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Danho Pascal Abrogoua1,2, Brou Jerome Kablan1, Boua Alexis Thierry Kamenan1,3, Gilles Aulagner4, Konan N'Guessan1, Christian Zohoré11Laboratoire de Pharmacie Clinique, Pharmacologie et Therapeutique – UFR Sciences Pharmaceutiques et Biologiques, 2Laboratoire de Pharmacologie Clinique, CHU de Cocody, 3Service de Pharmacie, CHU de Cocody, Abidjan, Cote d'Ivoire, 4Service Pharmaceutique Hopital Louis Pradel, Lyon, FranceObjective: The aim of this study was to quantify, by modeling, the impact of significant predictors on CD4 cell response during antiretroviral therapy in a resource-limited setting.Methods: Modeling was used to determine which antiretroviral therapy response predictors (baseline CD4 cell count, clinical state, age, and adherence) significantly influence immunological response in terms of CD4 cell gain compared to a reference value at different periods of monitoring.Results: At 6 months, CD4 cell response was significantly influenced by baseline CD4 count alone. The probability of no increase in CD4 cells was 2.6 higher in patients with a baseline CD4 cell count of ≥200/mm3. At 12 months, CD4 cell response was significantly influenced by both baseline CD4 cell count and adherence. The probability of no increase in CD4 cells was three times higher in patients with a baseline CD4 cell count of ≥200/mm3 and 0.15 times lower with adherent patients. At 18 months, CD4 cell response was also significantly influenced by both baseline CD4 cell count and adherence. The probability of no increase in CD4 cells was 5.1 times higher in patients with a baseline CD4 cell count of ≥200/mm3 and 0.28 times lower with adherent patients. At 24 months, optimal CD4 cell response was significantly influenced by adherence alone. Adherence increased the probability (by 5.8) of an optimal increase in CD4 cells. Age and baseline clinical state had no significant influence on immunological response.Conclusion: The relationship between adherence and CD4 cell response was the most significant compared to that of baseline CD4 cell count. Counseling before initiation of treatment and educational therapy during follow-up must always help to strengthen adherence and optimize the efficiency of antiretroviral therapy in a resource-limited setting.Keywords: antiretroviral therapy, CD4 cells response, adherence, predictors, modeling, Abidjan

Background: Syringes of ephedrine are usually prepared ahead of time in order to reduce the time to injection. Commercial pre-filled syringes of ephedrine have been introduced to minimize the amount of waste. Our primary objective was to determine the economic impact of commercial syringes. We hypothesized that costs could be reduced compared to standard syringes.Methods: Using data extracted from our medical records system, we retrospectively measured the total dose of ephedrine received per patient in 2013 to estimate the number of administered standard syringes. The proportion of administered standard syringes was calculated as the total number of administered standard syringes divided by the number of delivered ampoules in 2013. Thereafter, we calculated the annual cost difference as the difference between the cost for commercial syringes and the cost for standard syringes. Endpoints were calculated overall and for each operating room.Results: At least one dose of ephedrine was given in 19,422 patients (44,943 administrations). The overall proportion of administered standard syringes was estimated to 52.8%. The threshold proportion of administered standard syringes for which commercial syringes would add no extra cost was 20.4%. In 30/32 operating rooms, the proportion of administered standard syringes was higher than 20.4%. The overall cost increase with commercial syringes was estimated to 51,567 €. Among operating rooms, incremental costs varied between -703 and 5086 €.Conclusion: Based on our findings, pre-filled ephedrine commercial syringes do not appear to reduce costs. [ABSTRACT FROM AUTHOR]

