A Bayesian network approach to the study of historical epidemiological databases: modelling meningitis outbreaks in the Niger.

OBJECTIVE: To develop a tool for evaluating the risk that an outbreak of meningitis will occur in a particular district of the Niger after outbreaks have been reported in other, specified districts of the country. METHODS: A Bayesian network was represented by a graph composed of 38 nodes (one for each district in the Niger) connected by arrows. In the graph, each node directly influenced each of the "child" nodes that lay at the ends of the arrows arising from that node, according to conditional probabilities. The probabilities between "influencing" and "influenced" districts were estimated by analysis of databases that held weekly records of meningitis outbreaks in the Niger between 1986 and 2005. For each week of interest, each district was given a Boolean-variable score of 1 (if meningitis incidence in the district reached an epidemic threshold in that week) or 0. FINDINGS: The Bayesian network approach provided important and original information, allowing the identification of the districts that influence meningitis risk in other districts (and the districts that are influenced by any particular district) and the evaluation of the level of influence between each pair of districts. CONCLUSION: Bayesian networks offer a promising approach to understanding the dynamics of epidemics, estimating the risk of outbreaks in particular areas and allowing control interventions to be targeted at high-risk areas.

Cost-effectiveness modelling of sequential biologic strategies for the treatment of moderate to severe rheumatoid arthritis in Finland.

OBJECTIVE: The main objective was to compare the cost-effectiveness of therapeutic options in moderate or severe rheumatoid arthritis (RA) when a clinical response to a first TNF-blocker, either etanercept (ETA), adalimumab (ADA), or infliximab (INF), is insufficient. METHODS: Effectiveness criteria were defined as remission (RS), low disease activity (LDAS), and moderate to high disease activity (MHDAS). Cost-effectiveness was derived as cost per day in RS and in LDAS using simulation modelling to assess six sequential biologic strategies over 2 years. Each sequential treatment strategy was composed of three biologic agents and included a first anti-TNF agent, ETA, ADA or INF, followed by either abatacept (ABA) or rituximab (RTX) as a second therapeutic option in case of an insufficient response, followed by another anti-TNF agent in case of further insufficient response. RESULTS: Over two years and taking into account biologic costs, the following estimated mean costs per day in RS and LDAS were respectively of €829 and €428 for the biologic sequence composed of ADA-ABA-ETA, €1292 and €516 for the sequence ADA-RTX-ETA, €829 and €429 for the sequence ETA-ABA-ADA, €1292 and €517 for the sequence ETARTX- ADA, €840 and €434 for the sequence INF-ABA-ETA, and €1309 and €523 for the sequence INF-RTX-ETA. CONCLUSION: The treatment sequences including ABA as the second biologic option appear more cost-effective than those including RTX in a patients with moderate to severe RA and an insufficient response to a first anti-TNF agent.

Assessing the cost-effectiveness of biologic agents for the management of moderate-to-severe rheumatoid arthritis in anti-TNF inadequate responders in Italy: a modelling approach.

OBJECTIVES: The objective of this study is to assess cost-effectiveness of different biologic strategies in patients with moderate-to-severe active RA after an insufficient response to anti-TNF agents within the context of the Italian healthcare system. METHODS: Simulation models were developed allowing for potential biologic therapy switch at each 6-month time point in case of an insufficient response to the previous biologic agent. Biologic treatments included etanercept, abatacept, adalimumab, rituximab or infliximab. Effectiveness criteria for these models were defined as achieving a state of low disease activity (LDAS) [DAS28 ≤3.2] or remission (RS) [DAS28<2.6]. Monte-Carlo simulations were performed for each sequence to manage data variability. RESULTS: The biologic treatment sequence using abatacept after an insufficient response to a first anti-TNF agent appeared significantly more efficacious over 2 years (102 days in LDAS) compared to rituximab (82 days in LDAS). The sequence using abatacept after 2 anti-TNF agents appeared significantly more efficacious (63 days in LDAS) compared to using a third anti-TNF agent (32 days in LDAS). Mean cost-effectiveness ratios showed significantly lower costs per day in LDAS with abatacept used after one anti-TNF agent (€376) compared to rituximab (€456). The sequence using abatacept after 2 anti-TNF agents was also more cost-effective (€642 per day in LDAS) versus a sequential use of anti-TNF therapies (€1164 per day in LDAS). All comparisons were confirmed when using the remission effectiveness criteria. CONCLUSIONS: The results of this health economics modelling study suggest that the biologic treatment sequence using abatacept after an insufficient response to a first anti-TNF agent appears significantly more effective and cost-effective versus a similar sequence using rituximab for achieving remission or LDAS. The results also indicate that in the case of an insufficient reponse to 2 anti-TNF agents, abatacept appears more effective and cost-effective than using a 3rd anti-TNF agent.

