Characteristics of human metapneumovirus infection in adults hospitalized for community-acquired influenza-like illness in France, 2012-2018: a retrospective observational study.

OBJECTIVES: To describe the prevalence, clinical features and complications of human metapneumovirus (hMPV) infections in a population of adults hospitalized with influenza-like illness (ILI). METHODS: This was a retrospective, observational, multicenter cohort study using prospectively collected data from adult patients hospitalized during influenza virus circulation, for at least 24 h, for community-acquired ILI (with symptom onset <7 days). Data were collected from five French teaching hospitals over six consecutive winters (2012-2018). Respiratory viruses were identified by multiplex reverse transcription polymerase chain reaction (RT-PCR) on nasopharyngeal specimens. hMPV + patients were compared with hMPV- patients, influenza+ and respiratory syncytial virus (RSV)+ patients using multivariate logistic regressions. Primary outcome was the prevalence of hMPV in patients hospitalized for ILI. RESULTS: Among the 3148 patients included (1449 (46%) women, 1988 (63%) aged 65 and over; 2508 (80%) with chronic disease), at least one respiratory virus was detected in 1604 (51%, 95% confidence interval (CI) 49-53), including 100 cases of hMPV (100/3148, 3% 95% CI 3-4), of which 10 (10%) were viral co-infection. In the hMPV + patients, mean length of stay was 7 days, 62% (56/90) developed a complication, 21% (14/68) were admitted to intensive care unit and 4% (4/90) died during hospitalization. In comparison with influenza + patients, hMPV + patients were more frequently >65 years old (adjusted odds ratio (aOR) = 3.3, 95% CI 1.9-6.3) and presented more acute heart failure during hospitalization (aOR = 1.8, 95% CI 1.0-2.9). Compared with RSV + patients, hMPV + patients had less cancer (aOR = 0.4, 95% CI 0.2-0.9) and were less likely to smoke (aOR = 0.5, 95% CI 0.2-0.9) but had similar outcomes, especially high rates of respiratory and cardiovascular complications. CONCLUSIONS: Adult hMPV infections mainly affect the elderly and patients with chronic conditions and are responsible for frequent cardiac and pulmonary complications similar to those of RSV infections. At-risk populations would benefit from the development of antivirals and vaccines targeting hMPV.

[Cancers in systemic sclerosis : risk factors, impact on survival and literature review]. / Survenue de cancers au cours de la sclérodermie systémique : facteurs de risque, impact sur la survie et revue de la littérature.

INTRODUCTION: Patients with systemic sclerosis (SSc) have an increased risk of malignancy. In this study, we aimed to analyze the prevalence of cancer, the risk factors and the impact on overall survival. PATIENTS AND METHODS: We analyzed clinical (history of cancer, toxic exposition, organ involvement), immunological and treatment data in a monocentric cohort of SSc patients followed between January 2004 and December 2017. RESULTS: Two hundred and ten patients with SSc were included. During the follow-up, twenty-one patients (10 %) were diagnosed with malignancies. The underlying malignancies were breast adenocarcinoma (n=6, 28%), lung cancer (n=6, 28%), colorectal (colic adenocarcinoma, carcinoid tumor of the appendix), ovarian and cervix uteri, melanoma, kidney and papillary thyroid carcinoma (one of each). The median time between the first visit and the diagnosis of cancer was 4 [2-10] years. The overall survival in SSc patients with cancer was not significantly different from patients without cancer, with median survival during the first quartile (75%) at 12 years for patients with cancer and 11.6 years for those without cancer (P=0.9). The history of renal scleroderma crisis (HR 10.99, IC95% [1.95-62.07]; P=0.006) and the presence of anti-topoisomerase I antibodies (HR 5.5, IC95% [1.40-21.67]; P=0.01) were associated with an increased risk of cancer, whereas the presence of gastroesophageal reflux was inversely associated with the cancer occurrence (HR 0.22, IC95% [0.056-0.867]; P=0.03). CONCLUSION: The history of renal scleroderma crisis and the positivity of anti-topoisomerase I antibodies were associated with an increased risk of cancer in SSc patients in this monocentric study.

Self-reported patient history to assess hepatitis B virus serological status during a large screening campaign.

