Factors Associated With Aggressiveness of End-of-Life Care for Lung Cancer Patients and Associated Costs of Care.

BACKGROUND: Results of previous studies demonstrated that high-intensity end-of-life (EOL) care improves neither cancer patients' survival nor quality of life. Our objective was to assess the incidence of and factors associated with aggressiveness of care during the last 30 days of life (DOL) of lung cancer (LC) patients and the impacts of aggressiveness of care in EOL-care costs. PATIENTS AND METHODS: Using French national hospital database, all patients with LC who died between January 1, 2010, and December 31, 2011, or between January 1, 2015, and January 31, 2016, were included. EOL-care aggressiveness was assessed using the following criteria: chemotherapy administered within the last 14 DOL; more than one hospitalization within the last 30 DOL; admission to the intensive care unit within the last 30 DOL; and palliative care initiated < 3 days before death. Expenditures were limited to direct costs, from a health care payer's perspective. RESULTS: Among 79,746 adult LC patients identified; 57% had at least one indicator of EOL-care aggressiveness (49% repeated hospitalizations, 12% intensive care unit admissions, 9% chemotherapy, 5% palliative care). It increased significantly between the 2 periods (56% vs. 58%, P < .001). Young age, male sex, shorter time since diagnosis, comorbidities, no malnutrition, type of care facility other than general hospital, social deprivation, and low-density population were independently associated with having one or more indicator of aggressive EOL care. The mean EOL cost was €8152 ± 5117 per patient, but the cost was significantly higher for patients with at least one EOL-care aggressiveness criterion (€9480 vs. €6376, P < .001). CONCLUSION: In France, a majority of LC patients had at least one criterion of aggressive EOL care that had a major economic impact on the health care system.

Hospital burden of pulmonary arterial hypertension in France.

BACKGROUND & AIMS: Pulmonary arterial hypertension is a severe disease associated with frequent hospitalisations. This retrospective analysis of the French medical information PMSI-MSO database aimed to describe incident cases of patients with pulmonary arterial hypertension hospitalised in France in 2013 and to document associated hospitalisation costs from the national health insurance perspective. METHODS: Cases of pulmonary arterial hypertension were identified using a diagnostic algorithm. All cases hospitalised in 2013 with no hospitalisation the previous two years were retained. All hospital stays during the year following the index hospitalisation were extracted, and classified as incident stays, monitoring stays or stays due to disease worsening. Costs were attributed from French national tariffs. RESULTS: 384 patients in France were hospitalised with incident pulmonary arterial hypertension in 2013. Over the following twelve months, patients made 1,271 stays related to pulmonary arterial hypertension (415 incident stays, 604 monitoring stays and 252 worsening stays). Mean age was 59.6 years and 241 (62.8%) patients were women. Liver disease and connective tissue diseases were documented in 62 patients (16.1%) each. Thirty-one patients (8.1%) died during hospitalisation and four (1.0%) received a lung/heart-lung transplantation. The total annual cost of these hospitalisations was € 3,640,382. € 2,985,936 was attributable to standard tariffs (82.0%), € 463,325 to additional ICU stays (12.7%) and € 191,118 to expensive drugs (5.2%). The mean cost/stay was € 2,864, ranging from € 1,282 for monitoring stays to € 7,285 for worsening stays. CONCLUSIONS: Although pulmonary arterial hypertension is rare, it carries a high economic burden.

Cost-of-illness of inflammatory bowel disease patients treated with anti-tumour necrosis factor: A French large single-centre experience.

Background: No study has evaluated the direct annual costs of inflammatory bowel disease patients treated with anti-tumour necrosis factor therapy. Objectives: The purpose of this study was to identify annual direct costs and main cost drivers of anti-tumour necrosis factor-treated inflammatory bowel disease patients. Methods: All inflammatory bowel disease patients treated with infliximab or adalimumab at Nancy University Hospital were consecutively screened for inclusion from November 2016-February 2017. Data about hospitalisation, surgery, medication, outpatient visits, investigations and transport over the previous 12 months were retrospectively collected. Results: A total of 108 patients (n = 83 Crohn's disease; n = 25 ulcerative colitis) were included. The mean annual cost per patient was €15,775 (standard deviation €7221), with no difference between Crohn's disease and ulcerative colitis (p = 0.2). The main cost driver was medication, which accounted for 84% of the total direct cost. Hospitalisation and surgery represented 11% and 2% of the direct costs. History of switch to another anti-tumour necrosis factor treatment was identified as the only independent predictor of greater direct costs in the multivariate analysis (p = 0.0018). Conclusions: In a French tertiary referral centre, direct costs of anti-tumour necrosis factor therapy-treated patients were mainly driven by medication, while hospitalisation and surgery represented only a minor part of the costs. There was no difference between Crohn's disease and ulcerative colitis patients.

