Neoplasia-associated wasting diseases with economic relevance in the sheep industry

We review three neoplastic wasting diseases affecting sheep generally recorded under common production cycles and with epidemiological and economic relevance in sheep-rearing countries: small intestinal adenocarcinoma (SIA), ovine pulmonary adenocarcinoma (OPA) and enzootic nasal adenocarcinoma (ENA). SIA is prevalent in Australia and New Zealand but present elsewhere in the world. This neoplasia is a tubular or signet-ring adenocarcinoma mainly located in the middle or distal term of the small intestine. Predisposing factors and aetiology are not known, but genetic factors or environmental carcinogens may be involved. OPA is a contagious lung cancer caused by jaagsiekte sheep retrovirus (JSRV) and has been reported in most sheep-rearing countries, resulting in significant economic losses. The disease is clinically characterized by a chronic respiratory process as a consequence of the development of lung adenocarcinoma. Diagnosis is based on the detection of JSRV in the tumour lesion by immunohistochemistry and PCR. In vivo diagnosis may be difficult, mainly in preclinical cases. ENA is a neoplasia of glands of the nasal mucosa and is associated with enzootic nasal tumour virus 1 (ENTV-1), which is similar to JSRV. ENA enzootically occurs in many countries of the world with the exception of Australia and New Zealand. The pathology associated with this neoplasia corresponds with a space occupying lesion histologically characterized as a low-grade adenocarcinoma. The combination of PCR and immunohistochemistry for diagnosis is advised

Appropriate use of red blood cell transfusion in emergency departments: A study in five emergency departments

BACKGROUND: Transfusion of blood components continues to be an important therapeutic resource into the 21st century. Between 5 and 58% of transfusions carried out are estimated to be unnecessary. According to several studies, at least 20% of packed red blood cell transfusions (RBCT) are administered in hospital emergency departments (ED), but few data are available about the appropriateness of RBCT in this setting. This multicentre, cross-sectional observational study aims to assess the appropriateness of RBCT indications and transfused volumes in patients who attend ED. MATERIALS AND METHODS: The study cohort is made up of consecutive consenting adult patients (≥18 years old) who received RBCT in ED over a 3-month period and for whom relevant clinical data were collected and analysed. RESULTS: Data from 908 RBCT episodes (2±1 units per transfused patient) were analysed. RBCT was considered appropriate in 21.4% (n=195), with significant differences according to RBCT indication (p<0.001), hospital level (p<0.001) and prescribing physician (p=0.002). Pre-transfusion haemoglobin level (Hb) negatively correlated with RBCT appropriateness (r=-0.616; p<0.01). Only 72.4% of appropriate RBCT had a post-transfusion Hb assessment (n=516). Of these, 45% were considered to be over-transfused (n=232), with significant differences according to RBCT indication (p=0.012) and prescribing physician (p=0.047). Overall, 584/1,433 (41%) of evaluable RBC units were unnecessarily transfused. DISCUSSION: The appropriateness of RBCT in ED is similar to other hospital departments, but the rate of over-transfusion was high. These data support the need for a reassessment after transfusion of each RBC unit before further units are prescribed. In view of these results, we recommend that physicians should be made more aware of the need to prescribe RBCT appropriately in order to reduce over-transfusionThis project has received funding from the Spanish Ministry of Health, Social Policy and Equality through the SAS/2377/2010 call for granting aid for the promotion of independent clinical research (Department of Pharmacy and Health Products), file n. EC10-21

Toward a clinical practice guide in pharmacogenomics testing for functional polymorphisms of drug-metabolizing enzymes. Gene/drug pairs and barriers perceived in Spain

The development of clinica lpractice recommendations or guidelines for the clinical use of biomarkers is an issue of great importance withr regard to adverse drug reactions.The poten-tial of pharmacogenomicbiomarkers has been extensively investigated in recent years.However,several barriers to implementing the use of pharmacogenomics testing exist.We conducted a survey among members of the Spanish Societies of Pharmacology and Clinical Pharmacology to obtain information about the perception of such barriers and to compare the perceptions of participants about the relative importance of majorgene/drug pairs.Of 11 potential barriers,the highest importance was attributed to lack of institutional support for pharmacogenomic stesting,and to the issues related to the lack of guidelines.Of the proposed gene/drug pairs the highest importance was assigned to HLA-B/abacavir, UGT1A1/irinotecan, and CYP2D6/tamoxifen.In this perspective article,we compare the relative importance of 29 gene/drugpairs in the Spanish study with that of the same pairs in the American Society for Clinical Pharmacology and Therapeutic sstudy,and we provide suggestions and areas of focus to develop a guide for clinical practice in pharmacogenomics testingThe work in the author’s laboratory is financed by Grants PS09/00943, PS09/00469, RETICS RIRAAF RD07/0064/0016, and CIBERehd from Instituto de Salud CarlosIII,Madrid, Spain, and by Grants GR10068 from Junta de Extremadura, Spain. Financed in part with FEDER funds from the European Unio

