Does drinking water influence hospital-admitted sialolithiasis on an epidemiological level in Denmark?

OBJECTIVES: Sialolithiasis, or salivary stones, is not a rare disease of the major salivary glands. However, the aetiology and incidence remain largely unknown. Since sialoliths are comprised mainly of calcium phosphate salts, we hypothesise that drinking water calcium levels and other elements in drinking water could play a role in sialolithiasis. Owing to substantial intermunicipality differences in drinking water composition, Denmark constitutes a unique environment for testing such relations. DESIGN: An epidemiological study based on patient data extracted from the National Patient Registry and drinking water data from the Geological Survey of Denmark and Greenland retrieved as weighted data on all major drinking water constituents for each of the 3364 waterworks in Denmark. All patient cases with International Statistical Classification of Diseases 10th Revision (ICD-10) codes for sialolithiasis registered between the years 2000 and 2010 were included in the study (n=3014) and related to the drinking water composition on a municipality level (n=98). PRIMARY AND SECONDARY OUTCOME MEASURES: Multiple regression analysis using iterative search and testing among all demographic and drinking water variables with sialolithiasis incidence as the outcome in search of possible relations among the variables tested. RESULTS: The nationwide incidence of hospital-admitted sialolithiasis was 5.5 cases per 100 000 citizens per year in Denmark. Strong relations were found between the incidence of sialolithiasis and the drinking water concentration of calcium, magnesium and hydrogen carbonate, however, in separate models (p<0.001). Analyses also confirmed correlations between drinking water calcium and magnesium and their concentration in saliva whereas this was not the case for hydrogen carbonate. CONCLUSIONS: Differences in drinking water calcium and magnesium may play a role in the incidence of sialolithiasis. These findings are of interest because many countries have started large-scale desalination programmes of drinking water

Identification of predictive biomarkers in cancer chemotherapy

Le cancer est un problème de santé publique majeur et représente l'une des principales causes de décès dans le monde. Il représente ainsi un lourd fardeau humain et économique pour la société. Au cours de ces dernières années, l'innovation technologique avec notamment le séquençage d'acide désoxyribonucléique (ADN) a modifié la vision et la pratique de la cancérologie en proposant de sélectionner le traitement médical le plus approprié aux caractéristiques génotypiques de chacun. Dans certains types de cancer, la chimiothérapie est parfois prescrite abusivement avec de possibles effets délétères importants à long terme. La prescription de la chimiothérapie ne doit donc pas se faire de manière systématique et l'identification de biomarqueurs prédictifs de la réponse au traitement devient donc une étape cruciale. En effet un grand nombre de biomarqueurs voire des combinaisons de biomarqueurs doivent être testés afin d'identifier les patients susceptibles de bénéficier de la chimiothérapie. A cet effet, des analyses statistiques spécifiques à l'analyse de la mutation TP53 dans le cancer du poumon non à petites cellules ont été mises en place dans la première partie de cette thèse. Enfin, la seconde partie de cette thèse porte sur l'évaluation médico-économique de ces tests, primordiale pour le financement de ces innovations et donc pour avoir un impact direct sur les patients atteints de cancer. Nos résultats ont démontrés que bien que ces tests peuvent être coût-efficaces et recommandés dans plusieurs pays, leurs utilisations en France restent limitées en raison de l'absence de remboursementCancer is a leading cause of death around the world and thus a major worldwide public health problem and a heavy human and economic burden. In recent years, the practice of cancer medicine has evolved with technological innovation such as deoxyribonucleic acid (DNA) sequencing which allows the selection of the most suited treatment for each genotypic characteristic. With chemotherapy, a treatment with potentially significant long-term adverse effects, being overprescribed in some types of cancer, the identification of a predictive biomarker of response to treatment became a crucial step. Indeed a large number of biomarkers or combinations of biomarkers have to be tested to identify patients likely to benefit from chemotherapy and thus to avoid the systematic prescription of chemotherapy. Accordingly, the first part of this thesis focused on the specific statistical analysis of TP53 mutations in non-small cell lung cancer. The second part of this thesis’ aim was to study the medico-economic evaluation of these tests, since these evaluation are essential for these test’s financing. Results showed that although the tests may be cost-effective and recommended in several countries, their uses in France were limited due to the lack of reimbursemen

