Market access of cancer drugs in European countries: improving resource allocation

Public health systems need to make well-founded choices in order to distribute their scarce resources in the most efficient way. Given the number of cancer patients, public/private investments in oncology research, the growing number of new anti-cancer agents and consequent budget impact of cancer care, market access of cancer drugs has become delicate over the last decade. Furthermore, decision makers are challenged by ethical objections and endeavour to provide fair and equal access to treatments for cancer patients. The aim of this study is to generate an overview of market access procedures for cancer drugs in eight European countries and formulate advice for improvement of resource allocation. Results are obtained through a literature review and a qualitative questionnaire and validated by experts with proven knowledge about procedures for price setting and reimbursement of drugs. Diverse measures are applied in the studied countries to optimize reimbursement of cancer drugs such as adjusted cost-effectiveness threshold, regulations for off-label use and new market access agreements. Additionally, innovative cancer drugs are excluded from explicit cost control measures such as payback of budget excess by pharmaceutical companies and lump-sum payments per diagnostic related groups (DRG) in the hospital. The results suggest that cancer is prioritized above other disease areas. Further research is necessary to address the question if society attaches higher value to cancer drugs than to treatments for other diseases.     

Assessment of the involvement of the macrophage migration inhibitory factor–glucocorticoid regulatory dyad in the expression of matrix metalloproteinase‐2 during periodontitis

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine and counter‐regulator of endogenous glucocorticoids (GCs). It is implicated in acute and chronic inflammatory diseases. This study investigated the role of the MIF–GC regulatory dyad in the expression and release of matrix metalloproteinase‐2 (MMP‐2) during periodontitis, in vivo and in vitro. In a Mif‐knockout (KO) mouse model of ligature‐induced periodontitis, gingival tissues and blood were collected and analysed for levels of interleukin‐6 (IL‐6), MIF, MMP‐2, and corticosterone. In addition, human gingival fibroblasts (HGFs) were tested for production of IL‐6 and MMP‐2 after stimulation with hydrocortisone (HC), MIF, tumour necrosis factor‐alpha (TNF‐α), or Fusobacterium nucleatum, a pathogen known to elicit immune responses during periodontitis. Wild‐type (WT) mice showed a local and systemic increase of MIF levels during inflammation, which was confirmed by increased local IL‐6 concentrations. Systemic GC levels were reduced in WT and Mif‐KO mice during inflammation, with overall lower concentrations in Mif‐KO mice. In vivo and in vitro, MMP‐2 production was not dependent on MIF or inflammatory stimuli, but was inhibited by HC. Therefore, MIF does not appear to stimulate expression of MMP‐2 in the gingival tissues, whereas GC upregulates MIF and downregulates MMP‐2. Our findings further suggest that MIF may regulate systemic GC levels.     

Routine Determination of GFR in Renal Transplant Recipients by HPLC Quantification of Plasma Iohexol Concentrations and Comparison With Estimated GFR

Estimated glomerular filtration rate (eGFR) methods are not sufficiently reliable in renal transplant recipients (RTR) and should be replaced by iohexol plasma clearance measurement. However, this method has poor availability in health centers. The aim of our study was to develop a high‐performance liquid chromatography (HPLC) method for plasma iohexol measurement in routine practice and to evaluate its plasma clearance as a reference of GFR. We developed an HPLC method using UV detection. We evaluated sample storage conditions to provide recommendations for routine practice. Then, we compared GFRbased on plasma iohexol clearance (GFR‐iohexol) to eGFR using modification of diet in renal disease, Cockcroft and Gault, and CDK‐EPIequations in 40 RTR. The method was validated over a concentration range of 15–300 μg/l. Excellent linearity (r > 0.998), inter‐ and intraday precision (CV < 3.3%), and accuracy (>96.8%) were complied with ICH guidelines. We also demonstrated excellent samples stability (9 days). Although eGFR methods are not references in RTR, we found a correct concordance between eGFR and GFR‐iohexol in our population. To conclude, our method is simple, rapid, accurate, and reliable for routine clinical and research use especially in RTR. J. Clin. Lab. Anal. 26:376‐383, 2012. © 2012 Wiley Periodicals, Inc.     

