Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group.

BACKGROUND: Advancements in the field of precision medicine have prompted the European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update the recommendations for the use of tumour next-generation sequencing (NGS) for patients with advanced cancers in routine practice. METHODS: The group discussed the clinical impact of tumour NGS in guiding treatment decision using the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) considering cost-effectiveness and accessibility. RESULTS: As for 2020 recommendations, ESMO recommends running tumour NGS in advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer. Moreover, it is recommended to carry out tumour NGS in clinical research centres and under specific circumstances discussed with patients. In this updated report, the consensus within the group has led to an expansion of the recommendations to encompass patients with advanced breast cancer and rare tumours such as gastrointestinal stromal tumours, sarcoma, thyroid cancer, and cancer of unknown primary. Finally, ESMO recommends carrying out tumour NGS to detect tumour-agnostic alterations in patients with metastatic cancers where access to matched therapies is available. CONCLUSION: Tumour NGS is increasingly expanding its scope and application within oncology with the aim of enhancing the efficacy of precision medicine for patients with cancer.

ESMO study on the availability and accessibility of biomolecular technologies in oncology in Europe.

BACKGROUND: Access to biomolecular technologies has become an essential requirement to ensure optimal and timely treatment of patients with cancer. This study sought to provide a comprehensive overview of the availability and accessibility of biomolecular technologies to patients, the status of their use and prescription, barriers to access, and potential economic issues related to cost and reimbursement. MATERIALS AND METHODS: A total of 201 field reporters from 48 European countries submitted data through an electronic survey tool between July and December 2021. The survey methodology mirrored that from previous ESMO studies addressing the availability and accessibility of antineoplastic medicines, in Europe and worldwide. The preliminary data were posted on the ESMO website for open peer-review, and amendments were incorporated into the final report. RESULTS: Overall, basic single-gene techniques are widely available, whereas access to advanced biomolecular technologies, including large next-generation sequencing panels and complete genomic profiles, is highly heterogeneous. In most countries, advanced biomolecular technologies remain largely inaccessible in clinical practice, are limited to clinical trials or basic research, and associated with progressively increasing cost as the technique becomes more advanced. Differences also exist regarding national sequencing initiatives or molecular tumour boards. The most important barriers to multiple versus single-gene sequencing techniques are the reimbursement of the test (59% versus 24%), and the availability of a suitable medicine, either through reimbursement of treatment (48% versus 30%), off-label treatment (52% versus 35%), or clinical trial enrolment (53% versus 39%). CONCLUSIONS: Cost and availability of both treatment and test are the two main factors limiting patients' access to advanced biomolecular technologies and as a consequence to innovative anticancer strategies. In the era of precision medicine, tackling the accessibility to biomolecular technologies is a key step to reduce inequalities to transformative cancer care.

A randomized phase III trial comparing trabectedin to best supportive care in patients with pre-treated soft tissue sarcoma: T-SAR, a French Sarcoma Group trial.

BACKGROUND: The French Sarcoma Group assessed the efficacy, safety, and quality of life (QoL) of trabectedin versus best supportive care (BSC) in patients with advanced soft tissue sarcoma (STS). PATIENTS AND METHODS: This randomized, multicenter, open-label, phase III study included adults with STS who progressed after 1-3 prior treatment lines. Patients were randomized (1 : 1) to receive trabectedin 1.5 mg/m2 every 3 weeks or BSC, stratified into L-STS (liposarcoma/leiomyosarcoma) and non-L-STS groups (other histotypes). Patients from the BSC arm were allowed to cross over to trabectedin at progression. The primary efficacy endpoint was progression-free survival (PFS) confirmed by blinded central review and analyzed in the intention-to-treat population. RESULTS: Between 26 January 2015 and 5 November 2015, 103 heavily pre-treated patients (60.2% with L-STS) from 16 French centers were allocated to receive trabectedin (n = 52) or BSC (n = 51). Median PFS was 3.1 months [95% confidence interval (CI) 1.8-5.9 months] in the trabectedin arm versus 1.5 months (0.9-2.6 months) in the BSC arm (hazard ratio = 0.39, 95% CI 0.24-0.64, P < 0.001) with benefits observed across almost all analyzed subgroups, but particularly in patients with L-STS (5.1 versus 1.4 months, P = 0.0001). Seven patients (13.7%) in the trabectedin arm (all with L-STS) achieved a partial response, while no objective responses were observed in the BSC arm (P = 0.004). The most common grade 3/4 adverse events were neutropenia (44.2% of patients), leukopenia (34.6%), and transaminase increase (32.7%). Health-related 30-item core European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire evidenced no statistical differences between the arms for any domain and at any time point. After progression, 91.8% of patients crossed over from BSC to trabectedin. CONCLUSION: Trabectedin demonstrates superior disease control to BSC without impairing QoL in patients with recurrent STS of multiple histologies, with greater impact in patients with L-STS.

