Cost-effectiveness analysis of pharmaceutical treatment options in the first-line management of major depressive disorder in Belgium

The objective of this study was to assess the cost effectiveness of commonly used antidepressants as first-line treatment of major depressive disorder (MDD) in Belgium. The model structure was based on a decision tree developed by the Swedish TLV (TandvAyenrds- och lakemedelsformAyennsverket) and adapted to the Belgium healthcare setting, using primary local data on the patterns of treatment and following KCE [Federal Knowledge Center (Federaal Kenniscentrum voor de Gezondheidszorg)] recommendations. Comparators were escitalopram, citalopram, fluoxetine, paroxetine, sertraline, duloxetine, venlafaxine, and mirtazapine. In the model, patients not achieving remission or relapsing after remission on the assessed treatment moved to a second therapeutic step (titration, switch, add-on, or transfer to a specialist). In case of failure in the second step or following a suicide attempt, patients were assumed to be referred to secondary care. The time horizon was 1 year and the analysis was conducted from the National Institute for Health and Disability Insurance (NIHDI; national health insurance) and societal perspectives. Remission rates were obtained from the TLV network meta-analysis and risk of relapse, efficacy following therapeutic change, risk of suicide attempts and related death, utilities, costs (2012), and resources were derived from the published literature and expert opinion. The effect of uncertainty in model parameters was estimated through scenario analyses and a probabilistic sensitivity analysis (PSA). In the base-case analysis, escitalopram was identified as the optimal strategy: it dominated all other treatments except venlafaxine from the NIHDI perspective, against which it was cost effective with an incremental cost-effectiveness ratio of a,not sign6,352 per quality-adjusted life-year (QALY). Escitalopram also dominated all other treatments from the societal perspective. At a threshold of a,not sign30,000 per QALY and from the NIHDI perspective, the PSA showed that the probability of escitalopram being identified as the optimal strategy ranged from 61 % (vs. venlafaxine) to 100 % (vs. fluoxetine). Escitalopram was associated with the highest probability of being the optimal treatment from the NIHDI and societal perspectives. This analysis, based on new Belgian clinical practice data and following KCE requirements, provides additional information that may be used to guide the choice of treatments in the management of MDD in Belgium

A new paradigm evaluating cost per cure of HCV infection in the UK

Background: New interferon (IFN)-free treatments for hepatitis C are more effective, safer but more expensive than current IFN-based therapies. Comparative data of these, versus current first generation protease inhibitors (PI) with regard to costs and treatment outcomes are needed. We investigated the real-world effectiveness, safety and cost per cure of 1st generation PI-based therapies in the UK. Methods: Medical records review of patients within the HCV Research UK database. Patients had received treatment with telaprevir or boceprevir and pegylated interferon and ribavirin (PR). Data on treatment outcome, healthcare utilisation and adverse events (AEs) requiring intervention were collected and analysed overall and by subgroups. Costs of visits, tests, therapies, adverse events and hospitalisations were estimated at the patient level. Total cost per cure was calculated as total median cost divided by SVR rate. Results: 154 patients from 35 centres were analysed. Overall median total cost per cure was £44,852 (subgroup range,: £35,492 to £107,288). Total treatment costs were accounted for by PI: 68.3 %, PR: 26.3 %, AE management: 5.4 %. Overall SVR was 62.3 % (range 25 % to 86.2 %). 36 % of patients experienced treatment-related AEs requiring intervention, 10 % required treatment-related hospitalisation. Conclusions: This is the first UK multicentre study of outcomes and costs of PI-based HCV treatments in clinical practice. There was substantial variation in total cost per cure among patient subgroups and high rates of treatment-related discontinuations, AEs and hospitalisations. Real world safety, effectiveness and total cost per cure for the new IFN free combinations should be compared against this baseline

Aménagement d’ossuaires dans le baptistère paléochrétien de Brioude (Haute-Loire) : sélection, tri des ossements et relation À l’Âge au décès

