High incidence of postoperative infections after pancreaticoduodenectomy: A need for perioperative anti-infectious strategies.

OBJECTIVES: Postoperative infections occur frequently after pancreaticoduodenectomy, especially in patients with bile colonization. Recommendations for perioperative anti-infectious treatment are lacking, and clinical practice is heterogenous. We have analyzed the effects of bile colonization and antibiotic prophylaxis on postoperative infection rates, types and therapeutic consequences. METHODS: Retrospective observational study in patients undergoing pancreaticoduodenectomy with intraoperative bile culture. Data on postoperative infections and non-infectious complications, bile cultures and antibiotic prophylaxis adequacy to biliary bacteria were collected. RESULTS: Among 129 patients, 53% had a positive bile culture and 23% had received appropriate antibiotic prophylaxis. Postoperative documented infection rate was over 40% in patients with or without bile colonization, but antibiotic therapy was more frequent in positive bile culture patients (77% vs. 57%, P=0,008). The median duration of antibiotic therapy was 11 days and included a broad-spectrum molecule in 42% of cases. Two-thirds of documented postoperative infections involved one or more bacteria isolated in bile cultures, which was associated with a higher complication rate. While bile culture yielded Gram-negative bacilli (57%) and Gram-positive cocci (43%), fungal microorganisms were scarce. Adequate preoperative antibiotic prophylaxis according to bile culture was not associated with reduced infectious or non-infectious complication rates. CONCLUSION: Patients undergoing pancreaticoduodenectomy experience a high rate of postoperative infections, often involving bacteria from perioperative bile culture when positive, with no preventive effect of an adequate preoperative antibiotic prophylaxis. Increased postoperative complications in patients with bile colonization may render necessary a perioperative antibiotic treatment targeting bile microorganisms. Further prospective studies are needed to improve the anti-infectious strategy in these patients.

Predictive factors for utilization of a low-volume center in pancreatic surgery: A nationwide study.

STUDY OBJECTIVE: It has been demonstrated that mortality following pancreatectomy is correlated with surgical volume. However, up until now, no French study has focused on predictive factors to undergo pancreatectomy in low-volume centers. The objective of this study is to analyze the clinical characteristics, socio-economic status and medical density according to surgical volume and to analyze predictive factors for undergoing pancreatectomy in low-volume centers. PATIENTS AND METHODS: All patients who underwent pancreatectomy in France from 2012 to 2015 were identified fromthe PMSI database. Hopsitals were classified as low, intermediate and high volume (<10, 11-19, ≥20 resections/year, respectively). Clinical and socioeconomic data, travel distance and rurality were assesed to identify factors associated with undergoing pancreatectomy at low-volume hospitals. RESULTS: In overall, 12,333 patients were included. Those who underwent pancreatectomy in low-volume centers were more likely older, had high Charlson comorbidity index (CCI), had low socioeconomic status, and resided in rural locations.distance traveled by patients operated on in low-volume centers was significantly shorter (23 vs. 61km, P<0.001). In multivariable analysis, older age (P=0.04), CCI≥4 (P=0.008), short travel distance (P<0.001), low socio-economic status (P<0.001) and rurality (P<0.001) were associated withundergoing pancreatectomy in low-volume centers. CONCLUSION: Patients continue to undergo pancreatectomy at low-volume hospitals is due not only to clinical parameters, but also to socioeconomic and environmental factors. These factors should be taken into account in process of pancreatic surgery centralization.

Do complications following pancreatic resections impact hospital costs in France: Medico-economic study on 127 patients.

OBJECTIVE: To define the cost of pancreatectomies and to identify factors associated with increased hospital costs after pancreatic resection. METHODS: All patients undergoing pancreatic surgery in our department between January 2008 and December 2014 were included. All complications occurring during hospitalization or in the 90-day period after discharge were documented. The hospital costs were analyzed and predictive factors of increased hospital costs were determined. RESULTS: One hundred and twenty seven patients were identified. Most patients underwent pancreatectomy for malignant tumors (70%). Median hospital costs were 21,392 [15,998-29,667] euros. Age (P=0.011) and preoperative jaundice (P<0.001) were associated with higher hospital costs. Intraoperative surgical time and blood loss were correlated with increased costs (P=0.001 and P=0.002, respectively). Pancreatoduodenectomy was associated with statistically significantly higher costs compared to distal pancreatectomy (21,770 vs. 15,422 euros, P=0.001). Severe postoperative complications (Clavien-Dindo grade≥3) (P=0.001), septic complications (P=0.002) and hemorrhage (P=0.001) statistically significantly increased costs. In multivariate analysis, septic (P=0.003) and severe complications (P=0.01) were statistically significantly associated with increased hospital costs. CONCLUSION: Pancreatic surgery is associated with high hospital costs, essentially related to postoperative complications.

