Determinants of beta-lactam PK/PD target attainment in critically ill patients: A single center retrospective study.

PURPOSE: We aimed to identify factors associated with achieving target BL plasma concentrations and describe real world data for therapeutic drug monitoring (TDM). METHODS: A retrospective single center study was conducted. We collected data from patients admitted to ICU with at least one BL TDM. We assessed the proportion of patients attaining the recommended plasma concentrations (i.e 100%fT > 4 to 8 MIC). Univariate and multivariate analyses was performed to identify the determinants of BL target attainment. RESULTS: 156 patients were included. At the first dosing, 34% achieved target BL plasma concentrations, 50% were overdosed, and 16% were underdosed. Median time for 1st TDM were 4 (SD = 2.9) days. Multivariate analysis revealed that CKD-EPI estimated glomerular filtration rate (OR = 1.02; CI [1.01; 1.03]; p < 0.0001) and total body weight (OR = 1.03; CI [1.01; 1.04]; p = 0.0048) were the main determinant of BL target attainment. Conversely, Continuous Renal Replacement Therapy (OR = 0.28; CI [0.09; 0.89]; p = 0.0318) and meropenem use (OR = 0.31; CI [0.14; 0.69]; p = 0.0041) were identified as risk factors for overdosing. No factor was associated with underdosing. CONCLUSION: Achieving target BL plasma concentrations remains challenging in ICUs. Identifying predictive factors of BL target attainment would favor implementing rapid dosing optimization strategies in both under and overdosing high risk patients.

Epidemiologic study in a real-world analysis of patients with treatment for psoriasis in the French national health insurance database.

BACKGROUND: Psoriasis is one of the most frequent chronic inflammatory dermatoses in the world. Data on the prevalence of psoriasis in adults differ depending on the study. OBJECTIVE: To estimate the prevalence of patients with treatment for psoriasis in France and to identify and characterize patients receiving systemic treatments. METHODS: This was a French, nationwide cohort study based on health administrative data from the French national health insurance scheme linked to the national hospital discharge database (SNDS-PMSI). All adults with psoriasis registered in the SNDS between 1 January 2008 and 31 December 2016 were eligible for inclusion. All patients with a new prescription for a systemic treatment for psoriasis were included. RESULTS: A total of 874 549 patients were identified as having psoriasis (mean ± SD age 53.8 ± 17 years; 52.4% males); 112 969 (13%) had filled at least one prescription for a systemic medication used to treat psoriasis. The prevalence of patients with treatment for psoriasis was estimated at 1.3%. Overall, 73 168 and 16 545 were new users of conventional systemic treatments and biologics, respectively. The most frequent comorbidities associated with psoriasis were hypertension, dyslipidaemia, diabetes and chronic obstructive pulmonary disease. CONCLUSION: The prevalence of psoriasis we found was lower than in other studies. It was probably underestimated because we identified only patients with treatment for psoriasis. Our results concerning comorbidities associated with psoriasis patients requiring systemic treatment were similar to those from other published studies using other data sources, highlighting our ability to catch moderate-to-severe psoriasis. This study highlights the usefulness and reliability of the use of insurance databases in studies, because they allow for a better application to the general population.

Persistence of apremilast in moderate-to-severe psoriasis: a real-world analysis of 14 147 apremilast- and methotrexate-naive patients in the French National Health Insurance database.

BACKGROUND: Real-world data on the persistence of apremilast vs. methotrexate are inconclusive. OBJECTIVES: To assess and compare the long-term persistence of apremilast and methotrexate in a large cohort of patients with psoriasis. METHODS: All adult patients with psoriasis registered in the French national health insurance database ('Système National des Données de Santé') between 2009 and 2017 were eligible for inclusion. The study population comprised apremilast- and methotrexate-naive patients, defined as those with a first prescription of apremilast or methotrexate. Levels of persistence were compared using a Cox model with propensity-score matching that included potential confounders (notably age, sex, psoriatic arthritis, comorbidities and previous exposure to topical and systemic treatments). RESULTS: In this nationwide population-based cohort, 14 147 adult patients with psoriasis (mean age 52·3 years, 55·2% male) were found to be naive to both apremilast and methotrexate. After propensity-score matching, two subgroups of 4805 patients with similar baseline characteristics were included, of whom 3207 apremilast-treated patients and 2736 methotrexate-treated patients discontinued their treatment. Kaplan-Meier survival propensity-score analyses revealed a discontinuation rate of 69% for apremilast and 59% for methotrexate in the first year of treatment. Apremilast-treated patients had a higher risk of discontinuation than methotrexate-treated patients when considering the study population as a whole (hazard ratio 1·28, 95% confidence interval 1·23-1·34) or in a propensity-score-matched analysis (hazard ratio 1·34, 95% confidence interval 1·27-1·41; P < 0·001). CONCLUSIONS: Our real-world data suggest that in the first year of treatment, the discontinuation rate was significantly higher for apremilast-treated patients than for methotrexate-treated patients, regardless of the previous therapeutic lines received. What's already known about this topic? Psoriasis is a common chronic, relapse-remitting, inflammatory skin disease associated with severe psychosocial impact. Apremilast, a phosphodiesterase 4 inhibitor, is one of the most recently commercialized psoriasis drugs. Little is known about the long-term clinical effectiveness of apremilast. What does this study add? The discontinuation rate at 1 year for apremilast was 69%, compared with 58% for methotrexate, in a nationwide population-based cohort including 14 147 nonselected adult patients with psoriasis. Patients in the apremilast cohort had a higher risk of discontinuation than patients in the methotrexate cohort using propensity-score matching, including potentially relevant individual risk factors such as age, sex, comorbidities and psoriatic arthritis, and regardless of the previous therapeutic lines received. In daily practice, physicians should take these results into account when choosing between methotrexate and apremilast as a first-line systemic therapy.

