[Hip fractures in patients treated with antipsychotic drugs. Study of retrospective cohorts in Catalonia]. / Fracturas de cadera en pacientes tratados con fármacos antipsicóticos. Estudio de cohortes históricas en Cataluña.

OBJECTIVE: To evaluate the incidence of hip fracture in patients with antipsychotic treatment, comparing it with that of individuals who have not been treated with antipsychotics. DESIGN: Retrospective cohort study of patients treated with antipsychotic drugs (TAP) and patients without known treatment (non-TAP). The observation period was 2006-2014. SITE: All primary care teams in Catalonia of the Catalan Health Institute (ICS). PARTICIPANTS: Patients older than 44 years with TAP lasting at least 3 months. Control cohort: random selection of non-TAP patients matching for baseline comorbidities and other variables. A total of 22,010 are analyzed. Main measurements Incidence rate (1000× person-years: PY) of hip fracture in each group (TAP and non-TAP). Cox regression models to estimate adjusted risks (hazard ratio: HR). RESULTS: The hip fracture incidence rate was higher in TAP patients (5.83 vs 3.58 fractures per 1000 PY), and is higher in all strata according to sex, age and type of diagnosis. The risk of suffering a hip fracture was 60% higher (HR: 1.60 95% CI: 1.34-1.92) in the TAP group than in the non-TAP group. The risk was higher in the group with schizophrenia (HR: 3.57 95% CI: 1.75-7.30), followed by bipolar disorder (HR: 2.61; 95% CI: 1.39-4.92) and depression (HR: 1.51; 95% CI: 1.21-1.88). CONCLUSIONS: Patients with antipsychotic treatment have a higher risk of hip fracture than those who have not been treated with antipsychotics.

Understanding nitrogen recovery from wastewater with a high nitrogen concentration using microbial electrolysis cells.

This study was aimed at understanding the effect of applied voltage, catholyte and reactor scale on nitrogen recovery from two different organic wastes (digestate and pig slurry) by means of microbial electrolysis cell (MEC) technology. For this purpose, MEC sizes of 100, 500 and 1000 mL were tested at applied voltages of 0.6, 1 and 1.4 V using either a phosphate-buffered solution or NaCl solution as the catholyte. By increasing the reactor size from 500 to 1000 mL, a decrease in the ammonia recovery efficiency from 47 to 42% was observed. The results also showed that the phosphate-buffered solution is preferable as the catholyte and that the voltage applied does not have a noticeable effect on current production and ammonia recovery. Low biodegradability of the wastes was identified as the main bottleneck.

Increased blood draws for ultrasensitive ctDNA and CTCs detection in early breast cancer patients.

Early breast cancer patients often experience relapse due to residual disease after treatment. Liquid biopsy is a methodology capable of detecting tumor components in blood, but low concentrations at early stages pose challenges. To detect them, next-generation sequencing has promise but entails complex processes. Exploring larger blood volumes could overcome detection limitations. Herein, a total of 282 high-volume plasma and blood-cell samples were collected for dual ctDNA/CTCs detection using a single droplet-digital PCR assay per patient. ctDNA and/or CTCs were detected in 100% of pre-treatment samples. On the other hand, post-treatment positive samples exhibited a minimum variant allele frequency of 0.003% for ctDNA and minimum cell number of 0.069 CTCs/mL of blood, surpassing previous investigations. Accurate prediction of residual disease before surgery was achieved in patients without a complete pathological response. A model utilizing ctDNA dynamics achieved an area under the ROC curve of 0.92 for predicting response. We detected disease recurrence in blood in the three patients who experienced a relapse, anticipating clinical relapse by 34.61, 9.10, and 7.59 months. This methodology provides an easily implemented alternative for ultrasensitive residual disease detection in early breast cancer patients.

Description of a bivalent cannabinoid ligand with hypophagic properties.

A series of bivalent cannabinoid ligands is proposed. The synthesis of double amides based on the rimonabant structure separated by an alkyl chain and the evaluation of their affinities for cannabinoid receptors are reported. The data of 4d confirmed that a bivalent structure is a suitable scaffold for CB1 cannabinoid receptor binding. The compound 4d was selected for in vitro and in vivo pharmacological evaluations. Moreover, intraperitoneal administration of 4d to food-deprived rats resulted in a dose-dependent inhibition of feeding that was maintained up to 240 min.