What is new and objectives Trends in the care of glioblastoma in actual practice settings are poorly described. In a previous pharmacoepidemiologic study, we highlighted changes in the management of patients with glioblastoma ( GBM) newly diagnosed between 2004 and 2008. Our aim was to complete and to extend the previous report with a study of a cohort of patients diagnosed in 2011 to emphasize the trends in the pharmacotherapy of GBM over the last decade. Methods A single-centre study was undertaken of three historic cohorts of GBM patients newly diagnosed during years 2004, 2008 and 2011 (corresponding to groups 1, 2 and 3, respectively) but limited to patients eligible for radiotherapy after initial diagnosis. The type of medical management was described and compared, as well as overall survival and total cost from diagnosis to death or the last follow-up date. Cost analysis was performed from the French sickness fund perspective using tariffs from 2014. Results Two hundred and seventeen patients (49 in Group 1, 73 in Group 2, 95 in Group 3) were selected with similar baseline characteristics. Fluorescence-guided surgery using 5- ALA was increasingly used over the three periods. There was a strong trend towards broader use of temozolomide radiochemotherapy (39%, 73% and 83% of patients, respectively) as first-line treatment as well as bevacizumab regimen at recurrence (6%, 48% and 58% of patients, respectively). The increase in overall survival between Group 2 and Group 1 was confirmed for patients in Group 3 (17·5 months vs. 10 months in Group 1). The mean total cost per patient was 53368 € in Group 1, 70 201 € in Group 2 and 78355 € in Group 3. Hospital care represented the largest expenditure (75%, 59% and 60% in groups 1, 2 and 3, respectively) followed by chemotherapy drug costs (11%, 30% and 29%, respectively). What is new and conclusion This is the first study to report on changes in the management of GBM in real-life practice. The ten-year study indicates an improvement in overall survival but also an increase in total cost of care. The data should be useful for informing the care of GBM patients in settings similar to ours. [ABSTRACT FROM AUTHOR]

What is known and objective Therapeutic options for the management of glioblastoma ( GBM) have greatly evolved over the last decade with the emergence of new regimens combining radiotherapy plus temozolomide and the use of bevacizumab at recurrence. Our aim was to assess the clinical and economic impacts of those novel strategies in our center. Methods A single-center retrospective chart review was conducted on patients newly diagnosed with a GBM over two periods (year 2004, group 1 or year 2008, group 2) with limitations to those eligible to radiotherapy after initial diagnosis. The type of medical management was described and compared, as well as overall survival and total costs from diagnosis to death or the last follow-up date. Cost analysis was performed under the French Sickness Fund perspective using tariffs from 2012. Results One hundred twenty-two patients were selected (49 in group 1 and 73 in group 2) with similar baseline characteristics within the two groups. Patients from group 2 received more frequently temozolomide radiochemotherapy (71% vs. 39%, P < 0·05) as first-line treatment as well as bevacizumab regimen at recurrence (48% vs. 6%, P < 0·05); the median overall survival was increased between the two periods (respectively 17 vs. 10 months, P < 0·05). The mean total cost per patient was 54 388 € in group 1 and 71 148 € in group 2 ( P < 0·05). Hospital care represented the largest expenditure (76% and 58% in groups 1 and 2 respectively) followed by chemotherapy drugs costs (11% and 30% respectively). The total cost difference between the two groups was explained by the increasing use of temozolomide and bevacizumab. The incremental cost-effectiveness ratio was estimated at 54 355 € per life-year gained. What is new and conclusion As far as we know, this is the first study reporting the total cost of GBM management based on the French perspective, as well as the cost-effectiveness of clinical practices in term of cost per life-year gained. Those novel strategies have contributed to improve overall survival while inducing a substantial, but acceptable, increase of total costs. [ABSTRACT FROM AUTHOR]