Cost-effectiveness modeling of dental implant vs. bridge.

AIMS: We assess the cost-effectiveness of dental implant first-line strategy vs. fixed partial denture strategy in patients suffering from one single missing tooth. MATERIALS AND METHODS: The model used a simulation decision framework over a 20-year period. Potential treatment switches can occur every 5 years. Transition probabilities come from literature, epidemiological reports or expert opinions. They have been programmed using specific distribution ranges to simulate the patients' and practice variability, and to take into account parameter uncertainty. Direct medical costs have been assessed according to a cost survey. Probabilistic sensitivity analyses were conducted using 5000 Monte-Carlo simulations, generating confidence intervals of model outcomes. RESULTS: We found that mean cost-effectiveness of the bridge strategy is higher than the implant strategy. CONCLUSION: Implant as the first-line strategy appears to be the 'dominant' strategy, considering the lower overall costs and the higher success rate.

Cost-effectiveness modeling of intrathecal baclofen therapy versus other interventions for disabling spasticity.

OBJECTIVE: To assess by simulation the cost-effectiveness of intrathecal baclofen (ITB) therapy compared with conventional medical treatments for patients with disabling spasticity and functional dependence caused by any neurological disease. METHODS: Two models were created to simulate therapeutic strategies for managing severe spasticity, one with and one without the use of ITB, to assess various treatment sequences over 2 years based on current medical practices in France. Successful treatment at each evaluation was defined as a combination of: (1) the increased patient and caregiver satisfaction as assessed by goal attainment scaling (GAS), and (2) a decrease of at least 1 point on the Ashworth score. Probabilistic sensitivity analyses were performed using 5000 Monte-Carlo simulations taking into account specific distribution curves for direct costs and effectiveness parameters in each treatment option. RESULTS: The model simulations suggest that including ITB as a first option strategy in the management of function of severely impaired patients with disabling spasticity results in a higher success rate (78.7% vs 59.3%; P < .001). In addition, the ITB therapy model revealed a lower cost (pound 59,391 vs pound 88,272; P < .001) and an overall more favorable cost-effectiveness ratio (pound 75,204/success vs pound 148,822/success; P < .001), compared with conventional medical management without ITB. CONCLUSION: Within the assumptions of our modeling, ITB therapy evaluated by a combination of treatment success criteria at 6-month intervals over a 2-year period may be a cost-effective strategy compared to conventional medical management alone.

Cost-effectiveness sequential modeling of ranibizumab versus usual care in age-related macular degeneration.

AIMS: To assess effectiveness, cost, and cost-effectiveness of ranibizumab versus the current medical practices of treating age-related macular degeneration in France. METHODS: A simulation decision framework over 1 year compared ranibizumab versus the usual care using two effectiveness criteria: the "visual acuity improvement rate" (greater than 15 letters on the ETDRS scale) and the "rate of legal blindness avoided". Two decision trees included various sequences of current treatments, with or without ranibizumab. RESULTS: Ranibizumab appeared significantly more effective than the usual care (p < 0.001), providing greater treatment success rate of visual acuity improvement (48.8% versus 33.9%). The cost of the ranibizumab strategy was higher (9,123 euros over 1 year for ranibizumab versus 7,604 euros for the usual care) but the average cost-effectiveness was lower--18,721 euros/success for ranibizumab versus 22,543 euros/success for usual care (p < 0.001). Considering the "legal blindness avoided" success criterion, the ranibizumab strategy appeared significantly more effective (p < 0.001), providing greater treatment success rate for of legal blindness avoided than usual care (99.7% versus 93.1%) although it was more expensive (9,196 euros over 1 year for ranibizumab versus 5,713 euros for the usual care). CONCLUSION: Ranibizumab significantly improved the rate of visual acuity improvement and reduced the rate of legal blindness. Ranibizumab appeared significantly more cost-effective than the usual treatments in terms of visual acuity improvement.

Validation of the Multiple Sclerosis International Quality of Life questionnaire.

