Efficacy and safety of methylprednisolone pulse followed by oral prednisone vs. oral prednisone alone in sarcoidosis tubulointerstitial nephritis: a randomized, open-label, controlled clinical trial.

BACKGROUND: We determine the benefit of pulsed methylprednisolone for improving kidney function in patients with sarcoidosis tubulointerstitial nephritis. METHODS: We conducted a multicenter, prospective, randomized, open-label, controlled trial in patients with biopsy-proven acute tubulointerstitial nephritis caused by sarcoidosis at 21 sites in France. Patients were randomly assigned to receive a methylprednisolone pulse 15 mg/kg/day for 3 days, then oral prednisone (MP group) or oral prednisone 1 mg/kg/day alone (PRD group). The primary end point was a positive response at 3 months, defined as a doubling of estimated glomerular filtration rate (eGFR) compared with the eGFR before randomization. RESULTS: We randomized 40 participants. Baseline eGFR before PRD was 22 mL/min/1.73m2 {interquartile range [IQR], 16-44} and before MP was 25 mL/min/1.73m2 (IQR, 22-36) (P = .3). The two groups did not differ in underlying pathological lesions, including mean percentage of interstitial fibrosis and intensity of interstitial infiltrate. In the intent-to-treat population, the median eGFR at 3 months did not significantly differ between the PRD and MP groups: 45 (IQR, 34-74) and 46 (IQR, 39-65) mL/min/1.73m2. The primary end point at 3 months was achieved in 16 of 20 (80%) PRD patients and 10 of 20 (50%) MP patients (P = .0467). The eGFR was similar between the two groups after 1, 3, 6, and 12 months of treatment. For both groups, eGFR at 1 month was strongly correlated with eGFR at 12 months (P < .0001). The two groups did not differ in severe adverse events. CONCLUSION: Compared with a standard oral steroid regimen, intravenous MP may have no supplemental benefit for renal function in patients with tubulointerstitial nephritis caused by sarcoidosis.Trial Registration: ClinicalTrials.gov: NCT01652417; EudraCT: 2012-000149-11.

Household transmission and incidence of positive SARS-CoV-2 RT-PCR in symptomatic healthcare workers, clinical course and outcome: a French hospital experience.

OBJECTIVES: Although healthcare workers (HCWs) have been particularly affected by SARS-CoV-2, detailed data remain scarce. In this study, we investigated infection rates, clinical characteristics, occupational exposure and household transmission among all symptomatic HCWs screened by SARS-CoV-2 RT-PCR between 17 March (French lockdown) and 20 April. METHODS: SARS-CoV-2 RT-PCR was proposed to symptomatic (new cough or dyspnoea) HCWs at Creteil Hospital in one of the Parisian suburbs most severely affected by COVID-19. Data on occupational profile, living situation and household, together with self-isolation and mask use at home were collected, as well as the number of cases in the household. RESULTS: The incidence rate of symptomatic SARS-CoV-2 was estimated to be 5% (110/2188). A total of 110 (35%) of the 314 HCWs tested positive and 9 (8%) were hospitalised. On multivariate analysis, factors independently associated with positive RT-PCR were occupational profile with direct patient facing (OR 3.1, 95% CI 1.1 to 8.8), p<0.03), and presence of anosmia (OR 5.7, 95% CI 3.1 to 10.6), p<0.0001). Being a current smoker was associated with negative RT-PCR (OR 0.3, 95% CI 0.1 to 0.7), p=0.005). Transmission from HCWs to household members was reported in 9 (14%) cases, and 2 deaths occurred. Overall, self-isolation was possible in 52% of cases, but only 31% of HCWs were able to wear a mask at home. CONCLUSION: This is the first study to report infection rates among HCWs during the peak of the SARS-CoV-2 epidemic in France and the lockdown period, highlighting the risk related to occupational profile and household transmission.

Cascade of care for migrants tested Hepatitis C antibodies positive in France through a systematic screening programme: The PRECAVIR study.