Purpose: Vancomycin dosing remains challenging in patients receiving intermittent hemodialysis, especially in developing countries, where access to therapeutic drug monitoring and model-based dose adjustment services is limited. The objectives of this study were to describe vancomycin population PK in patients receiving hemodialysis in a Malian and French center and examine the optimal loading dose of vancomycin in this setting., Methods: Population pharmacokinetic analysis was conducted using Pmetrics in 31 Malian and 27 French hemodialysis patients, having a total of 309 vancomycin plasma concentrations. Structural and covariate analyses were based on goodness-of-fit criteria. The final model was used to perform simulations of the vancomycin loading dose, targeting a daily area under the concentration-time curve (AUC) of 400-600 mg.h/L or trough concentration of 15-20 mg/L at 48 hours., Results: After 48 hours of therapy, 68% of Malian and 63% of French patients exhibited a daily AUC of <400. The final model was a 2-compartment model, with hemodialysis influencing vancomycin elimination and age influencing the vancomycin volume distribution. Younger Malian patients exhibited a lower distribution volume than French patients. Dosing simulation suggested that loading doses of 1500, 2000, and 2500 mg would be required to minimize underexposure in patients aged 30, 50, and 70 years, respectively., Conclusions: In this study, a low AUC was frequently observed in hemodialysis patients in Mali and France after a standard vancomycin loading dose. A larger dose is necessary to achieve the currently recommended AUC target. However, the proposed dosing algorithm requires further clinical evaluation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate early predictive factors of visual loss in patients treated with anti-vascular endothelial growth factor (VEGF) injections under an as-needed regimen for neovascular age-related macular degeneration (AMD)., Design: Post hoc analysis from the randomized controlled trial Groupe d'Evaluation Français Avastin versus Lucentis (GEFAL)., Participants: A total of 393 patients with neovascular AMD., Methods: The present analysis is based on 1-year data from patients included in the study. Patients were separately categorized according to the best-corrected visual acuity (BCVA) change at 3 months and 1 year into 3 trajectories: (1) patients with no vision loss ≥5 letters at 3 months and 1 year (absence of loss ≥5 letters); (2) patients with no vision loss ≥5 letters at 3 months but loss ≥5 letters at 1 year (secondary loss ≥5 letters); and (3) patients with vision loss ≥5 letters at 3 months and 1 year (initial loss ≥5 letters)., Main Outcome Measures: The following factors were evaluated at baseline and 3 months: age, sex, BCVA, presence of fluid, central macular thickness, angiographic choroidal neovascularization (CNV) subtype, CNV area measured in disc area on fluorescein angiography, and number of intravitreal injections., Results: An absence of loss ≥5 letters was found in 225 patients (57.3%), a secondary loss ≥5 letters after 3 months was found in 109 patients (27.7%), and an initial loss ≥5 letters was found in 59 patients (15%). Baseline characteristics were comparable among the 3 groups except for the total CNV area, which was larger in the initial and secondary loss groups (P = 0.0412). At 3 months, a significant association was found between presence of subretinal fluid (SRF) (P = 0.0318) and vision loss ≥5 letters, and an even stronger significant association between the presence of intraretinal fluid (IRF) (P = 0.0066) and vision loss ≥5 letters., Conclusions: In the present study, we found that a large CNV area at baseline was significantly associated with initial or secondary loss of visual acuity ≥5 letters despite anti-VEGF injection. The presence of fluid, both SRF and IRF, at 3 months was found in patients with poorer trajectories., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: For metastatic colorectal cancer a series of novel therapies has emerged during the last decade but their use in routine clinical practice and their costs are not well documented., Aims: This study evaluated the clinical effectiveness of metastatic colorectal cancer patients in Lebanese oncologic units and estimated the costs., Methods: A prospective cohort study was conducted on metastatic colorectal cancer patients during 2008-2013. The type of medical management, overall survival and total costs from diagnosis to death were described. Cost analysis was performed using tariffs from 2013 in US dollars., Results: One hundred and seventy-nine metastatic patients were selected among which 84.9% had colorectal cancer involvement. The average follow-up from diagnosis until death or the latest news was 34.8 months. Around 49.7% were still alive at last follow-up date. Three lines of treatment accounted for 4.5%, 39.6% and 55.9% with an average duration of 14.5, 11.4 and 14.6 months respectively. A 73.2% of patients benefited from targeted therapy. The median overall survival was 20.8 months. The mean total costs of drugs was $22 256 in patients with standard therapy alone whereas the cost increased to $80 396 after the addition of targeted therapy. The mean global total cost was estimated at $64 805 per patient (min $3703; max $304 086)., Conclusions: Targeted therapy associated to standard therapy is highly prevalent in Lebanon in metastatic disease and the associated medical cost substantial. This study is the first to show the clinical effectiveness and costs of targeted therapy in patients with metastatic colorectal cancer., (Copyright © World Health Organization (WHO) 2019. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license (https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Purpose: To determine predictors of best-corrected visual acuity (BCVA) outcomes 1 year after ranibizumab or bevacizumab treatment for neovascular age-related macular degeneration, within the French Study Group Avastin versus Lucentis for neovascular age-related macular degeneration (GEFAL)., Methods: Patients aged ≥50 years presenting subfoveal neovascular age-related macular degeneration were randomized to receive ranibizumab or bevacizumab (3 monthly intravitreal injections followed by an as-needed regimen). The main outcome measures were BCVA and its change from baseline at 1 year. Variables with a P value <0.20 in the univariate model and/or which were clinically relevant were included in the multivariate analysis., Results: The following baseline factors were associated with a lower BCVA score at 1 year and with less improvement in BCVA (multivariate analysis): intraretinal fluid, thickness of central subfield macular ≤277 μm, predominantly classic choroidal neovascularization, and total area of choroidal neovascularization (all P ≤ 0.01). Pigment epithelium detachment and high baseline BCVA were associated with less improvement in BCVA (P = 0.03, P = 0.05, respectively). Patients who met retreatment criteria but did not receive the corresponding injection had significantly poorer outcomes (only tested in the univariate analysis)., Conclusion: This study confirms the predictors of BCVA score at 1 year posttreatment; the presence of intraretinal fluid was associated with a poor prognosis.