Variability and concordance of Cornell and Sokolow-Lyon electrocardiographic criteria in hypertensive patients.

AIM: To assess the variability and concordance of left ventricular hypertrophy electrocardiographic (LVH-ECG) criteria. METHODS AND RESULTS: Convenience sampling of hypertensive subjects without coronary disease or bundle branch blocks. Two electrocardiograms (ECGs) were performed on each patient. Two investigators carried out two blind-readings of each ECG (Cornell and Sokolow-Lyon criteria). The between-rater and within-rater reliability were assessed (intraclass correlation coefficient, ICC). Poor concordance was defined: mean voltage difference between both ECGs >2 mm; 824 ECG readings were performed in 103 subjects (58.3% females), aged 66.8±8.8 years, mean blood pressure 141±15.10/78±9.0 mmHg. The between-rater ICCs of the baseline ECG were 0.97(95% CI 0.96-0.98) and 0.98 (95% CI 0.97-0.99) for Cornell and Sokolow-Lyon criteria, respectively. Poor concordance was found in 39.8% and in 41.7% of the cases for Cornell and Sokolow-Lyon criteria, respectively. Systolic blood pressure was found to be significant and positively associated with both criteria. Elderly hypertensive subjects, with higher ECG voltages and lower pulse pressure presented poor concordance of Cornell criteria. CONCLUSIONS: The between-rater and within-rater reliability of Cornell and Sokolow-Lyon criteria is minimal. Approximately 40% of hypertensive subjects presented poor concordance in a second ECG. Older patients with lower pulse pressure and higher baseline voltages presented poorer reproducibility of LVH-ECG criteria.

Adenoid cystic carcinoma with a leptomeningeal dissemination in a 'wash' pattern.

A 39-year-old woman was referred to the neurology department due to headache, instability and difficulty walking for 5 months. Several ancillary tests were performed. The blood test showed leucocytosis and the cerebrospinal fluid revealed an increased total protein and glucose consumption. Other infections or autoimmune causes were excluded. The MRI showed non-specific brain and spinal cord lesions. Given the findings described, a differential diagnosis between granulomatous meningoencephalitis and primary tumour or metastasis was proposed. Empirical treatment with tuberculostatic agents and corticosteroids was started. The neurological state of the patient worsened, she fell into a non-responsive coma and died in few days. The clinical autopsy performed revealed an adenoid cystic carcinoma with involvement of the central nervous system that developed leptomeningeal dissemination along the spinal cord in a fluid 'wash' pattern.

Cytochrome P450 pathway contributes to methanandamide-induced vasorelaxation in rat aorta.

PURPOSE: The generation of hyperpolarising vasorelaxant endothelial cytochrome P450 epoxygenase (CYP)-derived metabolites of arachidonic may provide beneficial effects for the treatment of cardiovascular diseases in which the bioavailability of NO is impaired. The cannabinoid methanandamide has vasodilatory properties linked to hyperpolarisation. The aim of the present work was to investigate the vasorelaxant effects of methanandamide in rat aorta, focusing on the role of cytochrome P450 pathway. METHODS: Changes in isometric tension in response to a cumulative concentration-response curve of methanandamide (1 nM-100 µM) were recorded in aortic rings from male Wistar rats. The involvement of cannabinoid receptors, endothelial nitric oxide (NO)-, prostacyclin- and some hyperpolarising-mediated pathways were investigated. The activation of large-conductance Ca(2+)-activated K(+) (BKCa) channels have also been evaluated. RESULTS: Methanandamide provoked an endothelium-dependent vasorelaxation in rat aorta, reaching a maximal effect (Rmax) of 67% ± 2.6%. This vasorelaxation was clearly inhibited by the combination of CB(1) and CB(2) cannabinoid antagonists (Rmax: 21.6% ± 1.3%) and by the combination of guanylate cyclase and CYP inhibitors (Rmax: 16.7% ± 1.1%). The blockade induced separately by guanylate cyclase (31.3% ± 2.8%) or CYP (36.3% ± 6.6%) inhibitors on methanandamide vasorelaxation was not significantly modified by either CB(1) or CB(2) inhibition. BKCa channels inhibition caused a partial and significant inhibition of the methanandamide vasorelaxation (Rmax: 39.9% ± 3.3%). CONCLUSIONS: Methanandamide endothelium-dependent vasorelaxation is mediated by CB(1) and CB(2) cannabinoid receptors. The NO- and CYP-mediated pathways contribute in a concurrent manner in this vascular effect. Stimulation of both cannabinoid receptor subtypes is indistinctly linked to NO or CYP routes to cause vasorelaxation.