Migration of people from HCV endemic countries is a public health issue for the French healthcare system. The PRECAVIR study focused on migrant patients and provides a multidisciplinary, patient-centred approach to treat chronic HCV-infected migrants through a systematic screening programme. Between 2007 and 2017, 101 (2.98%) out of 3386 consecutive adult migrants attending two primary healthcare settings in Créteil, France, tested positive for HCV. The median age was 44.5 years old, and 55% were women. Patients were mainly from sub-Saharan Africa, Eastern Europe and Asia. Seventy-four patients were undocumented migrants, and 25 were asylum seekers. Eighty-four (83%) patients were unaware of their serological status. All patients were offered referral to a specialist in the same setting. HCV RNA testing was performed in 88 (87%) of the patients who tested anti-HCV positive. Forty-nine (57%) were chronically infected, while 39 (43%) had an undetectable viral load. All patients were treatment-naïve. More than half of patients had access to treatment. Before 2014, thirteen patients were treated with pegylated interferon and ribavirin, and an SVR was achieved in 8 (61.5%) of them. By 2017, 17 patients had begun oral, direct-acting antiviral treatment. An SVR was achieved in 16 of 17 patients (93%). However, all patients not initially eligible for treatment were lost to follow-up. This study showed the effectiveness of a coordinated care network when anti-HCV testing, linkage to care and treatment are organized for a migrant population in the same setting as long as universal treatment makes a test and treat policy possible.

Combined Measurement of Soluble ST2 and Amino-Terminal Pro-B-Type Natriuretic Peptide Provides Early Assessment of Severity in Cardiogenic Shock Complicating Acute Coronary Syndrome.

OBJECTIVES: Mortality in cardiogenic shock complicating acute coronary syndrome is high, and objective risk stratification is needed for rational use of advanced therapies such as mechanical circulatory support. Traditionally, clinical variables have been used to judge risk in cardiogenic shock. The aim of this study was to assess the added value of serial measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide to clinical parameters for risk stratification in cardiogenic shock. DESIGN: CardShock (www.clinicaltrials.gov NCT01374867) is a prospective European multinational study of cardiogenic shock. The main study introduced CardShock risk score, which is calculated from seven clinical variables at baseline, and was associated with short-term mortality. SETTING: Nine tertiary care university hospitals. PATIENTS: Patients with cardiogenic shock caused by acute coronary syndrome (n=145). INTERVENTIONS: In this substudy, plasma samples from the study patients were analyzed at eight time points during the ICU or cardiac care unit stay. Additional prognostic value of the biomarkers was assessed with incremental discrimination improvement. MEASUREMENTS AND MAIN RESULTS: The combination of soluble ST2 and amino-terminal pro-B-type natriuretic peptide showed excellent discrimination for 30-day mortality (area under the curve, 0.77 at 12 hr up to 0.93 at 5-10 d after cardiogenic shock onset). At 12 hours, patients with both biomarkers elevated (soluble ST2, ≥ 500 ng/mL and amino-terminal pro-B-type natriuretic peptide, ≥ 4,500 ng/L) had higher 30-day mortality (79%) compared to those with one or neither biomarkers elevated (31% or 10%, respectively; p < 0.001). Combined measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide at 12 hours added value to CardShock risk score, correctly reclassifying 11% of patients. CONCLUSIONS: The combination of results for soluble ST2 and amino-terminal pro-B-type natriuretic peptide provides early risk assessment beyond clinical variables in patients with acute coronary syndrome-related cardiogenic shock and may help therapeutic decision making in these patients.

CD4 T cell decline following HIV seroconversion in individuals with and without CXCR4-tropic virus.

