Use of the dried blood spot sampling process coupled with fast gas chromatography and negative-ion chemical ionization tandem mass spectrometry: application to fluoxetine, norfluoxetine, reboxetine, and paroxetine analysis.

The objective of this work was to combine the advantages of the dried blood spot (DBS) sampling process with the highly sensitive and selective negative-ion chemical ionization tandem mass spectrometry (NICI-MS-MS) to analyze for recent antidepressants including fluoxetine, norfluoxetine, reboxetine, and paroxetine from micro whole blood samples (i.e., 10 microL). Before analysis, DBS samples were punched out, and antidepressants were simultaneously extracted and derivatized in a single step by use of pentafluoropropionic acid anhydride and 0.02% triethylamine in butyl chloride for 30 min at 60 degrees C under ultrasonication. Derivatives were then separated on a gas chromatograph coupled with a triple-quadrupole mass spectrometer operating in negative selected reaction monitoring mode for a total run time of 5 min. To establish the validity of the method, trueness, precision, and selectivity were determined on the basis of the guidelines of the "Société Française des Sciences et des Techniques Pharmaceutiques" (SFSTP). The assay was found to be linear in the concentration ranges 1 to 500 ng mL(-1) for fluoxetine and norfluoxetine and 20 to 500 ng mL(-1) for reboxetine and paroxetine. Despite the small sampling volume, the limit of detection was estimated at 20 pg mL(-1) for all the analytes. The stability of DBS was also evaluated at -20 degrees C, 4 degrees C, 25 degrees C, and 40 degrees C for up to 30 days. Furthermore, the method was successfully applied to a pharmacokinetic investigation performed on a healthy volunteer after oral administration of a single 40-mg dose of fluoxetine. Thus, this validated DBS method combines an extractive-derivative single step with a fast and sensitive GC-NICI-MS-MS technique. Using microliter blood samples, this procedure offers a patient-friendly tool in many biomedical fields such as checking treatment adherence, therapeutic drug monitoring, toxicological analyses, or pharmacokinetic studies.

Availability, Cost or Culture ? : Obstacles to Childcare Services for Low-Income Families

Recent research has highlighted the existence of a social bias in the extent to which children have access to childcare. In general, children living in higher income households are more likely to be cared for in childcare centres. While the existence of a social bias in access to childcare services has been clearly demonstrated, we currently lack a clear explanation as to why this is the case. This paper uses a unique dataset based on survey data collected specifically to study patterns of childcare use in the Swiss canton of Vaud (N = 875). The paper exploits the variation in the way childcare is organised within the canton. Childcare is a municipal policy, as a result of which there are twenty-nine different systems in operation. Fees are progressive everywhere, but variation is substantial. Availability is also very different. This peculiar institutional setup provides an ideal situation to examine the determinants of childcare use by different income groups. Our findings suggest that differences in the fees charged to low-income households, as well as the degree of progressivity of the fee structure, are significant predictors of use, while availability seems to matter less.

An outcome and cost analysis of anal fistula plug insertion vs endorectal advancement flap for complex anal fistulae.

AIM: The study aimed to compare the rate of success and cost of anal fistula plug (AFP) insertion and endorectal advancement flap (ERAF) for anal fistula. METHOD: Patients receiving an AFP or ERAF for a complex single fistula tract, defined as involving more than a third of the longitudinal length of of the anal sphincter, were registered in a prospective database. A regression analysis was performed of factors predicting recurrence and contributing to cost. RESULTS: Seventy-one patients (AFP 31, ERAF 40) were analysed. Twelve (39%) recurrences occurred in the AFP and 17 (43%) in the ERAF group (P = 1.00). The median length of stay was 1.23 and 2.0 days (P < 0.001), respectively, and the mean cost of treatment was euro5439 ± euro2629 and euro7957 ± euro5905 (P = 0.021), respectively. On multivariable analysis, postoperative complications, underlying inflammatory bowel disease and fistula recurring after previous treatment were independent predictors of de novo recurrence. It also showed that length of hospital stay ≤ 1 day to be the most significant independent contributor to lower cost (P = 0.023). CONCLUSION: Anal fistula plug and ERAF were equally effective in treating fistula-in-ano, but AFP has a mean cost saving of euro2518 per procedure compared with ERAF. The higher cost for ERAF is due to a longer median length of stay.