Le baptistère de Brioude constitue actuellement un ensemble unique en Auvergne. Intégré au sanctuaire de Saint-Julien au début du haut Moyen âge, il présente des sépultures installées intra muros au moment de son fonctionnement, fait exceptionnel en Gaule mérovingienne. La datation particulièrement bien établie de l’ensemble des vestiges et, par conséquent, du rythme des changements qu’ils ont subis, a permis d’identifier deux phases funéraires : la première, datée du VIe s. ap. J.-C., est contemporaine de l’utilisation du baptistère. La seconde, désigne l’ensemble des sépultures installées dans le niveau de démolition du baptistère sur les tombes précédentes ; elles sont associées à un nouvel édifice élevé sur l’emprise du baptistère au début du VIIe s. L’analyse du fonctionnement de l’ensemble de cet espace funéraire a permis d’identifier une étape charnière entre ces deux principales phases chronologiques. Celle-ci correspond au réaménagement de plusieurs sépultures appartenant à la première phase, en raison de la construction de l’édifice funéraire remplaçant le baptistère. Ces perturbations ont entraîné le déplacement ou la destruction partielle de certains sarcophages. Une partie des ossements ainsi exhumés a été rassemblée en ossuaires. Trois ossuaires ont été mis au jour dans une fosse creusée dans le sol de la salle baptismale. La présence de liaisons ostéologiques de deuxième ordre entre ces différents ensembles démontre, d’une part, que leur mise en place résulte d’un processus unique, d’autre part, que la distribution de l’ensemble des vestiges osseux n’a pas été aléatoire. En effet, une sélection et un tri d’os matures en fonction de leur catégorie (os longs, blocs cranio-faciaux et os de petite et moyenne tailles) ont été réalisés et répartis en trois dépôts distincts. Nous constatons en outre, que les os pairs non matures ont été répartis dans deux ossuaires. Enfin, l’estimation de l’âge de ces jeunes sujets les place majoritairement parmi la classe des 5-9 ans, individus d’ailleurs absents du reste de l’espace sépulcral. Ces résultats laissent envisager l’existence d’une zone originelle réservée à cette classe d’âge au décès de la population, détruite lors de la construction du bâtiment de la seconde phase.The baptistery of Brioude is today a unique monument in Auvergne. It was associated with the sanctuary housing the relics of Saint Julien, which dates to the early Middle Ages. During its period of use, the baptistery provided for intra muros burial. This is a unique occurrence in Merovingian Gaul. Two phases of funerary use could be identified from the regularity with which the remains had been treated. The first, dating from the 6th century AD, is contemporary with the use of the baptistery. The second dates from the middle of Merovingian period (from the 7th century A.D.) and is associated with the building of a new structure on the site of the baptistery. This structure was accompanied by burials placed directly over those of the previous phase. The analysis of spatial relationships among burials enabled us to identify a transitional stage between these two phases. This stage was identified on the basis of the disturbance of several burials belonging to the first phase, subsequent to the construction of the structure of the second phase. These disturbances led to the displacement of partial destruction of some sarcophagi and the inclusion of some disturbed skeletal remains in ossuaries. Three ossuaries have been discovered under the floor of the baptistery. The identification of osteological relations of the second order among these different groups demonstrates that, first, the three ossuaries resulted from a single action and, second, the distribution of skeletal elements was not random but that selection and sorting of adult bones had been carried out according to their anatomical type (long bones, cranium, small and middle-sized bones), and these had been separated into three different deposits. Furthermore, we noted that paired immature skeletal elements were divided between two ossuaries. Finally, the age assessment of these young individuals classified them into the 5-9 age category, a group that was absent from the rest of the burial area. These results lead us to hypothesize that there had once been a burial area reserved for this part of the population. This area seems to have been destroyed during the construction of the second phase structure

Cost-Effectiveness Of Treatments For Mild-To-Moderate Obstructive Sleep Apnea In France

International audienceObjectives: Untreated obstructive sleep apnea-hypopnea syndrome (OSAHS) is associated with excessive daytime sleepiness, increased risk of cardiovascular (CV) disease, and road traffic accidents (RTAs), which impact survival and health-related quality of life. This study, funded by the French National Authority for Health (HAS), aimed to assess the cost-effectiveness of different treatments (i.e., continuous positive airway pressure [CPAP], dental devices, lifestyle advice, and no treatment) in patients with mild-to-moderate OSAHS in France.Methods: A Markov model was developed to simulate the progression of two cohorts, stratified by CV risk, over a lifetime horizon. Daytime sleepiness and RTAs were taken into account for all patients while CV events were only considered for patients with high CV risk.Results: For patients with low CV risk, incremental cost-effectiveness ratio (ICER) of dental devices versus no treatment varied between 32,976 EUR (moderate OSAHS) and 45,579 EUR (mild OSAHS) per quality-adjusted life-year (QALY), and CPAP versus dental devices, above 256,000 EUR/QALY. For patients with high CV risk, CPAP was associated with a gain of 0.62 QALY compared with no treatment, resulting in an ICER of 10,128 EUR/QALY.Conclusion: The analysis suggests that it is efficient to treat all OSAHS patients with high CV risk with CPAP and that dental devices are more efficient than CPAP for mild-to-moderate OSAHS with low CV risk. However, out-of-pocket costs are currently much higher for dental devices than for CPAP (i.e., 3,326 EUR versus 2,430 EUR) as orthodontic treatment is mainly non-refundable in France