Assessment of Public Health and Economic Impact of Intranasal Live-Attenuated Influenza Vaccination of Children in France Using a Dynamic Transmission Model.

OBJECTIVES: We estimated the epidemiological and economic impact of extending the French influenza vaccination programme from at-risk/elderly (≥65 years) only to healthy children (2-17 years). METHODS: A deterministic, age-structured, dynamic transmission model was used to simulate the transmission of influenza in the French population, using the current vaccination coverage with trivalent inactivated vaccine (TIV) in at-risk/elderly individuals (current strategy) or gradually extending the vaccination to healthy children (aged 2-17 years) with intranasal, quadrivalent live-attenuated influenza vaccine (QLAIV) from current uptake up to 50% (evaluated strategy). Epidemiological, medical resource use and cost data were taken from international literature and country-specific information. The model was calibrated to the observed numbers of influenza-like illness visits/year. The 10-year number of symptomatic cases of confirmed influenza and direct medical costs ('all-payer') were calculated for the 0-17- (direct and indirect effects) and ≥18-year-old (indirect effect). The incremental cost-effectiveness ratio (ICER) was calculated for the total population, using a 4% discount rate/year. RESULTS: Assuming 2.3 million visits/year and 1960 deaths/year, the model calibration yielded an all-year average basic reproduction number (R 0) of 1.27. In the population aged 0-17 years, QLAIV prevented 865,000 influenza cases/year (58.4%), preventing 10-year direct medical expenses of €374 million. In those aged ≥18 years with unchanged TIV coverage, 1.2 million cases/year were averted (27.6%) via indirect effects (additionally prevented expenses, €457 million). On average, 613 influenza-related deaths were averted annually overall. The ICER was €18,001/life-year gained. The evaluated strategy had a 98% probability of being cost-effective at a €31,000/life-year gained threshold. CONCLUSIONS: The model demonstrated strong direct and indirect benefits of protecting healthy children against influenza with QLAIV on public health and economic outcomes in France.

Factors associated with recurrence of catheter-related bloodstream infections in home parenteral nutrition patients.

Blood cultures from outpatients receiving home parenteral nutrition (HPN) via long-term central venous access (CVA) were retrospectively analyzed from January 2003 to May 2009. When infection of the CVA was not due to Staphylococcus aureus, Pseudomonas aeruginosa, or Candida, catheter salvage was attempted for a maximum of three consecutive infections on the same CVA. Factors influencing the time-to-next-infection were studied, whether the catheter was changed after the last infection or not. Neither the McCabe score, age, history of cancer, diabetes mellitus nor immunosuppression, curative antibiotic lock, type of bacteria, type or duration of treatment had an influence on the time-to-next-infection. The time-to-next-infection was significantly associated with the status of CVA (saved or changed) and its type (tunneled catheter with or without a cuff, or implanted port catheter).

Prevalence of residual excessive sleepiness in CPAP-treated sleep apnoea patients: the French multicentre study.

The percentage of compliant continuous positive airway pressure (CPAP)-treated apnoeic patients that continue to experience residual excessive sleepiness (RES) is unknown. RES was defined by an Epworth Sleepiness Scale (ESS) score of >or=11. In total, 502 patients from 37 French sleep centres using CPAP >3 h night(-1) attending their 1-yr follow-up visit were eligible. ESS and polysomnographic data as well as symptoms, quality of life, depression scores and objective CPAP compliance at 1 yr were collected. Overall, 60 patients remained sleepy on CPAP (ESS 14.3+/-2.5) leading to a prevalence rate of RES of 12.0% (95% confidence interval (CI) 9.1-14.8). After having excluded associated restless leg syndrome, major depressive disorder and narcolepsy as confounding causes, the final prevalence rate of RES was 6.0% (95% CI 3.9-8.01). Patients with RES were younger and more sleepy at diagnosis. The relative risk of having RES was 5.3 (95% CI 1.6-22.1), when ESS before treatment was >or=11. Scores of emotional and energy Nottingham Health Profile domains were two times worse in patients with RES. As 230,000 obstructive sleep apnoea patients are currently treated in France by continuous positive airway pressure, more than 13,800 of them might suffer from residual excessive sleepiness.