Cost evaluation and comparison of three decision strategies for cardiac revascularization : results of the suspected CAD protocol of the European CMR registry

Background: The public health burden of coronary artery disease (CAD) is important. Perfusion cardiac magnetic resonance (CMR) is generally accepted to detect and monitor CAD. Few studies have so far addressed its costs and costeffectiveness. Objectives: To compare in a large CMR registry the costs of a CMR-guided strategy vs two hypothetical invasive strategies for the diagnosis and the treatment of patients with suspected CAD. Methods: In 3'647 patients with suspected CAD included prospectively in the EuroCMR Registry (59 centers; 18 countries) costs were calculated for diagnostic examinations, revascularizations as well as for complication management over a 1-year follow-up. Patients with ischemia-positive CMR underwent an invasive X-ray coronary angiography (CXA) and revascularization at the discretion of the treating physician (=CMR+CXA strategy). Ischemia was found in 20.9% of patients and 17.4% of them were revascularized. In ischemia-negative patients by CMR, cardiac death and non-fatal myocardial infarctions occurred in 0.38%/y. In a hypothetical invasive arm the costs were calculated for an initial CXA followed by FFR testing in vessels with ≥50% diameter stenoses (=CXA+FFR strategy). To model this hypothetical arm, the same proportion of ischemic patients and outcome was assumed as for the CMR+CXA strategy. The coronary stenosis - FFR relationship reported in the literature was used to derive the proportion of patients with ≥50% diameter stenoses (Psten) in the study cohort. The costs of a CXA-only strategy were also calculated. Calculations were performed from a third payer perspective for the German, UK, Swiss, and US healthcare systems.

MRI/TRUS fusion software-based targeted biopsy: the new standard of care?

The advent of multiparametric MRI has made it possible to change the way in which prostate biopsy is done, allowing to direct biopsies to suspicious lesions rather than randomly. The subject of this review relates to a computer-assisted strategy, the MRI/US fusion software-based targeted biopsy, and to its performance compared to the other sampling methods. Different devices with different methods to register MR images to live TRUS are currently in use to allow software-based targeted biopsy. Main clinical indications of MRI/US fusion software-based targeted biopsy are re-biopsy in men with persistent suspicious of prostate cancer after first negative standard biopsy and the follow-up of patients under active surveillance. Some studies have compared MRI/US fusion software-based targeted versus standard biopsy. In men at risk with MRI-suspicious lesion, targeted biopsy consistently detects more men with clinically significant disease as compared to standard biopsy; some studies have also shown decreased detection of insignificant disease. Only two studies directly compared MRI/US fusion software-based targeted biopsy with MRI/US fusion visual targeted biopsy, and the diagnostic ability seems to be in favor of the software approach. To date, no study comparing software-based targeted biopsy against in-bore MRI biopsy is available. The new software-based targeted approach seems to have the characteristics to be added in the standard pathway for achieving accurate risk stratification. Once reproducibility and cost-effectiveness will be verified, the actual issue will be to determine whether MRI/TRUS fusion software-based targeted biopsy represents anadd-on test or a replacement to standard TRUS biopsy.

Cost-effectivness in a DRG system for two-step exchange of infected total joint arthroplasty

The costs related to the treatment of infected total joint arthroplasties represent an ever groving burden to the society. Different patient-adapted therapeutic options like débridement and retention, 1- or 2-step exchange can be used. If a 2-step exchange is used we have to consider short (2-4 weeks) or long (>4-6 weeks) interval treatment. The Swiss DRG (Diagnose related Groups) determines the reimboursement the hopsital receives for the treatment of an infected total arthroplasty. The review assesses the cost-effectiveness of hospitalisation practices linked to surgical treatment in the two-stage exchange of a prosthetic-joint infection. The aim of this retrospectiv study is to compare the economical impact between a short (2 to 4 weeks) versus a long (6 weeks and above) interval during a two-satge procedure to determine the financial impact. Retrospectiv study of the patients with a two-stage procedure for a hip or knee prosthetic joint infection at CHUV hospital Lausanne (Switzerland) between 2012 and 2013. The review analyses the correlation between the interval length and the length of the hospital stay as well as with the costs and revenues per hospital stay. In average there is a loss of 40′000 Euro per hospitalisation for the treatment of prosthetic joint infection. Revenues never cover all the costs, even with a short interval procedure. This economical loss increases with the length of the hospital stay if a long-term intervall is choosen. The review explores potential for improvement in reimbourement practices and hospitalisation practices in the current Swiss healthcare setting. There should be alternative setups to decrease the burden of medical costs by a) increase the reimboursment for the treatment of infected total joints or by b) splitting the hospital stay with partners (rapid transfer after first operation from center hospital to level 2 hospital and retransfer for second operation to center) in order to increase revenues.

