Mortality among homeless people in France, 2008-10.

BACKGROUND: Studies in various countries have shown that homeless people have high mortality levels. The aims of this study concerning the French population were to investigate mortality among the homeless and to study their causes of death in comparison to those of the general population. METHODS: A representative sample of 1145 homeless deaths registered by an association was matched to the national database of medical causes of death using common descriptive variables. Log-binomial regression was used to compare mortality among the homeless to that of the general population. Multiple imputation was used to manage missing causes of deaths. RESULTS: Out of the 1145 registered homeless deaths, 693 were matched to the causes of death database. Homeless deaths were young (average age: 49). Overall, homeless deaths were slightly more frequent during winter. Among all deaths, the probability of being homeless was higher when dying from hypothermia (RR = 6.4), alcohol-related deaths (RR = 1.7), mental disorders, diseases of the digestive and circulatory systems, and undetermined causes (RR from 1.5 to 3.7). CONCLUSION: The homeless died at 49 years old on average compared with 77 in the general population in 2008-10. The health of homeless people should be considered not only in winter periods or in terms of alcohol- or cold-related conditions. This study also highlights the need for more precise data to estimate the mortality risks of the homeless in France.

Estimating the number of homeless deaths in France, 2008-2010.

BACKGROUND: The homeless population of France has increased by 50% over the last 10 years. Studies have shown that homelessness is associated with a high risk of premature death. The aim of this study was to estimate the number of homeless deaths in France between 2008 and 2010, using a reproducible method. METHODS: We used the capture-recapture method to estimate the number of homeless deaths in France using two independent sources. An associative register of homeless deaths was matched with the national exhaustive database of the medical causes of death, using several matching approaches based on various combinations of the following variables: gender, age, place of death, date of death. RESULTS: The estimated number of homeless deaths between 2008 and 2010 was 6730 (95% CI: [4381-9079]), a number greatly underestimated by the two sources considered separately (less than 20%). CONCLUSIONS: In the absence of a register of the homeless deaths, the capture-recapture method provides an order of magnitude for evaluation of the resources that may be allocated by policy makers to manage the issue. Based on common and routinely produced databases, this estimate may therefore be used to monitor the mortality of the homeless population. Further studies about homeless mortality, particularly on the lead causes of deaths, are needed to manage this issue and to implement strategy to decrease the number of homeless deaths.

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.

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.

Quality comparison of electronic versus paper death certificates in France, 2010.

BACKGROUND: Electronic death certification was established in France in 2007. A methodology based on intrinsic characteristics of death certificates was designed to compare the quality of electronic versus paper death certificates. METHODS: All death certificates from the 2010 French mortality database were included. Three specific quality indicators were considered: (i) amount of information, measured by the number of causes of death coded on the death certificate; (ii) intrinsic consistency, explored by application of the International Classification of Disease (ICD) General Principle, using an international automatic coding system (Iris); (iii) imprecision, measured by proportion of death certificates where the selected underlying cause of death was imprecise. Multivariate models were considered: a truncated Poisson model for indicator (i) and binomial models for indicators (ii) and (iii). Adjustment variables were age, gender, and cause, place, and region of death. RESULTS: 533,977death certificates were analyzed. After adjustment, electronic death certificates contained 19% [17%-20%] more codes than paper death certificates for people deceased under 65 years, and 12% [11%-13%] more codes for people deceased over 65 years. Regarding deceased under and over 65 respectively, the ICD General Principle could be applied 2% [0%-4%] and 6% [5%-7%] more to electronic than to paper death certificates. The proportion of imprecise death certificates was 51% [46%-56%] lower for electronic than for paper death certificates. CONCLUSION: The method proposed to evaluate the quality of death certificates is easily reproducible in countries using an automatic coding system. According to our criteria, electronic death certificates are better completed than paper death certificates. The transition to electronic death certificates is positive in many aspects and should be promoted.

Impact of the 1998 football World Cup on suicide rates in France: results from the national death registry.