Economic evaluation of varicella vaccination in Spain: results from a dynamic model.

Varicella is a universal childhood disease in Spain, causing approximately 400,000 cases, 1,500 hospitalizations and 15 deaths every year. The aim of this study is to determine the economic impact of childhood varicella vaccination on the burden of disease and associated costs by using a dynamic model. The analysis is based on the varicella transmission model developed by Halloran and adapted to the Spanish context. Cost data (Euro, 2004) were derived from previous studies and official tariffs. Two vaccination scenarios were analysed: (1) routine vaccination program for children aged 1-2 years, and (2) routine vaccination program for children aged 1-2 years completed by a catch-up program during the first year of vaccine marketing for children aged 2-11 years. The analysis considers that a similar coverage rate to the MMR one would be achieved (97.15%). A societal perspective, including direct and indirect costs, and a health care payor perspective were adopted. A probabilistic sensitivity analysis was performed. A routine vaccination program has a positive impact on varicella-related morbidity: the number of varicella cases is estimated to be reduced by 89%, and 1230 hospitalizations are prevented. From the societal perspective, scenario (1) is cost-saving whether or not indirect costs are considered (-51 and -4%, respectively). From the Health Care System the strategy is cost-effective, with a cost-effectiveness ratio estimated at 3,982 Euro per life-year gained, although it leads to a small increase in the costs. Considering the impact of vaccination on morbidity and costs, a routine childhood vaccination program against varicella is worth while in Spain without taking into account the potential impact on HZ.

Cost-effectiveness analysis of breast cancer adjuvant treatment: FEC 50 versus FEC 100 (FASG05 study).

BACKGROUND: The aim of the study was to assess the incremental cost-effectiveness ratio (ICER) of the FEC 100 compared with the FEC 50 in the FASG05 trial. MATERIALS AND METHODS: A cost-effectiveness analysis was performed using a multi-state Markov process model. Relevant clinical data introduced into the model were obtained from 10-year follow-up of the clinical trial FASG05. Survival curves for each health state were assessed by survival parametric model. The model allowed assessments from the start of adjuvant chemotherapy until death. The costs of adjuvant treatment and follow-up were estimated. The costs of recurrence were evaluated from the medical records of 146 patients. A prospective survey was performed on a cohort of 87 patients to quantify the resources external to the hospital (including cost of transportation). The inpatient costs were evaluated using the French diagnosis-related groups. The ambulatory costs were assessed using the French nomenclature. Costs were expressed in 2002 Euro (), according to the French societal perspective. The ICER assessed the cost of one additional life year saved. A discount rate of 5% per year was used for cost, and alternatively 0%, 3% and 5% for effectiveness. We validated the results with a probabilistic sensitivity analysis incorporating parametric and non-parametric bootstraps, and with the acceptability curves. RESULTS: The mean total discounting cost of adjuvant treatments was 11 465 for FEC 50 and 13 815 for FEC 100; the mean total discounting cost of recurrences was 14 636 and 13 503, respectively. According to the discount rate of effectiveness, the life expectancy was 16.5, 11.4 and 9.3 years for FEC 50 and 18.4, 12.5 and 10.2 years for FEC 100. The ICER (cost per life year saved) were 642, 1084 and 1460, respectively. The probability according to which FEC 50 is strictly dominated by FEC 100 was 0.15. CONCLUSION: The clinical benefit of FEC 100 generates a negligible cost increase when compared with FEC 50.

[Advanced breast cancer: an evaluation of the cost of recurrence]. / Cancer du sein au stade avancé: évaluation du coût de la récidive.

In the context of a medicoeconomic study of the adjuvant treatment of breast cancer, we evaluated the cost of the recurrence. This cost was assessed from the medical records of 146 patients having presented either distant metastases, or a local recurrence followed or not by metastases between 1983 and 1990. We checked according to published data that the frequency of the metastatic risk is negligible if beyond 5 years after the local recurrence. Costs are expressed in 1995 French Francs (FF), with the French Social Security point of view. From the medical records, we calculated the mean cost of each type of recurrence using medical costs (visits, drugs and treatments, assessments, tests, hospital care, outpatient services.) and non medical costs (patient transportation). The costs are 175,168 FF (standard deviation or SD: 127,972) for metastatic recurrence, and respectively 287,582 FF (SD: 142,280) and 115,705 FF (SD: 78,677) for local recurrence followed or not by metastases. There is a significant difference between these figures (p < 0.001). The hospitalization costs are around 66% of the total cost of each type of recurrences and they are significantly higher (p < 0.005) when metastatic disease occurs after a local recurrence. The mean cost of isolated local recurrence added to metastatic recurrence, 290,873 FF, is not different from that of local recurrence followed by metastases, 287,582 FF (p = 0.15). These results will be integrated in a model in order to evaluate the long-term economic consequences of an adjuvant strategy in the treatment of breast cancer and presented in other publications.

