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.     

Giant pseudoaneurysm of the innominate artery late after surgical repair of type-A aortic dissection

A 49-year-old man was admitted to our department 6 months after emergent surgery for type-A acute aortic dissection. A chest computed tomography-scan revealed a huge aneurysm originating from the proximal aortic arch, strongly adherent to the upper part of the sternum. Extracorporeal circulation was instituted first, and chest was reopened in circulatory arrest. The mass was a giant pseudoaneurysm originating from a laceration at the base of the innominate artery. Due to tissue fragility and complete distortion of the origin of right carotid and subclavian arteries, we performed an extra-anatomic ascending aorta-to-right carotid artery bypass, followed by Teflon-reinforced suture of the proximal artery stumps. The postoperative course was uneventful.     

Role of Preoperative Basal Calcitonin Levels in the Timing of Prophylactic Thyroidectomy in Patients With Germline RET Mutations

Background

The American Thyroid Association (ATA) published recommendations for the timing of prophylactic surgery for medullary thyroid carcinoma based on the specific mutation, patient age, family history, and serum calcitonin levels. The aim of this study was to assess the role of preoperative basal calcitonin (prebCt) levels in predicting the presence of medullary carcinoma of the thyroid in patients with RET mutations.

Methods

We conducted a retrospective study in two endocrine surgery departments. Between 1986 and 2012, a total of 32 patients with RET mutations underwent prophylactic thyroidectomy. The patients were stratified into four ATA risk levels: A, B, C, and D.

Results

All of the patients were biologically cured. Microcarcinoma was observed in the final pathology report for four of the 20 patients with normal prebCt (25 %) and for nine of the 12 patients with elevated prebCt (75 %). In the level A group, four patients with normal prebCt and one patient with elevated prebCt presented with microcarcinoma. In the level C group, one patient with normal prebCt and six of the seven patients with elevated prebCt (86 %) presented with microcarcinoma.

Conclusions

PrebCt can predict the presence of microcarcinoma according to surgical pathological analysis. Patients with microcarcinoma can be biochemically and clinically cured using prophylactic thyroidectomy.     

The screening of Alzheimer’s patients with CSF biomarkers,modulates the distribution of APOE genotype: impact on clinical trials

Polymorphism of the apolipoprotein E gene (APOE) plays a role in the level of neuropathological lesions and in drug response in Alzheimer’s disease (AD). The aim of this study was to investigate whether the selection of AD patients based on cerebrospinal fluid (CSF) biomarkers assessment may be biased by their APOE distribution. We studied the relationships between APOE genotype and CSF biomarkers levels in a total of 432 patients (AD, n = 244; non-AD, n = 188) explored for cognitive disorders. We studied the distribution of APOE genotypes among AD patient subgroups selected by various cut-offs of CSF biomarkers. Strategies of screening based on CSF Aβ1–42 lead to overselection of ε4/ε4 patients in the AD group. Screening based on tau levels did not change Apoe4 distribution in the AD group. CSF Aβ1–42 discriminated better AD patients with at least one ε4 than AD patients with no ε4. A strong allele-effect relationship was detected between APOE genotype and CSF amyloid-β (Aβ1–42) in AD patients. Selecting AD patients on CSF amyloid levels only may create an overselection of ε4/ε4 carriers, and might potentially bias the population of patients included in clinical trial studies.     

Liver Perfusion Changes Occurring During Pancreatic Islet Engraftment: A Dynamic Contrast‐Enhanced Magnetic Resonance Study

The aim of this study was to investigate liver microvascular adaptation following the intraportal infusion of pancreatic islets (pancreatic islet transplantation [islet‐tx]) in diabetic patients using dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI). DCE‐MRI was performed before and 7 days after islet‐tx in six diabetic patients. Initial area under curve (AUC60) and volume transfer coefficient (Ktrans) were assessed as markers of liver perfusion. Clinical and metabolic monthly follow‐up was performed in all patients, considering fasting C‐peptide and β‐score as main indices of graft function. High variability in the response of liver microvasculature to islet infusion was observed: two patients showed a significant reduction in liver perfusion after transplantation (pt.2: AUC60 = ?23.4%, Ktrans = ?31.7%; pt.4: AUC60 = ?23.7%, Ktrans = ?27.9%); three patients did not show any significant variation of liver perfusion and one patient showed a significant increase (pt.3: AUC60 = +31%, Ktrans = +42.8%). Interestingly, a correlation between DCE‐MRI parameters and indices of graft function was observed and, in particular, both patients with DCE‐MRI evidence of posttransplantation liver perfusion reduction experienced premature graft failure. Our preliminary study demonstrated that DCE‐MRI may identify different adaptive responses of liver microvasculature in patients submitted to islet‐tx. These different responses could have an impact on islet engraftment, although reported findings need confirmation from larger studies.