Whole exome sequencing in molecular diagnostics of cancer decreases over time: evidence from a cost analysis in the French setting.

OBJECTIVES: Although high-throughput sequencing is revolutionising medicine, data on the actual cost of whole exome sequencing (WES) applications are needed. We aimed at assessing the cost of WES at a French cancer institute in 2015 and 2018. METHODS: Actual costs of WES application in oncology research were determined using both micro-costing and gross-costing for the years 2015 and 2018, before and after the acquisition of a new sequencer. The entire workflow process of a WES test was tracked, and the number and unit price of each resource were identified at the most detailed level, from library preparation to bioinformatics analyses. In addition, we conducted an ad hoc analysis of the bioinformatics storage costs of data issued from WES analyses. RESULTS: The cost of WES has decreased substantially, from €1921 per sample (i.e. cost of €3842 per patient) in 2015 to €804 per sample (i.e. cost of €1,608 per patient) in 2018, representing a decrease of 58%. In the meantime, the cost of bioinformatics storage has increased from €19,836 to €200,711. CONCLUSION: This study suggests that WES cost has decreased significantly in recent years. WES has become affordable, even though clinical utility and efficiency still need to be confirmed.

Rectoneovaginal fistula after sex reassignment surgery. Description of our experience and literature review. / Fístulas rectoneovaginales en pacientes tras cirugía de reasignación de sexo. Descripción de nuestra experiencia y revisión de la literatura.

Male-to-female reassignment surgery or vaginoplasty includes those surgical procedures that aim to recreate a functional and cosmetically acceptable female perineum with minimal scarring. The technique of choice at our center is penile inversion vaginoplasty with or without scrotal skin grafts. We present 4 cases diagnosed with rectoneovaginal fistulas treated at our center with favorable evolution. The first patient was diagnosed in the late postoperative period during dilation. She underwent 2 failed vaginal repair attempts. Finally, a temporary colostomy and a rectal flap were performed. The second patient was diagnosed 2 weeks after the initial surgery due to aggressive dilation and was treated with a temporary colostomy and secondary wound closure. The third patient was diagnosed on the fifth post-operative day after removal of the vaginal packing. Dietary restriction was indicated, and a rectal flap was performed. A fourth patient was diagnosed within the late postoperative period; she was submitted to surgical exploration and a rectal wall flap was created. Rectoneovaginal fistulas after sex reassignment surgery has an incidence of about 2-17% and they are the most common type of fistula after this procedure. In most cases, it is secondary to rectal injury during the initial surgery. The management of these fistulas ranges from primary closure, diverting colostomies, conservative management, or the performance of flaps. A multidisciplinary team approach is recommended for the diagnosis and treatment of this complication.

Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group.