Access to innovative drugs for metastatic lung cancer treatment in a French nationwide cohort: the TERRITOIRE study.

BACKGROUND: Territorial differences in the access to innovative anticancer drugs have been reported from many countries. The objectives of this study were to evaluate access to innovative treatments for metastatic lung cancer in France, and to assess whether socioeconomic indicators were predictors of access at the level of the municipality of residence. METHODS: All incident cases of metastatic lung cancer hospitalised for a chemotherapy in public hospitals in 2011 were identified from the French National Hospital discharge database. Information on prescription of innovative drugs from an associated database (FICHCOMP) was crossed with the population density of the municipality and a social deprivation index based on national census data. RESULTS: Overall, 21,974 incident cases of metastatic lung cancer were identified, all of whom were followed for 2 years. Of the 11,486 analysable patients receiving chemotherapy in the public sector, 6959 were treated with a FICHCOMP drug at least once, principally pemetrexed. In multivariate analysis, prescription of FICHCOMP drugs was less frequent in patients ≥66 years compared to those ≤55 years (odds ratio: 0.49 [0.44-0.55]), in men compared to women (0.86 [0.79-0.94]) and in patients with renal insufficiency (0.55 [0.41-0.73]) and other comorbidities. Prescription rates were also associated with social deprivation, being lowest in the most deprived municipalities compared to the most privileged municipalities (odds ratio: 0.82 [0.72-0.92]). No association was observed between the population density of the municipality and access to innovative drugs. CONCLUSION: Although access to innovative medication in France seems to be relatively equitable, social deprivation is associated with poorer access. The reasons for this need to be investigated and addressed.

Extra cost of brain metastases (BM) in patients with non-squamous non-small cell lung cancer (NSCLC): a French national hospital database analysis.

PURPOSE: To assess the incremental cost associated with the management of patients with primary non-squamous non-small cell lung cancer (NSCLC) with brain metastases at the time of diagnosis. METHODS: Data were extracted from the French Hospital medical information database (Programme de Médicalisation des Systèmes d'Information (PMSI)). Patients with non-squamous NSCLC were identified through a diagnosis of lung cancer and a prescription of bevacizumab or pemetrexed. All such patients hospitalised with lung cancer for the first time in 2013 and with metastases identified at the first hospitalisation were eligible. Two cohorts were identified, one with brain metastases (group B: n=971) and one with metastases at other sites (group A: n=1529). For each patient, total in-hospital medical resource consumption associated with the initial hospitalisation in 2013 and with any follow-up stays in the following 24 months was documented. Costs were attributed from official French national tariffs and expressed in 2017 euros. RESULTS: The mean number of hospitalisations per patient in the 24-moth follow-up period was 17 in group A and 21 in group B. >99% of patients in both groups received chemotherapy. 58% of patients in group B and 13% in group A were managed by radiotherapy. 37% in group B and 24% in group A received palliative care. The associated cost was €2979 per patient-month for patients in group B and €2426 for patients in group A, representing a differential cost of €553 per month. Radiotherapy (+€164/month) and palliative care (+€130/month) were the principal drivers of the incremental cost. CONCLUSIONS: The presence of brain metastases at the time of diagnosis of non-squamous NSCLC carries a significant burden, and ways of lowering this burden are needed.

Determinants of malignant pleural mesothelioma survival and burden of disease in France: a national cohort analysis.

This study was undertaken to determine the healthcare burden of malignant pleural mesothelioma (MPM) in France and to analyze its associations with socioeconomic deprivation, population density, and management outcomes. A national hospital database was used to extract incident MPM patients in years 2011 and 2012. Cox models were used to analyze 1- and 2-year survival according to sex, age, co-morbidities, management, population-density index, and social deprivation index. The analysis included 1,890 patients (76% men; age: 73.6 ± 10.0 years; 84% with significant co-morbidities; 57% living in urban zones; 53% in highly underprivileged areas). Only 1% underwent curative surgical procedure; 65% received at least one chemotherapy cycle, 72% of them with at least one pemetrexed and/or bevacizumab administration. One- and 2-year survival rates were 64% and 48%, respectively. Median survival was 14.9 (95% CI: 13.7-15.7) months. The mean cost per patient was 27,624 ± 17,263 euros (31% representing pemetrexed and bevacizumab costs). Multivariate analyses retained men, age >70 years, chronic renal failure, chronic respiratory failure, and never receiving pemetrexed as factors of poor prognosis. After adjusting the analysis to age, sex, and co-morbidities, living in rural/semi-rural area was associated with better 2-year survival (HR: 0.83 [95% CI: 0.73-0.94]; P < 0.01); social deprivation index was not significantly associated with survival. With approximately 1,000 new cases per year in France, MPMs represents a significant national health care burden. Co-morbidities, sex, age, and living place appear to be significant factors of prognosis.