When assessing hepatitis B virus (HBV) status in clinical settings, it is unclear whether self-reports on vaccination history and previous HBV-test results have any diagnostic capacity. Of 3997 participants in a multi-centre HBV-screening study in Paris, France, 1090 were asked questions on their last HBV-test result and vaccination history. Discordance between self-reported history compared with infection status (determined by serology) was calculated for participants claiming 'negative', 'effective vaccine', 'past infection', or 'chronic infection' HBV-status. Serological testing revealed that 320 (29.4%) were non-immunised, 576 (52.8%) were vaccinated, 173 (15.9%) had resolved the infection and 21 (1.9%) were hepatitis B surface antigen positive. In total 208/426 (48.8%) participants with a self-reported history of 'negative' infection had a discordant serological result, in whom 128 (61.5%) were vaccinated and 74 (35.6%) had resolved infections. A total of 153/599 (25.5%) participants self-reporting 'effective vaccine' had a discordant serological result, in whom 100 (65.4%) were non-immunised and 50 (32.7%) were resolved infections. Discordance for declaring 'past' or 'chronic infection' occurred in 9/55 (16.4%) and 3/10 (30.0%) individuals, respectively. In conclusion, self-reported HBV-status based on participant history is partially inadequate for determining serological HBV-status, especially between negative/vaccinated individuals. More adapted patient education about HBV-status might be helpful for certain key populations.

The negative impact of HBV/HCV coinfection on cirrhosis and its consequences.

BACKGROUND: Hepatitis B virus (HBV)/hepatitis C virus (HCV) confection has been rarely studied in nonasian series. AIM: To compare the characteristics of HBV/HCV coinfected patients to those of HBV- or HCV-monoinfected patients in the ANRS CO22 HEPATHER cohort study. PATIENTS AND METHODS: Of the 20 936 included patients, 95 had HBV/HCV coinfection (hepatitis B surface antigen, anti-HCV antibody and HCV RNA positive) and were matched with 375 HBV- and 380 HCV-monoinfected patients on age, gender and time since HBV or HCV diagnosis. RESULTS: F3-F4 fibrosis was more frequent in coinfected patients (58%) than in HBV- (32%, P < .0001), but similar in HCV-monoinfected patients (52%, P = .3142). Decompensated cirrhosis was more frequent in coinfected patients (11%) than in HBV- (2%, P = .0002) or HCV- (4%, P = .0275) monoinfected patients. Past excessive alcohol use was more frequent in coinfected patients (26%) than in HBV (12%, P = .0011), but similar in HCV monoinfected patients (32%, P = .2868). Coinfected patients had a higher proportion with arterial hypertension (42%) than HBV- (26%) or HCV-monoinfected patients (25%) (P < .003). Multivariable analysis confirmed the association between F3-F4 fibrosis and HCV infection in HBV-infected patients (OR = 3.84, 95% CI 1.99-7.43) and the association between decompensated cirrhosis and coinfection in HBV infected (OR = 5.58, 95% CI 1.42-22.0) or HCV infected patients (OR = 3.02, 95% CI 1.22-7.44). CONCLUSIONS: HCV coinfection harmfully affects liver fibrosis in HBV patients, while decompensated cirrhosis is increased in coinfected patients compared with HBV- or HCV-monoinfected patients. HCV treatment is as safe and effective in coinfected as monoinfected patients and should be considered following the same rules as HCV monoinfected patients.

The effects of aminosalicylates or thiopurines on the risk of colorectal cancer in inflammatory bowel disease.