Next-generation sequencing (NGS) allows sequencing of a high number of nucleotides in a short time frame at an affordable cost. While this technology has been widely implemented, there are no recommendations from scientific societies about its use in oncology practice. The European Society for Medical Oncology (ESMO) is proposing three levels of recommendations for the use of NGS. Based on the current evidence, ESMO recommends routine use of NGS on tumour samples in advanced non-squamous non-small-cell lung cancer (NSCLC), prostate cancers, ovarian cancers and cholangiocarcinoma. In these tumours, large multigene panels could be used if they add acceptable extra cost compared with small panels. In colon cancers, NGS could be an alternative to PCR. In addition, based on the KN158 trial and considering that patients with endometrial and small-cell lung cancers should have broad access to anti-programmed cell death 1 (anti-PD1) antibodies, it is recommended to test tumour mutational burden (TMB) in cervical cancers, well- and moderately-differentiated neuroendocrine tumours, salivary cancers, thyroid cancers and vulvar cancers, as TMB-high predicted response to pembrolizumab in these cancers. Outside the indications of multigene panels, and considering that the use of large panels of genes could lead to few clinically meaningful responders, ESMO acknowledges that a patient and a doctor could decide together to order a large panel of genes, pending no extra cost for the public health care system and if the patient is informed about the low likelihood of benefit. ESMO recommends that the use of off-label drugs matched to genomics is done only if an access programme and a procedure of decision has been developed at the national or regional level. Finally, ESMO recommends that clinical research centres develop multigene sequencing as a tool to screen patients eligible for clinical trials and to accelerate drug development, and prospectively capture the data that could further inform how to optimise the use of this technology.

Effect of chloride on the one step electrochemical treatment of an industrial textile wastewater with tin dioxide anodes. The case of trichromy procion HEXL.

The resulting solutions from the cotton fabrics dyeing using the trichromy Procion HEXL, with NaCl as electrolyte, were electrochemically treated. These dyes have two azo groups as chromophores and two monochlorotriazinic groups as reactive groups in their structure. The combined oxidation/reduction at 125 mA cm-2 in a filter-press cell without compartment separation was carried out using an anode of Ti/SnO2-Sb-Pt and a cathode of stainless steel. This procedure has been effective in previous experiments using sulphate as electrolyte. A significant decrease in total organic carbon (TOC), chemical oxygen demand (COD), and total nitrogen (TN) was obtained. Moreover, the process took place efficiently. The average oxidation state (AOS) and the carbon oxidation state (COS) data confirmed the presence of stable oxidized intermediates in the electrolysed solution. The chromatography and the UV-Visible spectrophotometry assays indicated that full decolourisation is obtained at a loaded charge of around 0.81 Ah L-1 which is associated with an electrical energy per order (EEO) of 1.20 kWh m-3.

On the behavior of reduced graphene oxide based electrodes coated with dispersed platinum by alternate current methods in the electrochemical degradation of reactive dyes.

The electrochemical behavior of different carbon-based electrodes with and without nanoparticles of platinum electrochemically dispersed on their surface has been studied. Among others, reduced graphene oxide based electrodes was used to determine the best conditions for the decolorization/degradation of the reactive dye C.I. Reactive Orange 4 in sulfuric medium. Firstly, the electrochemical behavior was evaluated by cyclic voltammetry. Secondly, different electrolyses were performed using two cell configurations: cell with anodic and cathodic compartments separated (divided configuration) and without any separation (undivided configuration). The best results were obtained when reduced graphene oxide based anodes were used. The degree of decolorization was monitored by spectroscopic methods and high performance liquid chromatography. It was found that all of them followed pseudo-first order kinetics. When reduced graphene oxide-based electrodes coated with dispersed platinum by alternate current methods electrodes were used, the lowest energy consumption and the higher decolorization kinetics rate were obtained. Scanning Electronic Microscopy was used to observe the morphological surface differences.

Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab.

BACKGROUND: Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. PATIENTS AND METHODS: Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. RESULTS: The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. CONCLUSION: The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. AFSSAPS NO: 2007-A00399-44.

Variation in rates of breast cancer surgery: A national analysis based on French Hospital Episode Statistics.