Background: Our objective was to review economic evaluations on stent-retriever thrombectomy (SRT) added/not added to intravenous (IV) tissue plasminogen activator (t-PA) in acute ischemic stroke (AIS) due to large-vessel occlusion (LVO)., Methods: We conducted a systematic review using several electronic databases and searching for studies published from January 2009 to September 2017., Inclusion Criteria: any publication type reporting the incremental cost-effectiveness ratio of SRT in people with AIS secondary to LVO. Quality assessment was undertaken with the CHEERS and the Philips' checklists., Results: Eight original articles (four from North America/four from Europe) were included; of these, seven were model-based cost-effectiveness studies and one was a study conducted alongside a clinical trial. The perspective was the healthcare system in seven studies, and societal in one. The time horizon was lifetime (minimum 20 years) in all but two studies where it was 1 and 5 years. Overall, studies were rated of good quality (mean score 79%; range 70-90). Data sources, effectiveness outcomes and other input parameters were heterogeneous across studies. In three studies, SRT was dominant (less expensive and more effective). In five studies, SRT was more expensive and generated more quality-adjusted life years but had a high probability (79-100%) to be cost-effective at conventional thresholds., Conclusion: This review shows that SRT added/not added to IV t-PA is likely to be cost-effective or even dominant, which is consistent with the opinion from several Health Technology Assessment bodies recommending SRT. However, our findings are supported by primary studies with substantial methodological heterogeneity.

Background: In France, a significant part of health expenditure is publicly funding. This put a heavy burden on society. In an economic context requiring tight control of public spending, it seems relevant to control the diffusion of medical innovations. That is why health technology assessment is subject to an increasing interest at national level for management and approval decisions. This article provides an overview of the assessment and diffusion of medical innovation in France. Method: The data are extracted from French authorities or organisations websites and documents and from French legislative texts. In addition, regarding discussion, a search in MEDLINE database was carried out. Results: An overview of the assessment and diffusion of medical innovation in France is given by presenting the different types of medical innovations according to French health system definition (I); introducing French authorities participating to health technology assessment and describe assessment procedures of medical innovations (II); and giving details about market access process of innovative health product in France (III). Key opportunities and challenges of medical innovation assessment and diffusion in France are discussed at the end of this article. Conclusion: In France, medical innovation is considered as a crucial component for quality of care and performance of healthcare system. The aim of health technology assessment is to promote a secure and timely access to innovation for patients. Nevertheless, it appears necessary to improve regulatory mechanisms.

