19 research outputs found
Targeted colonic release formulations of mesalazine - A clinical pharmaco-scintigraphic proof-of-concept study in healthy subjects and patients with mildly active ulcerative colitis.
Colonic targeting of orally applied therapeutic drugs remains a challenge. Tablet coatings relying on gastrointestinal pH and colonic bacterial enzymes as triggers in association with an inner alkaline layer are expected to improve targeting efficiency. Mesalazine release from three differently coated tablets labelled with 1 MBq 153Sm was characterised in a single centre, open-label, parallel group study in nineteen healthy subjects and seven patients with mildly active ulcerative colitis. Two semi-organic and one aqueous-based outer coating with different ratios of enteric polymer and resistant starch were tested. All coatings showed comparable release lagtimes in biorelevant dissolution media and were not affected by neutron-activation of the samarium tracer. Mesalazine pharmacokinetics and gamma scintigraphy were used to characterise drug release, anatomical site of tablet disintegration and gastrointestinal transit. Initial tablet disintegration occurred at the ileo-caecal junction or beyond in 92% of the subjects Time to initial tablet disintegration was inversely correlated with maximal plasma concentrations and systemic mesalazine exposure. Although high inter-subject variability precluded detection of differences between solvent types and different enteric polymer to polysaccharide ratios, the dual pH and enzymatic triggered release system in combination with an inner alkaline layer promoted mesalazine release at the target site with high accuracy
Presentations to an urban emergency department in Switzerland due to acute γ-hydroxybutyrate toxicity.
BACKGROUND
γ-Hydroxybutyrate (GHB) is a drug of abuse with dose-dependent sedative effects. Systematic data on the acute toxicity of GHB from emergency department (ED) presentations over a long period of time are currently missing from the literature. The present study described the clinical features of GHB toxicity.
METHODS
Retrospective case series of GHB intoxications seen in an urban ED.
RESULTS
From January 2002 to September 2015, 78 GHB-related intoxication cases were recorded (71 % male patients). The mean ± SD age was 29 ± 8 years. The co-use of alcohol and/or other illicit drugs was reported in 65 % of the cases. Neurological symptoms other than central nervous system depression included agitation (40 %) and clonus (21 %). The most frequent reasons for admission were coma (64 %) and agitation (23 %). The median time to regain consciousness was 90 min (range, 3-400 min). Sudden recovery was reported in 25 cases (32 %). Coma was not significantly associated with polyintoxication. Coma occurred in 77 % of the alcohol co-users and in 62 % ofthe non-alcohol users (p=0.052). The mean recovery time in comatose patients was 142 min in patients with co-use of alcohol compared with 89 min in patients without alcohol co-use (p=0.07). Alcohol co-use was not significantly associated with nausea/vomiting (p=0.07). The co-use of stimulants was not significantly associated with non-responsive coma (Glasgow Coma Scale = 3) or mean recovery time. Analytical confirmation of GHB was available in 37 cases (47 %), with additional quantitative analysis in 20 cases. The median GHB concentration was 240 mg/L (range, 8.3-373 mg/L). Intoxication was severe in 72 % of the cases. No fatalities occurred, and 72 % of the patients were discharged directly home from the ED.
DISCUSSION
There were trend associations between alcohol co-use and frequency and length of coma and nausea/vomiting which did not reach the significance level (all p=0.05-0.07) but may nevertheless be clinically relevant. As the exact time of use is not always known, and co-use of other substances can affect the severity of poisoning, no definitive conclusions can be drawn regarding the association between GHB concentration and severity.
CONCLUSION
Impaired consciousness and agitation were typical findings of GHB intoxication. The co-use of alcohol and/or other illicit substances is common but was not significantly associated with the severity of the intoxications in our study
Rates and features of methamphetamine‐related presentations to emergency departments: An integrative literature review
Aims and objectives: To review the clinical impact methamphetamine has on emergency departments by assessing the available research on the rates and features of methamphetamine-related presentations. Background: Globally, methamphetamine availability, distribution and use have rapidly increased. As a result, the number of methamphetamine-related presentations to emergency departments has also increased. In this context, it is timely to review the rate and features of methamphetamine-related presentations to understand the impact of methamphetamine on emergency departments and facilitate the allocation of services, staff and resources. Design: An integrative literature review. Methods: This study presents an integrated literature review, following the systematic review process as outlined in the PRISMA flow chart. Several databases were searched using a combination of search terms. Articles were measured against inclusion and exclusion criteria, and the final ten articles were subjected to quality appraisal and outcomes reported. Results: Methamphetamine accounted for 2.3% or less of all emergency departments presentations. The majority of methamphetamine users presenting to emergency departments were males, with a mean age 31-37. Methamphetamine-related presentations to emergency departments were more likely to present with trauma, psychosis, and be placed on 24-hr psychiatric hold. Methamphetamine-related presentations were more likely to present with agitation, aggression and homicidal behaviour and present to emergency departments out of hours and accompanied by police compared with other emergency departments substance-related presentations. Conclusions: Several important themes were highlighted in this review that has an impact on emergency departments services, resources and staff. Understanding the rate and patterns of methamphetamine-related presentations can help to provide evidence for policy development and staff education in emergency departments. Relevance to clinical practice: Methamphetamine-related presenters are more aggressive and agitated and more likely to be brought in by police. There is a need for policy development and staff training around these issues and further research in this area using stronger study designs
Scanning electron microscopic examination of pocket wall epithelium and associated plaque in localized juvenile periodontitis
In vivo chemotaxis evoked by Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus
A Case of Liver Failure Due to Dabigatran Treated with Venovenous Hemodiafiltration and Idarucizumab
Drug Saf
INTRODUCTION: Postmarketing pharmacovigilance reports have raised concerns about non-bleeding adverse events associated with direct oral anticoagulants (DOACs), but only limited results are available from large claims databases. OBJECTIVE: The aim of this study was to assess the potential association between DOAC initiation and the onset of four types of non-bleeding adverse events by sequence symmetry analysis (SSA). METHODS: SSA was performed using nationwide data from the French National Healthcare databases (Regime General, 50 million beneficiaries) to assess a cohort of 386,081 DOAC new users for the first occurrence of four types of non-bleeding outcomes: renal, hepatic, skin outcomes identified by using hospitalization discharge diagnoses, and gastrointestinal outcomes by using medication reimbursement. Asymmetry in the distribution of each investigated outcome occurring before and after initiation of DOAC therapy was used to test the association between DOAC therapy and these outcomes. SSA inherently controls for time-constant confounders, and adjusted sequence ratios were computed after correcting for temporal trends. Negative (glaucoma) and positive (bleeding, depressive disorders) control outcomes were used and analyses were replicated on a cohort of 310,195 patients initiating a vitamin K antagonist (VKA). RESULTS: This study demonstrated the expected positive association between either DOAC or VKA therapy and hospitalised bleeding and initiation of antidepressant therapy, while no association was observed between either DOAC or VKA therapy and initiation of antiglaucoma medications. For DOAC therapy, signals were the associations with hepatic outcomes, including acute liver injury [for the 3-month time window, aSR3 = 2.71, 95% confidence interval (CI) 1.79-4.52]; gastrointestinal outcomes, including initiation of drugs for constipation and antiemetic drugs (aSR3 = 1.31, 95% CI 1.27-1.36; and 1.17, 95% CI 1.12-1.22, respectively); and kidney diseases (aSR3 = 1.33, 95% CI 1.29-1.37). CONCLUSION: Results of this nationwide study suggest that DOACs are associated with rare but severe liver injury and more frequent gastrointestinal disorders. A low risk of kidney injury with DOAC therapy can also not be excluded