Publications by authors named "Olivier Epaulard"

52 Publications

Chronic use of Renin-Angiotensin-Aldosterone-System blockers and mortality in COVID-19: a multicenter prospective cohort and literature review.

Fundam Clin Pharmacol 2021 Apr 20. Epub 2021 Apr 20.

AP-HP, Hôpital Bichat, Service de Physiologie rénale, F-75018, Paris, France.

Aims: The role of renin-angiotensin-aldosterone system (RAAS) blockers on the course of coronavirus disease 2019 (COVID-19) is debated. We assessed the association between chronic use of RAAS blockers and mortality among inpatients with COVID-19, and explored reasons for discrepancies in the literature.

Methods And Results: We included adult hypertensive patients from a prospective nationwide cohort of 3512 inpatients with COVID-19 up to June 30, 2020. Cox proportional hazard models with various adjustment or propensity weighting methods were used to estimate the Hazard Ratios (HR) of 30-day mortality for chronic users versus non-users of RAAS blockers. We analyzed data of 1160 hypertensive patients; 719 (62%) were male, 777 (67%) were older than 65 years. The main comorbidities were diabetes (n=416, 36%), chronic cardiac disease (n=401, 35%) and obesity (n=340, 29%); 705 (61%) received oxygen therapy. We recorded 135 (11.6%) deaths within 30 days of diagnosis. We found no association between chronic use of RAAS blockers and mortality (unadjusted HR=1.13, 95% CI [0.8-1.6]; propensity inverse probability treatment weighted HR=1.09 [0.86-1.39]; propensity standardized mortality ratio weighted HR=1.08 [0.79-1.47]). Our comprehensive review of previous studies highlighted that significant associations were mostly found in unrestricted populations with inappropriate adjustment, or with biased in-hospital exposure measurement.

Conclusion: Our results do not support previous concerns regarding these drugs, nor a potential protective effect as reported in previous poorly designed studies and metanalyses. RAAS blockers should not be discontinued during the pandemic, while in-hospital management of these drugs will be clarified by randomized trials. NCT04262921.
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http://dx.doi.org/10.1111/fcp.12683DOI Listing
April 2021

Neglecting Plasma Protein Binding in COVID-19 Patients Leads to a Wrong Interpretation of Lopinavir Overexposure.

Clin Pharmacol Ther 2021 04 9;109(4):1030-1033. Epub 2021 Mar 9.

INTHERES, Université de Toulouse, INRA, ENVT, Toulouse Cedex 3, France.

Boffito et al. recalled the critical importance to correctly interpret protein binding. Changes of lopinavir pharmacokinetics in coronavirus disease 2019 (COVID-19) are a perfect illustration. Indeed, several studies described that total lopinavir plasma concentrations were considerably higher in patients with severe COVID-19 than those reported in patients with HIV. These findings have led to a reduction of the dose of lopinavir in some patients, hypothesizing an inhibitory effect of inflammation on lopinavir metabolism. Unfortunately, changes in plasma protein binding were never investigated. We performed a retrospective cohort study. Data were collected from the medical records of patients hospitalized for COVID-19 treated with lopinavir/ritonavir in intensive care units or infectious disease departments of Toulouse University Hospital (France). Total and unbound concentrations of lopinavir, C reactive protein, albumin, and alpha-1-acid glycoprotein (AAG) levels were measured during routine care on the same samples. In patients with COVID-19, increased total lopinavir concentration is the result of an increased AAG-bound lopinavir concentration, whereas the unbound concentration remains constant, and insufficient to reduce the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral load. Although international guidelines have recently recommended against using lopinavir/ritonavir to treat severe COVID-19, the description of lopinavir pharmacokinetics changes in COVID-19 is a textbook case of the high risk of misinterpretation of a total drug exposure when changes in protein binding are not taken into consideration.
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http://dx.doi.org/10.1002/cpt.2196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013748PMC
April 2021

Curvilinear associations between sexual orientation and problematic substance use, behavioural addictions and mental health among young Swiss men.