Background: The natural clinical and immunological courses following HIV seroconversion with CXCR4-tropic or dual-mixed (X4/DM) viruses are controversial. We compared spontaneous immunological outcome in patients harbouring an X4/DM virus at the time of seroconversion with those harbouring a CCR5-tropic (R5) virus. Methods: Data were included from patients participating in CASCADE, a large cohort collaboration of HIV seroconverters, with ≥2 years of follow-up since seroconversion. The HIV envelope gene was sequenced from frozen plasma samples collected at enrolment, and HIV tropism was determined using Geno2Pheno (false-positive rate 10%). The spontaneous CD4 T cell evolution was compared by modelling CD4 kinetics using linear mixed-effects models with random intercept and random slope. Results: A total of 1387 patients were eligible. Median time between seroconversion and enrolment was 1 month (range 0-3). At enrolment, 202 of 1387 (15%) harboured an X4/DM-tropic virus. CD4 decrease slopes were not significantly different according to HIV-1 tropism during the first 30 months after seroconversion. No marked change in these results was found after adjusting for age, year of seroconversion and baseline HIV viral load. Time to antiretroviral treatment initiation was not statistically different between patients harbouring an R5 (20.76 months) and those harbouring an X4/DM-tropic virus (22.86 months, logrank test P = 0.32). Conclusions: In this large cohort collaboration, 15% of the patients harboured an X4/DM virus close to HIV seroconversion. Patients harbouring X4/DM-tropic viruses close to seroconversion did not have an increased risk of disease progression, estimated by the decline in CD4 T cell count or time to combined ART initiation.

A multicentre study of 95 biopsy-proven cases of renal disease in primary Sjögren's syndrome.

OBJECTIVE.: Renal involvement is a rare event during primary SS (pSS). We aimed to describe the clinico-biological and histopathological characteristics of pSS-related nephropathy and its response to treatment. METHODS.: We conducted a French nationwide, retrospective, multicentre study including pSS patients fulfilling American-European Consensus Group criteria or enlarged American-European Consensus Group criteria, and with biopsy-proven renal involvement. RESULTS.: A total of 95 patients were included (median age 49 years). An estimated glomerular filtration rate (eGFR) of <60 ml/min was found in 82/95 patients (86.3%). Renal biopsy demonstrated tubulointerstitial nephritis (TIN) in 93 patients (97.9%), and frequent (75%) plasma cell infiltrates. Glomerular lesions were found in 22 patients (23.2%), mainly related to cryoglobulin. The presence of anti-SSA (76.8%) and anti-SSB (53.8%) antibodies was particularly frequent among patients with TIN and was associated with a worse renal prognosis. Eighty-one patients (85.3%) were treated, with CSs in 80 (98.8%) and immunosuppressive agents (mostly rituximab) in 21 cases (25.9%). Despite marked interstitial fibrosis at initial biopsy, kidney function improved significantly during the 12-month period following diagnosis (final eGFR 49.9 vs 39.8 ml/min/1.73 m 2 at baseline, P < 0.001). No proven benefit of immunosuppressive agents over steroid therapy alone was found in this study. CONCLUSION.: Renal involvement of pSS is mostly due to TIN with marked T, B and especially plasma cell infiltration. Renal dysfunction is usually isolated but can be severe. Use of CSs can improve the eGFR, but further studies are needed to define the best therapeutic strategy in this disease.

Prognostic Accuracy of Sepsis-3 Criteria for In-Hospital Mortality Among Patients With Suspected Infection Presenting to the Emergency Department.