AIMS: Minimum volume thresholds were introduced in France in 2008 to improve the quality of cancer care. We investigated whether/how the quality of treatment decisions in breast cancer surgery had evolved before and after this policy was implemented. METHODS: We used Hospital Episode Statistics for all women having undergone breast conserving surgery (BCS) or mastectomy in France in 2005 and 2012. Three surgical procedures considered as better treatment options were analyzed: BCS, immediate breast reconstruction (IBR) and sentinel lymph node biopsy (SLNB). We studied the mean rates and variation according to the hospital profile and volume. RESULTS: Between 2005 and 2012, the volume of breast cancer surgery increased by 11% whereas one third of the hospitals no longer performed this type of surgery. In 2012, the mean rate of BCS was 74% and similar in all hospitals whatever the volume. Conversely, IBR and SLNB rates were much higher in cancer centers (CC) and regional teaching hospitals (RTH) [IBR: 19% and 14% versus 8% on average; SLNB: 61% and 47% versus 39% on average]; the greater the hospital volume, the higher the IBR and SLNB rates (p < 0.0001). Overall, whatever the surgical procedure considered, inter-hospital variation in rates declined substantially in CC and RTH. CONCLUSIONS: We identified considerable variation in IBR and SLNB rates between French hospitals. Although more complex and less standardized than BCS, most clinical guidelines recommended these procedures. This apparent heterogeneity suggests unequal access to high-quality procedures for women with breast cancer.

Assessment of the in vivo formation of biofilm on external ventricular drainages.

Biofilm formation on external ventricular drainages (EVDs) has been postulated as the main pathogenic mechanism for EVD-associated ventriculitis. However, biofilm on EVDs has never been systematically studied and the in vivo effect of antibiotic-impregnated EVDs on biofilm has not been assessed. The aim of this study was to measure the prevalence of biofilm formation on EVDs and to analyze the influence of antibiotic-impregnated EVD on the risk of biofilm formation and ventriculitis. Consecutive patients with EVDs were included in the study. Surveillance cerebrospinal fluid (CSF) cultures were performed twice a week. Withdrawn EVDs were cultured using standard bacteriologic techniques and examined under a scanning electron microscope. We collected 32 EVDs, 18 of which (56 %) were antibiotic-impregnated EVDs. Biofilm was present on 24 EVDs (75 %), ventriculitis was diagnosed in 6 patients (19 %), and colonization occurred in 12 patients (38 %). All cases of ventriculitis were due to Gram-negative bacteria. Biofilm was more frequent on EVDs originating from patients with ventriculitis or bacterial colonization. Impregnated EVDs did not avoid ventriculitis or colonization, but biofilm development on these devices depended on the time from insertion and varied from 67 % for those used for <7 days to 88 % for those used for ≥ 7 days (p = 0.094). In conclusion, biofilm is a common phenomenon on EVDs. Currently available impregnated EVDs could not avoid ventriculitis due to multidrug-resistant Gram-negative bacteria, but a trend of delayment of biofilm development was observed.

Metastatic breast cancer: we do need primary cost data.

The lifetime cost of metastatic breast cancer is a key component for the economic evaluations of targeted therapies and biomarkers. In the literature, only few cost studies are available and provide discordant cost estimates for the management of metastatic recurrences. Our objective was to assess the lifetime costs of metastatic breast cancer and to investigate cost variability using primary cost data. We used individual data from a cohort of 290 French women treated at the Gustave Roussy Institute and who had died between 2005 and 2008. We separately analysed the determinants for survival after metastatic recurrence and for the monthly cost using two different models. The mean survival time after recurrence was 24.8 months. The mean hospital cost per patient amounted to € 36,516 and the mean cost per month € 3764. We identified three prognostic factors: age at breast cancer diagnosis, the histological grade and the site of the first recurrence. The factors significantly associated with the cost per month were hospitalisation in a palliative care unit, trastuzumab treatment, the number of sites of recurrence and whether or not the patient had died during the last hospital stay. We identified cost drivers of the lifetime costs of metastatic breast cancer. This provides useful information for the design of future economic studies. We also provide cost estimates in homogeneous subgroups of patients defined by patient characteristics and by the type of care received.