BACKGROUND: Whether aminosalicylates or thiopurines reduce the risk of colorectal cancer (CRC) in inflammatory bowel (IBD) disease is controversial. AIM: To assess simultaneously the chemopreventive effect of aminosalicylates or thiopurines in a case-control study nested in the CESAME observational cohort that enrolled consecutive patients with IBD between May 2004 and June 2005. Patients were followed up to December 2007. METHODS: Study population comprised 144 case patients who developed CRC from the diagnosis of IBD (65 and 79 cases diagnosed, respectively, before and from 2004, starting year of the prospective observational period of CESAME) and 286 controls matched for gender, age, IBD subtype and year of diagnosis, and cumulative extent of colitis. Exposure to aminosalicylates or thiopurines was defined by an exposure to the treatment during the year of the diagnosis of cancer. The propensity of receiving 5-ASA and thiopurines was quantified by a composite score taking into account patient and IBD characteristics. The role of aminosalicylates or thiopurines was assessed by multivariate analysis. Propensity scores and the history of primary sclerosing cholangitis were entered into the multivariate model for adjustment. RESULTS: By multivariate analysis adjusted for propensity, a significant protective effect of exposure to drugs during the year of cancer was found for aminosalicylates (OR = 0.587, 95% CI: 0.367-0.937, P = 0.0257), but not for thiopurines (OR = 0.762, 95% CI: 0.432-1.343, P = 0.3468). CONCLUSION: In a case-control study nested in the CESAME cohort, a significant decrease in the risk of colorectal cancer in IBD was associated with exposure to aminosalicylates, not to thiopurines.

Clinical characteristics and outcome of respiratory syncytial virus infection among adults hospitalized with influenza-like illness in France.

OBJECTIVES: The aim of this study was to analyse characteristics and outcome of respiratory syncytial virus (RSV) infection in adults hospitalized with influenza-like illness (ILI). METHODS: Patients hospitalized with ILI were included in this prospective, multicentre study carried out in six French hospitals during three consecutive influenza seasons (2012-2015). RSV and other respiratory viruses were detected by multiplex PCR in nasopharyngeal swabs. Risk factors for RSV infection were identified by backward stepwise logistic regression analysis. RESULTS: A total of 1452 patients hospitalized with ILI were included, of whom 59% (861/1452) were >65 years and 83% (1211/1452) had underlying chronic illnesses. RSV was detected in 4% (59/1452), and influenza virus in 39% (566/1452). Risk factors for RSV infection were cancer (adjusted OR 2.1, 95% CI 1.1-4.1, p 0.04), and immunosuppressive treatment (adjusted OR 2.0, 95% CI 1.1-3.8, p 0.03). Patients with RSV had a median length of stay of 9 days (6-25), and 57% of them (30/53) had complications, including pneumonia (23/53, 44%) and respiratory failure (15/53, 28%). Fifteen per cent (8/53) were admitted to an intensive care unit, and the in-hospital mortality rate was 8% (4/53). Pneumonia was more likely to occur in patients with RSV than in patients with RSV-negative ILI (44% (23/53) versus 26% (362/1393), p 0.006) or with influenza virus infection (44% versus 28% (157/560), p 0.02). CONCLUSION: RSV is an infrequent cause of ILI during periods of influenza virus circulation but can cause severe complications in hospitalized adults. Risk factors for RSV detection in adults hospitalized with ILI include cancer and immunosuppressive treatment. Specific immunization and antiviral therapy might benefit patients at risk.

Immunity against influenza A(H1N1) infections is determined by age at the time of initial strain circulation.

We explored age-dependent patterns in haemagglutination inhibition (HI) titre to seasonal [1956 A(H1N1), 1977 A(H1N1), 2007 A(H1N1)] and pandemic [A(H1N1)pdm09] influenza strains using serological data collected from an adult French influenza cohort. Subjects were recruited by their general practitioners from 2008 to 2009 and followed until 2010. We explored age-related differences between strain-specific HI titres using 1053 serological samples collected over the study period from 398 unvaccinated subjects. HI titres against the tested seasonal and pandemic strains were determined using the HI technique. Geometric mean titres (GMTs) were estimated using regression models for interval-censored data. Generalized additive mixed models were fit to log-transformed HI estimates to study the relationship between HI titre and age (age at inclusion and/or age at initial strain circulation). GMT against one strain was consistently highest in the birth cohort exposed to that strain during childhood, with peak titres observed in subjects aged 7-8 years at the time of initial strain circulation. Our results complete previous findings on influenza A(H3N2) strains and identify a strain-dependent relationship between HI titre and age at initial strain circulation.

Assessment of Public Health and Economic Impact of Intranasal Live-Attenuated Influenza Vaccination of Children in France Using a Dynamic Transmission Model.