Our objective was to determine whether the Fédération Internationale de Football Association (FIFA) World Cup in 1998 had a short-term impact on the number of suicides in France. Exhaustive individual daily data on suicides from 1979 to 2006 were obtained from the French epidemiological center on the medical causes of death (CepiDC-INSERM; France). These data were analyzed using the seasonal ARIMA model. The overall effect of the World Cup was tested together with potential specific impact on days following the French team games. Between 11th June and 11th July, a significant decline of 95 suicides was observed (-10.3%), this effect being the strongest among men and people aged between 30 and 44. A significant decrease was also observed for the days following French team games (-19.9%). Our results are in favor of an effect of nationwide sport events on suicidal behaviors and are consistent with other studies. Many of the theories explaining the relationship between sports and suicide are related to sense of belongingness and social integration, highlighting the importance of social link reinforcement in suicide prevention.

Trends in death attributed to heart failure over the past two decades in Europe.

AIMS: Little is known regarding temporal trends in mortality attributed to heart failure (HF) from a population perspective. The aim of this study was to assess the mortality related to HF as an underlying cause during the last 20 years in seven European countries. METHODS AND RESULTS: The number of deaths with HF as the underlying cause was collected in seven European states: Germany, Greece, England and Wales, Spain, France, Finland, and Sweden from 1987 to 2008. Disease coding for HF was based on the International Classification of Diseases (ICD 9th and 10th versions). We computed age-standardized death rates (SDRs) per 100 000 inhabitants. Mean age at death from HF was also calculated for the same period. In the seven studied countries, the HF SDR decreased continuously from 54.2 (1987) to 32.6 (2008). Despite differences in the early 1990s, SDRs related to HF seemed to converge, in these seven European countries, to ∼30 deaths per 100 000 population in the near future, for both men and women. During the study period, the mean age at death increased from 80.0 to 82.7 years. Half of the deaths from HF occurred in hospital, without change over time. CONCLUSION: There has been a 40% reduction of the SDR due to HF in seven European countries during two decades and a concomitant increase in the mean age at death from HF. We hypothesize that these results may be related to a better management of chronic and acute HF patients over the past 20 years.

Can mortality data provide reliable indicators for Creutzfeldt-Jakob disease surveillance? A study in France from 2000 to 2008.

BACKGROUND: Surveillance of Creutzfeldt-Jakob disease (CJD) is still an important issue because of the variant CJD epidemic, which is in decline and also because of the emergence of novel forms of animal transmissible spongiform encephalopathy with zoonotic potential and the risk of nosocomial and blood transfusion-related transmission. Active surveillance has been implemented in most European countries and requires important human resources and funding. Here, we studied whether national mortality and morbidity statistics can be used as reliable indicators. METHODS: CJD data collected by the French national CJD surveillance centre were compared with data registered in the national mortality statistics. RESULTS: From 2000 to 2008, the two sources reported fairly similar numbers of CJD deaths. However, analysis of individual data showed important between-sources disagreement. Nearly 24% of CJD reported by the mortality register were false-positive diagnoses and 21.6% of the CJD cases diagnosed by the surveillance centre were not registered as CJD in the national mortality statistics. One out of 22 variant CJD cases was not reported as having any type of CJD in the mortality statistics. CONCLUSIONS: These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data.

Cause-specific mortality time series analysis: a general method to detect and correct for abrupt data production changes.

BACKGROUND: Monitoring the time course of mortality by cause is a key public health issue. However, several mortality data production changes may affect cause-specific time trends, thus altering the interpretation. This paper proposes a statistical method that detects abrupt changes ("jumps") and estimates correction factors that may be used for further analysis. METHODS: The method was applied to a subset of the AMIEHS (Avoidable Mortality in the European Union, toward better Indicators for the Effectiveness of Health Systems) project mortality database and considered for six European countries and 13 selected causes of deaths. For each country and cause of death, an automated jump detection method called Polydect was applied to the log mortality rate time series. The plausibility of a data production change associated with each detected jump was evaluated through literature search or feedback obtained from the national data producers.For each plausible jump position, the statistical significance of the between-age and between-gender jump amplitude heterogeneity was evaluated by means of a generalized additive regression model, and correction factors were deduced from the results. RESULTS: Forty-nine jumps were detected by the Polydect method from 1970 to 2005. Most of the detected jumps were found to be plausible. The age- and gender-specific amplitudes of the jumps were estimated when they were statistically heterogeneous, and they showed greater by-age heterogeneity than by-gender heterogeneity. CONCLUSION: The method presented in this paper was successfully applied to a large set of causes of death and countries. The method appears to be an alternative to bridge coding methods when the latter are not systematically implemented because they are time- and resource-consuming.

