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To analyze the correlations between age-related macular degeneration (AMD) and genetic and environmental risk factors for in a Brazilian population. Cross-sectional study with a control group. We collected data on 236 participants 50 years of age or older (141 with AMD and 95 controls without the disease). Data was obtained using a questionnaire and included information on demographics, ocular and medical history, family history of AMD, lifestyle, and smoking and drinking habits. Genetic evaluations included direct sequencing for the LOC387715 (rs10490924) variant, as well as PCR and enzymatic digestion for the CFH Y402H (rs1061170) and HTRA1 (rs11200638) variants. We performed a risk assessment of environmental risk factors and genetic variants associated with AMD and determined correlations between AMD and the data collected using multiple linear regression analysis. Of the 141 AMD cases, 99 (70%) had advanced AMD in at least one eye (57% neovascular AMD and 13% geographic atrophy), and 42 (30%) had not-advanced AMD. Family history of AMD (OR: 6.58; 95% CI: 1.94-22.31), presence of cardiovascular disease (CVD) (OR: 2.39; 95% CI: 1.08-5.28), low physical activity level (OR: 1.39; 95% CI: 0.82-2.37), and high serum cholesterol (OR: 1.49; 95% CI: 0.84-2.65) were associated with an increased risk for AMD. There was a significant association between CVD and incidence of advanced AMD (OR: 2.29; 95% CI 0.81-6.44). The OR for the risk allele of the LOC387715 gene, the CFH gene and the HTRA1 gene were 2.21 (95% CI: 1.47-3.35), 2.27 (95% CI: 1.52-3.37), and 2.76 (95% CI: 1.89-4.03), respectively. In the stepwise multiple linear regression analyses, the HTRA1 and CFH risk alleles, family history of AMD, the LOC387715 risk allele, and CVD were associated with an increased risk of AMD for a total of 25.6% contribution to the AMD phenotype. The analysis correlating environmental and genetic risk factors such as family history of AMD, and CVD and the variants of HTRA1, CFH, and LOC387715 genes showed an expressive contribution for the development of AMD among this admixed population.

The potential of gas chromatography/tandem mass spectrometry with a triple quadrupole analyzer for determination of 12 polybrominated diphenyl ethers in human breast tissues has been investigated. After extraction with hexane, two purification procedures-automated normal-phase high-performance liquid chromatography and solid-phase extraction-were assayed. Both electron impact ionization, in selected reaction monitoring mode, and negative chemical ionization, in selected ion recording mode, were tested for the optimum determination of analytes. Isotopically labeled standards were added before extraction as surrogates: [¹³C]BDE47, [¹³C]BDE99 and [¹³C]BDE153 for electron impact ionization, and p,p'-DDE-d ₈ for negative chemical ionization. The method was validated in terms of accuracy, precision, limits of detection and limits of quantification, using human breast tissue spiked at three levels in the range 1-50 ng/g (5-250 ng/g for BDE209). The analytical approach using solid-phase extraction cleanup followed by gas chromatography/mass spectrometry (negative chemical ionization ) led to lower detection limits (0.006-2 ng/g) and allowed the determination of the most problematic congener, BDE209, whose poor sensitivity made difficult its determination at low residue levels. Special attention was given to the confirmation of the compounds detected in samples in order to avoid reporting false positives. Two tandem mass spectrometry transitions or three m/z ions were selected for each analyte when using electron impact ionization or negative chemical ionization modes, respectively. In both cases, the transition to ion intensity ratio was used as a confirmation parameter. The method developed was applied to the analysis of real human samples. Several brominated diphenyl ethers (congeners 47, 100, 99, 154, 153, 183 and 209) were detected in the range 0.08-0.23 ng/g.