[Development and validation of a new questionnaire to assess health care satisfaction and the device in stomized patients: espejo questionnaire]. / Cuestionario espejo. Valorar la satisfacción de pacientes ostomizados con la atención sanitaria y el dispositivo.

OBJECTIVES: To develop a questionnaire to measure the satisfaction of stomatised patients with healthcare professionals and with the stomal device. METHODS: An initial review of the literature was performed and in meetings with experts, the most relevant items were selected. In a pilot study with patients that had been recently stomatised (three months from intervention), the comprehensibility and discriminatory ability of each item was tested. Items were eliminated on the grounds of frequent "no response" or low correlation with others on the provisional scale (determined by means of Cronbach's alpha). RESULTS: Following meetings with experts, 12 items were eliminated by reason of irrelevance or low frequency of use. Subsequently by means of administration of the questionnaire to a sample of 72 patients, five more items were selected for elimination. An analysis of the 13 items that remained confirmed an acceptable level of reliability (Cronbach's alpha of 0.917) and also the significant differences in the global scores between the patients who have had stoma for more than three months (higher satisfaction) and patients who had been recently stomatised. The items in the questionnaire referred to aspects of easy and comfort of use of the stoma, as well as satisfaction with information received and interaction with healthcare professionals from the point of view of the patient. CONCLUSIONS: This is the first questionnaire to measure satisfaction with healthcare professionals and the stomal device from the perspective of the stomatised patient. In a subsequent study the other properties of the measurement tool (validity responsiveness and longitudinal validation) will be evaluated.

Degradation of 2-mercaptobenzothizaole in microbial electrolysis cells: Intermediates, toxicity, and microbial communities.

The compound 2-mercaptobenzothizaole (MBT) has been frequently detected in wastewater and surface water and is a potential threat to both aquatic organisms and human health (its mutagenic potential has been demonstrated). This study investigated the degradation routes of MBT in the anode of a microbial electrolysis cell (MEC) and the involved microbial communities. The results indicated that graphene-modified anodes promoted the presence of more enriched, developed, and specific communities compared to bare anodes. Moreover, consecutive additions of the OH substituent to the benzene ring of MBT were only detected in the reactor equipped with the graphene-treated electrode. Both phenomena, together with the application of an external voltage, may be related to the larger reduction of biotoxicity observed in the MEC equipped with graphene-modified anodes (46.2 eqtox∙m-3 to 27.9 eqtox∙m-3).

[Prostate pathology recommendations from the Uropathology working group of the Spanish Society of Pathology]. / Recomendaciones del grupo de trabajo de Uropatología de la Sociedad Española de Anatomía Patológica.

These guidelines from the uropathology working group of the Spanish Society of Pathology (SEAP) are based on the European and ISUP 2015 recommendations and those of the College of American Pathologists, as well as the latest WHO 2016, TNM (AJCC) 2017 classifications. They include recommendations for specimen sampling, macro- and microscopic examination and immunohistochemistry. Gleason patterns are specified: Gleason pattern 3 includes hyperplastic, atrophic and microcystic glands, while pattern 4 includes all cribriform or glomeruloid glands. The Gleason score in prostatectomy specimens may change; if a tertiary pattern occurs in more than 5% of the tumour, it becomes a secondary pattern. In both biopsies and prostatectomy specimens, if the Gleason score is 7, the percentage of pattern 4 should be stated. Gleason scoring in tumor variants and special situations should also be specified. These recommendations should be adapted according to the resources available.

Interarm blood pressure measurement and the reference-arm assignment variability.