Consensus of experts from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines

5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines

Consensus of experts from the Spanish pharmacogenetics and pharmacogenomics society and the Spanish society of medical oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines

5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidinesThis project has been financed with SEOM and SEFF resource

Distúrbios do trato respiratorio inferior de pequeños ruminantes

O artigo objetiva revisar alguns dos distúrbios do trato respiratório inferior de maior ocorrência em pequenos ruminantes. Sua rele- vância no manejo sanitário está relacionada à queda no desempenho produtivo, mortalidade, redução do ganho de peso e qualidade da carcaça de cordeiros/cabritos produzidos, e aumento da taxa de descarte e reposição. Aqui, apresentamos a pneumonia por aspiração, complexo respiratório ovino (CRO), adenocarcinoma pulmonar ovino (APO), lentiviroses de pequenos ruminantes (LVPR), pneu- monia parasitária e fúngica, assim como as formas pulmonares da linfadenite caseosa (LC) e das micoplasmoses. A pneumonia por aspiração é uma infecção comumente causada pela inalação de materiais estranhos, produzindo inflamação e necrose do parênquima pulmonar. O CRO é um processo que envolve uma variedade de interações hospedeiro-patógeno-ambiente, em que os mecanismos imunológicos e fisiológicos do hospedeiro interagem com vários agentes etiológicos, incluindo vírus, bactérias, além de fatores ambientais ou estressores. A forma pulmonar da LC comumente causa lesões nos linfonodos mediastinais e no parênquima pulmonar, produzindo sinais clínicos respiratórios, principalmente a tosse responsável pela transmissão da doença por aerossol. O APO é um câncer de pulmão, contagioso, causado pelo retrovírus jaagsiekte ovino, que induz a transformação de células epiteliais secretoras do trato respiratório distal. A afecção pulmonar pela LVPR é a forma de doença mais grave na espécie ovina. A infecção ocorre pelo contato direto entre animais e a via de infecção mais importante é pelo trato respiratório. A pneumonia parasitária e fúngica são menos frequentes, mas relevantes dentro do diagnóstico diferencial das enfermidades respiratórias. Dada a natureza multifacetada dessas doenças, as práticas de manejo (por exemplo, melhorias nas habitações, implementação de medidas de biossegurança e abate seletivo de animais infectados) precisam ser consideradas para sua prevenção; como as condições ambientais também desempenham um papel no desenvolvimento dessas doenças, elas devem ser levadas em consideração. Por fim, outras medidas sanitárias adequadas como protocolos vacinais contra alguns agentes visando a melhora na resposta imune animal também ajudam no controle destas doenças. e article aims to review some of the lower respiratory tract disorders of major occurrence in small ruminants. eir relevance within the health management are related to the drop in productive performance, reduction in weight gain and quality of the carcass of lambs/kids produced, and increase in the mortality, culling and replacement rate. Herein we examine the aspiration pneumonia, ovine respiratory complex (ORC), ovine pulmonary adenocarcinoma (OPA), small ruminant lentiviruses (SRLV ), parasitic and fungal pneumonia, as well as the pulmonary form of caseous lymphadenitis (CLA) and mycoplasmosis. Aspiration pneumonia is an infection commonly caused by inhalation of foreign materials, producing inflammation and necrosis of the lung parenchyma.e ORC is a process involving a range of host-pathogen-environment interactions,where host immunological and physiological mechanisms interact with multiple etiological agents including viruses, bacteria, plus environmental factors or stressors. Pulmonary form of CLA commonly causes lesions in mediastinal lymph nodes and lung parenchyma, producing respiratory clinical signs, particularly the coughing that is responsible for transmission of the disease by aerosol. OPA is a contagious lung cancer of sheep caused by jaagsiekte sheep retrovirus, which induces the transformation of secretory epithelial cells of the distal respiratory tract. Pulmonary affection due to SRLV is the most severe disease form in sheep species. e infection occurs by direct contact between animals and the most important infection routes are lactogenic and respiratory. Parasitic and fungal pneumonia are less frequent, but relevant in the differential diagnosis of respiratory diseases. Given the multi-faceted nature of these diseases, management practices (e.g., housing improvements, implementation of biosecurity provisions and selective culling of infected animals) need to be considered for their prevention; as environmental conditions also play a role in development of these diseases, they should be taken into account. Lastly, other appropriate health measures, such as vaccine protocols against some agents aiming at improving the animal immune response, also help in the control of these diseases