Budget impact model of Mydrane®, a new intracameral injectable used for intra-operative mydriasis, from a UK hospital perspective

Abstract Background During cataract surgery, maintaining an adequate degree of mydriasis throughout the entire operation is critical to allow for visualisation of the capsulorhexis and the crystalline lens. Good anaesthesia is also essential for safe intraocular surgery. Mydrane® is a new injectable intracameral solution containing two mydriatics (tropicamide 0.02% and phenylephrine 0.31%) and one anaesthetic (lidocaine 1%) that was developed as an alternative to the conventional topical pre-operative mydriatics used in cataract surgery. This study aimed to estimate the budget impact across a one year time frame using Mydrane® instead of topical dilating eye drops, for a UK hospital performing 3,000 cataract operations a year. Methods A budget impact model (BIM) was developed to compare the economic outcomes associated with the use of Mydrane® versus topical drops (tropicamide 0.5% and phenylephrine 10%) in patients undergoing cataract surgery in a UK hospital. The outcomes of interest included costs and resource use (e.g. clinician time, mydriasis failures, operating room time, number of patients per vial of therapy etc.) associated with management of mydriasis in patients undergoing cataract surgery. All model inputs considered the UK hospital perspective without social or geographical variables. Deterministic sensitivity analyses were also performed to assess the model uncertainty. Results Introduction of Mydrane® is associated with a cost saving of £6,251 over 3,000 cataract surgeries in one year. The acquisition costs of the Mydrane® (£18,000 by year vs. £3,330 for eye drops) were balanced by substantial reductions in mainly nurses’ costs and time, plus a smaller contribution from savings in surgeons’ costs (£20,511) and lower costs associated with auxiliary dilation (£410 due to avoidance of additional dilation methods). Results of the sensitivity analyses confirmed the robustness of the model to the variation of inputs. Except for the duration of one session of eye drop instillation and the cost of Mydrane®, Mydrane® achieved an incremental cost gain compared to tropicamide/phenylephrine eye drops. Conclusions Despite a higher acquisition cost of Mydrane®, the budget impact of Mydrane® on hospital budgets is neutral. Mydrane® offers a promising alternative to traditional regimes using eye drops, allowing for a better patient flow and optimisation of the surgery schedule with neutral budget impact

Determinants of orphan drugs prices in France: a regression analysis

Abstract Background The introduction of the orphan drug legislation led to the increase in the number of available orphan drugs, but the access to them is often limited due to the high price. Social preferences regarding funding orphan drugs as well as the criteria taken into consideration while setting the price remain unclear. The study aimed at identifying the determinant of orphan drug prices in France using a regression analysis. Methods All drugs with a valid orphan designation at the moment of launch for which the price was available in France were included in the analysis. The selection of covariates was based on a literature review and included drug characteristics (Anatomical Therapeutic Chemical (ATC) class, treatment line, age of target population), diseases characteristics (severity, prevalence, availability of alternative therapeutic options), health technology assessment (HTA) details (actual benefit (AB) and improvement in actual benefit (IAB) scores, delay between the HTA and commercialisation), and study characteristics (type of study, comparator, type of endpoint). The main data sources were European public assessment reports, HTA reports, summaries of opinion on orphan designation of the European Medicines Agency, and the French insurance database of drugs and tariffs. A generalized regression model was developed to test the association between the annual treatment cost and selected covariates. Results A total of 68 drugs were included. The mean annual treatment cost was €96,518. In the univariate analysis, the ATC class (p = 0.01), availability of alternative treatment options (p = 0.02) and the prevalence (p = 0.02) showed a significant correlation with the annual cost. The multivariate analysis demonstrated significant association between the annual cost and availability of alternative treatment options, ATC class, IAB score, type of comparator in the pivotal clinical trial, as well as commercialisation date and delay between the HTA and commercialisation. Conclusion The orphan drug pricing is a multivariate phenomenon. The complex association between drug prices and the studied attributes and shows that payers integrate multiple variables in decision making when setting orphan drug prices. The interpretation of the study results is limited by the small sample size and the complex data structure

Development of an instrument evaluating the impact of surgeon-patient relationship in patients on sick leave