Addict Behav 2021 01 13;112:106609. Epub 2020 Aug 13.

Addiction Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Addiction Switzerland, Lausanne, Switzerland; Center for Addiction and Mental Health, Toronto, Canada; University of the West of England, Bristol, United Kingdom. Electronic address:

Background And Aims: It is well documented that individuals with a minority sexual orientation face greater risks of problematic substance use (e.g. heavy episodic drinking, alcohol use disorder) and mental health problems. Far less is known about how that risk varies within this population and their risk of behavioural addictions. This study estimated the risks of problematic substance use, behavioural addiction and poor mental health across the spectrum of sexual orientation.

Sample And Method: A sample of young Swiss men (N = 5294; mean age = 25.5, SD = 1.25; representative of 21 of Switzerland's 26 cantons) completed a self-reporting questionnaire on sexual orientation (attraction, 5-point scale) and criterion variables: problematic substance use (e.g. alcohol, cigarettes, cannabis and other illegal drugs), behavioural addictions (gambling, gaming, cybersex, internet, smartphone, work, exercise) and indicators of mental health (e.g. depression, stress). Curvilinear associations between sexual orientation (heterosexual, mostly-heterosexual, bisexual, mostly-homosexual or homosexual individuals) and criterion variables were explored using fractional polynomial regressions.

Results: Although there were differences across criterion variables, in general, the highest risks of problematic substance use, behavioural addictions and mental health problems were estimated for mostly-heterosexual, bisexual or mostly-homosexual men, followed by homosexual men, and with heterosexual men facing the lowest risk.

Discussion And Conclusion: Aggregating the spectrum of sexual orientations into two or three distinct groups blurs important internal group differences. Outcome-specific explanations beyond minority stress and biphobia are necessary to understand the pathways between sexual orientation and risky behaviours. Considering sexual orientation is important to provide targeted healthcare prevention and interventions.
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http://dx.doi.org/10.1016/j.addbeh.2020.106609DOI Listing
January 2021

COVID-19: Underlying Adipokine Storm and Angiotensin 1-7 Umbrella.

Front Immunol 2020 21;11:1714. Epub 2020 Jul 21.

Laboratoire TIMC-TheREx UMR 5525 CNRS-Université Grenoble Alpes, La Tronche, France.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third coronavirus leading to a global health outbreak. Despite the high mortality rates from SARS-CoV-1 and Middle-East respiratory syndrome (MERS)-CoV infections, which both sparked the interest of the scientific community, the underlying physiopathology of the SARS-CoV-2 infection, remains partially unclear. SARS-CoV-2 shares similar features with SARS-CoV-1, notably the use of the angiotensin conversion enzyme 2 (ACE2) as a receptor to enter the host cells. However, some features of the SARS-CoV-2 pandemic are unique. In this work, we focus on the association between obesity, metabolic syndrome, and type 2 diabetes on the one hand, and the severity of COVID-19 infection on the other, as it seems greater in these patients. We discuss how adipocyte dysfunction leads to a specific immune environment that predisposes obese patients to respiratory failure during COVID-19. We also hypothesize that an ACE2-cleaved protein, angiotensin 1-7, has a beneficial action on immune deregulation and that its low expression during the SARS-CoV-2 infection could explain the severity of infection. This introduces angiotensin 1-7 as a potential candidate of interest in therapeutic research on CoV infections.
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http://dx.doi.org/10.3389/fimmu.2020.01714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385229PMC
August 2020

How is the microbial diagnosis of bacterial vertebral osteomyelitis performed? An 11-year retrospective study.

Eur J Clin Microbiol Infect Dis 2020 Nov 26;39(11):2065-2076. Epub 2020 Jun 26.

Infectious and Tropical Diseases Unit, Grenoble-Alpes University Hospital, Grenoble, France.