Plasma Retinol Concentration Is Mainly Driven by Transthyretin in Hemodialysis Patients.

OBJECTIVE: Micronutrients deficiencies in hemodialysis patients are due to low dietary intakes and intradialytic losses for hydrophilic micronutrients. Conversely, lipophilic nondialyzable compounds might accumulate because of a lack of elimination through renal metabolism or dialysis. Other compounds have complex metabolism: their concentration is not explained by these phenomenons. The aim of this study was to report plasma concentrations of lipophilic micronutrients in hemodialysis patients and to analyze if these concentrations were predictive of mortality. DESIGN: The design was monocentric observational longitudinal study. SUBJECTS: A total of 123 hemodialysis patients included in this observational study. MAIN OUTCOME MEASURE: Plasma concentration of lipophilic micronutrients retinol and its two co-transporters transthyretin and retinol-binding protein 4, tocopherol, and carotenoids (α-carotene and ß-carotene, ß-cryptoxanthin, lycopene, lutein, and zeaxanthin), and all factors associated with 1-year mortality. RESULTS: Within the 123 patients of the study, median age (interquartile range) was 77.5 (69.5-84.5) years and 58.5% were male. Median retinol plasma concentration was 4.07 (2.65-5.51) µmol/L, and 91.9% of patient had high plasma retinol concentrations. In monovariate analysis, retinol levels were inversely correlated with mortality (hazard ratio = 0.57 [0.45-0.72]; P < .001). This effect remained significant after adjustment with several parameters. Nevertheless, the correlation between retinol and mortality disappeared as soon as transthyretin was added in the statistical model, suggesting an effect of transthyretin as confusing bias. Median tocopherol plasma concentration was 34.8 (28.3-42.9) µmol/L and 72.4% of patients had high plasma tocopherol concentration. Neither tocopherol plasma levels nor carotenoids concentrations were correlated with death in multivariate analysis. CONCLUSIONS: In hemodialysis patients, the correlation between retinol plasma concentration and mortality represents the nutritional status but not a direct biological effect of retinol. Retinol is only a surrogate predictor of mortality. It might not represent vitamin A levels, but likely the transthyretin level. Plasma retinol levels should be interpreted cautiously in hemodialysis patients.

Five years after the accident, whiplash casualties still have poorer quality of life in the physical domain than other mildly injured casualties: analysis of the ESPARR cohort.

BACKGROUND: This study aims to compare health status and quality of life five years after a road accident between casualties with whiplash versus other mild injuries, to compare evolution of quality of life at 1 and 5 years after the accident, and to explore the relation between initial injury (whiplash vs. other) and quality of life. METHODS: The study used data from the ESPARR cohort (a representative cohort of road accident casualties) and included 167 casualties with "pure" whiplash and a population of 185 casualties with other mild injuries (MAIS-1). All subjects with lesions classified as cervical contusion (AIS code 310402) or neck sprain (AIS code 640278) were considered as whiplash casualties. Diagnosis was made by physicians, at the outset of hospital care, based on interview, clinical findings and X-ray. Whiplash injuries were then classified following the Quebec classification (grades 1 and 2). Quality of life was assessed on the WHOQoL-Bref questionnaire. Correlations between explanatory variables and quality of life were explored by Poisson regression and variance analysis. RESULTS: Between 1 and 5 years, global QoL improved for both whiplash and non-whiplash casualties; but, considering the two whiplash groups separately, improvement in grade 2 was much less than in grade 1. At 5 years, grade-2 whiplash casualties were more dissatisfied with their health (39.4%; p < 0.05) than non-whiplash (24.3%) or grade-1 whiplash casualties (27.0%). Deteriorated quality of life in the mental, social and environmental domains was mainly related to psychological and socioeconomic factors for both whiplash and other mildly injured road-accident casualties. While PTSD was a major factor for the physical domain, whiplash remained a predictive factor after adjustment on PTSD; unsatisfactory health at 5 years, with deteriorated quality of life in the physical domain, was observed specifically in the whiplash group, pain playing a predominant intermediate role. CONCLUSIONS: Deteriorated quality of life in the physical domain remained 5 years after the accident, specifically in the grade-2 whiplash group, pain playing a predominant intermediate role, which may be in line with the hypothesis of neuropathic pain.

A few seconds to have an accident, a long time to recover: consequences for road accident victims from the ESPARR cohort 2 years after the accident.