[Economic evaluation od the value of early diagnosis and management of hypothyroidism in hypercholesterolemia]. / Evaluation économique de l'intérêt du diagnostic et de la prise en charge précoce de l'hypothyroïdie devant une hypercholestérolémie.

OBJECTIVE: The aim of the study was to assess the economic consequences of the early screening and management for overt hypothyrodism in elderly women suffering from hypercholesterolaemia. METHODS: A cost analysis was performed using screening decision tree followed by a Markov model, targeted on an hypothetical cohort of elderly women (i.e. > or = 55 years of age) suffering from hypercholesterolaemia. Two arms were compared, "no diagnosis", patients being treated by lipid lowering drugs in the long run, "diagnosis", patients being screened for thyroid disturbance and proposed adequate correction by hormone treatment. Relevant clinical data introduced into the model were obtained from published data and from experts. At the end of the initial diagnostic, patients could enter three different health states: euthyroidism, subclinical hypothyroidism or overt hypothyroidism. During 30 years, patients were assumed to be seen each year by a general practitioner for clinical examination and cholesterol dosage, plus, according to the health state evolution, TSH and T4 screening. In the baseline analysis, euthyroidian patients who had a inexplicable degradation of hypercholesterolaemia control were tested for TSH and, if abnormal, T4 serum; for subclinical hypothyroidian patients, TSH and T4 were measured every year. The direct costs taken into account were concerning medical supervision, drug treatment and biologic exams. Costs were analysed from the societal perspective and were expressed in 1998 French Francs (FF) with an accounting rate of 5% by year. A sensitivity analysis was also performed. RESULTS: The total cost at 30-year was equal to 25,006 F for "diagnosis" strategy, to 24,390 F for "no diagnosis" strategy. The incremental cost of the first strategy decreased according to the time horizon. It was 6.8% at 5-year and 2.5% at 30-year. Results were sensitive to variation in response rate of hypercholesterolaemic patients to hormone treatment of hypothyroidism (0.25 in base-case). CONCLUSION: The investment cost in screening and treatment of hypercholesterolemic female patient aged 55 and more can be considered offset in the long run (30 years). Considering the other important outcomes in favour of hormonal drug treatment of hypothyroidism, such as enhancement of well-being, functional capacities and quality of life, the "diagnosis" strategy can be recommended in the ambulatory medical practice.

[The evaluation of the quality of life in asthma patients. Value and implementation]. / L'évaluation de la qualité de vie chez l'asthmatique. Intérêt et mise en oeuvre.

Asthma, as a chronic condition, alters individual's day-to-day life in functional, emotional and social domains. There has been a recent upsurge of interest in the assessment of quality of life in asthmatic patients. Indeed, there is growing evidence that conventional outcomes of asthma (symptoms assessments, functional measures...) although important, may not detect all the changes experienced by patients. Quality-of-life instruments target two distinct properties. First, discriminative instruments are needed to distinguish between individuals or groups of patients. Second, an evaluative instrument is required to detect such changes in an individual or group of patients, as occur in clinical trials. There are now a number of quality-of-life instruments, with strong measurement properties, that can be used in clinical trials.

Knowledge, self-management, compliance and quality of life in asthma: a cross-sectional study of the French version of the Asthma Quality of Life Questionnaire.

The Asthma Quality of Life Questionnaire (AQLQ) is a well-validated instrument. Our objectives were to explore the cross-sectional validity of the French version, using usual outcomes of asthma, as well as assessment of knowledge of asthma, self-management and compliance. A self-administered version of the AQLQ was given to 124 consecutive patients recruited from two out-patient clinics and an emergency room in order to reflect a wide range of asthma severity. The other outcomes of asthma measured were the FEV1, patient-perceived asthma severity using a visual analogue scale, compliance, knowledge of asthma condition and self-management autonomy. Correlations were predicted before analysis ( r > 0.5, strong correlation, ++ r = 0.35-0.5, moderate correlation and + r = 0.20-0.35, fair correlation). The AQLQ scores correlated moderately to strongly with asthma severity and fairly with the pulmonary function results. Of the behavioural outcomes assessed, only knowledge of asthma correlated fairly with the AQLQ scores, as expected. This study of the French version of the AQLQ, while showing similar cross-sectional correlations with functional assessment and asthma severity to those observed with the original English version, suggested in addition a positive association between quality of life and knowledge of asthma.