Background: To date, no specific instruments exist to measure the quality of the patient-surgeon relationship despite its potential to influence clinical and economic outcomes in patients undergoing surgery for musculoskeletal disorders (MSDs). Objective: The objective was to develop and validate an instrument to assess the quality of the patient-surgeon relationship, taking into account the return to work after functional restoration surgery. Methods: The instrument development was based on literature review, cognitive interviews and expert examinations. The instrument’s psychometric properties were explored in a sample of 50 French patients on sick leave with musculoskeletal disorders or hand injuries. Face validity, internal consistency and test-retest reliability were evaluated. The dimensionality of the instrument was studied using an exploratory principal component analysis. Results: The 11-item instrument showed good psychometric properties. The cognitive interviews allowed enhancing the validity of the instrument content by capturing patients’ point of view. The exploratory principal component analysis demonstrated the uni-dimensionality of the instrument with the first factor accounting for 83% of the total explained variance. Conclusion:This study has developed the first instrument capable of the specific assessment of the impact of the surgeon-patient relationship on recovery, in patients with hand traumas and MSDs

Additional file 1: of Determinants of orphan drugs prices in France: a regression analysis

Strategy of the targeted literature search. Strategy of the targeted literature search which was conducted to identify the covariates to be included in the analysis. (DOCX 15 kb

Summary of one-way sensitivity analysis outcomes for Onco<i>type</i> DX testing versus standard care.

<p>QALY, quality-adjusted life year; EUR, 2013 Euros; ICER, incremental cost-effectiveness ratio</p><p>* ICERs are presented in EUR per QALY gained; RS, Recurrence Score.</p><p>Summary of one-way sensitivity analysis outcomes for Onco<i>type</i> DX testing versus standard care.</p

Summary cost-effectiveness results for Onco<i>type</i> DX versus standard care to inform adjuvant chemotherapy decision making in French private hospitals.

<p>All costs are expressed in 2013 Euros (EUR). QALY, quality-adjusted life year; ICER, incremental cost-effectiveness ratio.</p><p>Summary cost-effectiveness results for Onco<i>type</i> DX versus standard care to inform adjuvant chemotherapy decision making in French private hospitals.</p

Economic Impact of Gene Expression Profiling in Patients with Early-Stage Breast Cancer in France

<div><p>Background and Aims</p><p>The heterogeneous nature of breast cancer can make decisions on adjuvant chemotherapy following surgical resection challenging. Onco<i>type</i> DX is a validated gene expression profiling test that predicts the likelihood of adjuvant chemotherapy benefit in early-stage breast cancer. The aim of this study is to determine the costs of chemotherapy in private hospitals in France, and evaluate the cost-effectiveness of Onco<i>type</i> DX from national insurance and societal perspectives.</p><p>Methods</p><p>A multicenter study was conducted in seven French private hospitals, capturing retrospective data from 106 patient files. Cost estimates were used in conjunction with a published Markov model to assess the cost-effectiveness of using Onco<i>type</i> DX to inform chemotherapy decision making versus standard care. Sensitivity analyses were performed.</p><p>Results</p><p>The cost of adjuvant chemotherapy in private hospitals was estimated at EUR 8,218 per patient from a national insurance perspective and EUR 10,305 from a societal perspective. Cost-effectiveness analysis indicated that introducing Onco<i>type</i> DX improved life expectancy (+0.18 years) and quality-adjusted life expectancy (+0.17 QALYs) versus standard care. Onco<i>type</i> DX was found cost-effective from a national insurance perspective (EUR 2,134 per QALY gained) and cost saving from a societal perspective versus standard care. Inclusion of lost productivity costs in the modeling analysis meant that costs for eligible patients undergoing Onco<i>type</i> DX testing were on average EUR 602 lower than costs for those receiving standard care.</p><p>Conclusions</p><p>As Onco<i>type</i> DX was found both cost and life-saving from a societal perspective, the test was considered to be dominant to standard care. However, the delay in coverage has the potential to erode the quality of the French healthcare system, thus depriving patients of technologies that could improve clinical outcomes and allow healthcare professionals to better allocate hospital resources to improve the standard of care for all patients.</p></div

Summary of patient characteristics in the chemotherapy costing analysis.

<p>C, cyclophosphamide; E, epirubicin; 5FU, fluorouracil; HER, human epidermal growth factor receptor; ER, estrogen receptor; PR, progesterone receptor.</p><p>Summary of patient characteristics in the chemotherapy costing analysis.</p