Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs

Objective - To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. Animals - 36 adult dogs. Procedures - Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment. Results - For serum γ-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen. Conclusions and Clinical Relevance - Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.

Adverse effects of drugs on the esophagus

Given the function of the esophagus to transport orally ingested solids and liquids into the stomach there are several medications with adverse effect on esophageal structures and function. Various pharmacologic agents can induce esophageal injury, promote gastroesophageal reflux by decreasing lower esophageal sphincter tone or affect esophageal perception and motility. The risks of bisphosphonates, doxycycline, ferrous sulfate, ascorbic acid, aspirin/NSAIDs and chemotherapeutic agents to induce esophageal lesions have been documented in case reports and short series. In addition to direct mucosal injury, many commonly used medications including nitroglycerins, anticholinergics, beta-adrenergic agonists, aminophyllines, and benzodiazepines promote/facilitate gastroesophageal reflux by reducing lower esophageal sphincter pressure. Additional evidence accumulates on the adverse effects of various medications on esophageal motility and perception. The treatment of medication-induced esophageal lesions includes (1) identifying and discontinuing the causative medication, (2) promoting healing of esophageal injury by decreasing esophageal acid exposure or coating already existing esophageal lesions, (3) eventual use of protective compounds.

Oral candidosis and the therapeutic use of antifungal agents in dentistry

This paper reviews the current concepts of mycology and candidal infections as they relate to the oral cavity. Proposed classification for the presentation of oral candidosis is outlined as are examples of these topical infections, such as erythematous, pseudomembranous and hyperplastic candidosis, as well as angular chelitis and median rhomboid glossitis. The diagnosis and principles of management of oral candidosis are discussed, the therapeutic agents available for the management of these infections are presented and a treatment protocol for the management of patients with oral candidosis is given.

Oral viral infections and the therapeutic use of antiviral agents in dentistry

This paper reviews the current concepts of viral classification, infection and replication. The clinical presentation of common oral viral infections encountered in the dental practice are discussed, including: herpes simplex virus types 1 and 2; Epstein-Barr virus; varicella-zoster virus; Coxsackie virus; human papilloma virus; and human immunodeficiency virus. The diagnosis, principles of management and pharmacological agents available for the treatment of oral viral infections are also discussed.

Long-term antidepressant use: patient perspectives of benefits and adverse effects

Long-term antidepressant treatment has increased and there is evidence of adverse effects; however, little is known about patients’ experiences and views of this form of treatment.This study used mixed methods to examine patients’ views and experiences of long-term antidepressant treatment, including benefits and concerns. Data from 180 patients, who were long-term users of antidepressants (3–15 years), were extracted from an anonymous online survey of patients’ experiences of antidepressants in New Zealand. Participants had completed rating scales about the effectiveness of antidepressants, levels of depression before and during antidepressant use, quality of life, and perceived adverse effects. Two open-ended questions allowed participants to comment on personal experiences. The majority (89.4%) reported that antidepressants had improved their depression although 30% reported moderate-to-severe depression on antidepressants. Common adverse effects included withdrawal effects (73.5%), sexual problems (71.8%), and weight gain (65.3%). Adverse emotional effects, such as feeling emotionally numb (64.5%) and addicted (43%), were also common. While the majority of patients were pleased with the benefits of antidepressant treatment, many were concerned about these adverse effects. Some expressed a need for more information about long-term risks and increased information and support to discontinue.

Assessing and Reporting the Adverse Effects of Antipsychotic Medication: A Systematic Review of Clinical Studies, and Prospective, Retrospective, and Cross-Sectional Research

Objective: Adverse effects (AEs) of antipsychotic medication have important implications for patients and prescribers in terms of wellbeing, treatment adherence and quality of life. This review summarises strategies for collecting and reporting AE data across a representative literature sample to ascertain their rigour and comprehensiveness. Methods: A PsycINFO search, following PRISMA Statement guidelines, was conducted in English-language journals (1980–July 2014) using the following search string: (antipsychotic* OR neuroleptic*) AND (subjective effect OR subjective experience OR subjective response OR subjective mental alterations OR subjective tolerability OR subjective wellbeing OR patient perspective OR self-rated effects OR adverse effects OR side-effects). Of 7,825 articles, 384 were retained that reported quantified results for AEs of typical or atypical antipsychotics amongst transdiagnostic adult, adolescent, and child populations. Information extracted included: types of AEs reported; how AEs were assessed; assessment duration; assessment of the global impact of antipsychotic consumption on wellbeing; and conflict of interest due to industry sponsorship. Results: Neurological, metabolic, and sedation-related cognitive effects were reported most systematically relative to affective, anticholinergic, autonomic, cutaneous, hormonal, miscellaneous, and non-sedative cognitive effects. The impact of AEs on patient wellbeing was poorly assessed. Cross-sectional and prospective research designs yielded more comprehensive data about AE severity and prevalence than clinical or observational retrospective studies. 3 Conclusions: AE detection and classification can be improved through the use of standardised assessment instruments and consideration of subjective patient impact. Observational research can supplement information from clinical trials to improve the ecological validity of AE data.