Inhaled Methoxyflurane Provides Greater Analgesia and Faster Onset of Action Versus Standard Analgesia in Patients With Trauma Pain: InMEDIATE: A Randomized Controlled Trial in Emergency Departments

STUDY OBJECTIVE: The objective of the InMEDIATE study was to evaluate the change in intensity of traumatic pain over the first 20 min in adult patients treated with methoxyflurane versus standard analgesic treatment in Spain. This the first randomized, active-controlled, multicenter trial of methoxyflurane in the emergency setting in Europe. METHODS: This was a randomized, controlled study that enrolled adult patients with acute moderate to severe (score >/=4 on the 11-point Numeric Rating Scale) trauma-associated pain in 14 Spanish emergency departments. Patients were randomized 1:1 to methoxyflurane (up to 2x3 mL) or standard analgesic treatment. Coprimary endpoints were the change from baseline in Numeric Rating Scale pain intensity score during the first 20 minutes of treatment and time to first pain relief. RESULTS: Three hundred five patients were randomized (methoxyflurane 156; standard analgesic treatment 149). Most patients in the standard analgesic treatment group (70%) received intravenous first-step analgesics and 9.4% of patients were treated with opioids. Mean decrease from baseline in Numeric Rating Scale pain intensity score was greater for methoxyflurane than standard analgesic treatment at all points, with a significant treatment difference overall up to 20 minutes (repeated-measures model 2.47 versus 1.39; treatment difference 1.00; 95% confidence interval 0.84 to 1.32). Median time to first pain relief was significantly shorter for methoxyflurane than standard analgesic treatment (3 versus 10 minutes). Methoxyflurane achieved better patient and clinician ratings for pain control and comfort of treatment than standard analgesic treatment and exceeded patient and clinician expectations of treatment in, respectively, 77% and 72% of cases compared with 38% and 19% for standard analgesic treatment. CONCLUSION: These results support consideration of methoxyflurane as a nonnarcotic, easy-to-administer, rapid-acting, first-line alternative to currently available analgesic treatments for trauma pain

Higher-dose sitagliptin and the risk of congestive heart failure in older adults with CKD

Background and objectives Sitagliptin, a dipeptidylpeptidase-4 inhibitor, is commonlyprescribed to patientswith type 2 diabetes. As this drug is primarily eliminated by the kidney, a reduced dose is recommended for patients with CKD. Some evidence suggests that sitagliptin is associated with a higher risk of congestive heart failure, particularly at higher doses.Wecompare the 1-year risk of death or hospitalizationwith congestive heart failure in patients with CKD newly prescribed sitagliptin at \u3c50 versus ≤50 mg/d. Design, setting, participants, & measurements This population-based cohort study included older adults (\u3e66 years) with type 2 diabetes and an eGFR\u3c45 ml/min per 1.73 m2 (but not receiving dialysis) who were newly prescribed sitagliptin between 2010 and 2017 in Ontario, Canada. We used inverse probability of treatment weighting on the basis of propensity scores to balance baseline characteristics. The primary composite outcome was death or hospitalization with congestive heart failure. Secondary outcomes included hospitalization with pancreatitis or hypoglycemia, all-cause hospitalization, and glycemic control. Weighted hazard ratios were obtained using Cox proportional hazards regression, and 95%confidence intervalswere obtained using bootstrap variance estimators. Results Of 9215 patients, 6518 started sitagliptin at \u3e50 mg/d, and 2697 started sitagliptin at ≤50 mg/d. The 1-year risk of death or hospitalization with congestive heart failure did not differ significantly between groups (79 versus 126 events per 1000 person-years; weighted hazard ratio, 0.88; 95% confidence interval, 0.67 to 1.14); hospitalization with pancreatitis (weighted hazard ratio, 0.98; 95% confidence interval, 0.32 to 3.03) and hypoglycemia (weighted hazard ratio, 1.10; 95% confidence interval, 0.64 to 1.90) also did not differ significantly between groups. Patients starting sitagliptin at \u3e50 mg/d had lower mean glycated hemoglobin concentrations (weighted between-group difference, 20.12%; 95% confidence interval, 20.19 to 20.06) and a lower risk of allcause hospitalization (weighted hazard ratio, 0.81; 95% confidence interval, 0.66 to 0.98). Conclusions The risk of death or congestive heart failure was not higher in older adults with CKD starting sitagliptin at \u3e50 versus ≤50 mg/d