OBJECTIVES: We estimated the epidemiological and economic impact of extending the French influenza vaccination programme from at-risk/elderly (≥65 years) only to healthy children (2-17 years). METHODS: A deterministic, age-structured, dynamic transmission model was used to simulate the transmission of influenza in the French population, using the current vaccination coverage with trivalent inactivated vaccine (TIV) in at-risk/elderly individuals (current strategy) or gradually extending the vaccination to healthy children (aged 2-17 years) with intranasal, quadrivalent live-attenuated influenza vaccine (QLAIV) from current uptake up to 50% (evaluated strategy). Epidemiological, medical resource use and cost data were taken from international literature and country-specific information. The model was calibrated to the observed numbers of influenza-like illness visits/year. The 10-year number of symptomatic cases of confirmed influenza and direct medical costs ('all-payer') were calculated for the 0-17- (direct and indirect effects) and ≥18-year-old (indirect effect). The incremental cost-effectiveness ratio (ICER) was calculated for the total population, using a 4% discount rate/year. RESULTS: Assuming 2.3 million visits/year and 1960 deaths/year, the model calibration yielded an all-year average basic reproduction number (R 0) of 1.27. In the population aged 0-17 years, QLAIV prevented 865,000 influenza cases/year (58.4%), preventing 10-year direct medical expenses of €374 million. In those aged ≥18 years with unchanged TIV coverage, 1.2 million cases/year were averted (27.6%) via indirect effects (additionally prevented expenses, €457 million). On average, 613 influenza-related deaths were averted annually overall. The ICER was €18,001/life-year gained. The evaluated strategy had a 98% probability of being cost-effective at a €31,000/life-year gained threshold. CONCLUSIONS: The model demonstrated strong direct and indirect benefits of protecting healthy children against influenza with QLAIV on public health and economic outcomes in France.

Intensification with pegylated interferon during treatment with tenofovir in HIV-hepatitis B virus co-infected patients.

In hepatitis B "e" antigen (HBeAg) positive patients with hepatitis B virus (HBV) mono-infection, intensification of nucleos(t)ide analogue treatment with pegylated interferon (PegIFN) could help induce higher HBeAg seroclearance rates. Our aim was to determine the long-term effect of adding PegIFN to tenofovir (TDF)-containing antiretroviral therapy on seroclearance in HBeAg-positive patients co-infected with the human immunodeficiency virus (HIV) and HBV. In this prospective matched cohort study, 46 patients with 1-year PegIFN intensification during TDF-containing antiretroviral therapy (TDF+PegIFN) were matched 1:1 to controls undergoing TDF without PegIFN (TDF) using a time-dependent propensity score based on age, CD4+ count and liver cirrhosis status. Kinetics of HBeAg quantification (qHBeAg) and hepatitis B surface antigen quantification (qHBsAg) were estimated using mixed-effect linear regression and time to HBeAg seroclearance or HBsAg seroclearance was modelled using proportional hazards regression. At baseline, previous TDF exposure was a median 39.8 months (IQR=21.4-59.4) and median qHBeAg and qHBsAg levels were 6.9 PEIU/mL and 3.72 log10 IU/mL, respectively (P>.5 between groups). Median follow-up was 33.4 months (IQR=19.0-36.3). During intensification, faster average declines of qHBeAg (-0.066 vs -0.027 PEIU/mL/month, P=.001) and qHBsAg (-0.049 vs -0.026 log10 IU/mL/month, P=.09) were observed in patients undergoing TDF+PegIFN vs TDF, respectively. After intensification, qHBeAg and qHBsAg decline was no different between groups (P=.7 and P=.9, respectively). Overall, no differences were observed in HBeAg seroclearance (TDF+PegIFN=13.2 vs TDF=12.6/100 person·years, P=.5) or HBsAg seroclearance rates (TDF+PegIFN=1.8 vs TDF=1.3/100 person·years, P=.7). In conclusion, PegIFN intensification in HBeAg-positive co-infected patients did not lead to increased rates of HBeAg or HBsAg clearance, despite faster declines of antigen levels while on PegIFN.

Excess risk of urinary tract cancers in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study.