[Extracorporeal lung support in patients with severe respiratory failure secondary to the 2010-2011 winter seasonal outbreak of influenza A (H1N1) in Spain]. / Uso de oxigenador de membrana extracorpóreo en pacientes con insuficiencia respiratoria aguda grave refractaria en la epidemia de gripe estacional 2010-2011 por influenza A (H1N1) en España.

OBJECTIVE: To describe the use of extracorporeal membrane oxygenation (ECMO) in refractory respiratory failure. DESIGN: A prospective, observational, multi-center study was carried out. SETTING: Intensive Care Units (ICU) in 148 Spanish hospitals. PATIENTS: Subjects admitted during epidemic weeks 50-52 of 2010 and weeks 1-4 of 2011, receiving respiratory support with ECMO. MAIN VARIABLES OF INTEREST: Clinical and blood gas features, complications and survival of patients with ECMO. RESULTS: Out of 300 ICU admitted patients, 239 (79.6%) were mechanically ventilated. ECMO was available in only 5 ICUs. Nine patients were treated with ECMO (3% of the total and 3.2% of the ventilated patients). In 77.7% of the cases some hypoxemia rescue technique was previously used. ECMO was initiated when ARDS proved refractory to standard treatment. ECMO therapy was started a median of 4.5 days after the onset of mechanical ventilation. The median duration of ECMO was 6 days. Veno-venous (VV) ECMO was the most frequent cannulation mode (88.9%). Four patients had complications associated with ECMO therapy. The median ICU and hospital stay was 17 and 29 days, respectively. In five patients (55.5%), ECMO assistance was satisfactory suspended. The ICU and hospital survival rate was 44.4%. CONCLUSIONS: The use of ECMO in refractory respiratory failure in patients with influenza A (H1N1) is rare in Spain. The hospital survival achieved with its use allows it to be regarded as a possible rescue technique in these patients.

[Recommendations of the Infectious Diseases Work Group (GTEI) of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) and the Infections in Critically Ill Patients Study Group (GEIPC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) for the diagnosis and treatment of influenza A/H1N1 in seriously ill adults admitted to the Intensive Care Unit]. / Recomendaciones del Grupo de Trabajo Enfermedades Infecciosas (GTEI) de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) y el Grupo de Estudio de Infecciones en el Paciente Crítico (GEIPC) de la Sociedad Española de Enfermedades Infecciosas y Microbiología clínica (SEIMC) para el diagnóstico y tratamiento de la gripe A/H1N1 en pacientes adultos graves hospitalizados en las Unidades de Cuidados Intensivos.