This study aims to validate the Multiple Sclerosis (MS) International Quality of Life (MusiQoL) questionnaire, a multi-dimensional, self-administered questionnaire, available in 14 languages, as a disease-specific quality of life scale that can be applied internationally. A total of 1992 patients with different types and severities of MS from 15 countries were recruited. At baseline and day 21 +/- 7, each patient completed the MusiQoL, a symptom checklist and the short-form (SF)-36 QoL questionnaire. Neurologists also collected socio-demographic, MS history and outcome data. The database was randomly divided into two subgroups and analysed according to different patient characteristics. For each model, psychometric properties were tested and the number of items was reduced by various statistical methods. Construct validity, internal consistency, reproducibility and external consistency were also tested. Nine dimensions, explaining 71% of the total variance, were isolated. Internal consistency and reproducibility were satisfactory for all the dimensions. External validity testing revealed that dimension scores correlated significantly with all SF-36 scores, but showed discriminant validity by gender, socio-economic and health status. Significant correlations were found between activity in daily life scores and clinical indices. These results demonstrate the validity and reliability of the MusiQoL as an international scale to evaluate QoL in patients with MS.

[Clinical study of Supranettes pads in the treatment of seasonal or perennial allergic conjunctivitis in children]. / Etude clinique des compresses Supranettes dans le traitement de l'allergie oculaire saisonnière ou per-annuelle de l'enfant.

PURPOSE: Ocular allergy is a common disease that is on the rise. Seasonal and perennial conjunctivitis are the most common forms of ocular allergy. Itching, hyperemia, foreign body sensation, irritation, blurred vision or ocular dryness sensations, tearing, and photophobia are the clinical signs observed in patients. A topical antiallergic treatment is prescribed associated with ocular cleaning to contribute to an antigen washing of the ocular surface. Our study aimed to evaluate the use of Supranettes pads as supplementation treatment in children for seasonal or perennial conjunctivitis. MATERIAL AND METHODS: Our prospective study was done in children with a diagnosis of seasonal or perennial clinical ocular allergy. Every symptom was rated from 0 to 4 according to the intensity described by the children and their parents. Twenty children (range, 4-10 years) presenting an ocular allergy were included in the study. A topical antiallergic treatment membrane stabilizer or antihistamine and Supranettes pads were prescribed for ocular cleaning of one randomized selected eye four times a day. Patients were seen in consultation 1 month later to evaluate the treatment. The ocular comfort of each eye, one treated with Supranettes pads and the other not treated by Supranettes pads, was evaluated by the child helped by parents on a graduated self-evaluation scale (range, 0-10). The Mann-Whitney statistical test was used to differentiate the two groups. RESULTS: Of the 20 patients, eleven presented seasonal conjunctivitis and nine perennial conjunctivitis. Six of them presented conjunctivitis with a slight to moderate superficial punctuate keratitis. At the consultation on day 28+/-3, patients who were first treated showed clear improvement of clinical signs with the prescribed treatment. The statistical comparison of the two groups confirmed a significant difference (p<0.05) to the advantage of the group using the Supranettes pads. DISCUSSION: Ocular washing is essential in the treatment of allergic conjunctivitis. The new galenic form of ocular cleaning by physiological serum-impregnated pads is simple to use for children. An objective significant difference is difficult to observe in 1 month. CONCLUSION: This study underlines the importance of the comfort of Supranettes pads evaluated in the treatment of children's conjunctivitis. It confirms the advantage of developing evaluation studies including patient satisfaction and quality of life in ophthalmology.

[Pharmacoeconomic advantages of recombinant FSH vs urinary derived FSH]. / Avantages pharmaco-économiques de la FSH d'origine recombinante par rapport à la FSH d'origine urinaire.

Nowadays, the use of urinary FSH is essentially justified by a lower acquisition price compared to modern products generated by Biotechnology (recombinant FSH). However, the public price of a product is only one element of the total cost of a therapeutic regimen that must be taken into account in medical decision-making. This is the role of pharmacoeconomic studies including cost-effectiveness models, which allow proceeding to complex situational comparisons such as several attempts of Assisted Reproduction Techniques. Different models have been carried out and published in several countries and present consistently that recombinant FSH is more cost-effective that urinary derived FSH.

Impact of urinary FSH price: a cost-effectiveness analysis of recombinant and urinary FSH in assisted reproduction techniques in the USA.