Vertebral osteomyelitis (VOM) is often diagnosed with delays, resulting in poorer outcomes. Microbial documentation is particularly challenging and obtained using blood cultures (BCs) and vertebral biopsies (VBs; CT-guided or surgical). We retrospectively analysed VOM cases in a tertiary reference centre between 2004 and 2015, focusing on how and how quickly microbiological diagnosis was performed. Among 220 VOM, 88.2% had documentation, including Gram-positive cocci (GPC) (70.6%), Gram-negative rods (GNR) (9.3%), anaerobes (3.6%), polybacterial infections (6.7%) and tuberculosis (9.8%). BCs were performed in 98.2% and positive in 59.3%, identifying most GPC (80.3%) and half of GNR (54.6%). VBs were performed in fewer cases (37.7%), but were more frequently positive (68.8% for CT-guided and 81.0% for surgical biopsies). They documented all anaerobes (100.0%), most M. tuberculosis (84.2%) and polybacterial infections (76.9%), and GNR (45.4%). Extra-vertebral samples highly contributed to tuberculosis diagnosis (52.6%, and 15.8% as the only positive sample). Documentations most often followed radiological diagnosis (53.4%). They were obtained earlier by BCs than by VB after first clinical symptoms (median of 14 versus 51 days). Antibiotic treatments were mostly initiated after samplings (88.0%). BCs allow the documentation of most VOM and should be performed without delay in case of clinical or radiological suspicion; however, they may miss 1 out of 5 GPC and 1 out of 2 GNR. VBs have a higher positivity rate and should be rapidly performed if negative BCs. It is likely that delayed and missed diagnoses result from the insufficient use of VB.
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http://dx.doi.org/10.1007/s10096-020-03929-1DOI Listing
November 2020

A prospective cohort study to identify clinical, biological and imaging features that predict etiology of acute encephalitis.

Clin Infect Dis 2020 May 20. Epub 2020 May 20.

Maladies infectieuses, CHUGA, Grenoble, France.

Background: New diagnostic tools have been developed to improve the diagnosis of infectious encephalitis. Using a prospective cohort of encephalitis patients, our objective was to identify possible clusters of patients with similar patterns among encephalitis of unknown cause, and to describe to what extent the patient's initial presentation may be predictive of encephalitis etiology, particularly Herpes simplex virus (HSV) and Varicella-zona virus (VZV).

Methods: The national cohort of infectious encephalitis in France (ENCEIF) is an ongoing prospective cohort study implemented in France in 2016. Patients presenting with a documented or suspected acute infectious encephalitis were included. Focusing on the variables describing the initial presentation, we performed a factor analysis of mixed data (FAMD) to investigate a pattern of association between the initial presentation of the patient and the etiologic pathogen.

Results: As of 1st August 2018, data from 349 patients were analysed. The most frequent pathogens were HSV (25%), VZV (11%), Tick-borne encephalitis virus (6%), Listeria (5%), Influenza virus (3%), and encephalitis of unknown cause (EUC) (34%). Using the FAMD, it was not possible to identify a specific pattern related to the group of EUC. Age, temporal or haemorrhagic lesions, and cerebral spinal fluid lymphocytosis were significantly associated with HSV/VZV encephalitis.

Conclusion: No initial clinical/imaging/biology pattern was identified at admission among EUC, despite the improvement of diagnostic tools. In this context, the recommendation for a universal, early probabilistic initial treatment against HSV and VZV is still relevant, regardless of the initial clinical presentation of the encephalitis.
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http://dx.doi.org/10.1093/cid/ciaa598DOI Listing
May 2020

Apolipoprotein C1 in synovial fluid discriminates septic arthritis from rheumatoid arthritis but not from pseudogout.

Clin Rheumatol 2020 07 12;39(7):2239-2241. Epub 2020 Apr 12.

GREPI University Grenoble-Alpes (UGA) EA74 08, Grenoble, France.