Objectives: Endovascular treatment of wide-neck intracranial aneurysms (IAs) is challenging, especially in bifurcation location. The intra-saccular flow-disruptor Woven EndoBridge (WEB) offers a new concept of endovascular therapy for wide-neck IAs. We performed an update of a systematic review aimed to report the feasibility, effectiveness and safety of WEB device therapy., Patients and Methods: A systematic review was conducted using several electronic databases (including PUBMED and EMBASE), searching for studies published between October 2015 and December 2017 (those published between January 2010 and September 2015 were included in our initial systematic review). Outcomes were: success of implantation, peri-procedural complications, mortality, and adequate occlusion (complete occlusion or neck remnant)., Results: In total (initial review + update), 12 uncontrolled case-series studies were included, reporting outcomes for 940 patients (68.6% female; mean age, 57 years) harboring 962 IAs. Most IAs were wide-neck bifurcation aneurysms (75%-100%), mainly at middle cerebral artery (37%) and anterior communicating artery (24.6%). Feasibility was 97% (95% confidence interval [CI], 95%-99%), and 9% (95%CI, 5%-14%) of cases required additional treatment. There were 14% (95%CI, 9%-19%) peri-procedural complications. After a median clinical follow-up of 7 months, mortality was 5% (95%CI, 1%-10%) and was higher in series with larger proportions of ruptured IAs. At last angiographic follow-up (median, 7 months; range, 3-27.9 months), adequate occlusion rate was 81% (95%CI, 73%-88%)., Conclusion: Although WEB showed high rates of adequate aneurysm occlusion at mid-term, procedure-related complications and mortality rates were not negligible. Future studies should compare the WEB device with other treatment options., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Purpose: Despite the improvement in technology, endovascular treatment of bifurcation intracranial wide-neck aneurysms remains challenging, mainly due to the difficulty of maintaining coils within the aneurysm sac without compromising the patency of bifurcation arteries. The Woven EndoBridge (WEB) device is a recent intrasaccular braided device specifically dedicated to treating such aneurysms with a wide neck by disrupting the flow in the aneurysmal neck and promoting progressive aneurysmal thrombosis., Materials and Methods: Using several health data bases, we conducted a systematic review of all published studies of WEB endovascular treatment in intracranial aneurysms from 2010 onward to evaluate its efficacy and safety profile., Results: The literature search identified 6 relevant studies (7 articles) including wide-neck bifurcation aneurysms in ≥80% of cases. Clinical data supporting the efficacy and safety of the WEB are limited to noncomparative cohort studies with large heterogeneity from a methodologic standpoint. The WEB deployment was feasible with a success rate of 93%-100%. Permanent morbidity (mRS of >1 at last follow-up) and mortality were measured at 2.2%-6.7% and 0%-17%, respectively. The adequate occlusion rate (total occlusion or neck remnant) varied between 65% and 85.4% at midterm follow-up (range, 3.3-27.4 months)., Conclusions: Endovascular treatment of bifurcation wide-neck aneurysms with the WEB device is feasible and allows an acceptably adequate aneurysm occlusion rate; however, the rate of neck remnants is not negligible. The WEB device needs further clinical and anatomic evaluation with long-term prospective studies, especially of the risk of WEB compression. Prospective controlled studies should be encouraged., (© 2016 by American Journal of Neuroradiology.)

Trastuzumab has transformed the treatment of HER2-positive breast cancer. Because of impending European patent expiry in 2017, numerous trastuzumab biosimilars are currently undergoing comparability exercises for marketing authorization. Although biosimilar products have been approved in Europe since 2006, many obstacles are expected for trastuzumab, resulting from its nature as a monoclonal antibody, its impact on overall survival, and its extensive biochemical complexities. Unsolved questions need to be addressed for the evaluation of biosimilars' activity in terms of appropriate clinical endpoint definitions for such anticancer drugs, specific assessment pathways and comparative testing of biosimilars, untested ensuing de facto combination of trastuzumab biosimilars with cytotoxics, and immunogenicity monitoring among immunocompromised patients. In such a context of uncertainties, the recent approval by the French parliament of biosimilar substitution, which would allow dispensing trastuzumab biosimilars in place of the originator, should interrogate the oncological community. A think tank of experts was created to delineate specificities and challenges stemming from trastuzumab biosimilars.