Persistence of treatment with biologics for patients with psoriasis: a real-world analysis of 16 545 biologic-naïve patients from the French National Health Insurance database (SNIIRAM).

BACKGROUND: Long-term clinical effectiveness of biologics in psoriasis is needed. OBJECTIVES: We aimed to assess the long-term persistence of biologics used to treat psoriasis in a real-life setting. METHODS: All adults with psoriasis having been registered in the French National Health Insurance database (SNIIRAM) between 2008 and 2016 were eligible for inclusion. Psoriasis was defined as the fulfilment of at least two prescriptions for topical formulations of a vitamin D derivative within a 2-year period. The study population comprised biologic-naïve patients, i.e. those with a first prescription of etanercept, infliximab, adalimumab or ustekinumab. Persistence of treatment with a biologic was defined as the time interval between initiation and discontinuation. RESULTS: In this nationwide population-based cohort, 16 545 out of 874 549 patients with psoriasis were biologic-naïve (mean age 48·6 years; males 57·3%, mean follow-up 3·6 years). The mean ± SD length of follow-up for biologic-naïve patients was 3·6 ± 2·4 years. There were 9988 treatment discontinuations. Kaplan-Meier survival analyses revealed a persistence rate of 61·9% for the first, 33·3% for the third and 22·6% for the fifth year. Ustekinumab had a higher persistence rate than the other biologics. This finding should be interpreted with caution, in view of differences in administration between the biologics. About 85% of patients, having discontinued their first biologic, resumed systemic treatment of some type in the following year (biologics in 85% of cases). CONCLUSIONS: Our data suggest that biologics are less effective than physicians have been led to believe in a real-life, nonselected population. Further, long-term disease control requires several courses of different biologics.

[Reimbursed health expenditures during the last year of life, in France, in the year 2008]. / Les dépenses de soins remboursés durant la dernière année de vie, en 2008, en France.

BACKGROUND: To measure the reimbursed health expenditures in the last year of life and the proportion it represents in total reimbursement costs in 2008, to analyse the structure of such expenditures and to identify costs by cause of death. METHODS: Data were obtained from the French national insurance information system (SNIIRAM). Data from the national hospital discharge database were linked to the outpatient reimbursement database for patients covered by the general health insurance scheme (n=49 million persons). The cost of the last year of life was calculated for the exhaustive population (361,328 deaths in 2008). The supposed cause of death was mainly derived from the primary diagnosis of the last hospital stay during which the patient died. RESULTS: The average reimbursed expenses during the last year of life were estimated at 22,000 € per person in 2008, with 12,500 € accounting for public hospital costs. Reimbursed health expenditures varied according to different medical causes of death: 52,300 € for HIV disease and about 40,000 € for tumors. A negative effect of age on the expenditure during the last year of life was observed. Health care spending increased with shorter time before death, the last month of life corresponding to 28% of reimbursed expenditures during the last year of life. Health care use in the last year of life represented 10.5% of the total health expenditures in 2008. CONCLUSION: This study found results similar to those observed in the past or in other countries. Our results show in particular that the weight of health expenditures during the last year of life on total health expenditures remains stable over the years.

[Role of French hospital claims databases from care units in epidemiological studies: the example of the "Cohorte Enfant Scanner" study]. / Utilisation des données du programme de médicalisation des systèmes d'information (PMSI) dans les études épidémiologiques : application à la Cohorte Enfant Scanner.

BACKGROUND: The "Cohorte Enfant Scanner", a study designed to investigate the risk of radiation-induced cancer after childhood exposure to CT (computed tomography) examinations, used clinical information contained in the "programme de médicalisation des systèmes d'information" (PMSI) database, the French hospital activities national program based upon diagnosis related groups (DRG). However, the quality and adequacy of the data for the specific needs of the study should be verified. The aim of our work was to estimate the percentage of the cohort's children identified in the PMSI database and to develop an algorithm to individualize the children with a cancer or a disease at risk of cancer from medical diagnoses provided by the DRGs database. METHODS: Of the 1519 children from the "Cohorte Enfant Scanner", who had had a CT scan in the radiology department of a university hospital in 2002, a cross linkage was performed with the DRGs database. All hospitalizations over the period 2002-2009 were taken into account. An algorithm was constructed for the items "cancer" and "disease at risk for cancer" on a sample of 150 children. The algorithm was then tested on the entire population. RESULTS: Overall, 74% of our population was identified in the DRGs database. The algorithm individualized cancer diagnoses with 91% sensitivity (95% confidence interval [95%CI]: 86%; 97%) and 98% specificity (95%CI: 97%; 99%) and 86% positive predictive value (95%CI: 80%; 93%). For the diagnosis of disease at risk for cancer, the sensitivity, specificity and positive predictive value were respectively 91% (95%CI: 84%; 98%), 94% (95%CI: 92%; 95%) and 52% (95%CI: 43%; 61%). CONCLUSION: The DRG database identified with excellent sensitivity and specificity children with diagnoses of cancer or disease at risk for cancer. Hence, potential confounding factors related to the disease of the child can be taken into account for analyses performed with the cohort.