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.

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.

Cost-benefit analysis of an enhanced recovery protocol for pancreaticoduodenectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) programmes have been shown to decrease complications and hospital stay. The cost-effectiveness of such programmes has been demonstrated for colorectal surgery. This study aimed to assess the economic outcomes of a standard ERAS programme for pancreaticoduodenectomy. METHODS: ERAS for pancreaticoduodenectomy was implemented in October 2012. All consecutive patients who underwent pancreaticoduodenectomy until October 2014 were recorded. This group was compared in terms of costs with a cohort of consecutive patients who underwent pancreaticoduodenectomy between January 2010 and October 2012, before ERAS implementation. Preoperative, intraoperative and postoperative real costs were collected for each patient via the hospital administration. A bootstrap independent t test was used for comparison. ERAS-specific costs were integrated into the model. RESULTS: The groups were well matched in terms of demographic and surgical details. The overall complication rate was 68 per cent (50 of 74 patients) and 82 per cent (71 of 87 patients) in the ERAS and pre-ERAS groups respectively (P = 0·046). Median hospital stay was lower in the ERAS group (15 versus 19 days; P = 0·029). ERAS-specific costs were euro922 per patient. Mean total costs were euro56 083 per patient in the ERAS group and euro63 821 per patient in the pre-ERAS group (P = 0·273). The mean intensive care unit (ICU) and intermediate care costs were euro9139 and euro13 793 per patient for the ERAS and pre-ERAS groups respectively (P = 0·151). CONCLUSION: ERAS implementation for pancreaticoduodenectomy did not increase the costs in this cohort. Savings were noted in anaesthesia/operating room, medication and laboratory costs. Fewer patients in the ERAS group required an ICU stay.

The economic cost of hospital malnutrition in Europe; a narrative review

Background: Malnutrition among hospitalized patients increases length of stay (LOS) and carries extra hospitalization costs. Objective: To review the impact of malnutrition on hospital LOS and costs in Europe. Methods: PubMed and Google Scholar search. All articles from January 2004 until November 2014 were identified. Reference lists of relevant articles were also manually searched. Results: Ten studies on LOS and nine studies on costs were reviewed. The methods used to assess malnutrition and to calculate costs differed considerably between studies. Malnutrition led to an increased LOS ranging from 2.4 to 7.2 days. Among hospitalized patients, malnutrition led to an additional individual cost ranging between 1640 V and 5829 V. At the national level, the costs of malnutrition ranged between 32.8 million V and 1.2 billion V. Expressed as percentage of national health expenditures, the values ranged between 2.1% and 10%. Conclusions: In Europe, malnutrition leads to an increase in LOS and in hospital costs, both at the individual and the national level. Standardization of methods and results reported is needed to adequately compare results between countries. © 2015 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Life span and reproductive cost explain interspecific variation in the optimal onset of reproduction.

Fitness can be profoundly influenced by the age at first reproduction (AFR), but to date the AFR-fitness relationship only has been investigated intraspecifically. Here, we investigated the relationship between AFR and average lifetime reproductive success (LRS) across 34 bird species. We assessed differences in the deviation of the Optimal AFR (i.e., the species-specific AFR associated with the highest LRS) from the age at sexual maturity, considering potential effects of life history as well as social and ecological factors. Most individuals adopted the species-specific Optimal AFR and both the mean and Optimal AFR of species correlated positively with life span. Interspecific deviations of the Optimal AFR were associated with indices reflecting a change in LRS or survival as a function of AFR: a delayed AFR was beneficial in species where early AFR was associated with a decrease in subsequent survival or reproductive output. Overall, our results suggest that a delayed onset of reproduction beyond maturity is an optimal strategy explained by a long life span and costs of early reproduction. By providing the first empirical confirmations of key predictions of life-history theory across species, this study contributes to a better understanding of life-history evolution.

Pleiotropy and the low cost of individual traits promote cooperation.

The evolution of cooperation is thought to be promoted by pleiotropy, whereby cooperative traits are coregulated with traits that are important for personal fitness. However, this hypothesis faces a key challenge: what happens if mutation targets a cooperative trait specifically rather than the pleiotropic regulator? Here, we explore this question with the bacterium Pseudomonas aeruginosa, which cooperatively digests complex proteins using elastase. We empirically measure and theoretically model the fate of two mutants-one missing the whole regulatory circuit behind elastase production and the other with only the elastase gene mutated-relative to the wild-type (WT). We first show that, when elastase is needed, neither of the mutants can grow if the WT is absent. And, consistent with previous findings, we show that regulatory gene mutants can grow faster than the WT when there are no pleiotropic costs. However, we find that mutants only lacking elastase production do not outcompete the WT, because the individual cooperative trait has a low cost. We argue that the intrinsic architecture of molecular networks makes pleiotropy an effective way to stabilize cooperative evolution. Although individual cooperative traits experience loss-of-function mutations, these mutations may result in weak benefits, and need not undermine the protection from pleiotropy.