Swiss consensus statement: Recommendations for optimising re-treatment with MabThera (rituximab) in rheumatoid arthritis.

Rituximab is an effective treatment of rheumatoid arthritis (RA), which has been approved for the treatment of moderate to severe disease in patients with an inadequate response to anti-TNF therapies. Rituximab differs from other available biological agents for RA by way of its unique mode of action and unrivalled long dosing interval. The efficacy of rituximab subsides progressively over time and re-therapy is generally required to maintain long term disease control. The timing of re-treatment is currently not well established and varies widely in clinical practice. The present document is a concise recommendation regarding re-treatment with rituximab, based on validated outcomes such as the DAS28 and the EULAR response criteria. The recommendation was established through consensus between practitioners familiar with rituximab therapy in RA. Optimisation of the rituximab re-treatment schedule may improve patient outcomes and balance risks and benefits for the individual patient.

Clinical experience of clobazam as add-on treatment in a cohort of adults with epilepsy

Objective: Epilepsy is a common neurologic disorder affecting 1% of the world population with one-third of these patients failing to have seizure control for more than one year. Clobazam is a long-acting benzodiazepine used worldwide for the treatment of epilepsy. This antiepileptic drug has demonstrated great clinical benefits with mild side effects. The objective of this study was to better understand the efficacy of clobazam treatment on adult patients with refractory epilepsy. Design: A retrospective review of 44 adult patients with diagnosis of epilepsy that were seen at our Epilepsy Clinic between January 2014 and May 2015. Setting: An outpatient epilepsy clinic at the Hospital Universitario Fundación Santa Fe de Bogota, Colombia. Participants: 44 adult patients with diagnosis of epilepsy. Measurements: Seizure frequency, adverse effects and the use of concomitant AEDs were reviewed in each of the patient´s clinical charts. Results: The responder rate of patients with clobazam was 52% at 3 months, 50% at 6 months and 55% at 12 month. Seizure freedom rates at 3, 6 and 12 months were 18%, 25% and 25% respectively. Clobazam related adverse events occurred only in four patients (9%) at the end of the twelve months with somnolence being the most common. Conclusion: These findings suggest that clobazam treatment in adult patients with focal or generalized epilepsy is effective and safe. Its use should be considered early when first-line agents fail to provide seizure control.

Pollination and other ecosystem services produced by mobile organisms: a conceptual framework for the effects of land-use change

Many ecosystem services are delivered by organisms that depend on habitats that are segregated spatially or temporally from the location where services are provided. Management of mobile organisms contributing to ecosystem services requires consideration not only of the local scale where services are delivered, but also the distribution of resources at the landscape scale, and the foraging ranges and dispersal movements of the mobile agents. We develop a conceptual model for exploring how one such mobile-agent-based ecosystem service (MABES), pollination, is affected by land-use change, and then generalize the model to other MABES. The model includes interactions and feedbacks among policies affecting land use, market forces and the biology of the organisms involved. Animal-mediated pollination contributes to the production of goods of value to humans such as crops; it also bolsters reproduction of wild plants on which other services or service-providing organisms depend. About one-third of crop production depends on animal pollinators, while 60-90% of plant species require an animal pollinator. The sensitivity of mobile organisms to ecological factors that operate across spatial scales makes the services provided by a given community of mobile agents highly contextual. Services vary, depending on the spatial and temporal distribution of resources surrounding the site, and on biotic interactions occurring locally, such as competition among pollinators for resources, and among plants for pollinators. The value of the resulting goods or services may feed back via market-based forces to influence land-use policies, which in turn influence land management practices that alter local habitat conditions and landscape structure. Developing conceptual models for MABES aids in identifying knowledge gaps, determining research priorities, and targeting interventions that can be applied in an adaptive management context.

Comparison of prophylactic and therapeutic use of short-chain fatty acid enemas in diversion colitis: a study in Wistar rats