Les vaccins contre le zona : efficacité, sécurité, et rapport coût/bénéfices [Vaccines against Herpes zoster: Effectiveness, safety, and cost/benefit ratio].

CONTEXT: A vaccination against herpes zoster and its complication is available in France since June 2015. Its exact benefit for public health is still controversial and its level of protection is not optimal. All those reasons seem to suggest a low acceptation rate from general practitioners. OBJECTIVE: To evaluate the effectiveness, the safety, and the cost/benefit ratio of the vaccination against herpes zoster in people aged 50 year or over. DOCUMENTARY SOURCE: Systematic review in Medline and PubMed with research by key words: "herpes zoster vaccine", "zoster vaccine" and "post herpetic neuralgia vaccine". SELECTION OF STUDIES: Randomized and observational studies published in English and French language have been selected by two readers. RESULTS: On 1886 articles identified, 62 studies were included in this systematic review of which 21 randomized trials, 21 observational studies, and 17 medico-economic studies concerned the unadjuvanted vaccine. Considered studies showed an effectiveness of 50% against herpes zoster and 60% on post-herpetic neuralgia incidence of the unadjuvanted vaccine. Five randomized controlled studies were identified for the adjuvanted vaccine. The overall effectiveness of this vaccine was > 90% whatever the age of subjects including those over age 70 and 80. The medico-economic studies conducted in many countries have shown that vaccine policies were beneficial in individuals aged 60 years or over. LIMITATION OF THE WORK: Most of data of effectiveness, and tolerance result from 2 large controlled studies only (SPS and ZEST) for the unadjuvanted vaccine and only one for the adjuvanted vaccine. CONCLUSION: Despite controversy and few uncertainties, the vaccine significantly reduces herpes zoster and its complication incidence. In terms of public health objectives, it reduces the burden of the disease and has a positive medico-economic impact. Preliminary data concerning the adjuvanted vaccine, whilst very promising, are still too limited. Up to now, no group of people with particularly high risk of herpes zoster-related complication who will beneficiate the most of the vaccination has been identified yet and only an age criteria has been considered for the recommendation.

Cost-minimization analysis of three decision strategies for cardiac revascularization : results of the "suspected CAD"cohort of the european cardiovascular magnetic resonance registry.

BACKGROUND: Coronary artery disease (CAD) continues to be one of the top public health burden. Perfusion cardiovascular magnetic resonance (CMR) is generally accepted to detect CAD, while data on its cost effectiveness are scarce. Therefore, the goal of the study was to compare the costs of a CMR-guided strategy vs two invasive strategies in a large CMR registry. METHODS: In 3'647 patients with suspected CAD of the EuroCMR-registry (59 centers/18 countries) costs were calculated for diagnostic examinations (CMR, X-ray coronary angiography (CXA) with/without FFR), revascularizations, and complications during a 1-year follow-up. Patients with ischemia-positive CMR underwent an invasive CXA and revascularization at the discretion of the treating physician (=CMR + CXA-strategy). In the hypothetical invasive arm, costs were calculated for an initial CXA and a FFR in vessels with ≥50 % stenoses (=CXA + FFR-strategy) and the same proportion of revascularizations and complications were applied as in the CMR + CXA-strategy. In the CXA-only strategy, costs included those for CXA and for revascularizations of all ≥50 % stenoses. To calculate the proportion of patients with ≥50 % stenoses, the stenosis-FFR relationship from the literature was used. Costs of the three strategies were determined based on a third payer perspective in 4 healthcare systems. RESULTS: Revascularizations were performed in 6.2 %, 4.5 %, and 12.9 % of all patients, patients with atypical chest pain (n = 1'786), and typical angina (n = 582), respectively; whereas complications (=all-cause death and non-fatal infarction) occurred in 1.3 %, 1.1 %, and 1.5 %, respectively. The CMR + CXA-strategy reduced costs by 14 %, 34 %, 27 %, and 24 % in the German, UK, Swiss, and US context, respectively, when compared to the CXA + FFR-strategy; and by 59 %, 52 %, 61 % and 71 %, respectively, versus the CXA-only strategy. In patients with typical angina, cost savings by CMR + CXA vs CXA + FFR were minimal in the German (2.3 %), intermediate in the US and Swiss (11.6 % and 12.8 %, respectively), and remained substantial in the UK (18.9 %) systems. Sensitivity analyses proved the robustness of results. CONCLUSIONS: A CMR + CXA-strategy for patients with suspected CAD provides substantial cost reduction compared to a hypothetical CXA + FFR-strategy in patients with low to intermediate disease prevalence. However, in the subgroup of patients with typical angina, cost savings were only minimal to moderate.