Changing mortality for motor neuron disease in France (1968-2007): an age-period-cohort analysis.

The incidence and mortality of motor neuron disease (MND) increase with age and appear to have increased with time. The examination of period and cohort effects using age-period-cohort (APC) models can help characterize temporal trends. Our objective was to describe mortality from MND in France (1968-2007), and to examine the role of age, period of death, and birth-cohort on changes in mortality. The number of people who died from MND and population statistics (1968-2007) were extracted from French national records. Annual standardized (age/sex) mortality ratios (SMRs) were computed. Using Poisson regression, APC models examined the relationship between mortality rates and age, period of death, and birth-cohort in subjects aged 40-89 years. Deviance/degrees-of-freedom ratios evaluated model fit; ratios close to one indicated adequate fit. Between 1968 and 2007, 38,863 individuals died from MND (mortality rate = 1.74/100,000); 37,624 were aged 40-89 years. SMRs increased from 54 (95% CI = 49-59) in 1968 to 126 (120-132) in 2007. Male-to-female ratios declined from 1.80 in 1968 to 1.45 in 2007. Changing mortality rates were best explained by cohort effects (deviance/degrees-of-freedom = 1.09). The relative risk of dying from MND increased markedly for persons born between 1880 and 1920, and more slowly after 1920. In conclusion, mortality rates for MND increased between 1968 and 2007, and more rapidly in women than men. This increase was better explained by the birth-cohort of individuals than by period effects. Changing environmental exposures may be a possible explanation and these findings warrant the continued search for environmental risk factors for MND.

Time trends in hospital-referred stroke and transient ischemic attack: results of a 7-year nationwide survey in France.

BACKGROUND: Nationwide evaluations of the burden of stroke are scarce. We aimed to evaluate trends in stroke and transient ischemic attack (TIA) hospitalization, in-hospital case fatality rates (CFRs) and mortality rates in France during 2000-2006. METHODS: Hospitalizations for stroke and TIA were determined from National Hospital Discharge Diagnosis Records that used the International Classification of Disease, 10th revision, codes I60, I61, I63, I64, G45, G46. CFRs and mortality rates were estimated from the national death certificates database. RESULTS: The total number of stays for stroke increased between 2000 and 2006 (88,371 vs. 92,118) contrasting with a decrease in that for TIA. The age-standardized (European population) hospitalization rates for TIA decreased in men (52.2 vs. 44.5/100,000/year, p = 0.002), whereas they remained stable in women (32.4 vs. 31.0/ 100,000/year). Concerning stroke, a decrease in hospitalization rates was observed in both men (from 135.3 to 123.4/ 100,000/year, p < 0.001) and women (from 85.1 to 80.7, p < 0.001). Whatever the age group and the sex, a sharp decrease in in-hospital stroke CFRs was noted. In addition, a 23% decrease in mortality rates was observed. This decrease was greater in patients >65 years. CONCLUSION: Our results demonstrate a decline in hospitalization rates for stroke, and in both stroke CFRs and mortality rates between 2000 and 2006. Improvements in stroke prevention and acute stroke care may have contributed to these results, and may have been initiated by recent advances in health policy with regard to this disease in France.

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.

Suboptimal care in the initial management of children who died from severe bacterial infection: a population-based confidential inquiry.

OBJECTIVES: To study the frequency and types of suboptimal care and medical errors in children who died of severe bacterial infection as the first-stage procedure intended to improve quality of care. DESIGN: Population-based confidential inquiry. SETTING: Two adjoining administrative districts in France. PATIENTS: Children older than 3 months dead from severe bacterial infection from 2000 through 2006. INTERVENTIONS: The medical files were summarized on standardized forms and then evaluated independently by two experts, who determined whether the initial management before the patients' arrival in intensive care was or was not optimal, in comparison with current guidelines. MEASUREMENTS AND MAIN RESULTS: Of 23 deaths from severe bacterial infection, 21 could be analyzed; management was considered suboptimal in 76%. The coefficient of agreement between the experts was high, with a weighted kappa of 0.73. The types of errors identified included parental delay in seeking medical care (33%; 95% confidence interval, [12-54]), physicians' delay in administering appropriate treatment (antibiotic therapy in the case of purpura; 38%; 95% confidence interval, 16-60), insufficient doses of or failure to repeat fluid resuscitation (24%; 95% confidence interval, [9 -35]), and overall underestimation of disease severity (38%; 95% confidence interval, [16-60]). CONCLUSION: This study found a high frequency of suboptimal care in the initial management of children who died of severe bacterial infection, with four separate types of errors. Other studies are needed to assess the potential avoidability of this type of death.

HIV-specific regulatory T cells are associated with higher CD4 cell counts in primary infection.

OBJECTIVE: Expansion of regulatory T (Treg) cells has been described in chronically HIV-infected individuals. We investigated whether HIV-suppressive Treg could be detected during primary HIV infection (PHI). METHODS: Seventeen patients diagnosed early after PHI (median: 13 days; 1-55) were studied. Median CD4 cell count was 480 cells/microl (33-1306) and plasma HIV RNA levels ranged between 3.3 and 5.7 log10 copies/ml. Suppressive capacity of blood purified CD4CD25 was evaluated in a coculture assay. Fox-p3, IL-2 and IL-10 were quantified by reverse transcriptase (RT)-PCR and intracellular staining of ex vivo and activated CD4+CD25 T cells. RESULTS: The frequency of CD4CD127CD25 T cells among CD4 T cells was lower in patients with PHI compared with chronic patients (n = 19). They exhibited a phenotype of memory T cells and expressed constitutively FoxP3. Similar to chronic patients, Treg from patients with PHI inhibited the proliferation of purified tuberculin (PPD) and HIV p24 activated CD4CD25 T cells. CD4CD25 T cells from patients with PHI responded specifically to p24 stimulation by expressing IL-10. In untreated patients with PHI, the frequency as well as HIV-specific activity of Treg decreased during a 24-month follow-up. A positive correlation between percentages of Treg and both CD4 cell counts and the magnitude of p24-specific suppressive activity at diagnosis of PHI was found. CONCLUSION: Our data showed that HIV drives Treg, as PHI and these cells persist throughout the course of the infection. A correlation between the frequency of Treg and CD4 T-cell counts suggest that these cells may impact on the immune activation set point at PHI diagnosis.

Defective dendritic cell function in HIV-infected patients receiving effective highly active antiretroviral therapy: neutralization of IL-10 production and depletion of CD4+CD25+ T cells restore high levels of HIV-specific CD4+ T cell responses induced by dendritic cells generated in the presence of IFN-alpha.

We previously demonstrated that GM-CSF/IFN-alpha combination allowed the differentiation of monocytes from HIV-infected patients into dendritic cells (DCs) exhibiting high CD8(+) T cell stimulating abilities. The present study was aimed at characterizing the ability of DCs generated in the presence of GM-CSF and IFN-alpha to induce CD4 T cell responses. DCs were generated from monocytes of HIV-infected patients in the presence of GM-CSF with either IFN-alpha (IFN-DCs) or IL-4 (IL-4-DCs) for 7 days. Eleven patients receiving highly active antiretroviral therapy and exhibiting CD4 cell counts above 400/mm(3) and plasma HIV-RNA <50 copies/ml for at least 1 year were included in the study. Both DC populations were found to be defective in inducing autologous (in response to tuberculin or HIV-p24) or allogeneic CD4 T cell proliferation. Neutralization of IL-10 during the differentiation of IFN-DCs, but not during the DC-T cell coculture, significantly increased their ability to stimulate autologous CD4 T cell proliferation in response to tuberculin and allogeneic CD4 T cell proliferation (4.1-fold and 3.0-fold increases, respectively, at the DC to T cell ratio of 1:10). Moreover, IL-10 neutralization and CD4(+)CD25(+) T cell depletion synergistically act to dramatically increase HIV-p24-specific CD4 T cell responses induced by IFN-DCs (31.7-fold increase) but not responses induced by IL-4-DCs. Taken together, our results indicate that IFN-DCs are more efficient than IL-4-DCs to stimulate CD4(+) T cell proliferation, further supporting their use for immune-based therapy in HIV infection.

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.