The diagnosis of influenza A/H1N1 is mainly clinical, particularly during peak or seasonal flu outbreaks. A diagnostic test should be performed in all patients with fever and flu symptoms that require hospitalization. The respiratory sample (nasal or pharyngeal exudate or deeper sample in intubated patients) should be obtained as soon as possible, with the immediate start of empirical antiviral treatment. Molecular methods based on nucleic acid amplification techniques (RT-PCR) are the gold standard for the diagnosis of influenza A/H1N1. Immunochromatographic methods have low sensitivity; a negative result therefore does not rule out active infection. Classical culture is slow and has low sensitivity. Direct immunofluorescence offers a sensitivity of 90%, but requires a sample of high quality. Indirect methods for detecting antibodies are only of epidemiological interest. Patients with A/H1N1 flu may have relative leukopenia and elevated serum levels of LDH, CPK and CRP, but none of these variables are independently associated to the prognosis. However, plasma LDH> 1500 IU/L, and the presence of thrombocytopenia <150 x 10(9)/L, could define a patient population at risk of suffering serious complications. Antiviral administration (oseltamivir) should start early (<48 h from the onset of symptoms), with a dose of 75 mg every 12h, and with a duration of at least 7 days or until clinical improvement is observed. Early antiviral administration is associated to improved survival in critically ill patients. New antiviral drugs, especially those formulated for intravenous administration, may be the best choice in future epidemics. Patients with a high suspicion of influenza A/H1N1 infection must continue with antiviral treatment, regardless of the negative results of initial tests, unless an alternative diagnosis can be established or clinical criteria suggest a low probability of influenza. In patients with influenza A/H1N1 pneumonia, empirical antibiotic therapy should be provided due to the possibility of bacterial coinfection. A beta-lactam plus a macrolide should be administered as soon as possible. The microbiological findings and clinical or laboratory test variables may decide withdrawal or not of antibiotic treatment. Pneumococcal vaccination is recommended as a preventive measure in the population at risk of suffering severe complications. Although the use of moderate- or low-dose corticosteroids has been proposed for the treatment of influenza A/H1N1 pneumonia, the existing scientific evidence is not sufficient to recommend the use of corticosteroids in these patients. The treatment of acute respiratory distress syndrome in patients with influenza A/H1N1 must be based on the use of a protective ventilatory strategy (tidal volume <10 ml / kg and plateau pressure <35 mmHg) and positive end-expiratory pressure set to high patient lung mechanics, combined with the use of prone ventilation, muscle relaxation and recruitment maneuvers. Noninvasive mechanical ventilation cannot be considered a technique of choice in patients with acute respiratory distress syndrome, though it may be useful in experienced centers and in cases of respiratory failure associated with chronic obstructive pulmonary disease exacerbation or heart failure. Extracorporeal membrane oxygenation is a rescue technique in refractory acute respiratory distress syndrome due to influenza A/H1N1 infection. The scientific evidence is weak, however, and extracorporeal membrane oxygenation is not the technique of choice. Extracorporeal membrane oxygenation will be advisable if all other options have failed to improve oxygenation. The centralization of extracorporeal membrane oxygenation in referral hospitals is recommended. Clinical findings show 50-60% survival rates in patients treated with this technique. Cardiovascular complications of influenza A/H1N1 are common. Such problems may appear due to the deterioration of pre-existing cardiomyopathy, myocarditis, ischemic heart disease and right ventricular dysfunction. Early diagnosis and adequate monitoring allow the start of effective treatment, and in severe cases help decide the use of circulatory support systems. Influenza vaccination is recommended for all patients at risk. This indication in turn could be extended to all subjects over 6 months of age, unless contraindicated. Children should receive two doses (one per month). Immunocompromised patients and the population at risk should receive one dose and another dose annually. The frequency of adverse effects of the vaccine against A/H1N1 flu is similar to that of seasonal flu. Chemoprophylaxis must always be considered a supplement to vaccination, and is indicated in people at high risk of complications, as well in healthcare personnel who have been exposed.

First influenza season after the 2009 pandemic influenza: report of the first 300 ICU admissions in Spain.

INTRODUCTION: During the 2009 influenza pandemic, several reports were published, nevertheless, data on the clinical profiles of critically ill patients with the new virus infection during this second outbreak are still lacking. MATERIAL METHODS: Prospective, observational, multi-center study conducted in 148 Spanish intensive care units (ICU) during epidemiological weeks 50-52 of 2010 and weeks 1 - 4 of 2011. RESULTS: Three hundred patients admitted to an intensive care unit (ICU) with confirmed An/H1N1 infection were analyzed. The median age was 49 years [IQR=38-58] and 62% were male. The mean APACHE II score was 16.9 ± 7.5 and the mean SOFA score was 6.3 ± 3.5 on admission. Comorbidities were present in 76% (n=228) of cases and 111 (37.4%) patients were reportedly obese and 59 (20%) were COPD. The main presentation was viral pneumonia with severe hypoxemia in 65.7% (n=197) of the patients whereas co-infection was identified in 54 (18%) patients. All patients received antiviral treatment and initiated empirically in 194 patients (65.3%), however only 53 patients (17.6%) received early antiviral treatment. Vaccination was only administered in 22 (7.3%) patients. Sixty-seven of 200 patients with ICU discharge died. Haematological disease, severity of illness, infiltrates in chest X-ray and need for mechanical ventilation were variables independently associated with ICU mortality. CONCLUSIONS: In patients admitted to the ICU in the post-pandemic seasonal influenza outbreak vaccination was poorly implemented and appear to have higher frequency of severe comorbidities, severity of illness, incidence of primary viral pneumonia and increased mortality when compared with those observed in the 2009 pandemic outbreak.