Importance: An international task force recently redefined the concept of sepsis. This task force recommended the use of the quick Sequential Organ Failure Assessment (qSOFA) score instead of systemic inflammatory response syndrome (SIRS) criteria to identify patients at high risk of mortality. However, these new criteria have not been prospectively validated in some settings, and their added value in the emergency department remains unknown. Objective: To prospectively validate qSOFA as a mortality predictor and compare the performances of the new sepsis criteria to the previous ones. Design, Settings, and Participants: International prospective cohort study, conducted in France, Spain, Belgium, and Switzerland between May and June 2016. In the 30 participating emergency departments, for a 4-week period, consecutive patients who visited the emergency departments with suspected infection were included. All variables from previous and new definitions of sepsis were collected. Patients were followed up until hospital discharge or death. Exposures: Measurement of qSOFA, SOFA, and SIRS. Main Outcomes and Measures: In-hospital mortality. Results: Of 1088 patients screened, 879 were included in the analysis. Median age was 67 years (interquartile range, 47-81 years), 414 (47%) were women, and 379 (43%) had respiratory tract infection. Overall in-hospital mortality was 8%: 3% for patients with a qSOFA score lower than 2 vs 24% for those with qSOFA score of 2 or higher (absolute difference, 21%; 95% CI, 15%-26%). The qSOFA performed better than both SIRS and severe sepsis in predicting in-hospital mortality, with an area under the receiver operating curve (AUROC) of 0.80 (95% CI, 0.74-0.85) vs 0.65 (95% CI, 0.59-0.70) for both SIRS and severe sepsis (P < .001; incremental AUROC, 0.15; 95% CI, 0.09-0.22). The hazard ratio of qSOFA score for death was 6.2 (95% CI, 3.8-10.3) vs 3.5 (95% CI, 2.2-5.5) for severe sepsis. Conclusions and Relevance: Among patients presenting to the emergency department with suspected infection, the use of qSOFA resulted in greater prognostic accuracy for in-hospital mortality than did either SIRS or severe sepsis. These findings provide support for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria in the emergency department setting. Trial Registration: clinicaltrials.gov Identifier: NCT02738164.

High Soluble CD14 Levels at Primary HIV-1 Infection Predict More Rapid Disease Progression.

The soluble CD14 (sCD14) level was found associated with mortality during the chronic phase of human immunodeficiency virus (HIV) infection. Here we assessed its prognostic value in 138 patients with primary HIV infection. Higher sCD14 levels were associated with death, from myocardial infarction, but this was based on 3 deaths only. Among 68 untreated patients, those with higher sCD14 levels had more rapid spontaneous CD4 cell decline during the first 18 months following primary infection. This association persisted after adjustment for age, the CD4 cell count, and HIV viral load at diagnosis.

Does transient cART started during primary HIV infection undermine the long-term immunologic and virologic response on cART resumption?

BACKGROUND: We explored the impact of transient cART started during the primary HIV-infection (PHI) on the long-term immunologic and virologic response on cART resumption, by comparison with treatment initiation during the chronic phase of HIV infection (CHI). METHODS: We analyzed data on 1450 patients enrolled during PHI in the ANRS PRIMO cohort between 1996 and 2013. "Treatment resumption" was defined as at least 3 months of resumed treatment following interruption of at least 1 month of treatment initiated during PHI. "Treatment initiation during CHI" was defined as cART initiated ≥6 months after PHI. The virologic response to resumed treatment and to treatment initiated during CHI was analyzed with survival models. The CD4 cell count dynamics was modeled with piecewise linear mixed models. RESULTS: 136 patients who resumed cART for a median (IQR) of 32 (18-51) months were compared with 377 patients who started cART during CHI for a median of 45 (22-57) months. Most patients (97%) achieved HIV-RNA <50 cp/mL after similar times in the two groups. The CD4 cell count rose similarly in the two groups during the first 12 months. However, after 12 months, patients who started cART during CHI had a better immunological response than those who resumed cART (p = 0.01); therefore, at 36 months, the gains in √CD4 cells/mm(3) and CD4% were significantly greater in patients who started treatment during CHI. CONCLUSION: These results suggest that interruption of cART started during PHI has a significant, albeit modest negative impact on CD4 cell recovery on cART resumption.

Management of noninfectious mixed cryoglobulinemia vasculitis: data from 242 cases included in the CryoVas survey.