BackgroundExtravasation of cytostatic agents is one of the major complications in cancer treatment with anthracyclines. There is a lot of information about the management of extravasations with ‘classical’ anthracyclines but liposomal anthracyclines have distinctive pharmacokinetics and a different toxic-effect profile. Currently, dexrazoxane is only licensed to treat extravasation with ‘classical’ anthracyclines. However, the efficacy of desrazoxane has been reported in some cases reports. This review collects all extravasation cases that have been published with liposomal and pegylated liposomal anthracyclines, with special emphasis on the use of dexrazoxane.PurposeTo review the scientific literature on the development and managenement of anthracycline extravasation injuries, including clinical evidence for desrazoxane.Material and methodsA bibliographic review was conducted using the Pubmed database with the following keywords: antracyclines, extravasations and chemotherapy. The period covered was from database inception to September 2015, inclusive. Articles about clinical cases and literature in English or Spanish were included. Practice guidelines and expert consensus were also analysed.ResultsPractice guidelines and expert consensus were not found. 7 articles fulfilled the inclusion criteria: 5 cases reports (including 6 patients) and 2 series of cases (each series treated in the same way).Extravasated drugs: 3 liposomal doxorubicin, 1 liposomal daunorubicin and 4 pegylated liposomal doxorubicin. General therapy: local cold packs, topical and subcutaneous corticosteroids, painkillers, subcutaneous lidocaine and low weight molecular heparin. Desrazoxane was administered in 3 cases but only 1 article reported the dosage. Symptoms: local oedema, pain, burning, erythema and haematoma. Outcome: only 1 patient treated with local cold packs and washing had necrotic areas and scars; the rest of the cases completely resolved in 2 or 3 months with no skin injury. Since 2006, the date of approval of desrazoxane, 3 of 4 reported cases have been treated with this medicine.ConclusionThere is a lack of consensus in the management of extravasations with liposomal anthracyclines, and desrazoxane could be used to treat severe extravasations of liposomal anthracyclines. Therefore, the introduction of this antidote for this medicine needs further study to ensure its efficacy and safety. Hence all oncology services should make a protocol including general interventions and the off-label use of this medicine.No conflict of interest.

Background The use of enteral nutrition (EN) has expanded as a practice of first choice in patients who are malnourished or at risk of malnutrition. Purpose To explore the practice of EN in order to identify aspects that hospital pharmacy could possibly improve. Materials and methods A six-month retrospective descriptive study (January–August 2013) was conducted in a tertiary hospital. The variables analysed were: a) refering to the patient: age, sex, medical service and length of stay (LOS) and b) related to EN: formula type, route and duration of enteral administration and daily calorific intake. Prescription data were collected from the electronic prescribing program; patient data were obtained from the electronic medical record. Results A total of 217 patients received EN during the study period, 66.2% were men, mean age 68 years (range 32–95). The mean LOS was 20 days (minimum: 1, maximum: 103). The average days with EN were 8 (minimum: 1, maximum 95). The clinical service distribution was: Internal Medicine (33.3%), Neurology (12.9%), Otorhinolaryngology (11.3%), General Surgery (9.4%), Pneumology (6.9%), Digestive (5.2%), Mental Health (5.1%), Angiology and Vascular Surgery (5.0%), Traumatology (3.1%) and others (7.7%). 89 patients (41.0%) were malnourished at the outset of feeding; the mean daily calories fed were 1,105.55 K cal/day. More than half of the enteral support was complete diets (68.5%), the rest (31.5%) were supplement diets. According to calorie-protein content four different diets were used: normoprotein-isocaloric (39.3%), high protein-isocaloric (31.9%), high protein-high calorie (19.7%) and normoprotein-high calorie (9.1%). 19.5% were special diets, including: 66.6% complete diet for diabetes, 20.5% diet with fibre, 11.7% supplement for diabetes, 0.4% complete diet for hepatic disease and 0.8% was dialysis and predialysis EN. Conclusions Commonly, these studies are conducted in an intensive care unit or in ambulatory patients, where the baselines characteristics differ from the general population in a hospital. Thus, our results were consistent with those from similar studies done by Ballesteros Cabañas GI et al. in terms of days with EN (7.5 days), majority medical service prescription (78%) and prevalence of malnutrition (43.2%). However, according to the calorie-protein content in that study a high protein-high calorie formula was the most prescribed (54.5%). This contrasts with our results in which a normoprotein-isocaloric formula was the most used (39.3%). These results support the view that the increasing availability of different brands and varieties of EN requires the creation of nutritional support groups including a pharmacist that would guide the choice of formulas, write procedures and educate teams working with EN to improve feeding practice. No conflict of interest.