Colorectal cancer represents 8% of metastatic cancers. For decades, the gold standard therapy has been infusional chemotherapy with 5-Fluorouracil (5-FU) associated to folinic acid. The discovery of irinotecan, oxaliplatin and oral forms of 5-FU in the nineties is considered a milestone in the treatment of this disease. Since 2004, targeted therapy with monoclonal antibodies including anti-EGFR and angiogenesis inhibitors showed superiority in terms of mortality compared to conventional therapy. Metastatic colorectal cancer, however, remains an incurable disease. We present the current treatments of metastatic colorectal cancer, the clinical development of these emerging treatments, and their position in the Lebanese health care system.

Objective: To evaluate the relative efficacy and safety profile of bevacizumab versus ranibizumab intravitreal injections for the treatment of neovascular age-related macular degeneration (AMD)., Design: Multicenter, prospective, noninferiority, double-masked, randomized clinical trial performed in 38 French ophthalmology centers. The noninferiority limit was 5 letters., Participants: Patients aged ≥50 years were eligible if they presented with subfoveal neovascular AMD, with best-corrected visual acuity (BVCA) in the study eye of between 20/32 and 20/320 measured on the Early Treatment of Diabetic Retinopathy Study chart and a lesion area of less than 12 optic disc areas (DA)., Methods: Patients were randomly assigned to intravitreal administration of bevacizumab (1.25 mg) or ranibizumab (0.50 mg). Hospital pharmacies were responsible for preparing, blinding, and dispensing treatments. Patients were followed for 1 year, with a loading dose of 3 monthly intravitreal injections, followed by an as-needed regimen (1 injection in case of active disease) for the remaining 9 months with monthly follow-up., Main Outcome Measures: Mean change in visual acuity at 1 year., Results: Between June 2009 and November 2011, 501 patients were randomized. In the per protocol analysis, bevacizumab was noninferior to ranibizumab (bevacizumab minus ranibizumab +1.89 letters; 95% confidence interval [CI], -1.16 to +4.93, P < 0.0001). The intention-to-treat analysis was concordant. The mean number of injections was 6.8 in the bevacizumab group and 6.5 in the ranibizumab group (P = 0.39). Both drugs reduced the central subfield macular thickness, with a mean decrease of 95 μm for bevacizumab and 107 μm for ranibizumab (P = 0.27). There were no significant differences in the presence of subretinal or intraretinal fluid at final evaluation, dye leakage on angiogram, or change in choroidal neovascular area. The proportion of patients with serious adverse events was 12.6% in the bevacizumab group and 12.1% in the ranibizumab group (P = 0.88). The proportion of patients with serious systemic or ocular adverse events was similar in both groups., Conclusions: Bevacizumab was noninferior to ranibizumab for visual acuity at 1 year with similar safety profiles. Ranibizumab tended to have a better anatomic outcome. The results are similar to those of previous head-to-head studies., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Open-heart surgery can result in adhesions, which can complicate resternotomy., Aims: To document the occurrence of adhesions after the use of a new collagen membrane; to evaluate its tolerability; and to compare surgical parameters with control patients., Methods: Paediatric patients who underwent cardiac surgery with the collagen membrane (Cova™ CARD; Biom'up, Saint Priest, France) were analysed retrospectively for levels of adhesion and tolerability. The times of dissection and intervention and the transfusion of packed red blood cells and haemostatic products were compared to a historic cohort who did not receive an anti-adhesion device., Results: From January 2010 to December 2011, 36 patients received a collagen membrane. Nineteen re-interventions were performed, after a mean of 169 days. No grade 3 adhesions were observed and no tolerability problems were reported. During re-interventions after more than 30 days, the propensity score-adjusted durations of dissection and the total process for patients with and without a collagen membrane were 32 vs 41 minutes and 151 vs 182 minutes, respectively (not significant). The mean quantities of red blood cells and biological glue administered in the two groups were 98 vs 139 mL and 1.2 vs 0.5 mL, respectively (not significant)., Conclusions: This feasibility study shows the potential use of the new membrane in paediatric patients, both in terms of prevention from severe adherence and tolerability. This is the first study of this membrane in humans. A prospective, controlled study is necessary to provide strong evidence of its efficiency., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Flow diversion prostheses represent a new endovascular approach aimed at treating patients with large wide-neck aneurysms. Our objective is to present this new technology, to review the clinical studies on efficacy, and to emphasize its current limits. Flow diversion prostheses consist of a cylinder made of a large number of braided microfilaments providing a large metallic surface when deployed and inducing a blood flow diversion outside the aneurysm. Two different brands are currently available. Clinical data supporting their efficacy are currently limited to six non comparative cohort studies that included between 18 and 107 patients. Procedural implantation was shown to be feasible in more than 90% and safe with a thirty-day mortality between 2.8 and 5.5%. Complete occlusion rates at twelve months varied between 85.7 and 100%. Even though promising, the current status of flow diversion prostheses needs further evaluation with randomized, prospective, clinical trials with comparison to conventional strategies including endovascular coiling or surgical clipping.