BACKGROUND: The risk of urinary tract cancers, including kidney and bladder cancers, was increased in transplant recipients receiving thiopurines. AIM: To assess the risk of urinary tract cancers in patients with inflammatory bowel disease (IBD) receiving thiopurines in the CESAME observational cohort. METHODS: Between May 2004 and June 2005, 19 486 patients with IBD, 30.1% of whom were receiving thiopurines, were enrolled. Median follow-up was 35 months (IQR: 29-40). RESULTS: Ten and six patients developed respectively kidney and bladder cancer. The incidence rates of urinary tract cancer were 0.48/1000 patient-years in patients receiving thiopurines (95% CI: 0.21-0.95), 0.10/1000 patient-years in patients who discontinued thiopurines (95% CI: 0.00-0.56) and 0.30/1000 patient-years in patients never treated with thiopurines (95% CI: 0.12-0.62) at entry. The standardised incidence ratio of urinary tract cancer was 3.40 (95% CI: 1.47-6.71, P = 0.006) in patients receiving thiopurines, 0.64 (95% CI: 0.01-3.56, P = 0.92) in patients previously exposed to thiopurines and 1.17 (95% CI: 0.47-12.42, P = 0.78) in patients never treated with thiopurines. The multivariate-adjusted hazard ratio (HR) of urinary tract cancer between patients receiving thiopurines and those not receiving thiopurines was 2.82 (95% CI: 1.04-7.68, P = 0.04). Other significant risk factors were male gender (HR: 3.98, 95% CI: 1.12-14.10, P = 0.03) and increasing age (HR after 65 years (ref <50): 13.26, 95% CI: 3.52-50.03, P = 0.0001). CONCLUSION: Patients with IBD receiving thiopurines have an increased risk of urinary tract cancers. Clinically relevant excess risk is observed in older men.

A Model-Based Illustrative Exploratory Approach to Optimize the Dosing of Peg-IFN/RBV in Cirrhotic Hepatitis C Patients Treated With Triple Therapy.

Hézode et al. recently reported the frequent occurrence of anemia and thrombocytopenia in the ANRS-CO20-CUPIC cohort of hepatitis C virus (HCV) cirrhotic experienced patients treated with pegylated-interferon (Peg-IFN), ribavirin (RBV), and telaprevir or boceprevir.1,2 Using frequent measurements of serum drug concentrations, hemoglobin, and platelet concentrations obtained in 15 patients of this cohort, we show how an on-treatment model-based approach could be used to individualize dose regimen and avoid the occurrence of RBV-induced anemia and Peg-IFN-induced thrombocytopenia.

Comparison of liver biopsy and noninvasive techniques for liver fibrosis assessment in patients infected with HCV-genotype 4 in Egypt.

In Egypt, as elsewhere, liver biopsy (LB) remains the gold standard to assess liver fibrosis in chronic hepatitis C (CHC) and is required to decide whether a treatment should be proposed. Many of its disadvantages have led to develop noninvasive methods to replace LB. These new methods should be evaluated in Egypt, where circulating virus genotype 4 (G4), increased body mass index and co-infection with schistosomiasis may interfere with liver fibrosis assessment. Egyptian CHC-infected patients with G4 underwent a LB, an elastometry measurement (Fibroscan(©)), and serum markers (APRI, Fib4 and Fibrotest(©)). Patients had to have a LB ≥15 mm length or ≥10 portal tracts with two pathologists blinded readings to be included in the analysis. Patients with hepatitis B virus co-infection were excluded. Three hundred and twelve patients are reported. The performance of each technique for distinguishing F0F1 vs F2F3F4 was compared. The area under receiver operating characteristic curves was 0.70, 0.76, 0.71 and 0.75 for APRI, Fib-4, Fibrotest© and Fibroscan©, respectively (no influence of schistosomiasis was noticed). An algorithm using the Fib4 for identifying patients with F2 stage or more reduced by nearly 90% the number of liver biopsies. Our results demonstrated that noninvasive techniques were feasible in Egypt, for CHC G4-infected patients. Because of its validity and its easiness to perform, we believe that Fib4 may be used to assess the F2 threshold, which decides whether treatment should be proposed or delayed.

The impact of cytomegalovirus reactivation and its treatment on the course of inflammatory bowel disease.