Background Asthma treatment with omalizumab is very expensive. The transfer of omalizumab dispensing from community to hospital pharmacy in April 2012 increased spending. This turned the spotlight on prescription practice. Purpose To assess the difference in pharmaceutical spending related to omalizumab after the transfer to hospital dispensing, and to check whether use corresponded to the approved indications. Materials and methods Omalizumab spending was assessed in Granada during 2 periods of time: 1st, from April 2011 to March 2012, and 2nd, from April 2012 to March 2013. Afterwards, prescriptions were evaluated in 72 patients who began or continued omalizumab in April 2012. Data were obtained from the clinical history when the patient started the treatment. The variables we examined are indicated in the SPC: diagnosis, age, skin or in vitro allergen-specific testing (ASST), forced expiratory volume in 1 second (FEV1), nocturnal symptoms (NS) and prevalence of exacerbations, pre-treatment with inhaled glucocorticoids (ICS) and long-acting beta-agonists (LABA), and dose determined by body weight and total serum IgE level (SEIL). Results Cost. Spending first period: 709.331 €. Spending second period: 1,254,655 €. Increase in spending: 545,324 € (76.87%). Prescription adequacy level. 67 of 72 patients (89.33%) were diagnosed with severe asthma and the other 5 (5.94%) with other illnesses. All patients except one were older than 6 years. Positive ASST: 46 patients (63.88%), and negative or unmeasured ASST: 29 patients (37.5%). FEV1 <80%: 25 patients (34.72%), and FEV1 >80% or unmeasured in 47 patients (65.27%). All the patients (100%) had NS and frequent exacerbations. 91.66% of patients had already been treated with ICS and LABA. In accordance with SEIL, the range approved goes from 30 to 1500 IU/ml, but only 40 patients were in this range (55.55%) whereas the other 32 patients were out of range or the SEIL was not measured. The dose had been chosen correctly in 11 patients (11.27%). Conclusions Only 2 of 72 patients complied with all requirements indicated in the SPC. The great cost and the increased spending in Granada (Spain) on omalizumab suggest that all Services involved in prescribing and dispensing this medicine must unite to achieve rational drug use. No conflict of interest.

Starburst galaxies exhibit in their central regions a highly increased rate of supernovae, the remnants of which are thought to accelerate energetic cosmic rays up to energies of ~1015 electron volts. We report the detection of gamma rays—tracers of such cosmic rays—from the starburst galaxy NGC 253 using the High Energy Stereoscopic System (H.E.S.S.) array of imaging atmospheric Cherenkov telescopes. The gamma-ray flux above 220 billion electron volts is F = (5.5 ± 1.0stat ± 2.8sys) × 10−13 cm−2 s−1, implying a cosmic-ray density about three orders of magnitude larger than that in the center of the Milky Way. The fraction of cosmic-ray energy channeled into gamma rays in this starburst environment is five times as large as that in our Galaxy

Q & U Bolometric Interferometer for Cosmology (QUBIC) is an international ground-based experiment dedicated in the measurement of the polarized fluctuations of the Cosmic Microwave Background. It is based on bolometric interferometry, an original detection technique which combines the immunity to systematic effects of an interferometer with the sensitivity of low-temperature incoherent detectors. QUBIC will be deployed in Argentina, at the Alto Chorrillos mountain site near San Antonio de los Cobres, in the Salta Province. The QUBIC detection chain consists in 2048 NbSi transition edge sensors (TESs) cooled to 350 mK.The voltage-biased TESs are read out with time domain multiplexing based on Superconducting QUantum Interference Devices at 1 K and a novel SiGe application-specific integrated circuit at 60 K allowing to reach an unprecedented multiplexing factor equal to 128. The QUBIC experiment is currently being characterized in the laboratory with a reduced number of detectors before upgrading to the full instrument. I will present the last results of this characterization phase with a focus on the detectors and readout system.

