires were used to assess the therapeutic adherence. Results. Of a total of 103 candidates, we asked 94 patients to participate, of whom 53 agreed; women 60.4%, mean age: 76.8±6.9years. Exclusion criteria: refusal to participate (19.5%), non-appearance of patient or usual caregiver (70.7%), andinstitutionalised patients (9.8%). Average number of drugs per patient: 10.8±2.97. A total of 88.7% had no difficulty in taking medication (Haynes-Sackett) and 73.6% were considered compliant (Morisky-Green). Differences were observed when comparing both methods (P=.036). Patients with difficulty in taking medication were less compliant (45.6%). The Morisky-Green questionnaire was used for a second time on 78.6% of unreliable patients, and obtained a 45.5% increase in compliance, increasing the overall compliance to 87.8% (P=.00003). Fifty-two drug-related problems (DRP) were detected. Conclusions. The initial compliance of patients with stage 3-5 CRD was was noteworthy. However, after pharmaceutical intervention there was a statistically significant improvement in adherence to therapy(AU)

[Pharmaceutical intervention on the therapeutic adherence in patients with chronic renal disease]. / Intervención farmacéutica en la adherencia al tratamiento de pacientes con enfermedad renal crónica.

OBJECTIVES: To assess the therapeutic adherence in patients with stage 3-5 chronic renal disease (CRD), and evaluate whether pharmaceutical intervention improves medication adherence. MATERIAL AND METHODS: A prospective uncontrolled before-after study (July 2008-March 2009) was carried out in the Pharmaceutical Care Unit of a tertiary hospital. Polymedicated patients >65 years with stage 3-5 CRD, and on treatment with erythropoietin. Infowin(®) program was used to provide written information during the interviews with patients, who signed the informed consent. The Haynes-Sackett and Morisky-Green questionnaires were used to assess the therapeutic adherence. RESULTS: Of a total of 103 candidates, we asked 94 patients to participate, of whom 53 agreed; women 60.4%, mean age: 76.8 ± 6.9 years. EXCLUSION CRITERIA: refusal to participate (19.5%), non-appearance of patient or usual caregiver (70.7%), and institutionalised patients (9.8%). Average number of drugs per patient: 10.8 ± 2.97. A total of 88.7% had no difficulty in taking medication (Haynes-Sackett) and 73.6% were considered compliant (Morisky-Green). Differences were observed when comparing both methods (P=.036). Patients with difficulty in taking medication were less compliant (45.6%). The Morisky-Green questionnaire was used for a second time on 78.6% of unreliable patients, and obtained a 45.5% increase in compliance, increasing the overall compliance to 87.8% (P=.00003). Fifty-two drug-related problems (DRP) were detected. CONCLUSIONS: The initial compliance of patients with stage 3-5 CRD was was noteworthy. However, after pharmaceutical intervention there was a statistically significant improvement in adherence to therapy.

PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer.

There is a strong rationale to therapeutically target the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway in breast cancer since it is highly deregulated in this disease and it also mediates resistance to anti-HER2 therapies. However, initial studies with rapalogs, allosteric inhibitors of mTORC1, have resulted in limited clinical efficacy probably due to the release of a negative regulatory feedback loop that triggers AKT and ERK signaling. Since activation of AKT occurs via PI3K, we decided to explore whether PI3K inhibitors prevent the activation of these compensatory pathways. Using HER2-overexpressing breast cancer cells as a model, we observed that PI3K inhibitors abolished AKT activation. However, PI3K inhibition resulted in a compensatory activation of the ERK signaling pathway. This enhanced ERK signaling occurred as a result of activation of HER family receptors as evidenced by induction of HER receptors dimerization and phosphorylation, increased expression of HER3 and binding of adaptor molecules to HER2 and HER3. The activation of ERK was prevented with either MEK inhibitors or anti-HER2 monoclonal antibodies and tyrosine kinase inhibitors. Combined administration of PI3K inhibitors with either HER2 or MEK inhibitors resulted in decreased proliferation, enhanced cell death and superior anti-tumor activity compared with single agent PI3K inhibitors. Our findings indicate that PI3K inhibition in HER2-overexpressing breast cancer activates a new compensatory pathway that results in ERK dependency. Combined anti-MEK or anti-HER2 therapy with PI3K inhibitors may be required in order to achieve optimal efficacy in HER2-overexpressing breast cancer. This approach warrants clinical evaluation.

Medical comorbidity in recurrent versus first-episode depressive patients.