Study of the electrochemical oxidation and reduction of C.I. Reactive Orange 4 in sodium sulphate alkaline solutions.

Synthetic solutions of hydrolysed C.I. Reactive Orange 4, a monoazo textile dye commercially named Procion Orange MX-2R (PMX2R) and colour index number C.I. 18260, was exposed to electrochemical treatment under galvanostatic conditions and Na2SO4 as electrolyte. The influence of the electrochemical process as well as the applied current density was evaluated. Ti/SnO2-Sb-Pt and stainless steel electrodes were used as anode and cathode, respectively, and the intermediates generated on the cathode during electrochemical reduction were investigated. Aliquots of the solutions treated were analysed by UV-visible and FTIR-ATR spectroscopy confirming the presence of aromatic structures in solution when an electro-reduction was carried out. Electro-oxidation degraded both the azo group and aromatic structures. HPLC measures revealed that all processes followed pseudo-first order kinetics and decolourisation rates showed a considerable dependency on the applied current density. CV experiments and XPS analyses were carried out to study the behaviour of both PMX2R and intermediates and to analyse the state of the cathode after the electrochemical reduction, respectively. It was observed the presence of a main intermediate in solution after an electrochemical reduction whose chemical structure is similar to 2-amino-1,5-naphthalenedisulphonic acid. Moreover, the analysis of the cathode surface after electrochemical reduction reveals the presence of a coating layer with organic nature.

Influence of electrochemical reduction and oxidation processes on the decolourisation and degradation of C.I. Reactive Orange 4 solutions.

The electrochemical treatment of wastewaters from textile industry is a promising treatment technique for substances which are resistant to biodegradation. This paper presents the results of the electrochemical decolourisation and degradation of C.I. Reactive Orange 4 synthetic solutions (commercially known as Procion Orange MX2R). Electrolyses were carried out under galvanostatic conditions in a divided or undivided electrolytic cell. Therefore, oxidation, reduction or oxido-reduction experiences were tested. Ti/SnO(2)-Sb-Pt and stainless steel electrodes were used as anode and cathode, respectively. Degradation of the dye was followed by TOC, total nitrogen, COD and BOD(5) analyses. TOC removal after an oxidation process was higher than after oxido-reduction while COD removal after this last process was about 90%. Besides, the biodegradability of final samples after oxido-reduction process was studied and an improvement was observed. UV-Visible spectra revealed the presence of aromatic structures in solution when an electro-reduction was carried out while oxido-reduction process degraded both azo group and aromatic structures. HPLC analyses indicated the presence of a main intermediate after the reduction process with a chemical structure closely similar to 2-amine-1, 5-naphthalenedisulfonic acid. The lowest decolourisation rate corresponded to electrochemical oxidation. In these experiences a higher number of intermediates were generated as HPLC analysis demonstrated. The decolourisation process for the three electrochemical processes studied presented a pseudo-first order kinetics.

[Cost of an intraperitoneal chemohyperthermia (IPCH) related to cytoreductive surgery]. / Coûts et financement de la chimiohyperthermie intrapéritonéale (CHIP) associée à une chirurgie d'exérèse.

