Simone Mathoulin‐Pélissier

Background: Geriatric Assessment is an appropriate method for identifying older cancer patients at risk of life-threatening events during therapy. Yet, it is underused in practice, mainly because it is time-and resource-consuming. This study aims to identify the best screening tool to identify older cancer patients requiring geriatric assessment by comparing the performance of two short assessment tools the G8 and the Vulnerable Elders Survey (VES-13).

BACKGROUND: Cryptococcosis is a life-threatening opportunistic fungal infection in both HIV-positive and -negative patients. Information on clinical presentation and therapeutic guidelines, derived mostly from clinical trials performed before introduction of highly active antiretroviral therapy in patients with cryptococcal meningoencephalitis, is missing data on extrameningeal involvement and infections by serotype D as opposed to serotype A of Cryptococcus neoformans. METHODS AND FINDINGS: The prospective multicenter study CryptoA/D was designed in France (1997-2001) to analyse the factors influencing clinical presentation and outcome without the bias of inclusion into therapeutic trials. Of the 230 patients enrolled, 177 (77%) were HIV-positive, 50 (22%) were female, and 161 (72.5%) were infected with serotype A. Based on culture results at baseline, cryptococcosis was more severe in men, in HIV-positive patients, and in patients infected with serotype A. Factors independently associated with mycological failure at week 2 independent of HIV status were initial dissemination (OR, 2.4 [95% confidence interval (CI), 1.2-4.9]), high (>1:512) serum antigen titre (OR, 2.6 [1.3-5.4]), and lack of flucytosine during induction therapy (OR, 3.8 [1.9-7.8]). The three-month survival was shorter in patients with abnormal neurology or brain imaging at baseline, and in those with haematological malignancy. CONCLUSIONS: Thus sex, HIV status, and infecting serotype are major determinants of presentation and outcome during cryptococcosis. We propose a modification of current guidelines for the initial management of cryptococcosis based on systematic fungal burden evaluation.

BACKGROUND: The Cox model relies on the proportional hazards (PH) assumption, implying that the factors investigated have a constant impact on the hazard - or risk - over time. We emphasize the importance of this assumption and the misleading conclusions that can be inferred if it is violated; this is particularly essential in the presence of long follow-ups. METHODS: We illustrate our discussion by analyzing prognostic factors of metastases in 979 women treated for breast cancer with surgery. Age, tumour size and grade, lymph node involvement, peritumoral vascular invasion (PVI), status of hormone receptors (HRec), Her2, and Mib1 were considered. RESULTS: Median follow-up was 14 years; 264 women developed metastases. The conventional Cox model suggested that all factors but HRec, Her2, and Mib1 status were strong prognostic factors of metastases. Additional tests indicated that the PH assumption was not satisfied for some variables of the model. Tumour grade had a significant time-varying effect, but although its effect diminished over time, it remained strong. Interestingly, while the conventional Cox model did not show any significant effect of the HRec status, tests provided strong evidence that this variable had a non-constant effect over time. Negative HRec status increased the risk of metastases early but became protective thereafter. This reversal of effect may explain non-significant hazard ratios provided by previous conventional Cox analyses in studies with long follow-ups. CONCLUSIONS: Investigating time-varying effects should be an integral part of Cox survival analyses. Detecting and accounting for time-varying effects provide insights on some specific time patterns, and on valuable biological information that could be missed otherwise.