Clinical Outcomes of a New Self‐Help Booklet for Premature Ejaculation

IntroductionPremature ejaculation (PE) is quite common. Although effective treatments do exist, only a few affected people consult a practitioner in order to overcome their problem. At the same time, studies have shown that reading didactical documents about their PE problem (bibliotherapy) can be useful to men.AimThe aim of this study was to improve the bibliotherapy approach using up‐to‐date knowledge and techniques. The expected benefits were the following: (i) an effective manual shorter than previous ones; (ii) easier to assimilate therapeutic principles; and (iii) a method thereby made accessible to a broad population most of whom usually do not consult for this type of sexual problem.MethodA short bibliotherapy titled The Practical Guide of PE[in French] was tested among PE subjects who were diagnosed with PE according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria. Assessments were made at baseline (N = 421), at 4–8 months (N = 120), and at 10–14 months (N = 79) after they read The Practical Guide. A control group of 66 subjects was left on a waiting list and was assessed 2 months after baseline.Main Outcome MeasuresThe main outcome measures are self‐reported ejaculatory latency time, feeling of control upon ejaculation, sexual satisfaction, distress related to PE, anxiety experienced during sexual intercourse, and sexual cognitions (Sexual Irrationality Questionnaire).ResultsSignificant improvements were found for all the self‐reported parameters, both at 4–8 and at 10–14 months after the bibliotherapy. The improvements were associated with an adjustment of sexual cognitions. The response to treatment seemed better for those subjects with moderate PE. Although the severity criteria used in this study did not precisely meet the International Society for Sexual Medicine criteria for lifelong PE, they were likely related. The response did not seem to be affected by variables such as age, education, or personality.ConclusionIts cost/benefit ratio makes The Practical Guide a valuable therapeutic tool. Kempeneers P, Andrianne R, Bauwens S, Georis I, Pairoux J‐F, and Blairy S. Clinical outcomes of a new self‐help booklet for premature ejaculation. J Sex Med 2012;9:2417–2428.     

Interventions promoting physical activity among obese populations: a meta‐analysis considering global effect,long‐term maintenance,physical activity indicators and dose characteristics

As the benefits that regular physical activity (PA) have on obesity are well known, many interventions promote active lifestyle adoption among obese populations. This meta‐analysis aims to determine (i) the global effect that interventions promoting PA among obese populations have on their PA behaviour; (ii) variations in the effect of interventions depending on the PA indicator used; (iii) the programme's dose characteristics and (iv) maintenance of the intervention effects after the intervention has ended. A comprehensive search through databases and review articles was completed. Forty‐six studies met the inclusion criteria. Calculations of effect size (Cohen's d) and a moderator analysis were conducted. The meta‐analysis showed that interventions globally have an impact on the PA behaviour of obese populations (d = 0.44; 95% CI = 0.31, 0.57). The moderator analysis revealed that interventions of less than 6 months reported significantly larger effects than longer interventions. Moreover, the interventions had a stronger impact on the number of steps and the PA indexes (i.e. composite scores reflecting PA practice) than on other PA indicators. Finally, the analysis revealed that interventions succeed in maintaining PA behaviour after the intervention is over. However, relatively few studies addressed this issue (n = 9). Despite global positive effects, further research is needed to determine the optimal dose for interventions and to evaluate the maintenance of intervention effects.     

Qui sont les élèves à besoins éducatifs particuliers ? La part d’aléatoire du signalement pour une mesure d’aide renforcée de pédagogie spécialisée dans un canton suisse

In this article, we begin by questioning the notion of special educational needs, which is used today in Switzerland, by going back over its historical foundations and developing the main issues and problems it raises. We then present the results of a comprehensive research aimed at uncovering the factors at work in the process of designating certain students for an enhanced special education support measure during their compulsory schooling. On the basis of a content analysis of the reports for an enhanced special education support measure produced during the 2016–2017 school year in a Swiss canton, as well as comprehensive interviews conducted with permanent teachers, we highlight various factors that can lead to the designation of a student for an enhanced special education support measure. We show how there is a degree of randomness in being designated for a special education support measure and critically discuss the role of the school institution and its actors in this process.