Cost-effectiveness of Tenofovir / Emtricitabine / Efavirenz versus Zidovudine / Lamivudine / Efavirenz as fist-line regimens for the treatment of HIV-infected patients in low-income settings

The Highly Active Antiretroviral Therapy (HAART) is the combination of at least three antiretroviral compounds. The combination purpose is to reduce the likelihood of drug resistance. However in the long-term the resistance to the first-line combination occurs and leads to treatment failure. Thus, a second-line and even a third-line regimen are recommended in the long run. [...] [P. 5] The two treatment alternatives under comparison: Tenofovir (300 mg) CO-formulated with Emtricitabine (200 mg) and Efavirenz (600 mg) currently known under the brand name Atripla (R) was introduced in July 2006 in the United States market. The excellent safety profile and ease of use make this combination a perfect first-line regimen in low-income settings. Therefore, this treatment option was recommended in WHO 2006 reviewed guidelines. Unfortunately, Tenofovir and Emtricitabine compounds are still costly and not yet widely available. For a matter of simplification this regimen is referred in this report as "the recent" therapy. Initially, we had in mind to consider the most frequently used first-line regimen in low-income countries (Stavudine / Larnivudme / Nevirapine) as a comparator for this economic evaluation. Unfortunately, according to the literature review results (see Annex 3); there was no data available comparing head to head the effectiveness of this regimen with the recent one. Instead, we selected a less frequently but commonly used first-line regimen in low-income countries as a comparator: Zidovudine, Lamivudine, Efavirenz. This combination has extensive experience in durability, safety and toxicity and seems to be an optimal choice for a first-line regimen according to the clinical trial group 384 team. Furthermore, Zidovudine, one of the compounds of this combination is now recommended as one of the preferred NNRTI [Non Nucleoside Reverse Transcriptase Inhibitors] options to be considered by countries instead of Stavudine (the most used NNRTI in limited-income countries). As this combination has been included in the WHO guidelines as a first-line therapy since 2003 when WHO launched the "3 by 5" scaling-up initiative, this combination of drugs is referred in this report as the "old" therapy. Objectives: The primary objective of this economic evaluation is to compare the two first-line HAARTs introduced above, in a low-income setting context. Both of these combinations are recommended by the 2006 WHO guidelines as potential first-line regimens. The secondary objective is to provide a simplified and comprehensible cost-effectiveness modeling tool in order to help policy makers, in resource-limited settings, make decisions about which first-line HAART to fund using the scarce resources available. [P. 6-7]

Current and future trens in the quality control of pharmaceuticals and biopharmaticals : impacts on Cost of Goods Sold (COGS)

[Summary] 2. Roles of quality control in the pharmaceutical and biopharmaceutical industries. - 2.1. Pharmaceutical industry. - 2.2. Biopharmaceutical industry. - 2.3. Policy and regulatory. - 2.3.1. The US Food and Drug Administration (FDA). - 2.3.2. The European Medicine Agency (EMEA). - 2.3.3. The Japanese Ministry of Work, Labor and Welfare (MHLW). - 2.3.4. The Swiss Agency for Therapeutic Products (Swissmedic). - 2.3.5. The International Conference on Harmonization (ICH). - - 3. Types of testing. - 3.1. Microbiological purity tests. - 3.2. Physiochemical tests. - 3.3. Critical to quality steps. - 3.3.1. API starting materials and excipients. - 3.3.2. Intermediates. - 3.3.3. APIs (drug substances) and final drug product. - 3.3.4. Primary and secondary packaging materials fro drug products. - - 4. Manufacturing cost and quality control. - 4.1.1. Pharmaceutical manufacturing cost breakdown. - 4.1.2. Biopharmaceutical manufacturing cost breakdown. - 4.2. Batch failure / rejection / rework / recalls. - - 5. Future trends in the quality control of pharmaceuticals and biopharmaceuticals. - 5.1. Rapid and real time testing. - 5.1.1. Physio-chemicals testing. - 5.1.2. Rapid microbiology methods