Data on the clinical spectrum and therapeutic management of noninfectious mixed cryoglobulinemia vasculitis (CryoVas) in the era of hepatitis C virus screening are lacking. We analyzed data from 242 patients with noninfectious mixed CryoVas included in the French multicenter CryoVas survey. Baseline manifestations were purpura (75%), peripheral neuropathy (52%), arthralgia or arthritis (44%), glomerulonephritis (35%), cutaneous ulcers (16%), and cutaneous necrosis (14%). A connective tissue disease was diagnosed in 30% and B-cell non-Hodgkin lymphoma in 22%, whereas the CryoVas was considered to be essential in 48%. With the use of Cox-marginal structural models, rituximab plus corticosteroids showed the greater therapeutic efficacy compared with corticosteroids alone and alkylating agents plus corticosteroids to achieve complete clinical, renal, and immunologic responses and a prednisone dosage < 10 mg/d at 6 months. However, this regimen was also associated with severe infections, particularly when high doses of corticosteroids were used, whereas death rates did not differ between the therapeutic regimens. The role of each of these strategies remains to be defined in well-designed randomized controlled trials.

Insufficient vaccine coverage and vaccine hesitancy in people living with HIV: A prospective study in outpatient clinics in the Paris region.

Vaccine prevention strategies play a crucial role in the management of people living with HIV (PLWH). The aim of this study was to assess vaccination coverage and identify barriers to vaccine uptake in PLWH in the Paris region. A cross-sectional survey was conducted in PLWH in 16 hospitals in the Paris region. The vaccination status, characteristics, opinions, and behaviors of participants were collected using a face-to-face questionnaire and from medical records. A total of 338 PLWH were included (response rate 99.7 %). The median age of participants was 51 years (IQR: 41-58). Vaccination coverage was 77.3 % for hepatitis B (95 % CI: 72.3-81.8 %), 62.7 % for hepatitis A (57.3-67.9 %), 61.2 % for pneumococcal vaccines (55.8-66.5 %), 56.5 % for diphtheria/tetanus/poliomyelitis (DTP) (51.0-61.9 %), 44.7 % for seasonal influenza (39.3-50.1 %), 31.4 % for measles/mumps/rubella (26.4-36.6 %) and 38.5 % for meningococcal vaccine (13.9-68.4 %). The main reason for vaccine reluctance was related to the lack of vaccination proposals/reminders. The overall willingness to get vaccinated was 71.0 % (65.9-75.8 %). In the multivariable analysis, several factors were associated with a higher vaccine uptake; for DTP vaccine: higher education level, having vaccination records, being registered with a general practitioner; for seasonal influenza vaccine: age > 60 years, higher education level, being employed. The overall vaccination coverage was suboptimal. Development of strategies reducing missed opportunity to offer vaccines is needed.

Prognostic factors of survival in patients with non-infectious mixed cryoglobulinaemia vasculitis: data from 242 cases included in the CryoVas survey.

BACKGROUND: Data on the prognosis of non-infectious mixed cryoglobulinaemia vasculitis (CryoVas) in the era of hepatitis C virus screening are lacking. METHODS: The French multicentre and retrospective CryoVas survey included 242 patients with non-infectious mixed CryoVas. Causes of death and prognostic factors of survival were assessed and a prognostic score was determined to predict survival at 5 years. RESULTS: After a median follow-up of 35 months, 42 patients (17%) died. Causes of death were mainly serious infections (50%) and vasculitis flare (19%). One-, 2-, 5- and 10-year overall survival rates were 91%, 89%, 79% and 65%, respectively. A prognostic score, the CryoVas score (CVS), for the prediction of survival at 5 years was devised. Pulmonary and gastrointestinal involvement, glomerular filtration rate <60 ml/min and age >65 years were independently associated with death. At 5 years the death rates were 2.6%, 13.1%, 29.6% and 38.5% for a CVS of 0, 1, 2 and ≥3, respectively. At 1 year the death rates were 0%, 3.2%, 18.5% and 30.8% for a CVS of 0, 1, 2 and ≥3, respectively. The CVS was strongly correlated with the Five Factor Score (FFS) 2009, another prognostic score validated in primary necrotising vasculitis (r=0.82; p<0.0001). The area under the curve for the CVS was 0.74 compared with 0.67 for the FFS, indicating a better performance of the CVS (p=0.052). CONCLUSIONS: In patients with non-infectious mixed CryoVas, the main prognostic factors are age >65 years, pulmonary and gastrointestinal involvement and renal failure. A score including these variables is significantly associated with the prognosis.