OBJECTIVE: The arm with the higher blood pressure (BP) is assigned as the follow up arm for hypertensive patients (reference-arm). We evaluated the reproducibility of this assignment. METHODS: BP was measured simultaneously on both arms with a double cuff validated device in two visits separated <10 days (two sets of three readings per visit). Two reference-arms were assigned in each visit (the arm with higher BP, at least ≥1 mmHg). The intravisit and intervisit agreements of this assignment were evaluated. RESULTS: We included 313 hypertensive patients. First visit mean right arm BP was 131.6 (16.6)/75.3 (9.4) mmHg and left arm BP was 132.4 (16.9)/75.7 (9.7) mmHg (P = 0.002). Intravisit concordance at the first and second visits were κ = 0.60 [95% confidence interval (CI), 0.516-0.696] and κ = 0.45 [95% CI, 0.356-0.555], respectively. Therefore, 21.8% of patients (at the first visit) and 29.1% (at the second visit) with the right arm as the reference-arm in the first round of readings changed to the left arm in the same visit in the second round of readings. The intervisit κ index was 0.25 [95% CI, 0.147-0.365]. After that, 36.8% of patients with the right arm as the reference-arm at the first visit changed to the left arm at the second visit. The subgroup (9.5%) with an interarm systolic BP difference ≥10 mmHg at the first visit did not differ significantly from the rest of patients. CONCLUSION: The reference-arm assignment agreement is weak to moderate. The assignment of the reference-arm should be individualized and not considered as definitive.

Involvement of central and peripheral cannabinoid receptors on antinociceptive effect of tetrahydrocannabinol in muscle pain.

Cannabinoid (CB) receptors have emerged as an attractive therapeutic target for pain management in recent years and the interest in the use of cannabinoids is gradually increasing, particularly in patients where conventional treatments fail. Muscle pain is a major clinical problem and new pharmacological approaches are being studied. Recently, we have demonstrated that cannabinoid synthetic agonists are useful to reduce muscular pain in two animal models, where the local administration is effective. Now, we want to know if tetrahydrocannabinol (THC), a cannabinoid natural derivative with therapeutic use in humans, is also effective in reducing acute muscle pain. The antinociceptive effect of THC by systemic (i.p.) and local (i.m.) administration was tested in two animal models of acute muscle pain, rat masseter and gastrocnemius, induced by hypertonic saline (HS) injection. The drugs used were the non-selective agonist THC and two selective cannabinoid antagonists, AM251 (CB1) and AM630 (CB2). THC, i.p. and i.m. administered, reduced the nociceptive behaviours induced by HS in both muscular pain models. The antinociceptive effect induced by the systemic administration of THC was mediated by CB1 receptors in the masseter muscle whereas in gastrocnemius both CB1 and CB2 receptors participated. When THC was administered locally, only CB2 receptors were involved in the antinociceptive effect in both muscles. This study suggests that THC could be a future pharmacological option in the treatment of muscle pain. The local administration of THC could be an interesting option to treat this type of pain avoiding the central adverse effects.

Adamantyl analogues of paracetamol as potent analgesic drugs via inhibition of TRPA1.

Paracetamol also known as acetaminophen, is a widely used analgesic and antipyretic agent. We report the synthesis and biological evaluation of adamantyl analogues of paracetamol with important analgesic properties. The mechanism of nociception of compound 6a/b, an analog of paracetamol, is not exerted through direct interaction with cannabinoid receptors, nor by inhibiting COX. It behaves as an interesting selective TRPA1 channel antagonist, which may be responsible for its analgesic properties, whereas it has no effect on the TRPM8 nor TRPV1 channels. The possibility of replacing a phenyl ring by an adamantyl ring opens new avenues in other fields of medicinal chemistry.

Combining rimonabant and fentanyl in a single entity: preparation and pharmacological results.

Based on numerous pharmacological studies that have revealed an interaction between cannabinoid and opioid systems at the molecular, neurochemical, and behavioral levels, a new series of hybrid molecules has been prepared by coupling the molecular features of two wellknown drugs, ie, rimonabant and fentanyl. The new compounds have been tested for their affinity and functionality regarding CB1 and CB2 cannabinoid and µ opioid receptors. In [(35)S]-GTPγS (guanosine 5'-O-[gamma-thio]triphosphate) binding assays from the post-mortem human frontal cortex, they proved to be CB1 cannabinoid antagonists and µ opioid antagonists. Interestingly, in vivo, the new compounds exhibited a significant dual antagonist action on the endocannabinoid and opioid systems.

Cardiovascular risk factors in chronic treatment with antipsychotic agents used in primary care.