OBJECTIVES: To study the effect of short-chain fatty-acids on atrophy and inflammation of excluded colonic segments before and after the development of diversion colitis. INTRODUCTION: Diversion colitis is a chronic inflammatory process affecting the dysfunctional colon, possibly evolving with mucous and blood discharge. The most favored hypotheses to explain its development is short-chain fatty-acid deficiency in the colon lumen. METHODS: Wistar rats were submitted to colostomy with distal colon exclusion. Two control groups (A1 and B1) received rectally administered physiological saline, whereas two experimental groups (A2 and B2) received rectally administered short-chain fatty-acids. The A groups were prophylactically treated (5th to 40th days postoperatively), whereas the B groups were therapeutically treated (after post-operative day 40). The mucosal thickness of the excluded colon was measured histologically. The inflammatory reaction of the mucosal lamina propria and the lymphoid tissue response were quantified through established scores. RESULTS: There was a significant thickness recovery of the colonic mucosa in group B2 animals (p = 0.0001), which also exhibited a significant reduction in the number of eosinophilic polymorphonuclear cells in the lamina propria (p = 0.0126) and in the intestinal lumen (p = 0.0256). Group A2 showed no mucosal thickness recovery and significant increases in the numbers of lymphocytes (p = 0.0006) and eosinophilic polymorphonuclear cells in the lamina propria of the mucosa (p = 0.0022). CONCLUSION: Therapeutic use of short-chain fatty-acids significantly reduced eosinophilic polymorphonuclear cell numbers in the intestinal wall and in the colonic lumen; it also reversed the atrophy of the colonic mucosa. Prophylactic use did not impede the development of mucosal atrophy

Evaluation of the adverse effects of oral firocoxib in healthy dogs

This study evaluated the adverse effects of oral firocoxib in dogs. Six dogs (20.2 +/- 6.3 kg) were studied. Values for complete blood count (CBC), serum urea, creatinine, alanine transaminase, alanine phosphatase, -glutamyl transferase, occult blood in feces, platelet aggregation, and buccal mucosal bleeding time were measured before and 7, 14, 21, and 29 days after SID treatment with firocoxib 5.3 +/- 0.34 mg/kg (FG) or lactose 1 mg/kg (LG) for 2 8 days, in a randomized crossover study. Gastrointestinal (GI) tract endoscopy was performed before treatment began and at 29 days. Lesions were scored from grade 0 to 6. Data were analyzed using ANOVA and paired t-tests (P < 0.05). None of the dogs presented adverse clinical effects. There were no significant changes in CBC, biochemical profiles within groups, or differences between groups. Pretreatment mean SD bleeding time (LG, 70.7 +/- 32.1 sec; FG, 75.8 +/- 38.1 sec) and platelet aggregation (LG, 86.4 +/- 10.2%; FG, 85.6 +/- 9.2%) were not significantly different from readings at 29 days (LG, 95.2 +/- 25 sec; FG, 91.7 +/- 24 sec and LG, 73.2 +/- 15.1%; FG, 84 +/- 10.3%) nor the groups were different. None of the dogs had positive fecal occult blood tests, and endoscopic lesion scores were grade 0 both before treatment and at 29 days. Administration of firocoxib did not cause any adverse effects on GI, or hematological or serum biochemical variables and appears to have been well tolerated by dogs.

Effects of N-acetylcysteine on alcohol abstinence and alcohol-induced adverse effects in rats

Alcoholism is rampant in modern society and some antioxidant compound could perhaps be useful to reduce the damage done by alcohol consumption and abstinence. The present study was undertaken to investigate the association of N-acetylcysteine (NAC) intake, alcoholism, and alcohol abstinence on lipid profile, in vivo low-density lipoprotein (LDL) oxidation, oxidative stress, and antioxidant status in serum and liver of rats. Initially, male Wistar 30 rats were divided into two groups: (C, N = 6) given standard chow and water; (E, N = 24) receiving standard chow and aqueous ethanol solution in semi-voluntary research. After 30 days of ethanol exposure, (E) group was divided into four subgroups (N = 6/group): (E-E) continued drinking 30% ethanol solution; (E-NAC) drinking ethanol solution containing 2 g/L NAC (AB) changed ethanol solution to water; (AB-NAC) changed ethanol to aqueous solution 2 g/L NAC. After 15 days of the E-group division, E-E rats had higher serum alanine transaminase, lower body weight, and surface area, despite higher energy intake than C. E-E rats had also lower feed efficiency, dyslipidemia with enhanced triacyl glycerol, very low-density lipoprotein (VLDL), lipid hydroperoxide (LH) and in vivo oxidized-LDL (ox-LDL). AB, E-NAC, and AB-NAC rats ameliorated serum oxidative stress markers and normalized serum lipids. E-E rats had higher hepatic LH and lower reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio than C, indicating hepatic oxidative stress. AB and E-NAC rats normalized hepatic LH, GSSG, and the GSH/GSSG ratio, compared to E-E. AB-NAC rats had the lowest serum ox-LDL, hepatic LH levels, and the highest GSH reductase activity in hepatic tissue. In conclusion, the present study brought new insights into alcohol consumption, because ethanol exposure enhanced serum in vivo ox-LDL, as well as serum and hepatic oxidative stress. N-acetylcysteine offers promising therapeutic value to inhibit ethanol-induced adverse effects. Ethanol withdrawal had beneficial effects on serum lipids, but was more effective when coupled with NAC supplementation. Ethanol abstinence and NAC intake interact synergistically, improving serum lipids and hepatic antioxidant defenses. (c) 2009 Elsevier B.V. All rights reserved.