Early variation of quick sequential organ failure assessment score to predict in-hospital mortality in emergency department patients with suspected infection.

BACKGROUND: The quick sequential organ failure assessment (qSOFA) score showed good prognostic performance in patients with suspicion of infection in the emergency department (ED). However, previous studies only assessed the performance of individual values of qSOFA during the ED stay. As this score may vary over short timeframes, the optimal time of measurement, and the prognostic value of its variation are unclear. The objective of the present study was to prospectively assess the prognostic value of the change in qSOFA over the first 3 h (ΔqSOFA = qSOFA at 3 h-qSOFA at inclusion). PATIENTS AND METHODS: This is an international prospective cohort study conducted in 17 EDs in France, Belgium, and Spain. From November 2016 to March 2017, patients with a suspected infection and a qSOFA score of 2 or higher were included and followed up until death or hospital discharge. qSOFA was measured at inclusion, 1 h and 3 h. Primary end point was in-hospital mortality, truncated at 28 days. RESULTS: Of 534 recruited patients, 512 were included in the analysis. The qSOFA was improved at 3 h (ΔqSOFA < 0) in 287 (55%) patients. Overall in-hospital mortality was 27%: 44% when ΔqSOFA greater than 0, 36% when ΔqSOFA = 0, and 18% when ΔqSOFA less than 0. A positive ΔqSOFA was independently associated with reduced in-hospital mortality (adjusted hazard ratio of 0.48, 95% confidence interval: 0.34-0.68). After modeling qSOFA kinetics in the first 3 h, there was a significant difference in adjusted slopes between patients who died and those who survived (0.15, 95% confidence interval: 0.09-0.22, P < 0.001). CONCLUSION: In patients with suspected infection presenting to the ED with a qSOFA of 2 or higher, the early change in qSOFA is a strong independent predictor of mortality.

Effect of emergency physician burnout on patient waiting times.

Burnout is common in emergency physicians. This syndrome may negatively affect patient care and alter work productivity. We seek to assess whether burnout of emergency physicians impacts waiting times in the emergency department. Prospective study in an academic ED. All patients who visited the main ED for a 4-month period in 2016 were included. Target waiting times are assigned by triage nurse to patients on arrival depending on their severity. The primary endpoint was an exceeded target waiting time for ED patients. All emergency physicians were surveyed by a psychologist to assess their level of burnout using the Maslach Burnout Inventory. We defined the level of burnout of the day in the ED as the mean burnout level of the physicians working that day (8:30 to the 8:30 the next day). A logistic regression model was performed to assess whether burnout level of the day was independently associated with prolonged waiting times, along with previously reported predictors. Target waiting time was exceeded in 7524 patients (59%). Twenty-six emergency physicians were surveyed. Median burnout score was 35 [Interquartile (24-49)]. A burnout level of the day higher than 35 was independently associated with an exceeded target waiting time (adjusted odds ratio 1.54, 95% confidence interval 1.39-1.70), together with previously reported predictors (i.e., day of the week, time of the day, trauma, age and daily census). Burnout of emergency physicians was independently associated with a prolonged waiting time for patients visiting the ED.

Role of Epidural Analgesia within an ERAS Program after Laparoscopic Colorectal Surgery: A Review and Meta-Analysis of Randomised Controlled Studies.