This study compares the cost-effectiveness of recombinant human FSH (r(h)FSH, Gonal-F) and urinary FSH (uFSH) in assisted reproduction techniques in the USA, using several hypothetical prices for uFSH. A specifically designed Markov model and Monte-Carlo simulation techniques were used to model the possible outcomes during three treatment cycles. Data included in the model were derived from randomized clinical trials and databases. An expert panel determined probability distributions for each decision point throughout each virtual treatment cycle. The assumed unit cost of r(h)FSH was $58.52 (based on the average retail cost) and three unit prices ($49, $45, $40) were used for uFSH. A total of 5000 simulations was performed on a virtual cohort of 100,000 patients. The mean number of assisted reproduction treatment cycles/success (ongoing pregnancy at 12 weeks) was 4.34 with r(h)FSH and 4.75 with uFSH. The total number of pregnancies achieved was 40,665 and 37,890, respectively. The mean cost per successful pregnancy with r(h)FSH was $40 688. For uFSH at unit costs of $40, $45 and $49, the mean costs per successful pregnancy were $43,500, $44,400 and $45,000, respectively (each P < 0.0001 versus r(h)FSH). Thus, despite its greater cost per unit dose, r(h)FSH is more cost-effective than uFSH over a wide range of uFSH prices, reflecting the greater clinical efficacy of r(h)FSH.

[Evaluation of the quality of life in ophthalmology]. / Evaluation de la qualité de vie en ophtalmologie.

THE IMPORTANCE OF VISUAL FUNCTION IN THE ASSESSMENT OF QUALITY OF LIFE: The notion of visual function is related to visual acuity but also to many other parameters such as the visual field, perception of colour, contrasts, and the resistance to blinding. These factors are difficult to measure during routine ophthalmic examination but can be assessed during questionnaires on quality of life. MARKERS OF QUALITY OF LIFE IN OPHTHALMOLOGY: Various quality of life questionnaires have been developed in ophthalmology because the non-specific generic instruments appear inadequate. The SF 36 and SF 20 scales, which are generic instruments widely used in many fields, do not adequately explore the problems related to vision. The first efficient instrument is the VF 14, which is a questionnaire specific to ophthalmic diseases, developed by C. Mangione in 1992. This self-administered questionnaire permits calculation of a 0 to 100 score exploring 5 dimensions (long-sight acuity, near-sight acuity, unclear sight, and driving during the day and at night) during 14 activities with 18 questions. It was translated and adapted into French by Gresset in 1997. Today it is the most commonly used questionnaire in ophthalmology, particularly in the assessment of efficacy and impact in surgery. Along the other specific questionnaires developed, there is the NEI-VQF which was created in 1995 to assess vision and the impact of visual problems on the quality of life of patients, independently of an ophthalmic pathology. Many studies have been conducted on various diseases that affect vision, such as diabetes or hypertension. THE LIMITS OF EXISTING INSTRUMENTS: The specific scales appear far more sensitive and specific than generic scales with regard to ophthalmic problems, but they provide less information on the general status of the patient, except for the NEI-VQF. They are limited in some parameters and do not, unfortunately, take into account the patient's age. No specific scale has been developed for children or adolescents, although the impact of vision on daily life is fundamental. The complexity of vision means that the elaboration of an ideal instrument is difficult. However, in the meantime, it is essential that the practitioners continue to use and to test the instruments available in order to improve with regard to pathologies, or in particular sub-groups of the population.

Cost-effectiveness modelling of recombinant FSH versus urinary FSH in assisted reproduction techniques in the UK.

BACKGROUND: The purpose of this study was to undertake an economic evaluation to compare the cost-effectiveness of recombinant (r)FSH with urinary (u)FSH for attaining clinical pregnancy with assisted reproduction. METHODS: Mathematical modelling was utilized incorporating a Markovian decision framework and a Monte Carlo simulation. Statistical representations of recurrent events over time were incorporated into a decision analysis involving fresh and frozen cycles in any sequence (after the first fresh embryo transfer cycle) over three successive assisted reproduction attempts. The mean values of transition probabilities were derived from randomized controlled clinical trials and published reports. The distributions of these transition probabilities were agreed upon by a panel of experts. Cost data for procedures and drugs were derived and validated according to the perspectives of the National Health Service and private clinics in the UK. RESULTS: The study involved 5000 Monte-Carlo simulations of treatment on a Markov cohort of 100 000 patients. The total number of pregnancies attained was significantly higher in the rFSH (40 575) compared with the uFSH (37 358) group. The cost per successful pregnancy was significantly lower for rFSH (5906 pounds sterling) compared with uFSH (6060 pounds sterling) and overall, fewer cycles of treatment were required with rFSH to achieve an ongoing pregnancy. The incremental cost-effectiveness ratio is 4148 pounds sterling for each additional clinical pregnancy with rFSH. CONCLUSIONS: In addition to the increased effectiveness of rFSH in ART, this study demonstrated that it is more cost-effective and more efficient than uFSH in attaining an ongoing pregnancy.