OBJECTIVE: The aim of the present study was to describe the consequences of a road accident in adults, taking account of the type of road user, and to determine predictive factors for consequences at 2 years. DESIGN: Prospective follow-up study. METHODS: The cohort was composed of 1168 victims of road traffic accidents, aged ≥16 years. Two years after the accident, 912 victims completed a self-administered questionnaire. Weighted logistic regression models were implemented to compare casualties still reporting impact related to the accident versus those reporting no residual impact. Five outcomes were analysed: unrecovered health status, impact on occupation or studies, on familial or affective life, on leisure or sport activities and but also the financial difficulties related to the accident. RESULTS: 46.1% of respondents were motorised four-wheel users, 29.6% motorised two-wheel (including quad) users, 13.3% pedestrians (including inline skate and push scooter users) and 11.1% cyclists. 53.3% reported unrecovered health status, 32.0% persisting impact on occupation or studies, 25.2% on familial or affective life, 46.9% on leisure or sport activities and 20.2% still had accident-related financial difficulties. Type of user, adjusted on age and gender, was linked to unrecovered health status and to impact on leisure or sport activities. When global severity (as measured by NISS) was integrated in the previous model, type of user was also associated with impact on occupation or studies. Type of user was further associated with impact on occupation or studies and on leisure or sport activities when global severity and the sociodemographic data obtained at inclusion were taken into account. It was not, however, related to any of the outcomes studied here, when the models focused on the injured body region. Finally, type of road user did not seem, on the various predictive models, to be related to financial difficulties due to the accident or to impact on familial or affective life. CONCLUSIONS: Overall, victims were affected by their accident even 2 years after it occurred. The severity of lesions induced by the accident was the main predictive factor. However, considering lesion as intermediary factors between the accident and the recovery status at 2 year post-accident, impact on health status was lower for cyclists than M4W users or M2W users.

Health status recovery at one year in children injured in a road accident: a cohort study.

Despite the frequency of traumatic injuries due to road accidents and potential importance of identifying children at risk of impaired recovery one year after a road accident, there is a lack of data on long-term recovery of health status, except in children with severe traumatic brain injury. The aim of the present study was to evaluate predictive factors of recovery in children one year after road traffic injuries. The prospective cohort study was composed of children aged <16 years, admitted to public or private sector hospitals in the Rhône administrative area of France following a road accident. Recovery of health status one year after the accident and information concerning quality of life and the consequences of the accident for the child or family 1 year after the accident were collected by questionnaire, usually completed by the parents. Victims were in majority male (64.6%) and had mild or moderate injuries (81.9% with Maximum Abbreviated Injury Scale (M-AIS) <3). One year after the accident, 75.0% of the mild-to-moderate and 34.8% of the severe cases estimated health status as fully recovered. After adjustment, severity score (M-AIS≥3) and lower limb injury (AIS>1) were associated with incomplete recovery of health status: weighted odds ratio (ORw), 4.3 [95% confidence interval (95% CI), 1.3-14.6] and ORw, 6.5 [95% CI, 1.9-21.7], respectively. Recovery status correlated significantly with quality of life physical scores (r=0.46), especially body pain (r=0.48) and role/social-physical (r=0.50) and, to a lesser extent, quality of life psychosocial scores (r=0.21). In a cohort of children injured in a road accident, those with high injury severity score and those with lower limb injuries are less likely to recover full health status by 1 year. Impaired health status was associated with a lower physical quality of life score at 1 year.

One year after mild injury: comparison of health status and quality of life between patients with whiplash versus other injuries.

OBJECTIVE: To compare health status, effect on family, occupational consequences, and quality of life (QOL) 1 year after an accident between patients with whiplash versus other mild injuries, and to explore the relationship between initial injury (whiplash vs other) and QOL. METHODS: This was a prospective cohort study. The study used data from the ESPARR cohort (a representative cohort of road accident victims) and included 173 individuals with "pure" whiplash and 207 with other mild injuries. QOL at 1-year followup was assessed on the World Health Organization Quality of Life questionnaire. Correlations between explanatory variables and QOL were explored by Poisson regression to provide adjusted relative risks, with ANOVA for the various QOL scores explored. RESULTS: One year post-accident, more patients who had whiplash than other casualties complained of nonrecovery of health status (56% vs 43%) and of the occupational effect of pain (31% vs 23%). QOL and posttraumatic stress disorder (PTSD) were similar in the 2 groups. Impaired QOL did not correlate with whiplash when models were adjusted on sociodemographic variables and history of psychological distress. Whatever the initial lesion, PTSD was a determining factor for poorer QOL. CONCLUSION: Sociodemographic factors, preaccident psychological history prior to the accident, and PTSD were the main factors influencing QOL, rather than whether the injury was whiplash. PTSD may also be related to pain.