[Adjuvant treatment of cancer of the breast: cost assessment of the protocol used]. / Traitement adjuvant du cancer du sein: évaluation du coût de la stratégie mise en oeuvre.

In this study a cost analysis of therapeutics used in the adjuvant treatment of breast cancer has been performed. Four strategies were considered: chemotherapy (FEC, 6 courses), hormone therapy (tamoxifen, 20 mg/day during 3 years), the association of chemotherapy and hormone therapy, or standard follow-up with neither chemotherapy nor hormone therapy. The costs of these strategies were analysed according to the payer's perspective (social security system). In order to complete the economic data, specific investigations were performed at the Centre Oscar-Lambret (COL), a Cancer Center located in Lille (France). The study shows a high cost for chemotherapy (63,767 FF at 5 years) and a high cost for the association (68,891 FF), in comparison to the cost of hormone therapy alone (45,540 FF) or to the follow-up without adjuvant therapy (38,416 FF). These costs could be confronted to the efficacy data of these different strategies and to the cost of avoided relapses. Cost-effectiveness and cost-benefit ratios of these adjuvant strategies could then be assessed.

[Medico-economical assessment in cancerology]. / Evaluation médico-économique en cancérologie.

In recent studies, the economic criteria has begun to be integrated to the appraisal in cancerology. The question asked by the economist can be framed as follows: what incremental cost should the collectivity or the health insurance system consent, in order to improve the care of cancer patients? This involves first that the cost of the strategies, foreseen or already implemented, can be appraised, then, that indicators can be defined to capture health improvement, and finally, that this health improvement can be quantified. In this article, we present the process of integrated appraisal (cost/result approach). We specifically analyze costs in cancerology, their source and their evolution. We demonstrate the meaning of the integration of economic costs and medical results. We emphasize on the fact that part of the costs, especially those supported by the patient and his close relations, are most of the time excluded from the analysis. Two main points should be carefully analyzed, when proceeding to an appraisal in cancerology: the measurement of the patient's QoL, which represents an expression of the results of the strategy of care; the financing modalities, for the same type of care, if we consider the specificity of the structures involved and the organization of the care. We conclude by mentioning how difficult this task is and under which conditions it should be developed.

Attempt to establish a classification of patients suffering from coma and admitted to a hospital structure for short or medium term treatment: medical aspects and costs of hospital care.

We dispose of a database, constituted between 1987 and 1993, containing medical and cost information concerning 515 patients suffering from coma and admitted, after a period of resuscitation, to a French hospital establishment--Etablissement Hélio-Marin of Berck-sur-Mer (EHMB)--for short and medium term treatment, between 1974 and 1986. From this base, which contains demographic and clinical data (age, sex, condition upon admission, duration of consciousness disorders, Glasgow Outcome Scale (GOS) upon discharge) we devised a hierarchical classification analysis following a factorial analysis of multiple correspondences, on 2 sets: a sample of 515 patients (all causes of coma being merged) and a sample of 266 patients suffering from brain injuries. Four groups were determined for each typology. These groups were first described on the basis of the variables used for their construction, and later by considering other available variables: origin of coma, duration of stay at EHMB, future evolution of patients and cost of treatment (cost of specific care, average daily cost, total cost of hospitalization). Thus, typical clinical situations were identified in each classification, depending on age of patient, origin of coma and condition upon admission. These situations led to extremely different treatment costs (ratio from 1 to 5 in the general typology and 1 to 2.85 in the classification of brain injuries.

[Prognostic factors of post-traumatic vegetative states: 522 cases]. / Facteurs pronostics des états végétatifs post-traumatiques: 522 cas.

Long-term prognosis of post-traumatic vegetative state (VS) remains poorly defined. Three kinds of data have been collected for 522 patients in VS 1 month after head injury: pre-traumatic data; early data, collected during the first two weeks after trauma; late data, collected one month or more after trauma. Statistical relationships have been searched for, between these data and outcome one year after trauma, according to the Glasgow Outcome Scale. Some late data appear as essential prognostic factors of VS: threat blink; complications; ventricular dilatation; motor score (Glasgow Coma Score); spontaneous eye movements. Pretraumatic data then take place: age; previous deficiencies. Other data (especially early data) seem to have a weaker influence or outcome.