Causes of death among HIV-infected patients in France in 2010 (national survey): trends since 2000.

OBJECTIVE: The Mortalité 2010 survey aimed at describing the causes of death among HIV-infected patients in France in 2010 and their evolution since 2000. DESIGN AND METHODS: A national sample of clinical sites, providing HIV care and treatment, notified and documented deaths using a standardized questionnaire. RESULTS: The 90 participating wards notified 728 deaths. Median age at death was 50 years (interquartile range 45-58) and 75% were men. The main underlying causes of death were AIDS-related (25% in 2010 vs. 36% in 2005 and 47% in 2000), non-AIDS non-viral hepatitis-related malignancy (22 vs. 17 and 11%), liver-related (11 vs. 15 and 13%), cardiovascular diseases (10 vs. 8 and 7%) and non-AIDS-related infections (9 vs. 4 and 7%). Malignancies (AIDS and non-AIDS-related) accounted for a third of all causes of death. AIDS accounted for 33% of all causes of death among patients mono-infected with HIV vs. only 13% among those co-infected with hepatitis B virus or hepatitis C virus. CONCLUSION: In 2010, 25% of the causes of death among HIV-infected patients remained AIDS-related. Improved screening and earlier HIV treatment should lead to a smaller proportion of deaths due to AIDS. The majority of patients died of various causes, whereas their HIV infection was well controlled under treatment. Improving case management of HIV-infected patients should include a multidisciplinary approach (prevention, screening, treatment), especially in oncology. Smoking cessation should be a priority goal.

Automated comparison of last hospital main diagnosis and underlying cause of death ICD10 codes, France, 2008-2009.

BACKGROUND: In the age of big data in healthcare, automated comparison of medical diagnoses in large scale databases is a key issue. Our objectives were: 1) to formally define and identify cases of independence between last hospitalization main diagnosis (MD) and death registry underlying cause of death (UCD) for deceased subjects hospitalized in their last year of life; 2) to study their distribution according to socio-demographic and medico-administrative variables; 3) to discuss the interest of this method in the specific context of hospital quality of care assessment. METHODS: 1) Elaboration of an algorithm comparing MD and UCD, relying on Iris, a coding system based on international standards. 2) Application to 421,460 beneficiaries of the general health insurance regime (which covers 70% of French population) hospitalized and deceased in 2008-2009. RESULTS: 1) Independence, was defined as MD and UCD belonging to different trains of events leading to death 2) Among the deaths analyzed automatically (91.7%), 8.5% of in-hospital deaths and 19.5% of out-of-hospital deaths were classified as independent. Independence was more frequent in elder patients, as well as when the discharge-death time interval grew (14.3% when death occurred within 30 days after discharge and 27.7% within 6 to 12 months) and for UCDs other than neoplasms. CONCLUSION: Our algorithm can identify cases where death can be considered independent from the pathology treated in hospital. Excluding these deaths from the ones allocated to the hospitalization process could contribute to improve post-hospital mortality indicators. More generally, this method has the potential of being developed and used for other diagnoses comparisons across time periods or databases.

Role of cancer treatment in long-term overall and cardiovascular mortality after childhood cancer.

PURPOSE: The purpose of this study was to assess the role of treatment in long-term overall and cardiovascular mortality after childhood cancer. PATIENTS AND METHODS: We studied 4,122 5-year survivors of a childhood cancer diagnosed before 1986 in France and the United Kingdom. Information on chemotherapy was collected, and the radiation dose delivered to the heart was estimated for 2,870 patients who had received radiotherapy. RESULTS: After 86,453 person-years of follow-up (average, 27 years), 603 deaths had occurred. The overall standardized mortality ratio (SMR) was 8.3-fold higher (95% CI, 7.6-fold to 9.0-fold higher) in relation to the general populations in France and the United Kingdom. Thirty-two patients had died as a result of cardiovascular diseases (ie, 5.0-fold [95% CI, 3.3-fold to 6.7-fold] more than expected). The risk of dying as a result of cardiac diseases (n = 21) was significantly higher in individuals who had received a cumulative anthracycline dose greater than 360 mg/m(2) (relative risk [RR], 4.4; 95% CI, 1.3 to 15.3) and in individuals who received an average radiation dose that exceeded 5 Gy (RR, 12.5 and 25.1 for 5 to 14.9 Gy and > 15 Gy, respectively) to the heart. A linear relationship was found between the average dose of radiation to the heart and the risk of cardiac mortality (estimated excess [corrected] RR at 1 Gy, 60%). CONCLUSION: This study is the first, to our knowledge, to establish a relationship between the radiation dose received by the heart during radiotherapy for a childhood cancer and long-term cardiac mortality. This study also confirms a significant excess risk of cardiac mortality associated with a high cumulative dose of anthracyclines.

Dendritic cells generated in the presence of granulocyte-macrophage colony-stimulating factor and IFN-alpha are potent inducers of HIV-specific CD8 T cells.

OBJECTIVE: To investigate the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-alpha to induce the differentiation of peripheral monocytes into dendritic cells (DC) and their ability to trigger an HIV-specific CD8 T-cell response. METHODS: Monocytes isolated from both seronegative controls and HIV-infected individuals were differentiated into DC using GM-CSF with either IL-4 or IFN-alpha for 7 days. We assessed the phenotypic characteristics and IL-12 production by flow cytometry. The ability of DC to trigger CD8 T-cell responses was assessed by means of ELISpot and cytotoxicity assays. In addition, HIV-1-RNA levels were measured in culture supernatants. RESULTS: Compared with control DC generated in the presence of GM-CSF and IL-4, DC generated in the presence of GM-CSF and IFN-alpha expressed higher levels of MHC class I molecules and produced similar or higher levels of IL-12 after CD40 ligation or Staphyloccus aureus Cowan stimulation. GM-CSF/IFN-alpha DC expressed low levels of CD4, CXCR4 and DC-SIGN and did not produce detectable virus during the differentiation period. Pulsed GM-CSF/IFN-alpha DC were found to prime CD8 T cells from HIV-negative controls to exert cytotoxic activity against target cells expressing HIV antigens. HIV peptide-pulsed GM-CSF/IFN-alpha DC promote specific IFN-gamma production by autologous CD8 T cells from HIV-seronegative donors. Furthermore, GM-CSF/IFN-alpha DC from HIV-seropositive patients efficiently present HIV peptides to autologous CD8 T lymphocytes. CONCLUSION: GM-CSF and IFN-alpha allow the generation of DC with high CD8 T-cell stimulating abilities. Therefore, this strategy may represent a novel approach to therapeutic vaccination in HIV disease.