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http://dx.doi.org/10.1007/s10067-019-04912-8DOI Listing
July 2020

Cluster of Coronavirus Disease 2019 (COVID-19) in the French Alps, February 2020.

Clin Infect Dis 2020 07;71(15):825-832

French National Public Health Agency, Auvergne-Rhône-Alpes Regional Office, Lyon, France.

Background: On 7 February 2020, French Health authorities were informed of a confirmed case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an Englishman infected in Singapore who had recently stayed in a chalet in the French Alps. We conducted an investigation to identify secondary cases and interrupt transmission.

Methods: We defined as a confirmed case a person linked to the chalet with a positive reverse-transcription polymerase chain reaction sample for SARS-CoV-2.

Results: The index case stayed 4 days in the chalet with 10 English tourists and a family of 5 French residents; SARS-CoV-2 was detected in 5 individuals in France, 6 in England (including the index case), and 1 in Spain (overall attack rate in the chalet: 75%). One pediatric case, with picornavirus and influenza A coinfection, visited 3 different schools while symptomatic. One case was asymptomatic, with similar viral load as that of a symptomatic case. Seven days after the first cases were diagnosed, 1 tertiary case was detected in a symptomatic patient with from the chalet a positive endotracheal aspirate; all previous and concurrent nasopharyngeal specimens were negative. Additionally, 172 contacts were monitored; all contacts tested for SARS-CoV-2 (N = 73) were negative.

Conclusions: The occurrence in this cluster of 1 asymptomatic case with similar viral load as a symptomatic patient suggests transmission potential of asymptomatic individuals. The fact that an infected child did not transmit the disease despite close interactions within schools suggests potential different transmission dynamics in children. Finally, the dissociation between upper and lower respiratory tract results underscores the need for close monitoring of the clinical evolution of suspected cases of coronavirus disease 2019.
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http://dx.doi.org/10.1093/cid/ciaa424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184384PMC
July 2020

Screening of hepatitis E in patients presenting for acute neurological disorders.

J Infect Public Health 2020 Jul 26;13(7):1047-1050. Epub 2020 Mar 26.

Department of Internal Medicine, Grenoble University Hospital, Grenoble, France; Univ. Grenoble Alpes, Department of Internal Medicine CHU Grenoble, Inserm (U1036), CEA, BIG-BCI, France.

Introduction: Hepatitis E virus (HEV) infection has been reported to be associated with neurological disorders. However, the real prevalence of acute hepatitis E in those diseases is still unknown. We determined the prevalence of anti-HEV IgM antibody in a population with acute non-traumatic, non-metabolic, non-vascular neurological injury.

Method: A registry was created in Grenoble Hospital University from 2014 to 2018 to collect data on patients with acute (<3 months) non-traumatic, non-metabolic, non-vascular neurological injuries. Acute hepatitis E was defined as anti-HEV IgM-positive serum in immunocompetent patient, and as anti-HEV IgM-positive serum or HEV RNA-positive serum in immunocompromised patients.

Results: One hundred fifty-nine patients were included. Anti-HEV IgM seroprevalence in our cohort of non-traumatic, non-metabolic, non-vascular neurological injuries was 6.9% (eleven patients, including 4 Parsonage-Turner syndrome (PTS) and 2 Guillain-Barré syndrome (GBS)). Elevated transaminases were observed in only 64% of hepatitis E patients and cholestasis in 64%.

Conclusion: In this study, 6·9% of patients with acute non-traumatic, non-metabolic, non-vascular neurological injuries had a probable recent HEV infection. HEV serology should be systematically performed in this population, even in patients with normal transaminase level.
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http://dx.doi.org/10.1016/j.jiph.2019.12.012DOI Listing
July 2020

Men having sex with men and the HPV vaccine in France: A low vaccine coverage that may be due to its infrequent proposal by physicians.

Vaccine 2020 02 31;38(9):2160-2165. Epub 2020 Jan 31.