[Pharmacoeconomics as a tool for the synthesis of available information on drugs]. / La pharmaco-économie comme outil de synthèse de l'information disponible sur le médicament.

Data on refundable pharmaceutical drugs are numerous and of various kinds. The clinical approach and the economic approach could be used together. This new approach allows for not only the synthesis but also the structuring of all the available information. The new information obtained is involved in decision trees.

[Evaluation of the quality of life in children and adolescents]. / Evaluation de la qualité de vie chez l'enfant et l'adolescent.

UNLABELLED: HEALTH-RELATED QUALITY OF LIFE: Personal perception of health is proposed as an innovating assessment alternative for making medical and therapeutic choices on an individual and population basis. Standardized questionnaires have been developed to assess health-related quality of life (HRQL). ASSESSMENT OF HRQL IN ADOLESCENTS AND CHILDREN: Several approaches have been used. Some questionnaires assess health status in specific diseases or populations. More general instruments developed for the general population are useful for comparing between programs involving different diseases. PRACTICAL APPLICATIONS: We present here the criteria of quality required for HRQL instruments and examine the difficulties encountered when applying these instruments to children and adolescents. We reviewed the main general instruments in the literature as well as those specifically designed for asthmatic children. None of the self-administered questionnaires available in France are fully satisfactory for children or adolescents in terms of robustness, sensitivity and discriminative power. The French versions of the Childhood Asthma Questionnaire developed in Great Britain and the Paediatric Asthma Quality of Life Questionnaire developed in Canada were tested in a transcultural validation scheme.

Evaluation of benefits related to reduced length of stays in postanesthesia care units.

The study's purpose was to estimate the potential economic benefit of the optimization of postanesthesia care units (PACUs). A simulation model was designed and used to test the economic impact of a reduction of length of stay. For the studied PACU, a reduction of 25% of length of stay is required to yield significant economic results.

[Evaluation of drug iatrogeny by medico-economic modelling techniques]. / Evaluation de la iatrogénie médicamenteuse par les techniques de modélisation médico-économique.

Decision-making methods can be extremely useful in managing the large amount of information available on the complex effects of medication over various time spans. Event trees help to formulate data and visualise the medical strategies with the highest performance in regard to clinical benefits, adverse side effects, cost and cost-benefit ratios. However when the quantity of phenomena becomes too diversified (i.e. multiplicity of events, long observation periods, changing variables, etc.) we can use one of the more sophisticated modelling techniques available with today's more powerful computers.

[Evaluation of direct theoretical cost of passage in anesthesia recovery room]. / Evaluation du coût direct théorique d'un passage en salle de surveillance postinterventionnelle.

OBJECTIVE: To assess the direct cost of a stay in a postanaesthesia care unit (PACU). STUDY DESIGN: Standard cost study based on information gathered from staff and suppliers in accordance with government regulations and recommendations. Results reviewed by a group of anaesthesists. TYPE OF PACU: PACU working in ideal conditions with optimal safety conditions for and accommodation surgical patients). METHOD: Estimation of three cost components: 1) depreciation and maintenance costs of equipment, 2) physician and other staff wages, and 3) variable costs such as drugs and disposable devices. We computed an annual budget for three PACU which was defined according to size (4, 8 or 12 beds) and working hours. RESULTS: Fixed annual costs (staff and equipment) were 1,134,938 FF for a 4 bed room: 3,820,339 FF for an 8 bed room: and 6,481,792 FF for a 12 bed room. Variable costs per stay were 75,43 FF. The cost of a stay in an 8 bed PACU based on a rate of 3,500 stays per year therefore was 1,167 FF (87.0% for staff, 6.6% for equipment, 6.4% for variable costs).