BACKGROUND: A complete cytoreductive surgery followed with an intraperitoneal chemohyperthermia (IPCH) is a new treatment allowing curing some patients with a peritoneal carcinomatosis. The cost of this treatment, evaluated in different countries, is high. In France, we do not have any cost evaluation of this therapy, and this state slows its diffusion in our country. The aim of this study is to evaluate the real cost of maximal cytoreductive surgery with IPCH, and to compare it with the financial support given by the Ministery of Health. MATERIALS AND METHODS: The real cost of this therapy was established on the standard analytic accountancy of our Institute. The analysis of the financial support received was done after the classification of the patients in the current official diagnosis-related groups, and according to the current rates of reimbursing of these acts. RESULTS: Seventy-three patients were treated with IPCH in our Institute during 2002 and 2003. The real mean cost for our hospital was 39,358 euros per patient, with a mean hospital staying of 27.7 days. In counterpart, our hospital received a mean financial support of 20,485 euros, resulting in a deficit of 18,873 euros per patient (and close to 1.4 million of euros for the two years). CONCLUSION: Our current classification of diagnosis-related groups does not allow to describe the real importance of this therapy which combines a maximal cytoreductive surgery with IPCH. In our system of reimbursing, the hospital which offers this type of new therapy to its patients receives only half of the real rate. Two correctives measures are suitable: to describe this combining treatment in the official list of medical acts, and to determine its specific cost for reimbursing.

The epidemiology, economics and quality of life burden of age-related macular degeneration in France, Germany, Italy and the United Kingdom.

Age-related macular degeneration (AMD) is a major public health issue, but little is known about the economics of the disease. This contribution describes the epidemiology and the economics of AMD in four European countries: France, Germany, Italy and the United Kingdom (UK). We reviewed published information on AMD, including guidelines, official statistics, and local literature and interviewed AMD experts. All available health-related quality of life studies (HRQoL) on AMD were also reviewed. Data collection focused on epidemiology, medical management and resource use (both medical and non-medical items). Prevalence of AMD among persons older than 65 years is 8% and increases with age. There are two forms of the disease: atrophic (80-85% of AMD cases) and exudative, which is characterised by choroidal neovascularisation (CNV; 15-20% of AMD cases). No treatment for the atrophic form is available. Laser photocoagulation is the mainstay of treatment for CNV, although less than 30% of persons with CNV can benefit from it. Photodynamic therapy (PDT), a new treatment for CNV, reduces the risk of vision loss in forms with predominantly visible lesions. Several other new procedures are also under development. Rehabilitation and low-vision aids are useful palliative interventions when there is a residual visual acuity. The yearly budget impact of AMD was found to be between 51.3 and 101.1 million euros in the four countries studied. Information on social services and resource use was scant and little is reported on the impact of AMD on HRQoL. Economic studies of AMD should be conducted in order to assist public health decision making.

[Medico-economic evaluation of abciximab]. / Evaluation médico-économique d'abciximab.

Abciximab (RéoPro) is a chimeric monoclonal antibody directed against platelet glycoprotein IIb-IIIa. It reduces the frequency of major cardiac ischaemic events after percutaneous transluminal coronary angioplasty (PTCA). This treatment is more expensive than the commonly used treatment (aspirin and heparin). However, a treatment can only be validly assessed in term of its cost-benefit ratio. The authors present the results of a medico-economic evaluation of abciximab in the French institutional context, based on the three-year clinical results of the EPIC study (Evaluation of abciximab for the Prevention of Ischemic Complications). The efficacy of treatment was expressed by means of two quantitative indicators: the number of patients with no major ischaemic event (MIE) and the number of years of life without myocardial infarction or revascularization. According to French good practice recommendations for economic evaluation of therapeutic strategies, major ischaemic events were assessed by using the complete cost of the corresponding homogeneous groups of diseases (GHM). Medico-economic evaluation of abciximab showed that the net excess cost per patient for national health insurance was 395 Francs, while the cost of the product is 5,300 Francs. The incremental cost per additional patient with no major ischaemic event is 6,585 Francs and the incremental cost per additional year of life without myocardial infarction or revascularization is 2,469 F. From a public health point of view, abciximab administered by bolus injection plus a 12-hour infusion, presents a good cost-effectiveness ratio in the prevention of cardiac ischaemic complications in high-risk patients after PTCA.