Prevalence of diabetes in france and drug use: study based on the French pharmacovigilance database

AIM: The aim of this study was to investigate the use of the French Pharmacovigilance Database to estimate characteristics of drug utilization in specific diseases. MATERIALS AND METHOD: We identified diabetic patients from the French Pharmacovigilance Database between 2002 and 2005. In this population, we studied demographic characteristics, and the patterns of drug use, particularly hypoglycemiant drug use and other drug exposure. In order to validate this approach, we compared our data to a population of patients with diabetes identified from the French Health Insurance System claims database in one French area. RESULTS: The estimation of prevalence of diabetes was very close in the sources: 2.7% in the French Pharmacovigilance Database and 3.2% in the French Health Insurance System claims database. We found similar results as well for demographic characteristics as for hypoglycemiant drug use and other drug exposure. CONCLUSION: These results suggest that the French Pharmacovigilance Database may be used to investigate drug utilization patterns.     

Relationship between Optimum Mini‐doses of Glucagon and Insulin Levels when Treating Mild Hypoglycaemia in Patients with Type 1 Diabetes – A Simulation Study

Hypoglycaemia remains the main limiting factor in type 1 diabetes management. We developed an insulin‐dependent glucagon dosing regimen for treatment of mild hypoglycaemia based on simulations. A validated glucose–insulin–glucagon model was used to describe seven virtual patients with insulin pump‐treated type 1 diabetes. In each simulation, one of ten different and individualized subcutaneous insulin boluses was administered to decrease plasma glucose (PG) from 7.0 to ≤3.9 mmol/l. Insulin levels were estimated as ratio of actual to baseline serum insulin concentration (se/ba‐insulin), insulin on board (IOB) or percentage of IOB to total daily insulin dose (IOB/TDD). Insulin bolus sizes were chosen to provide pre‐defined insulin levels when PG reached 3.9 mmol/l, where one of 17 subcutaneous glucagon boluses was administered. Optimum glucagon bolus to treat mild hypoglycaemia at varying insulin levels was the lowest dose that in most patients caused PG peak between 5.0 and 10.0 mmol/l and sustained PG ≥ 3.9 mmol/l for 2 hr after the bolus. PG response to glucagon declined with increasing insulin levels. The glucagon dose to optimally treat mild hypoglycaemia depended exponentially on insulin levels, regardless of how insulin was estimated. A 125‐μg glucagon dose was needed to optimally treat mild hypoglycaemia when insulin levels were equal to baseline levels. In contrast, glucagon doses >500 μg were needed when se/ba‐insulin >2.5, IOB >2.0 U or IOB/TDD >6%. Although the proposed model‐based glucagon regimen needs confirmation in clinical trials, this is the first attempt to develop an insulin‐dependent glucagon dosing regimen for treatment of insulin‐induced mild hypoglycaemia in patients with type 1 diabetes.     

Influence of circadian rhythm on mortality after myocardial infarction: data from a prospective cohort of emergency calls

Myocardial infarction (MI) occurs more frequently in the morning as a result of the concomitant unfavorable timing of several physiological parameters and/or biochemical conditions. However, little is known about the possible influence of this circadian pattern on prognosis. To evaluate whether the time of symptom onset could potentially influence mortality from acute MI, this prospective study considered all consecutive MIs admitted to the ED of Ferrara, Italy, after a call to the Emergency Coordinating Unit from January 1, 1998, to December 31, 2001. The total sample consisted of 442 MIs (mean age, 68.7 years; males, 72%). Eighty patients (males, 82.5%) died in the ED; the remaining 362 were admitted to the hospital. Of these, 50 (males, 60%) died during their hospital stay. Based on the timing of their symptom onset, cases were categorized both into 24 1-hour intervals and four 6-hour intervals (midnight to 5:59 am, 6:00 am to 11:59 am, noon to 5:59 pm, and 6:00 pm to 11:59 pm), and the circadian distributions of fatal versus nonfatal MIs were compared. The circadian variation of MI peaked between 6:00 am and noon (P < .001), and in this period, there was a trend toward a higher frequency of fatal cases (41.5% vs. 35.2%; chi(2) = 1.911, P = .167). To verify whether this higher frequency of fatal events in the morning hours could be related to possible higher severity of cases observed in that hours, a further separate analysis considering age, infarct site, and peak levels of MB was made. Again, no significant temporal differences among the four 6-hour intervals were found between fatal and nonfatal Mis, although a trend toward older age was observed in morning MIs. Not only the frequency, but also the mortality, of acute MI could be increased in the morning hours. This could be of practical interest for emergency doctors and could have significant implications for acute treatment, because several studies have reported a lowered efficacy of thrombolytic drugs in the morning hours.     