     

Drug-induced adverse reactions via breastfeeding: a descriptive study in the French Pharmacovigilance Database

Purpose

Most drugs are excreted in maternal milk and may therefore be ingested by children during breastfeeding. Data concerning the safety of the use of drugs by breastfeeding women are patchy, and almost nothing is known about this issue for many drugs.

Methods

The aim of this study was to describe the adverse drug reactions of drugs transmitted in breast milk on the basis of the data collected in the French Pharmacovigilance Database. All spontaneous reports of adverse drug reactions (ADRs) in breastfed infants recorded in the National Pharmacovigilance Database by the 31 French regional pharmacovigilance centres between 1984 and June 2011 were investigated.

Results

Between January 1985 and June 2011, 276 adverse drug reactions in 174 breastfed children were notified to the French Pharmacovigilance Network. The most frequently reported adverse drug reactions were neurological (28.6 %) and gastrointestinal (20.3 %). Sixty-five of the adverse drug reactions recorded were considered to be serious (37.4 %). The results of our study confirm that certain drugs were frequently implicated in serious adverse drug reactions. Two cases of ADRs (1.1 %) had a ‘certain’ causality score (I4) and 13 (7.5 %) a ‘likely’ score (I3). The suspected drugs include antiepileptic drugs, opiate analgesics and benzodiazepines. These results also demonstrate that some drugs that were thought to be anodyne or for which no data were available, such as ketoprofen and hydroxyzine, may be implicated in adverse effects. Finally, these data show that certain drugs, like pseudoephedrine, which should not be used during breastfeeding, were nevertheless implicated in several of the adverse drug reactions recorded.

Conclusion

This study shows that ADR via breastfeeding are rarely reported due to low awareness or low occurrence of ADR via breast milk. These results highlight the need for additional pharmacokinetic, clinical and epidemiological studies, given the paucity of published data. They also demonstrate the need to improve information for the general public about drugs and self-medication during breastfeeding.     

Colorectal Anastomotic Stenosis After Elective Laparoscopic Sigmoidectomy for Diverticular Disease: A Prospective Evaluation of 68 Patients

Purpose  This prospective study was designed to find the incidence of symptomatic anastomotic stenosis after elective laparoscopic sigmoidectomy for diverticular disease. Methods  Sixty-eight patients who underwent elective laparoscopic sigmoidectomy with double-stapling colorectal anastomosis between November 1998 and June 2007 were included. Follow-up after hospitalization was performed by using sequential rectoscopy for all patients. Symptomatic patients with anastomotic stricture were treated. Results  No patient died postoperatively and no patient had anastomotic leak or abdominal septic complication. Twenty-two patients (32 percent) had postoperative symptoms that suggested anastomotic stenosis; 12 of them (17.6 percent) eventually needed dilatation of their anastomosis (median diameter of the stenosis: 7 mm) a mean time of 176 days postoperatively. Eight patients had only one session, three patients had two sessions, and one patient had three sessions. There were no complications and all patients were symptom-free after dilatation. Age, sex, obesity, hypertension, diabetes, and vascular preservation had no influence on the risk of anastomotic stenosis. Conclusions  Incidence of symptomatic anastomotic stenosis after elective laparoscopic sigmoidectomy is high (17.6 percent). No risk factor could be identified. Endoscopic dilatations were successful without complication in all cases. Regular rigid rectoscopy definitely should be part of the postoperative follow-up in symptomatic patients.     