Neonicotinoid insecticides severely affect honey bee queens

Queen health is crucial to colony survival of social bees. Recently, queen failure has been proposed to be a major driver of managed honey bee colony losses, yet few data exist concerning effects of environmental stressors on queens. Here we demonstrate for the first time that exposure to field realistic concentrations of neonicotinoid pesticides during development can severely affect queens of western honey bees (Apis mellifera). In pesticide-exposed queens, reproductive anatomy (ovaries) and physiology (spermathecal-stored sperm quality and quantity), rather than flight behaviour, were compromised and likely corresponded to reduced queen success (alive and producing worker offspring). This study highlights the detriments of neonicotinoids to queens of environmentally and economically important social bees, and further strengthens the need for stringent risk assessments to safeguard biodiversity and ecosystem services that are vulnerable to these substances

Intraoperative ketorolac in high-risk breast cancer patients : A prospective, randomized, placebo-controlled clinical trial

Funding: This work is financed by grants received by PF, in the name of his institution: the Anticancer Fund (no grant number) (www.anticancerfund.org); the Belgian Society of Anaesthesia and Resuscitation (no grant number) (www.sarb.be); the Fondation Saint-Luc (no grant number) (www.uclouvain.be); the Commission du Patrimoine of the Université catholique de Louvain, St-Luc Hospital (exceptional grant, no number) (www.uclouvain.be). None of the funders had any role in the study design, data collection and analysis, decision to publish or preparation of the manuscript except the scientific advise of GB, scientific director of the Anticancer Fund.Peer reviewedPublisher PD

Development of a pharmacovigilance system in a resource-limited country : the experience of the Democratic Republic of Congo

Implementation of pharmacovigilance (PV) systems in resource-limited countries is a real endeavor. Despite country- and continent-specific challenges, the Democratic Republic of the Congo (DRC) has been able to develop one of the most active PV systems in the sub-Saharan Africa. The World Health Organization (WHO) regional Office identified the DRC experience to set up a PV system for antimalarial drugs safety monitoring as a 'best practice' that needed to be documented in order to help DRC improve its PV system and to be scaled up in other African countries. In response to the WHO request, a best practices and bottlenecks analysis was conducted in 2015. This analysis was updated in 2018 in the light of the minimum requirements of the WHO to set up a PV system taking into account other guidance for PV systems. The following themes were retained for analysis: (1) creation of the national PV center; (2) implementation of PV in the health system; (3) data collection and analysis; (4) collaboration with public health programs; (5) collaboration with the National Regulatory Authority. Lessons learnt from the DRC experience show that it is possible to implement PV systems in order to promote patients' safety in resource limited sub-Saharan African countries with no guaranteed funding. The ability of national PV centers to collaborate with Public health stakeholders, including public health authorities at all levels as well as public health programs, and to use existing health information systems are considered the main key to success and may substantially reduce the cost of PV activities

LRP1 Receptor Controls Adipogenesis and Is Up-Regulated In Human and Mouse Obese Adipose Tissue

The cell surface low-density lipoprotein receptor-related protein 1, LRP1, plays a major role in lipid metabolism. The question that remains open concerns the function of LRP1 in adipogenesis. Here, we show that LRP1 is highly expressed in murine preadipocytes as well as in primary culture of human adipocytes. Moreover, LRP1 remains abundantly synthesised during mouse and human adipocyte differentiation. We demonstrate that LRP1 silencing in 3T3F442A murine preadipocytes significantly inhibits the expression of PPARγ, HSL and aP2 adipocyte differentiation markers after adipogenesis induction, and leads to lipid-depleted cells. We further show that the absence of lipids in LRP1-silenced preadipocytes is not caused by lipolysis induction. In addition, we provide the first evidences that LRP1 is significantly up-regulated in obese C57BI6/J mouse adipocytes and obese human adipose tissues. Interestingly, silencing of LRP1 in fully-differentiated adipocytes also reduces cellular lipid level and is associated with an increase of basal lipolysis. However, the ability of mature adipocytes to induce lipolysis is independent of LRP1 expression. Altogether, our findings highlight the dual role of LRP1 in the control of adipogenesis and lipid homeostasis, and suggest that LRP1 may be an important therapeutic target in obesity

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe