Interest of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography for the diagnosis of relapse in patients with spinal infection: a prospective study.

Relapse after treatment of a spinal infection is infrequent and difficult to diagnose. The aim of this study was to assess the diagnostic performance of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in this setting. Thirty patients (21 men, nine women; median age 61.2 years) with a suspected spinal infection relapse were prospectively included between March 2010 and June 2013. The initial diagnosis of spinal infection was confirmed by positive bacterial cultures. The patients underwent [(18)F]FDG PET/CT and magnetic resonance imaging (MRI) 1 month after antibiotic treatment interruption. PET/CT data were interpreted both visually and semi-quantitatively (SUVmax). The patients were followed for ≥12 months and the final diagnosis of relapse was based on new microbiological cultures. Seven patients relapsed during follow up. Sensitivity, specificity, positive predictive value and negative predictive value were 66.6%, 61.9%, 33.3% and 86.6%, respectively for MRI and 85.7, 82.6, 60.0 and 95.0 for PET/CT. Although these values were higher for PET/CT than for MRI, the difference was not statistically significant (p=0.3). [(18)F]FDG PET/CT may be useful for diagnosing a relapse of spinal infections, in particular if metallic implants limit the performance of MRI.

The incidence of AIDS-defining illnesses at a current CD4 count ≥ 200 cells/µL in the post-combination antiretroviral therapy era.

BACKGROUND: Few studies consider the incidence of individual AIDS-defining illnesses (ADIs) at higher CD4 counts, relevant on a population level for monitoring and resource allocation. METHODS: Individuals from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) aged ≥14 years with ≥1 CD4 count of ≥200 µL between 1998 and 2010 were included. Incidence rates (per 1000 person-years of follow-up [PYFU]) were calculated for each ADI within different CD4 strata; Poisson regression, using generalized estimating equations and robust standard errors, was used to model rates of ADIs with current CD4 ≥500/µL. RESULTS: A total of 12 135 ADIs occurred at a CD4 count of ≥200 cells/µL among 207 539 persons with 1 154 803 PYFU. Incidence rates declined from 20.5 per 1000 PYFU (95% confidence interval [CI], 20.0-21.1 per 1000 PYFU) with current CD4 200-349 cells/µL to 4.1 per 1000 PYFU (95% CI, 3.6-4.6 per 1000 PYFU) with current CD4 ≥ 1000 cells/µL. Persons with a current CD4 of 500-749 cells/µL had a significantly higher rate of ADIs (adjusted incidence rate ratio [aIRR], 1.20; 95% CI, 1.10-1.32), whereas those with a current CD4 of ≥1000 cells/µL had a similar rate (aIRR, 0.92; 95% CI, .79-1.07), compared to a current CD4 of 750-999 cells/µL. Results were consistent in persons with high or low viral load. Findings were stronger for malignant ADIs (aIRR, 1.52; 95% CI, 1.25-1.86) than for nonmalignant ADIs (aIRR, 1.12; 95% CI, 1.01-1.25), comparing persons with a current CD4 of 500-749 cells/µL to 750-999 cells/µL. DISCUSSION: The incidence of ADIs was higher in individuals with a current CD4 count of 500-749 cells/µL compared to those with a CD4 count of 750-999 cells/µL, but did not decrease further at higher CD4 counts. Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/µL.

Menopause and HIV infection: age at onset and associated factors, ANRS CO3 Aquitaine cohort.

The aim of the paper is to describe the characteristics of postmenopausal HIV-infected women and to investigate the factors associated with an earlier onset of menopause in a hospital-based cohort. Information was collected using a self-administered questionnaire. A Cox model was used to determine factors associated with menopause. Among the 404 women who completed the questionnaire, 69 were naturally postmenopausal at the time of the study (median age at onset: 49 years, premature menopause <40 years: 12%). The onset of menopause was studied among the 41 women still menstruating at the enrollment in the cohort, and who experienced menopause during follow-up. African origin (hazard ratio [HR] = 8.16; 95% confidence interval [CI] = 2.23-29.89) and history of injecting drug use (IDU) (HR = 2.46; 95% CI = 1.03-5.85) were associated with an increased risk of earlier menopause. Women with a CD4 cell count <200 cells/mm(3) tended to reach menopause earlier (HR = 2.25; 95% CI = 0.94-5.39). Earlier occurrence of menopause seems to be associated with factors already reported in HIV-negative women (IDU, ethnicity) and with HIV-related immunodeficiency.

Prevalence and factors associated with renal impairment in HIV-infected patients, ANRS C03 Aquitaine Cohort, France.

OBJECTIVES: The aims of the present study were to estimate the prevalence of renal impairment (RI) among HIV-infected adult patients and to investigate the associated factors. METHODS: A cross-sectional survey was conducted in a French hospital-based cohort. Clearance of creatinine (CC) was calculated using the Cockcroft-Gault formula. Four stages of RI were defined: mild (60-90 mL/min), moderate (30-60), severe (15-30) and end stage (<15). Logistic regression models were used to investigate factors associated with RI. RESULTS: The male/female ratio of the 2588 patients enrolled was 3:1 and the median age was 42 years. At the time of assessment of CC, the median CD4 count was 430 cells/microL and HIV plasma viral load (VL) was<50 copies/mL in 60%. The overall prevalence of RI was 39.0%: 34.2% mild, 4.4% moderate, 0.3% severe and 0.2% end-stage. Mild RI was associated with female gender [odds ratio (OR)=3.3: 95% CI 2.6-4.3)], age >50 years (OR=9.8: 7.4-13.0) and 40-50 years (OR=1.9: 1.5-2.4), body mass index (BMI) <22 kg/m(2) (OR=3.3: 2.7-4.3) and tenofovir exposure (OR=1.4: 1.0-1.9 for <1 year and OR=1.5: 1.2-2.0 for >1 year). Advanced RI (CC <60 mL/min) was associated with age >50 years (OR=5.6: 2.9-10.9) and 40-50 years (OR=2.2: 1.1-1.4), BMI <22 kg/m(2) (OR=1.5: 1.0-2.4), hypertension (OR=2.5: 1.4-2.5) and indinavir (IDV) exposure >1 year (OR=2.3: 1.5-3.6). CONCLUSION: This survey confirms the high prevalence of RI in HIV-infected patients and indicates the importance of the investigation of renal function especially in women, older patients, those with a low BMI or treated with tenofovir or IDV.

Trends and determinants of severe morbidity in HIV-infected patients: the ANRS CO3 Aquitaine Cohort, 2000-2004.

OBJECTIVE: The aim of the study was to characterize the causes, trends and determinants of severe morbidity in a large cohort of HIV-infected patients between 2000 and 2004. METHOD: Severe morbid events were defined as medical events associated with hospitalization or death. Epidemiological and biological data were recorded at the time of the morbid event. Trends were estimated using Poisson regression. RESULTS: Among 3863 individuals followed between 2000 and 2004, 1186 experienced one or more severe events, resulting in 1854 hospitalizations or deaths. The severe events recorded included bacterial infections (21%), AIDS events (20%), psychiatric events (10%), cardiovascular events (9%), digestive events including cirrhosis (7%), viral infections (6%) and non-AIDS cancers (5%). Between 2000 and 2004, the incidence rate of AIDS events decreased from 60 to 20 per 1000 person-years, that of bacterial infections decreased from 45 to 24 per 1000 person-years, and that of psychiatric events decreased from 26 to 14 per 1000 person-years (all P<0.01), whereas the incidences of cardiovascular events and of non-AIDS cancers remained stable at 14 and 10 per 1000 person-years, on average, respectively. CONCLUSION: Severe morbidity has shifted from AIDS-related to non-AIDS-related events during the course of HIV infection in developed countries. Limiting endpoints to AIDS events and death is insufficient to describe HIV disease progression in the era of combination antiretroviral therapy.

Carotid intima-media thickness is slightly increased over time in HIV-1-infected patients.

OBJECTIVES: HIV-infected patients are at risk of atherosclerosis and cardiovascular diseases. In a 12-month follow-up study, we aimed to investigate changes in carotid intima-media thickness (IMT), a surrogate marker of atherosclerosis, and its determinants in HIV-1-infected patients. METHODS: Our multicentre prospective longitudinal cohort study included 346 HIV-infected patients, for each of whom two IMT measurements were taken by B-mode ultrasonography at baseline (M0) and 1 year later (M12). RESULTS: We observed a significant but moderate increase in the common carotid artery (CCA) median IMT, from 0.54 to 0.56 mm (P<10(-4)), i.e. an increase of 0.020 mm (95% confidence interval 0.012-0.029). There was a significant association between cross-sectional CCA IMT measures at M12 and conventional cardiovascular risk factors (higher CCA IMT with older age, P<10(-4); male gender, P=0.02; tobacco consumption, P=0.05), as well as higher CD4 cell count at M12 (>median 455 cells/microL, P=0.01). Only CD4 cell count at M0 was strongly and positively associated with the variation in IMT between M0 and M12 (P=4 x 10(-3)). IMT progression was +0.0020 mm for the lowest quartile of CD4 cell count distribution at M0, i.e. 3-253 cells/microL, +0.010 mm for 253-402 cells/microL, +0.043 mm for 402-590 cells/microL, and +0.028 mm for 590-2270 cells/microL. No association was found with type or duration of antiretroviral exposure. CONCLUSIONS: Conventional cardiovascular risk factors are major determinants of IMT evolution. The link between immunological status and carotid IMT requires further study.

Symptomatic bone disorders in HIV-infected patients: incidence in the Aquitaine cohort (1999-2002).

BACKGROUND: Since the inception of highly active antiretroviral therapy (HAART), mortality among HIV-infected patients has decreased, but this has been accompanied by the appearance of several complications. OBJECTIVES: To estimate the incidence of symptomatic bone disorders in HIV-infected patients of the Aquitaine cohort (from south-west France) for the period 1999-2002, and to describe cases. METHODS: We retrospectively studied the records of 2700 patients of the Aquitaine cohort, which was derived from a hospital-based surveillance system of HIV infection in France. All cases of symptomatic bone disorders diagnosed from 1 January 1999 to 30 June 2002 were reviewed. RESULTS: Fourteen cases of bone disorders were diagnosed, eight cases of aseptic osteonecrosis and six cases of severe osteoporosis, representing incidences of 0.3/1000 patient-years [95% confidence interval (CI): 0.14-0.62] and 0.22/1000 patient-years (95% CI: 0.09-0.52), respectively. All patients with aseptic osteonecrosis were male, while all but one with osteoporosis were female. The ages of patients ranged from 36 to 54 years for osteonecrosis and from 39 to 50 for severe osteoporosis. At the time of clinical diagnosis, all patients were treated with nucleoside reverse transcriptase inhibitors (duration of treatment ranging from 19 to 123 months for osteonecrosis and from 46 to 132 months for severe osteoporosis). Ten patients were treated with nonnucleoside reverse transcriptase inhibitors [duration of treatment ranging from 6 to 31 months for osteonecrosis (n=6) and from 4 to 29 months for severe osteoporosis (n=4)]. Thirteen patients were treated with protease inhibitors [duration of treatment ranging from 12 to 62 months for osteonecrosis (n=8) and from 3 to 44 months for severe osteoporosis (n=5)]. All osteonecrosis and five osteoporosis patients had at least one known risk factor or comorbidity associated with the bone disorder occurrence. CONCLUSIONS: In our study, the aetiology of clinical bone disorders seemed to be multifactorial, as almost all the patients had at least one possible risk factor in addition to HAART exposure.

A cohort study of nevirapine tolerance in clinical practice: French Aquitaine Cohort, 1997-1999.

We performed a retrospective study to evaluate, under routine circumstances, the tolerance and immunovirological changes associated with antiretroviral regimens that contain nevirapine in 137 patients (88% were antiretroviral experienced). During a mean follow-up of 11 months, 33% of patients reported side effects attributed to nevirapine, and 21% discontinued treatment because of poor tolerance. Administration of antihistamines or corticosteroids at the initiation of treatment was not protective against adverse events (relative risk, 0.82; 95% confidence interval, 0.49-1.38). The proportion of patients with hepatitis C virus (HCV) and/or hepatitis B virus (HBV) coinfection who had alanine aminotransferase levels of >100 IU/L increased from 19.4% at baseline to 42.9% at month 12 of follow-up (P=.02). We noticed a significant increase of the proportion of patients with total cholesterol levels of >5.5 mM (P=.02). We have shown that there is a high level of discontinuation of nevirapine therapy in clinical practice and that side effects were not prevented by administration of antihistamines or corticosteroids. Coinfection with HCV or HBV increased the risk of hepatotoxicity, which lead to the cautious use of nevirapine for such patients.

[Cost-benefit analysis of screening strategies by human immunodeficiency virus in French blood donors]. / Analyse coût-efficacité des stratégies de dépistage de l'infection par le virus de l'immunodéficience humaine sur les dons de sang en France.

BACKGROUND: The residual risk of human immunodeficiency virus (HIV) infection from screened blood transfusion was estimated to be 1.7/10(6) between 1993 and 1995 in France. To orient blood safety policies, we have evaluated what would be, from the perspective of blood banks, the best screening strategy in terms of gain in effectiveness and added costs. METHODS: A cost-effectiveness analysis compared 20 HIV-testing protocols using (1) available data for performances of the current screening tests; and, (2) national insurance estimates for the cost of tests. Results were expressed as the number of false negative donations that would be avoided and the cost by avoided false negative donation. RESULTS: For 3 million donated blood units a year and a prevalence of 24 per million, there would be 72 infectious donated blood units, 70.56 of which would be detected by the current screening strategy. The number of additional donated blood infections avoided in all other strategies would be low (between 0.25 and 1.28) with a very high cost (280 million French francs per added false negative avoided or more). CONCLUSION: A change in screening strategies for blood donations in France is not currently justified. If such a change was to be done, adding p24 antigen detection to the current screening strategy would be one of the worst solutions.

Epidemiology of blood collection in France.

The objectives of the cross-sectional study (EpiCoS) were to describe, at different stages, volunteers offering their blood, and to characterize various ways of collecting blood. From 15 September 1996 to 31 December 1996, individuals presenting at fixed or mobile sessions in one of 11 randomly selected blood banks were included after they had a medical examination. Variables studied were relative to type of collection, individuals, medical examination, patterns of blood letting, use of collected donations and if unused, reasons for discarding. Sixty four thousand and ninety two volunteers, aged 17-66 years old were included. The proportion of exclusion during medical examination was 10.8% (95% confidence interval (CI): 10.6-11.0%). Exclusions were more frequent among new volunteers and were mostly related to the safety of recipients. Most of the 57,003 donations were whole blood (94.0%) and collected in mobile sessions (89.9%). Five percent of collected donations were discarded; 3.5% (95% CI: 3.4-3.7%) of donations discarded for biological abnormalities, including 1.5% only for initial screen reactions to infectious disease markers (HBs antigen, anti-HBc antibodies, anti-HCV antibodies, anti-HIV antibodies, anti-HTLV antibodies, malaria antibodies and anti-syphilitic antibodies). The most frequent biological abnormality was a high alanine aminotransferase level. A follow-up of these indicators, within the French haemovigilance system, should allow further identification of risk factors and high-risk contexts, and planning means of optimizing blood collection in France.

[Screening and early detection in blood transfusion: when are they indicated?]. / Dépistage et détection précoce en transfusion sanguine: quand sont-ils indiqués?

Screening is proposed to allow an early intervention concerning a diseased individual, but its public health consequences are seldom considered. We propose criteria to judge whether a screening program can be associated to a benefit to patients or society. These criteria refer to the magnitude of disease, the characteristics of the pre-clinical stage, the availability of reliable and valid tests, the effectiveness and risk for all individuals, whether they are diseased or not, and acceptability to the health-care system and to individuals. We illustrate the application of these criteria to screening of human immunodeficiency virus among blood donors, hepatitis among recipients of labile blood products, and bacterial contaminations among febrile recipients. These criteria should be considered in decision analyses including alternatives to screening and all aspects of safety regarding patients and population.

[Infection risk and efficacy of clinical selection techniques for volunteer blood donors]. / Risque infectieux et efficacité des techniques de sélection clinique des volontaires au don du sang.

One of the objectives of predonation selection is to exclude blood donors with possible infection. Our aim was to evaluate the efficacy of the different blood donor selection techniques. The approach chosen for this review of literature was the best evidence synthesis. A bibliographic search was carried out to identify all articles on the subject published between 1986 and 1996 which presented quantitative results of evaluation. Only nine relevant studies were selected. These referred to self exclusion before interview, health history interview and confidential deferral after donation. None of the articles evaluated the physical examination. The results suggested an efficacy for self exclusion before interview. One study considered the blood donor selection and compared various ways of combining self exclusion before interview, health history interview and confidential deferral after donation. No combination emerged as more effective than the others. This analysis shows that the efficacy of predonation blood donor selection applied to transfusion transmitted infections has not been evaluated adequately. The different techniques of blood donor selection must be considered as public health actions and hence evaluated according to a rigorous methodology using valid criteria.

[Fresh frozen plasma: a pilot study of the context of utilization and the indications]. / Plasma frais congelé: étude pilote du contexte d'utilisation et des indications.

The aim of this pilot study was to assess the feasibility of a tolerance study of qualified (secured by quarantine or solvent-detergent-treated) fresh frozen plasma (FFP) in real conditions of use. We included all patients receiving qualified FFP during a one-month observation period in three french hospitals (Besançon, Brest, Lyon). The 192 FFP transfusion episodes corresponded to 111 patients. Only two thirds of all prescriptions corresponded to indications mentioned in the ministerial order of december 1991. Forty-two episodes consisted of FFP only; in the 150 remaining episodes, at least one product (mostly labile blood products) had been injected within 24 hours before or after the plasma injection. The free interval between FFP transfusion and the nearest associated product was usually less than three hours. Only one side effect was notified. This pilot study points out the difficulties of a tolerance study of qualified FFP in real conditions of use. It also raises the necessity to clarify current indications of FFP.

[Transfusion risks: importance of blood surveillance]. / Les risques transfusionnels: intérêt d'une hémovigilance.

Transfusion risks result from the transfusion chain complexity and are due to human errors and limits of screening technics. Causes, mechanisms and manifestations of the main risks are mostly well known. Transfusion risks can be related to the donor, the blood donation or the transfusion act. The mechanisms are immediate or delayed. Environment can be a favorable factor. In France, rates of transfusion risks and the part of risk attributable to the environment are not known with accuracy because of the absence of a mandatory reporting system. The assessment of the existing prevention policies, essential for envisaging new actions, lacks rigour. The setting of means assessment and follow-up of transfusion safety as it was mentioned by the Comity of transfusion safety follow-up (L. Degos, A. Goudeau, R. Salamon) in november 1991, and in the law no. 93-5 of january 4, 1993 would allow the improvement of epidemiologic features of blood donation, blood use and transfusion risks.

[Evaluation of risks related to blood transfusions in industrialized countries]. / Evaluation des risques liés aux transfusions sanguines dans les pays industrialisés.

Although numerous progresses have been accomplished, transfusion of labile blood products still has side effects. Transfusion-associated risks are related to the complex environment of the transfusion chain which goes from volunteers for blood collection to receivers of products. Severe hemolytic accidents remain very worrying and neglected problems. Risks related to products are mostly infectious; hepatitis C has become the major infectious risk, even if contaminations linked to the serological window of HIV are still worrying. Measurement of residual risks can be done a priori, by modeling existing data, or a posteriori, by epidemiological studies. The issue of new risks, related to the diffusion of new products, or to unconventional infectious agents, underscores the importance of setting up a blood transfusion surveillance mechanism.