Introduction. Epidural analgesia has been a cornerstone of any ERAS program for open colorectal surgery. With the improvements in anesthetic and analgesic techniques as well as the introduction of the laparoscopy for colorectal resection, the role of epidural analgesia has been questioned. The aim of the review was to assess through a meta-analysis the impact of epidural analgesia compared to other analgesic techniques for colorectal laparoscopic surgery within an ERAS program. Methods. Literature research was performed on PubMed, Embase, and the Cochrane Library. All randomised clinical trials that reported data on hospital stay, postoperative complications, and readmissions rates within an ERAS program with and without an epidural analgesia after a colorectal laparoscopic resection were included. Results. Five randomised clinical trials were selected and a total of 168 patients submitted to epidural analgesia were compared to 163 patients treated by an alternative analgesic technique. Pooled data show a longer hospital stay in the epidural group with a mean difference of 1.07 (95% CI 0.06-2.08) without any significant differences in postoperative complications and readmissions rates. Conclusion. Epidural analgesia does not seem to offer any additional clinical benefits to patients undergoing laparoscopic colorectal surgery within an ERAS program.

The passive leg raising test to guide fluid removal in critically ill patients.

BACKGROUND: To investigate whether haemodynamic intolerance to fluid removal during intermittent renal replacement therapy (RRT) in critically ill patients can be predicted by a passive leg raising (PLR) test performed before RRT. METHODS: We included 39 patients where intermittent RRT with weight loss was decided. Intradialytic hypotension was defined as hypotension requiring a therapeutic intervention, as decided by the physicians in charge. Before RRT, the maximal increase in cardiac index (CI, pulse contour analysis) induced by a PLR test was recorded. RRT was then started. RESULTS: Ultrafiltration rate was similar in patients with and without intradialytic hypotension. Thirteen patients presented intradialytic hypotension, while 26 did not. In patients with intradialytic hypotension, it occurred 120 min [interquartile range 60-180 min] after onset of RRT. In the 26 patients without intradialytic hypotension, the PLR test induced no significant change in CI. Conversely, in patients with intradialytic hypotension, PLR significantly increased CI by 15 % [interquartile range 11-36 %]. The PLR-induced increase in CI predicted intradialytic hypotension with an area under the ROC curve of 0.89 (95 % interval confidence 0.75-0.97) (p < 0.05 from 0.50). The best diagnostic threshold was 9 %. The sensitivity was 77 % (95 % confidence interval 46-95 %), the specificity was 96 % (80-100 %), the positive predictive value was 91 % (57-100 %), and the negative predictive value was 89 % (72-98 %). Compared to patients without intolerance to RRT, CI decreased significantly faster in patients with intradialytic hypotension, with a slope difference of -0.17 L/min/m(2)/h. CONCLUSION: The presence of preload dependence, as assessed by a positive PLR test before starting RRT with fluid removal, predicts that RRT will induce haemodynamic intolerance.

Influence of lifelong cumulative HIV viremia on long-term recovery of CD4+ cell count and CD4+/CD8+ ratio among patients on combination antiretroviral therapy.

OBJECTIVE: We explored the impact of lifelong cumulative HIV viremia on immunological recovery during antiretroviral therapy, according to the timing of treatment initiation. METHODS: We estimated lifelong cumulative HIV viremia in patients followed in the ANRS PRIMO cohort since primary infection, including 244 patients who started treatment during PHI and had at least one treatment interruption, and 218 patients who started treatment later but with no interruptions. The impact of cumulative viremia on current immunological status was analysed using linear and logistic regression models. RESULTS: At the last visit on treatment, median CD4 cell count was 645 cells/µl in the early/intermittent treatment group (median time from infection 9.5 years, 4.8 years of continuous treatment since last resumption), and 654 cells/µl in the deferred/continuous treatment group (median time from infection 6.1 years, 3.0 years of continuous treatment). Only 36.1 and 39.8% of patients achieved a CD4/CD8 ratio of more than 1, respectively. Current CD4 cell count was not associated with cumulative HIV viremia in either group. In contrast, patients with high cumulative HIV viremia (>66th percentile vs. <33rd percentile) were less likely to achieve a CD4/CD8 ratio of more than 1 (26.8 vs. 43.3%, P = 0.003), even after controlling for the baseline CD4/CD8 ratio, treatment duration, sex and age. Much higher CD4 cell count and CD4/CD8 ratio were reached in early/continuous treatment, that is low viremia exposure group. CONCLUSION: Our results underline the critical need in early-treated patients to maintain adherence, in order to limit cumulative HIV viremia and optimize immunological recovery, notably the CD4/CD8 ratio.