Introduction: Human cytomegalovirus infection is still a major complication after pediatric bone marrow transplantation and could be fatal in some cases. The toxicity of the drug in dividing transplanted haematopoietic cells combined with the suppression of cell growth caused by the virus remains a major problem in managing human cytomegalovirus infection., Methods: The aim of the current in vitro study was to evaluate the effect of the intensity (1-20 mg/l) and duration (1, 2, 7 or 14 days) of ganciclovir exposure on toxicity in B lymphoblastoid cells (using cell counting and viability measurements)., Results: A correlation was found between the dose of ganciclovir exposure and a decrease in total cell number when duration exceeded 2 days (r(2)=0.92 and 0.93 after 7 and 14 days, respectively). High levels (20 mg/l) of ganciclovir were not more toxic than lowest levels (1 mg/l) for the shortest durations of ganciclovir exposure (1 and 2 days). Moreover, 50% cytotoxic concentrations markedly decreased with the duration of ganciclovir exposure (374-3 mg/l from 1 to 14 days respectively) after 14 days of culture., Conclusions: This in vitro study demonstrated for the first time that ganciclovir exhibited an in vitro duration-dependent toxicity on haematopoietic-derived cells when in vivo doses of the drug were used.

We report the case of a patient referred to us for mitral and aortic valvular disease with a rheumatic appearance. The unusual macroscopic appearance on valve resection was not compatible with a rheumatic cause. A detailed review of this patient's clinical history (ie, a history of treatment with fenfluramine) suggested an iatrogenic cause, which was confirmed by histology. For the first time, a case of valvular heart disease that deteriorated was discovered 7 years after treatment with fenfluramine, whereas this iatrogenic disease classically resolves after discontinuation of treatment. This case illustrates the need for continuing heart valve surveillance of patients who have used these anorectics.

A reversed-phase liquid chromatographic method with ultraviolet detection has been developed to determine busulfan concentrations in plasma of children undergoing bone marrow transplantation. Plasma samples (200 microl) containing busulfan and 1,6-bis(methanesulfonyloxy)hexane as an internal standard were prepared by a simple derivatization method with diethyldithiocarbamate followed by extraction with ethyl acetate and solid-phase purification on C8 columns conditioned with methanol and water and eluted with acetonitrile (recovery 99%). Chromatography was accomplished using a Hypersil octadecylsilyl column (10 cm x 4.6 mm I.D.) and a mobile phase of acetonitrile, tetrahydrofuran and distilled water (65:5:30, v/v). The limit of detection was 25 ng/ml (signal-to-noise ratio of 5). Calibration curves were linear up to 25,000 ng/ml. Intra-day and inter-day coefficients of variation of the assay were < or =5%. This method was used to analyse busulfan plasma concentrations after oral administration within the framework of therapeutic drug monitoring and pharmacokinetic studies in children.