BACKGROUND: Consequences of latent cytomegalovirus (CMV) infection reactivation on inflammatory bowel disease (IBD) flare, as a flare-worsening factor or simple bystander, are debated. Impact of anti-viral treatment on IBD course is poorly known. AIM: To assess the impact of CMV reactivation on patients hospitalised for IBD flare and the effect of anti-viral treatment on IBD flare in patients with CMV reactivation. METHODS: First, a population of UC patients from Saint-Antoine hospital, in flare with positive blood CMV PCR without anti-viral treatment (n = 26), were compared to matched patients with negative blood CMV PCR in a case-control study. Secondly, a total of 110 hospitalisations between October 2003 and May 2012 for IBD flare-up with CMV reactivation (80 diagnosed on blood PCR, 33 on tissue PCR) were identified in three French referral centres. Evolution following CMV reactivation diagnosis was compared between patients receiving anti-viral treatment and those who did not. RESULTS: In the case-control study, no differences were observed between the two groups regarding length of hospital stay and colectomy rate. Comparing treated and untreated patients, no differences were observed at inclusion regarding age, gender, IBD type, immunosuppressant, CRP and haemoglobin level. No differences were observed regarding CRP level decrease at 10 days and colectomy rate at 3 months. Anti-viral treatment was associated with lower serum albumin level at inclusion and longer hospitalisation. CONCLUSIONS: CMV reactivation does not appear to alter the course of IBD flare. CMV treatment does not seem to impact the course of IBD. These results should be confirmed prospectively.

Trends in influenza vaccination behaviours--results from the CoPanFlu cohort, France, 2006 to 2011.

Controversies over the effectiveness and safety of the pandemic influenza A(H1N1)pdm09 vaccine in 2009/10 may have altered the influenza vaccination coverage in France after the pandemic season. The purpose of this study was to determine whether the pandemic affected seasonal influenza vaccination behaviours in the general population by analysing vaccination behaviours from 2006/07 to 2011/12 among the 1,451 subjects of the Cohort for Pandemic Influenza (CoPanFlu) France.We found that vaccination behaviours in 2010/11 and 2011/12 significantly differed from behaviours before the pandemic, with the notable exception of the targeted risk groups for seasonal influenza-related complications. Among the population with no risk factors,the post-pandemic influenza vaccine coverage decreased, with people aged 15 to 24 years and 45to 64 years being most likely to abandon vaccination.Therefore, this study documents a moderate negative effect of the 2009/10 pandemic episode on vaccination behaviours in the French metropolitan population that was apparent also in the following two seasons.Moreover, it does not exclude that the general trend of reduced vaccination has also affected certain targeted groups at high risk for complications.

Complications and factors associated with severity of influenza in hospitalized children and adults during the pandemic wave of A(H1N1)pdm2009 infections--the Fluco French cohort.

BACKGROUND: The emergence of novel A(H1N1)pdm2009 virus threatened to lead to frequent severe manifestations. OBJECTIVES: To describe the clinical, virological, and biological characteristics of the disease and identify the factors associated with severe presentations. STUDY DESIGN: This prospective multicenter study recruited consecutive hospitalized patients with confirmed A(H1N1)pdm2009 disease. Clinical, virological and biological assessments were carried out at inclusion and 30 days post-inclusion. Disease manifestations were assessed by an adjudication committee using pre-identified definitions of complications and severity scores. RESULTS: The study analyzed from November 30th, 2009 to February 8th, 2010, 40 hospitalized patients, 21 children and 19 adults. Eighteen (45%) were considered to have severe presentations. Except age, main characteristics in children and adults did not differ. The majority (18/21) of children and all adults had a respiratory presentation; extra-respiratory manifestations tended to be more frequent in children (12 vs. 6, P=0.10). Two children against 5 adults presented acute respiratory distress syndrome (ARDS, P=0.23), but more children suffered respiratory failure (7 vs. 1, P=0.046) without ARDS. At day 30, one death had occurred in each group. The main factor associated with non-severe presentation was an early (<48 h) implementation of oseltamivir treatment (P=0.038). CONCLUSIONS: Although the study failed to achieve its main objective, due mainly to the difficulty of carrying a study of this nature in the midst of a pandemic, it allowed the description of a panel of unusual and complicated forms and confirmed the added value of early oseltamivir treatment in limiting severity in hospitalized children and adults.