OBJECTIVE: This study compares the comorbidity of affective disorders and medical diseases in primary care patients with either a first or recurrent depressive episode. METHOD: A cross-sectional epidemiological study in primary care centres in Spain was designed. A total of 10,257 primary care patients suffering a DSM-IV major depressive episode (MDD) were analysed. Depression was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS), and World Health Organization (WHO) medical diagnoses were provided by the patient's general practitioner according to medical records revised on the basis of radiology or laboratory test data. RESULTS: A total of 88.6% of recurrent patients and 71.1% of first-episode depressive patients reported a medical condition (aOR = 2.61, CI = 2.31-2.93). All medical conditions were more prevalent in the recurrent group than in first-episode group, and with the exception of myocardial infarction, psoriasis and migraine, all other crude ORs showed statistically significant differences between first- and recurrent episodes patients after adjusting for gender, age, education, socioeconomic status and body mass index (BMI). CONCLUSION: Recurrent depression is associated with a decrement in health that is significantly greater than in first-episode depression. Special attention needs to be paid to the physical health in the middle- and long-term management of patients with affective disorders.

Validation of a Spanish language version of the pain self-perception scale in patients with fibromyalgia.

BACKGROUND: The Pain Self-Perception Scale (PSPS) is a 24-item questionnaire used to assess mental defeat in chronic pain patients. The aim of this study was to develop a Spanish language version of the PSPS (PSPS-Spanish), to assess the instrument's psychometric properties in a sample of patients with fibromyalgia and to confirm a possible overlapping between mental defeat and pain catastrophizing. METHODS: The PSPS was translated into Spanish by three bilingual content and linguistic experts, and then back-translated into English to assess for equivalence. The final Spanish version was administered, along with the Hospital Anxiety Depression Scale (HADS), Pain Visual Analogue Scale (PVAS), Pain Catastrophizing Scale (PCS) and Fibromyalgia Impact Questionnaire (FIQ), to 250 Spanish patients with fibromyalgia. RESULTS: PSPS-Spanish was found to have high internal consistency (Cronbach's α = 0.90 and the item-total r correlation coefficients ranged between 0.68 and 0.86). Principal components analysis revealed a one-factor structure which explained 61.4% of the variance. The test-retest correlation assessed with the intraclass correlation coefficient, over a 1-2 weeks interval, was 0.78. The total PSPS score was significantly correlated with all the questionnaires assessed (HADS, PVAS, PCS, and FIQ). CONCLUSIONS: The Spanish version of the PSPS appears to be a valid tool in assessing mental defeat in patients with fibromyalgia. In patients with fibromyalgia and Post-Traumatic Stress Disorder (PTSD), PSPS-Spanish correlates more intensely with FIQ than in patients without PTSD. Mental defeat seems to be a psychological construct different to pain catastrophizing.

Dietary changes and colorectal cancer trends in Spain during 1951-2007.

OBJECTIVES: Analysis of the evolution of colorectal cancer in Spain during the period 1951-2007 and its relationship with diet. MATERIAL AND METHODS: Calculation of incidence rates, standardized mortality and years of potential life lost (world population) and per capita consumption of different foods. RESULTS: Red and processed meats, poultry, fish and fruits intake has increased and consumption of vegetables, cereals and legumes has decreased. The incidence of colorectal cancer has steadily increased in both genders, more markedly among men, and across all age groups, in contrast to what has been observed in other countries. Mortality increased during the period 1951-2000, but from that time until 2007 these rates have kept steady in men and fallen in women. The years of potential life lost (YPLL) shows a similar distribution to mortality. The correlation coefficients have values close to one for consumption of red meat, poultry, fish, vegetables and fruits and strongly negative values for the consumption of cereals and vegetables with the incidence and mortality in both genders, and the YPLL, but only among men, with weaker correlations for women. CONCLUSIONS: In colorectal cancer, a minimal time span of ten-fifteen years is necessary for changes in exposure to risk factors to be able to modify the incidence of this tumour. Therefore, Spanish State and Regional Governments should implement legislative and educational measures in the field of Health Promotion regarding the diet urgently.