AIM: To compare the prevalence of cardiovascular risk factors (CVRF) and vascular events, between patients treated and untreated with antipsychotic drugs. SUBJECTS AND METHODS: A cross-sectional study was done in Barcelona. We compared patients attended in Primary Health Care Centres, treated with or without antipsychotics between 2008 and 2010. Anthropometric measurements, clinical variables, and CVRF were assessed. Adult and elderly patients, typical and atypical antipsychotics, were studied separately. RESULTS: 14,087 patients had been prescribed antipsychotics (63.4% atypical), the most common being risperidone. We selected 13,724 patients with the same age and gender but not treated (total of 27,811 patients). Patients receiving antipsychotic had higher prevalence of obesity (16.9% vs. 11.9%), smoking (22.2% vs. 11.1%), diabetes mellitus (16% vs. 11.9%), and dyslipidemia (32.8% vs. 25.8%) (p < 0.001). The prevalence of stroke was significantly higher in the treated patients, both in adults (odds ratio = 2.33) and the elderly (odds ratio = 1.64). The prevalence of coronary heart disease was similar in both groups (odds ratio = 0.97). Among patients treated with antipsychotic, differences were not observed depending typical or atypical ones. CONCLUSIONS: Patients treated with antipsychotic drugs had a greater prevalence of several CVRF (diabetes mellitus, obesity, and smoking). The presence of stroke was higher in those treated with antipsychotics. No relevant differences were observed between patients receiving typical or atypical antipsychotics.

TITLE: Factores de riesgo cardiovascular en el tratamiento cronico con antipsicoticos en atencion primaria.Objetivo. Comparar la prevalencia de factores de riesgo cardiovascular (FRCV) y eventos vasculares en pacientes tratados con antipsicoticos, comparandolos con los no tratados. Sujetos y metodos. Estudio descriptivo transversal de pacientes atendidos en atencion primaria de la ciudad de Barcelona y tratados con antipsicoticos entre el 2008 y el 2010, comparandolos con una poblacion no tratada. Se registraron las variables antropometricas y clinicas y los FRCV. Se estudio por separado a pacientes adultos y ancianos, y a los tratados con antipsicoticos tipicos y atipicos. Resultados. Un total de 14.087 pacientes habian sido tratados con antipsicoticos (63,4% atipicos). El mas prescrito fue la risperidona. Se aparejaron 13.724 pacientes de la misma edad y genero, pero no tratados (n total = 27.811). Los tratados con antipsicoticos presentaron una prevalencia superior de obesidad (16,9% frente a 10,6%), tabaquismo (22,2% frente a 11,1%), diabetes mellitus (16% frente a 11,9%) y dislipemia (32,8% frente a 25,8%) (p < 0,001). La prevalencia de accidente vascular cerebral fue significativamente superior entre los tratados, tanto en los adultos (odds ratio = 2,33) como en los ancianos (odds ratio = 1,64). La prevalencia de cardiopatia isquemica fue similar en ambos grupos (odds ratio = 0,97). No se observaron diferencias significativas entre los tratados con un antipsicotico tipico o atipico. Conclusiones. Los pacientes tratados con antipsicoticos presentaron una mayor prevalencia de FRCV (diabetes, obesidad y tabaquismo). La presencia de ictus fue superior entre los tratados con antipsicoticos. No se detectaron diferencias importantes entre los pacientes tratados con antipsicoticos tipicos y atipicos.

Spinal cord astrocytoma: multidisciplinary experience.

BACKGROUND: Astrocytomas of the spinal cord have rarely been reported. We examined our experience, treatment and outcome of patients treated during the last four years. MATERIAL AND METHODS: We reviewed the charts from patients treated for this neoplasm in a multidisciplinary team of Granada, Spain. The information was retrospectively obtained from the patients' hospital records. The patients were evaluated with clinical history, physical exam, spinal magnetic resonance (MR), surgery, location and histology, treatment, and follow-up. RESULTS: In the last four years, we have treated 37 astrocytomas, of which only 3 were intramedullary. All patients underwent surgery, radiotherapy and chemotherapy. Two patients died, but one is alive and practically asymptomatic. CONCLUSION: The optimal treatment remains controversial. Radiotherapy should be considered for tumors with high-grade histopathology, clinically progressive and when a substantial resection cannot be achieved. New therapeutic strategies need to be studied to improve survival.