Acoustic excitations and elastic heterogeneities in disordered solids

In the recent years, much attention has been devoted to the inhomogeneous nature of the mechanical response at the nanoscale in disordered solids. Clearly, the elastic heterogeneities that have been characterized in this context are expected to strongly affect the nature of the sound waves which, in contrast to the case of perfect crystals, cannot be completely rationalized in terms of phonons. Building on previous work on a toy model showing an amorphization transition, we investigate the relationship between sound waves and elastic heterogeneities in a unified framework by continuously interpolating from the perfect crystal, through increasingly defective phases, to fully developed glasses. We provide strong evidence of a direct correlation between sound wave features and the extent of the heterogeneous mechanical response at the nanoscale.In crystals, molecules thermally oscillate around the periodic lattice sites and vibrational excitations are well understood in terms of quantized plane waves, the phonons (1). The vibrational density of states (vDOS) in the low-frequency regime is well described by the Debye model, where the vibrational modes are the acoustic phonons. In contrast, disordered solids, including structural glasses and disordered crystals, exhibit specific vibrational properties compared with the corresponding pure crystalline phases. It is not possible here to give a fair review of the extensive theoretical and experimental work generated by these issues; we therefore mention below a few facts that we consider the most relevant in the present context. The origin of the vDOS modes in excess over the Debye prediction around ω ∼1 THz, the so-called Boson peak (BP), is still debated (see, among many others, refs. 2 and 3). At the BP frequency, Ω^BP, localized modes have also been observed (4). Acoustic plane waves, which are exact normal modes in crystals, can still propagate in disordered solids. Indeed, at low frequencies, Ω, and long wavelengths, Λ, acoustic sound waves do not interact with disorder and can propagate conforming to the expected macroscopic limit. However, as Ω is increased beyond the Ioffe–Regel (IR) limit, Ω^IR, acoustic excitations interact with the disorder and are significantly scattered (5–7). Interestingly, this strong scattering regime occurs around the BP position, Ω^IR ∼ Ω^BP (8, 9). The exact origin of this phenomenon and its connection to the BP remain elusive.A possible rationalization of the above issues is based on the existence of elastic heterogeneities (10), which can originate from structural disorder, as in structural glasses (2), or disordered interparticle potentials, even in lattice structures such as disordered colloidal crystals (11). In the heterogeneous-elasticity theory of refs. 7 and 12 this amounts to consider spatial statistical fluctuations of the shear modulus. Within the framework of jamming approaches and using effective medium theories, elastic heterogeneities are related to the proximity of local elastic instabilities (13). Recent simulation work (14–16) has clearly demonstrated their existence in disordered solids. This is at variance with the case of simple crystals, which are characterized by a fully affine response and homogeneous moduli distributions (17). More specifically, in the large length scale limit, macroscopic moduli are observed. In contrast, as the length scale is reduced, moduli heterogeneities are detected, at a typical length scale ξ ≃ 10−15σ (15), where σ is the typical atomic diameter. Breakdown of both continuum mechanics (18) and Debye approximation (5, 6) has been demonstrated at the same mesoscopic length-scale ξ, where they are still valid for crystals. Remarkably, the wave frequency corresponding to the wavelength Λ ∼ ξ is very close to Ω^IR ∼ Ω^BP (19). Altogether these results indicate that a close connection must exist between elastic heterogeneities and acoustic excitations. In this paper we precisely address this point.In ref. 20 we considered a numerical model featuring an amorphization transition (21). We showed how to systematically deform the local moduli distributions, evaluated by coarse-graining the system in small domains of linear length scale w. We characterized the degree of elastic heterogeneity in terms of SD of those distributions and studied the effect on normal modes (eigenvalues of the Hessian matrix) and thermal conductivity. Building on that work, we are now in the position to investigate the relation between elastic heterogeneities and acoustic excitations, unifying in a single framework ordered and disordered solid states and considering quantities directly probed by experiments. By interpolating in a controlled way from perfect crystals, through increasingly defective phases, to fully developed amorphous structures, we (i) calculate the dynamical structure factors, extracting the relevant spectroscopic parameters; (ii) characterize the wave vector dependence of sound velocity and broadening of the acoustic excitations and clarify their nature in terms of the IR limit; and (iii) provide, for the first time to our knowledge, direct evidence of the correlation of the excitations lifetimes and Ω^IR with the magnitude of the elastic heterogeneities.