Acute effects of cypermethrin, a pesticide used to treat ectoparasite infestations of salmon, were assessed using the calanoid copepod Acartia tonsa. A. tonsa has been widely used for hazard assessment of chemicals in the marine environment using acute toxicity tests, but only with randomly selected adults, assuming a sex ratio of 1:1. The present study assesses the environmental hazard of cypermethrin by exposing nauplii and adult males and females, separately. Our results showed that the naupliar stages were 28 times more sensitive to cypermethrin than adults after 96 h of exposure, with LC50s of 0.005 microg x L(-1) and 0.142 microg x L(-1), respectively. Significant differences in sensitivity between sexes were only found during the first 24 h of exposure, with males being approximately twice as sensitive as females. The results of age-related variation in sensitivity are supported by studies with other species of copepods and toxicants, where the increased capacity of the adults for detoxification, the allometric differences in weight and size, and the molting process are given as explanations. Variation in sensitivity between sexes is discussed in terms of faster depuration rates in females through egg production and implications of feeding rate changes after 24 h of exposure. Our results suggested that standard toxicity test methods using A. tonsa are unsatisfactory because the most sensitive life stage is not included and sex-related differences in tolerance are not taken into account. We also found that cypermethrin caused significant mortality in Acartia at exposures concentrations from one to three orders of magnitudes lower than the recommended field treatment concentration for copepodic infestations.

BackgroundNon-valvular atrial fibrillation (NVAF) is the most common cardiac arrhythmia in clinical practice, affecting nearly 1% of the general population. In Spain, the following recommendations are set for the choice of anticoagulant: novel oral anticoagulants (NOACs) are used in the case of poor INR control (<65% of the time in the target range (TTR)), vitamin K antagonist (VKA) intolerance or adverse events, impediment in INR controls or patients with history of stroke.1 PurposeTo determine whether NOAC prescriptions fulfil the criteria of the Ministry of Health in Spain.Material and methodsObservational, non-interventional retrospective cohort study of adult patients diagnosed with NVAF during the study period (June 2010–June 2014) and treated with NOACs. TTR calculation was performed using the Rosendaal method. We estimated a right TTR if 65% or more of the time was in the range 2–3.Results952 patients were included in the study with a diagnosis of NVAF treated with NOACs, of whom 37% (n = 351) were treated with rivaroxaban, 57% (n = 541) with dabigatran and 6% (n = 60) with apixaban. 48% (n = 457) were male and 52% (n = 495) female, and mean age was 75.9 ± 10.7 years.The results showed that only 64% (n = 609) met the criteria issued by the Ministry of Health, of which 11% (n = 102) were due to AVK intolerance or adverse event, 42% (n = 398) due to poor INR control (48.41 ± 19.5% mean of days in target range), 2% (n = 23) due to impediment in the INR control and 3% (n = 33) due to switching from another NOAC.According to the different NACOs, 44% (n = 242) of dabigatran treatments did not follow the recommendations of the Ministry of Health, compared with 26% (n = 93) of treatments with rivaroxaban and 13% (n = 8) of treatments with apixaban.ConclusionThere was a high percentage (36%) of patients treated with NOACs that did not meet the criteria of the Ministry of Health.There was a high percentage (42%) of patients who could benefit from these new anticoagulant drugs.References and/or AcknowledgementsCriterios y recomendaciones generales para el uso de nuevos anticoagulantes orales (NACO). INFORME DE POSICIONAMIENTO TERAPÉUTICO UT/V4/23122013. 23 diciembre de 2013. In http://www.aemps.gob.es/No conflict of interest.

The Q & U Bolometric Interferometer for Cosmology, QUBIC, is an innovative experiment designed to measure the polarization of the cosmic microwave background and in particular the signature left therein by the inflationary expansion of the Universe. The expected signal is extremely faint; thus, extreme sensitivity and systematic control are necessary in order to attempt this measurement. QUBIC addresses these requirements using an innovative approach combining the sensitivity of transition-edge sensor cryogenic bolometers, with the deep control of systematics characteristic of interferometers. This makes QUBIC unique with respect to others' classical imagers experiments devoted to the CMB polarization. In this contribution, we report a description of the QUBIC instrument including recent achievements and the demonstration of the bolometric interferometry performed in laboratory. QUBIC will be deployed at the observation site in Alto Chorrillos, in Argentina, at the end of 2019.