Search

The advent of immune checkpoint-inhibitors (CPI) has transformed treatment for several cancer types. This review was performed to assess the rate of adverse events (AEs) associated with the use of CPI, alone or in combinations. A review of AEs reporting quality was also performed. All publications of Randomized Clinical Trials (RCTs) assessing CPI published before December 2017 were included. To investigate the quality of AEs reporting, a set of items was defined based on the 2004 CONSORT harms extension statement. Rates of Grade 5, serious, and study-withdrawal related AEs were collected in each treatment category. Specific immune related AEs (irAEs) were also collected when available. Pooled estimates of adverse event rates were calculated by using generalized linear mixed model. A total of 35 RCTs including 16,485 patients were included. The overall quality of AEs reporting was satisfactory, but items pertaining to methods of data collection and analysis were infrequently reported. Grade ≥ 3 AEs were reported for 14% (95% CI 12-16) of patients treated with PD(L)-1 inhibitors, 34% (95% CI 27-42) of patients treated with CTLA-4 inhibitors, 55% (95% CI 51-59) of patients on CPI combinations and 46% (95% CI 40-53) of patients on immunotherapy-chemotherapy combination. The profile of irAEs was different among the treatment categories. The use of CPI, especially in combination, is associated with significant rates of Grade ≥ 3 AEs. Healthcare planning should anticipate the expected high number of patients presenting with irAEs in the future.

BACKGROUND: The objective of this study was to describe the implementation of comprehensive geriatric assessment (CGA) in clinical trials dedicated to older patients before and after the creation of the International Society of Geriatric Oncology in the early 2000s. SUBJECTS, MATERIALS, AND METHODS: All phase I, II, and III trials dedicated to the treatment of cancer among older patients published between 2001 and 2004 and between 2011 and 2014 were reviewed. We considered that a CGA was performed when the authors indicated an intention to do so in the Methods section of the article. We collected each geriatric domain assessed using a validated tool even in the absence of a clear CGA, including nutritional, functional, cognitive, and psychological status, comorbidity, comedication, overmedication, social status and support, and geriatric syndromes. RESULTS: A total of 260 clinical trials dedicated to older patients were identified over the two time periods: 27 phase I, 193 phase II, and 40 phase III trials. CGA was used in 9% and 8% of phase II and III trials, respectively; it was never used in phase I trials. Performance status was reported in 67%, 79%, and 75% of phase I, II, and III trials, respectively. Functional assessment was reported in 4%, 11%, and 13% of phase I, II, and III trials, respectively. Between the two time periods, use of CGA increased from 1% to 11% (p = .0051) and assessment of functional status increased from 3% to 14% (p = .0094). CONCLUSION: The use of CGA in trials dedicated to older patients increased significantly but remained insufficient. IMPLICATIONS FOR PRACTICE: This article identifies the areas in which research efforts should be focused in order to offer physicians well-addressed clinical trials with results that can be extrapolated to daily practice.

L'ultrafiltration et la chromatographie d'exclusion stérique haute performance sont utilisées pour la séparation et la caractérisation des composés organiques présents dans les lixiviats de centres d'enfouissement technique de déchets ménagers. Le fractionnement de la matière organique est obtenu sur des colonnes type TSK PW, en élution eau pH 4 et eau-méthanol. La spectroscopie en UV-visible et en fluorescence, un détecteur évaporatif à diffusion de lumière sont utilisés pour la caractérisation des fractions. Cette méthode rapide de séparation associée à une multidétection permet une mise en évidence, dans les fractions issues de l'ultrafiltration, de composés organiques caractéristiques. Dans la fraction de poids moléculaires inférieurs à 1000 Daltons, trois familles sont détectées. Les substances humiques et les protéines sont les principaux groupes présents dans la fraction de poids moléculaires supérieurs à 10000 Daltons., Landfill leachates represent a source of organic pollution characterized by an important organic load, with high chemical oxygen demand in recent sanitary landfills and some organic compounds refractory to biodegradation. Several researchers have examined the organic matter in these landfill leachates. In addition to measuring parameters such as chemical and biological oxygen demands (COD and BOD) and UV-absorbance, different analytical techniques were applied: gas chromatography with flame ionization or mass detection; high performance liquid chromatography; infrared spectroscopy; nuclear magnetic resonance spectrometry; and elementary analysis. Raw leachates or samples after fractionation on Sephadex gel were characterized by ultrafiltration or adsorption on XAD resins.Conclusions from these earlier studies were as follows: - physico-chemical properties of leachates revealed not only a high organic pollution but also diversity and variability according to the age of the sanitary landfill and the climatic conditions; - gel permeation chromatography and ultrafiltration revealed two main fractions in the leachates: one with molecular weights below 1000 Daltons (Da), and another with molecular weights above 5000-10000 Da; - infrared spectroscopy and nuclear magnetic resonance spectrometry showed functional groups present in the humic and fulvic acid fractions of natural organic matter; - a varying number of peaks detected by gas chromatography with flame ionization or mass detection proved the complexity of the matrix. Few compounds were identified and quantified, with the exception of fatty acids. Moreover this technique was only applicable to molecules with low molecular weight.The purpose of the present work was to develop a new method of fractionation of organic matter in landfill leachates and to study their characterization and treatment biodegradation. Ultrafiltration, as a prefractionation step, divided the leachate into four fractions according to their mole