D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0

Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action

Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or “golden rules,” for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Amphetamine Poisoning in a Dog: Case Report, Literature Review and Veterinary Medical Perspectives

Amphetamine abuse in human beings has increased, resulting in many reports of toxicity and death. In the US over 4 million people have abused amphetamines at least once, thus small animals are exposed to increased accidental poisoning risk. This report describes an acute amphetamine poisoning in a dog due to ingestion of 15 mg/kg fenproporex, leading to typical signs of catecholamines release and effects in different organ systems. Similar clinical and laboratory findings observed in human beings are reviewed and physiopathogenic mechanisms discussed, as well as the therapeutic approaches available in veterinary medicine

Expression of P-glycoprotein, multidrug resistance-associated protein, glutathione-S-transferase pi and p53 in canine transmissible venereal tumor

The overexpression of proteins P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP1), mutant p53, and the enzyme glutathione-S-transferase (GSTpi) are related to resistance to chemotherapy in neoplasms. This study evaluated the expression of these markers by immunohistochemistry in two groups of canine TVT, without history of prior chemotherapy (TVT1, n=9) and in TVTs presented unsatisfactory clinical response to vincristine sulfate (TVT2, n=5). The percentage of specimens positively stained for P-gp, MRP1, GSTpi and p53 were, respectively 88.8%, 0%, 44.5% and 22.2% in TVT1 and 80%, 0%, 80% and 0% in TVT2. In TVT1, one specimen presented positive expression for three markers and four specimens for two markers. In TVT2, three specimens expressed P-gp and GSTpi. In conclusion, the canine TVTs studied expressed the four markers evaluated, but just P-gp and GSTpi were significantly expressed, mainly at cytoplasm and cytoplasm and nuclei, respectively, either before chemotherapy as after vincristine sulfate exposure. Future studies are needed to demonstrate the function of these two markers in conferring multidrug resistance (MDR) or predict the response to chemotherapy in canine TVT.A superexpressão das proteínas glicoproteína-P (Gp-P), proteína associada à resistência à múltiplas drogas 1 (MRP1) e p53 mutante e a enzima glutationa-S-transferase pi (GSTpi) está relacionada com resistência à quimioterapia em neoplasias humanas e caninas. Este estudo avaliou a expressão, por meio da imuno-histoquímica desses marcadores em espécimes de TVT caninos sem histórico de quimioterapia prévia (TVT1, n=9) e em TVT caninos que apresentaram resposta clínica insatisfatória ao sulfato de vincristina (TVT2, n=5). A porcentagem de espécimes positivos para Gp-P, MRP1, GSTpi e p53 foram, respectivamente 88,8%, 0%, 44,5% e 22,2% no grupo TVT1 e 80%, 0%, 80% e 0% no grupo TVT2. No TVT1, um espécime apresentou expressão positiva para três marcadores e quatro para dois marcadores. No TVT2, três espécimes expressaram a Gp-P e GSTpi. Em conclusão, os TVTs caninos estudados expressaram os quatro marcadores avaliados, no entanto apenas a Gp-P e GSTpi foram significativamente expressas, principalmente no citoplasmas e no citoplasma e no núcleo, respectivamente, tanto antes da quimioterapia quanto após à exposição ao sulfato de vincristina. Estudos futuros são necessários para demonstrar a função desses dois marcadores em conferir resistência à multiplas drogas (RMD) ou predizer a resposta a quimioterapia no TVT canino.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Lung biopsy with guillotine cutting needle and biopsy forceps though transdiaphragmatic thoracoscopy in dogs with pulmonary alterations

ABSTRACT: Lung diseases are common in small animal clinical routine. Diagnosis is usually affected due to nonspecific symptoms. Imaging features such as radiography and chest ultrasound are acceptable screening tests, although lung biopsy can provides a precise diagnosis. Thus thoracoscopy provides a minimally invasive diagnostic assessment for chest diseases and offers the benefits such as improved illumination and magnification of the image when compared with thoracotomy. In this study we evaluated the transdiaphragmatic thoracoscopic-assisted techniques of lung biopsy with a the guillotine cutting needle and biopsy forceps, in dogs presenting radiographic suspicion on pulmonary tumors. Fourteen dogs regardless of breed, gender, age and body weight admitted at the Hospital of Veterinary Clinics (HCV) of the Veterinary College (FAVET) of Universidade Federal do Rio Grande do Sul (UFRGS), were assessed. Inclusion criteria were presence of nodules on chest radiography and triage tests without changes that could hinder general anesthesia and surgical approach. The animals were positioned in dorsal recumbence and two thoracoscopic ports were established: the first port for working instruments; the second paraxyphoid port for the telescope. Three samples were collected using each sampling method from each lesion or from tumors macroscopically similar whenever their size was less than one centimeter. The samples were sent for histopathological examination in the Veterinary Pathology Laboratory of FAVET/UFRGS. Surgical time was recorded from first incision to wound closure and surgical complications were reported. The dogs were evaluated for the presence of subcutaneous emphysema, hematoma, seroma, local infection and dehiscence. No conversion to open surgery was necessary during the thoracoscopic procedure in any patient. Thoracoscopic assisted biopsy using guillotine needle and biopsy forceps was a safe and fast technique, without perioperative complications. Both devices provided good quality samples for histopathological analysis of lung abnormalities. However the cutting guillotine needle was more efficient especially in larger pulmonary nodules. The transdiaphragmatic access provided optimal approach for both hemithoraces

General Characteristics of Edaravone Use in the Natural History of ALS and Other Motor Neuron Disorders Consortium Dataset (NeuroBANK™)

Objective: To report percentage and general information on patients receiving edaravone in the clinics members of ALS Natural History Study Consortium. Background: The ALS Natural History Study protocol was developed with the goal of sharing longitudinal natural history data from several ALS multidisciplinary clinics participating in the ALS Natural History Consortium. Edaravone was approved by the FDA in May 2018 as a new treatment for ALS. There is not yet much data available regarding edaravone use in the United States. We report on edaravone use in our clinics since its approval. Design/Methods: All patients followed regularly in seven multidisciplinary ALS clinics are being offered participation in the study. Consenting participants are assigned a Neurological Global Unique Identifier (NeuroGUID), and a predefined clinical dataset is captured in NeuroBANK™. All medications, including edaravone, are recorded. The dataset will be queried for edaravone use, duration of use, and selected clinical and demographic information. Results: As July of 2018, 105 of 419 consented PALS had received edaravone. Ten PALS were not included due to incomplete data. Of the remaining 95, 61 are male, 34 are female, and age range is from 37 to 82 years. Sixteen PALS (17%) have stopped edaravone, on average after 2.6 months of onset of treatment (range:treatment). Average ALSFRS-R score of all patients on edaravone was 33.6, and of the patients that discontinued the medication was 29.8. Enrollment has accelerated since that time and updated results, vital capacity slopes, and data for the aggregate population through March 2019 will be reported at the meeting. Conclusions: The ALS Natural History Study Consortium provides an opportunity to participating sites to aggregate heterogeneous patient population, and to provide usage and efficacy information on concomitant medications, including post-marketing review of approved drugs as edaravone