Re-treatment of chronic HCV infection in HIV co-infected patients and predictors of sustained viral response.

BACKGROUND: In HIV-HCV co-infected patients who failed to achieve sustained viral response (SVR) with PEG-IFN + RBV, data on SVR rate after re-treatment with Peginterferon (PEG-IFN) + ribavirin (RBV) are scarce. AIM: The aim of this study was to identify factors predictive of SVR after re-treatment in a large cohort of HIV/HCV co-infected patients - the ANRS-CO7 Ribavic cohort study, which is a long term follow-up study of patients who were included in the randomized controlled trial ANRS-HC02 RIBAVIC. RESULTS: Among the 176 patients who did not achieve a SVR during the RIBAVIC trial, sixty-six patients (38%) experienced a re-treatment with PEG-IFN + RBV. The SVR observed to the second course of HCV treatment was 44% overall, i.e. 93% in patients who were relapsers and 29% in nonresponders. In the nonresponders subgroup, the SVR rate was 42% in patients with genotype 2-3 and 26% in patients with genotype 1-4. In multivariate analysis, age ≤ 40 years (OR 12.4 95% CI 1.9-171, p = 0.003), genotype 2-3 versus 1-4 (OR 8.1 95% CI 8.1 1.2-97, p = 0.002) and relapser status at first treatment (OR 32.9 95% CI 3.2-278, p < 0.0001) were significantly associated with SVR. CONCLUSION: Our findings strongly suggest that patients who relapse after first treatment, particularly those infected with HCV genotype 2-3, or living in countries with no access to the direct acting antiviral drugs for HCV, could be successfully re-treated with standard bi-therapy of PEG-IFN + RBV regimen.

Is clinical practice concordant with the changes in guidelines for antiretroviral therapy initiation during primary and chronic HIV-1 infection? The ANRS PRIMO and COPANA cohorts.

OBJECTIVE: Guidelines for initiating HIV treatment are regularly revised. We explored how physicians in France have applied these evolving guidelines for ART initiation over the last decade in two different situations: chronic (CHI) and primary HIV-1 infection (PHI), since specific recommendations for PHI are also provided in France. METHODS: Data came from the ANRS PRIMO (1267 patients enrolled during PHI in 1996-2010) and COPANA (800 subjects enrolled at HIV diagnosis in 2004-2008) cohorts. We defined as guidelines-inconsistent during PHI and CHI, patients meeting criteria for ART initiation and not treated in the following month and during the next 6 months, respectively. RESULTS: ART initiation during PHI dramatically decreased from 91% of patients in 1996-99 to 22% in 2007 and increased to 60% in 2010, following changes in recommendations. In 2007, however, after the CD4 count threshold was raised to 350 cells/mm(3) in 2006, only 55% of the patients with CD4≤350 were treated and 66% in 2008. During CHI, ART was more frequently initiated in patients who met the criteria at entry (96%) than during follow-up: 83% when recommendation to treat was 200 and 73% when it was 350 cells/mm(3). Independent risk factors for not being treated during CHI despite meeting the criteria were lower viral load, lower educational level, and poorer living conditions. CONCLUSION: HIV ART initiation guidelines are largely followed by practitioners in France. What can still be improved, however, is time to treat when CD4 cell counts reach the threshold to treat. Risk factors for lack of timely treatment highlight the need to understand better how patients' living conditions and physicians' perceptions influence the decision to initiate treatment.