Marion Lepelley

Lactic Acidosis in Diabetic Population: Is Metformin Implicated? Results of a Matched Case-Control Study Performed on the Type 2 Diabetes Population of Grenoble Hospital University

Introduction. To evaluate the strength of association between lactic acidosis (LA) and well-recognized risk factors for LA, particularly the weight of metformin. Methods. This study is a matched case-control analysis concerning the type 2 diabetes population from Grenoble Hospital University. Cases of LA were defined biologically with pH < 7.35 and lactates > 5 mmol/L. They were matched to 2 controls defined as type 2 diabetic inpatients who did not present a LA during the study period. We performed a conditional logistic regression. Results. We included 302 cases and 604 controls; mean age was 69.5 years (SD 11.93). Intercurrent diseases were significantly associated with LA. Chronic medical conditions had a minor impact on LA incidence, except hepatocellular dysfunction. Metformin was significantly associated with a higher LA probability in case of acute kidney injury (AKI) (OR = 1.79; p value = 0.020) but not in patients without AKI. Discussion and Conclusions. According to this study, metformin, compared to acute medical conditions, seemed not to be associated with LA in patients with type 2 diabetes; however in case of AKI, metformin may be associated with LA.

Chronic use of proton pump inhibitors, adverse events and potential biological mechanisms: A translational analysis

Proton pump inhibitors (PPIs) are among the most frequently prescribed drugs. Even if PPI are usually considered as safe, there is a growing concern for a range of adverse effects of chronic PPI therapy often in the absence of appropriate indications. We propose, after a summary of renal, cardiovascular and neurological complications (dementia, chronic kidney disease, myocardial infarction and stroke), an integrative overview of the potential biological mechanisms involved. Eleven positive pharmacoepidemiological studies, mainly based on health insurance database linkage to hospital database, reported an increased risk of complications associated to PPI use and often a graded association suggesting also a possible dose-response relationship. Several mechanisms have been suggested through in vitro studies (endothelial dysfunction, endothelial senescence, hypomagnesemia, increase of chromogranin A levels, decrease of nitric oxide in endothelial cells) leading to the impairment of vascular homesostasis, paving the way to these complications. Evidence that PPIs may have off-targets and pleiotropic effects are mounting and may impose a cautious attitude in the prescription of PPIs, especially in elderly and/or in the context of chronic use.

Doctor shopping of opioid analgesics relative to benzodiazepines: A pharmacoepidemiological study among 11.7 million inhabitants in the French countries

BACKGROUND The abuse of prescription opioids and its subsequent consequences is an important public concern particularly in the USA. The literature on opioid analgesic abuse is scarce. OBJECTIVE We assess the extent and risk of opioid analgesics abuse relative to benzodiazepines (BZD) using the doctor shopping method, taken into account the pharmacological characteristics (dosage, route of administration, extended or immediate release). METHODS We used SNIIRAM database covering 11.7 million inhabitants. All individuals with at least one reimbursement for non-injectable opioid analgesic or BZD in 2013 were included. Opioids for mild to moderate pain and for moderately severe to severe pain were studied. The Doctor Shopping Quantity (DSQ) is the quantity obtained by overlapping prescriptions from several prescribers. The Doctor Shopping Indicator (DSI) is the DSQ divided by the total dispensed quantity. RESULTS The strong opioid analgesics have the highest DSI (2.79%) versus 2.06% for BZD hypnotics. Flunitrazepam ranked first according to its DSI (13.2%), followed by morphine (4%), and zolpidem (2.2%). The three-strong opioids having the highest DSI were morphine, oxycodone and fentanyl (respectively 4%, 1.7% and 1.5%). The highest DSI was observed for the highest dosages of morphine (DSI = 8.4% for 200 mg) and oxycodone (DSI = 2.8% for 80 mg). The highest DSI for fentanyl was described with nasal and transmucosal forms (4.1% and 3.3% respectively). The highest DSI for morphine was described for extended-release (4.1%). CONCLUSION There is a need to reinforce surveillance systems to track opioid misuse and to increase awareness of healthcare professionals.

Bradykinin mechanism is the main responsible for death by isolated asphyxiating angioedema in France

Angioedema (AE) is a sudden localized, subcutaneous or submucosal, swelling due to one of two major possible mechanisms: mast cell induced (MC-AE) or bradykinin mediated (BkAE). MC-AE may be allergic or non-allergic (mast cell degranulation non-specific to the antigen). BkAE may be hereditary, with (C1-INH-HAE) or without C1 inhibitor (C1-INH) deficiency. BkAE may also be acquired with C1-INH deficiency (C1-INH-AAE), complicating some blood diseases, dysimmunities or be iatrogenic, mainly due to angiotensin converting enzyme inhibitors (ACEi). This article is protected by copyright. All rights reserved.

Fluoxetine and Raynaud's phenomenon: friend or foe?

Whether fluoxetine, a selective serotonin reuptake inhibitor, is an effective treatment for Raynaud’s phenomenon (RP) has been debated for about 20 years. Based on one positive efficacy trial [5] and some preliminary observations [6], fluoxetine is recommended in RP secondary to systemic sclerosis (SSc), after failure of calcium channel blockers [7]. However, when one looks closely at the available evidence, the lack of a homogeneous effect of fluoxetine in RP patients is obvious. The crossover study comparing the efficacy of nifedipine and fluoxetine in 56 patients with primary or secondary RP showed a significant improvement in the Raynaud’s condition score (RCS) [4.35 (0.39) vs. 2.3 (0.35); P = 0.0002] and daily frequency of attacks [2.98 (0.31) vs. 1.7 (0.25); British Journal of Clinical Pharmacology Br J Clin Pharmacol (2017) 83 2307–2309 2307