Counter incision is a safe and effective method for alternative reservoir placement during inflatable penile prosthesis surgery

BackgroundAlternative reservoir placement is increasingly popular during inflatable penile prosthesis (IPP) surgery to prevent intraperitoneal positioning, bowel, bladder, or vascular injury in patients with prior pelvic surgeries. Counter incision (CI) can be used for submuscular reservoir placement in high risk patients, however series exploring the safety remain limited.MethodsA database of IPP surgeries was queried for use of a CI during reservoir placement to compare 90-day clinical outcomes in a retrospective case-control study. Primary outcome was device infections, with secondary outcomes including reservoir herniation, hematoma, device malfunction rates, and operative times. Groups were compared using Kruskal-Wallis and Chi-Squared tests, with multivariate logistic regression models to identify predictors of infectious complications.ResultsA total of 534 cases met criteria, of which 51 (9.6%) used a CI for reservoir placement. The CI cohort included significantly more removal and replacements, 45.1% vs. 20.9% (P<0.001). Thirty-one CI patients (61.0%) had undergone prior prostatectomy compared to 134 (27.7%) non-CI patients (P=0.001). The most common reasons for CI were prior prostatectomy and inguinal hernia repair. Median operative time was 17 minutes longer in the CI group (74 vs. 57 minutes, P<0.001). Device infection rates were similar (2.0% vs. 4.1%, P=0.71), as were rates of hematoma (5.9% vs. 2.7%, P=0.19), and device malfunction (0.0% vs. 1.4% P=1.00).ConclusionsComplication rates were similar between CI and non-CI cohorts, even in a subset where approximately half the cases were removal and replacements. For physicians not comfortable with alternative placement through a penoscrotal or infrapubic incision, this offers a reasonable alternative and permits use of three-piece devices in patients with a hostile pelvis.     

Radiation‐induced nausea and vomiting in head and neck cancer: Is it something worth considering in the intensity modulated radiotherapy era? “A narrative review”

Radiation therapy is one of the cornerstones in the treatment of head and neck squamous cell carcinomas (HNSCC), alone or in combination with chemotherapy or surgery. Technological advances which occurred over the last few decades have increased the efficacy of radiotherapy (RT), particularly, intensity‐modulated RT (IMRT). IMRT can deliver treatments on complex tumoral targets with dose escalation while sparing organs at risk; anyway IMRT deposits dose in unpredictable patterns outside of the target volume with the purpose of improving conformality. Radiation‐induced nausea and vomiting (RINV) is a frequent albeit neglected side effect of RT that can lead to delays in treatment with serious consequences on cure rates. According to several guidelines (MASCC 2016, NCCN 2018), RT for HNSCC has traditionally been regarded as a low emetic risk treatment. Nevertheless, several works suggest that IMRT could increase RINV. Further studies are needed to define the exact incidence and the detailed pathophysiology of RINV in patients with HNSCC treated with state of art IMRT techniques, with and without concurrent chemotherapy.     

Induction of Suicidal Erythrocyte Death by Nelfinavir

The HIV protease inhibitor, nelfinavir, primarily used for the treatment of HIV infections, has later been shown to be effective in various infectious diseases including malaria. Nelfinavir may trigger mitochondria-independent cell death. Erythrocytes may undergo eryptosis, a mitochondria-independent suicidal cell death characterized by cell shrinkage and phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress and increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i). During malaria, accelerated death of infected erythrocytes may decrease parasitemia and thus favorably influence the clinical course of the disease. In the present study, phosphatidylserine abundance at the cell surface was estimated from annexin V binding, cell volume from forward scatter, reactive oxidant species (ROS) from 2'',7''-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, and [Ca²⁺]_i from Fluo3-fluorescence. A 48 h treatment of human erythrocytes with nelfinavir significantly increased the percentage of annexin-V-binding cells (≥5µg/mL), significantly decreased forward scatter (≥2.5µg/mL), significantly increased ROS abundance (10 µg/mL), and significantly increased [Ca²⁺]_i (≥5 µg/mL). The up-regulation of annexin-V-binding following nelfinavir treatment was significantly blunted, but not abolished by either addition of the antioxidant N-acetylcysteine (1 mM) or removal of extracellular Ca²⁺. In conclusion, exposure of erythrocytes to nelfinavir induces oxidative stress and Ca²⁺ entry, thus leading to suicidal erythrocyte death characterized by erythrocyte shrinkage and erythrocyte membrane scrambling.     

Synthesis of 5,6‐dihydro‐4H‐benzo[d]isoxazol‐7‐one and 5,6‐dihydro‐4H‐isoxazolo[5,4‐c]pyridin‐7‐one Derivatives as Potential Hsp90 Inhibitors

A novel class of 5,6‐dihydro‐4H‐benzo[d]isoxazol‐7‐ones and 5,6‐dihydro‐4H‐isoxazolo[5,4‐c]pyridin‐7‐ones was designed, synthesized, and assayed to investigate the affinity toward Hsp90 protein. The synthetic route was based on a 1,3‐dipolar cycloaddition of nitriloxides, generated in situ from suitable benzaldoximes, with 2‐bromocyclohex‐2‐enones or 3‐bromo‐5,6‐dihydro‐1H‐pyridin‐2‐ones. Whereas all the compounds bearing a benzamide group on the bicyclic scaffold were devoid of activity, the derivatives carrying a resorcinol‐like fragment showed a remarkable inhibitory effect on Hsp90. Docking calculations were performed to investigate the orientation of the new compounds within the binding site of the enzyme.