Cambios en la dieta y tendencia del cáncer colorrectal en España durante 1951-2007 / Dietary changes and colorectal cancer trends in Spain during 1951-2007

Objetivos: análisis de la evolución del cáncer colorrectal enEspaña durante el periodo 1951-2007 y su relación con la dieta.Material y métodos: cálculo de tasas de incidencia, mortalidady años potenciales de vida perdidos ajustadas (población mundial),así como de consumos per capita de distintos alimentos.Resultados: el consumo de carnes rojas y procesadas, pollo,pescado y frutas ha aumentado y el de hortalizas, cereales y legumbresha descendido.La incidencia de cáncer colorrectal ha experimentado un aumentoconstante en ambos géneros, más marcado en varones, entodos los grupos de edad, en contraposición con lo ocurrido enotros países. La mortalidad aumentó durante el periodo 1951-2000, pero desde ese momento hasta 2007 se ha estabilizado envarones y decrecido en mujeres.Los años potenciales de vida perdidos muestran una distribuciónsimilar a la mortalidad.Los coeficientes de correlación presentan valores cercanos auno para el consumo de carnes rojas, pollo, pescado, hortalizas yfrutas y valores fuertemente negativos para el consumo de cerealesy legumbres con la incidencia y la mortalidad, en ambos géneros,y con los años potenciales de vida perdidos, aunque sólo envarones, con correlaciones débiles en mujeres.Conclusiones: en el cáncer colorrectal es necesario un mínimode diez-quince años para que cambios en la exposición a factoresde riesgo y protección puedan modificar su incidencia. Porello, se deben aplicar medidas legislativas y educativas en materiade Promoción de la Salud respecto a dieta por parte del Estado ylos Gobiernos Regionales de forma urgente(AU)

Objectives: analysis of the evolution of colorectal cancer inSpain during the period 1951-2007 and its relationship with diet.Material and methods: calculation of incidence rates, standardizedmortality and years of potential life lost (world population)and per capita consumption of different foods.Results: red and processed meats, poultry, fish and fruits intakehas increased and consumption of vegetables, cereals andlegumes has decreased.The incidence of colorectal cancer has steadily increased inboth genders, more markedly among men, and across all agegroups, in contrast to what has been observed in other countries.Mortality increased during the period 1951-2000, but from thattime until 2007 these rates have kept steady in men and fallen inwomen.The years of potential life lost (YPLL) shows a similar distributionto mortality.The correlation coefficients have values close to one for consumptionof red meat, poultry, fish, vegetables and fruits andstrongly negative values for the consumption of cereals andvegetables with the incidence and mortality in both genders,and the YPLL, but only among men, with weaker correlationsfor women.Conclusions: in colorectal cancer, a minimal time span often-fifteen years is necessary for changes in exposure to risk factorsto be able to modify the incidence of this tumour. Therefore,Spanish State and Regional Governments should implement legislativeand educational measures in the field of Health Promotionregarding the diet urgently(AU)

Características sociodemográficas y psicopatológicas del paciente hiperfrecuentados en atención primaria / Sociodemographic and psychopathological features of frequent attenders in Primary Care

Objetivo. Determinar las características sociodemográficas, clínicas y psicopatológicas de un grupo de pacientes hiperfrecuentadores comparándolo con otro grupo de normofrecuentadores en tres centros de atención primaria. Método. La muestra está compuesta por 232 hiperfrecuentadores (definidos por un número de consultas igual o superior a 12 en el último año) y 93 normofrecuentadores. Los instrumentos utilizados son: un cuestionario de elaboración propia para la evaluación de las características sociodemográficas y clínicas y el Cuestionario de Salud General de Goldberg en su versión de 28 ítems (GHQ-28).Resultados. La regresión logística muestra que el aumento de edad, un nivel educativo bajo, la presencia de enfermedad crónica (diabetes e hipertensión), un diagnóstico psiquiátrico y presencia de sintomatología psicopatológica «menor» establecen diferencias significativas en el grupo de hiperfrecuentadores frente al grupo de normofrecuentadores. No existen diferencias significativas entre hombres y mujeres. Conclusión. Los pacientes hiperfrecuentadores presentan altas tasas de quejas físicas, mentales y sociales. La edad, determinadas enfermedades crónicas y la psicopatología son los factores más importantes en relación a la hiperfrecuentación (AU)

Objective. To determine the sociodemographic and clinical characteristics of frequent attenders and compare them with another group of routine attenders in three primary care centers. Method. The sample is composed by 232 frequent attenders (defined by number of consultations in the last year of 12 or more) and 93 routine attenders. The instruments used are: a questionnaire for the evaluation of the sociodemographic and clinical characteristics and the 28-item Goldberg General Health Questionnaire (GHQ-28).Results. The logistic regression shows that increase of age, low level of education, presence of chronic disease, psychiatric diagnosis and presence of psychopathological «minor» symptomatology establish significant differences in the group of frequent attenders in relation to the routine attenders group. There are no significant differences between men and women. Conclusion. Frequent attenders present higher rates of physical, mental and social complaints. Age, some chronic conditions and psychopathology are the most important factors for frequent attendance (AU)