Service des Maladies Infectieuses, Centre hospitalier universitaire Grenoble Alpes, Grenoble, France; Fédération d'infectiologie multidisciplinaire de l'arc alpin, Université Grenoble Alpes, Grenoble, France; Institut de Biologie Structurale, "Virus humains persistants" Team, UMR 5075 CEA-CNRS-UGA, Grenoble, France. Electronic address:

Introduction: In France, the human papilloma (HPV) vaccine is recommended to all female adolescents, and since 2016 to men having sex with men (MSM) under the age of 27. Here, we aimed to explore HPV vaccine coverage in adult MSM living in France.

Methods: We elaborated an anonymous online questionnaire targeting MSM and disseminated it between October 7, 2018 and January 15, 2019 by various means, including a Facebook® discussion forum for pre-exposure prophylaxis (PrEP) users.

Results: Overall, 2094 participants completed the questionnaire (mean age 35.4 ± 11 years); 25.8% were in the age class targeted by the HPV vaccine recommendation; 16.1% were in a PrEP program. On a 1-10 scale, they evaluated being "in favor of vaccination" at a median of 10, and general vaccine usefulness and harmfulness at medians of 10 and 2, respectively; 62.4% considered that the HPV vaccine was rather not or not at all dangerous. Those using PrEP had better perceptions of vaccination in general and of the HPV vaccine in particular. For the 1728 participants with a family physician, he/she had proposed the HPV vaccine in 9.9% of cases (9.1% of those in the targeted age class [<27 years]). Overall, 1994 knew their HPV vaccine status; 8.0% had received at least 1 dose of the vaccine, including 17.9% of those in the targeted age class (and 52.2% among the 40 participants in this age group who received PrEP). When the 1935 participants who declared to be unvaccinated against HPV were asked whether they would accept to be vaccinated, 34.4% answered "rather yes" and 45.5% "definitely yes".

Conclusion: HPV vaccine coverage is low among French MSM. Our results suggest that this trend has more to do with the infrequent proposals made by clinicians than with negative vaccine perceptions.
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http://dx.doi.org/10.1016/j.vaccine.2020.01.049DOI Listing
February 2020

Factors Associated With Severe Nonmeningitis Invasive Pneumococcal Disease in Adults in France.

Open Forum Infect Dis 2019 Dec 30;6(12):ofz510. Epub 2019 Nov 30.

Hospital Centre Annecy Genevois, Annecy, France.

Background: In France, pneumococcal vaccination in adults is recommended for risk groups (chronic conditions/immunosuppression). We conducted a study on invasive pneumococcal disease (IPD) in adults to identify factors associated with disease severity and death.

Methods: We included IPD cases, excluding meningitis, from 25 acute care hospitals in 6 regions. We defined severe cases as those with shock or severe sepsis or intensive care unit admission/mechanical ventilation. We included deaths occurring within 30 days of hospitalization. Infectious disease specialists collected clinical/microbiological data on cases.

Results: During 2014-2017, 908 nonmeningitis IPD cases were diagnosed; 48% were severe, 84% had comorbidities, 21% died. Ninety percent of cases with comorbidities who previously sought health care were not vaccinated against pneumococcus. Compared with previously healthy cases, the risk of severe IPD increased from 20% (adjusted risk ratio [aRR], 1.2; 95% confidence interval [CI], 1.0-1.4) in cases with 1-2 chronic diseases to 30% (aRR, 1.3; 95% CI, 1.0-7.0) in those with >2 chronic diseases. Among risk groups, 13-valent pneumococcal conjugate vaccine (PCV13) serotypes and 23-valent pneumococcal polysaccharide vaccine (PPSV23) nonPCV13 serotypes were more likely to induce severe IPD compared with nonvaccine serotypes (aRR, 1.5; 95% CI, 1.3-1.9; aRR, 1.3; 95% CI, 1.0-1.5, respectively).

Conclusions: We observed a cumulative effect of concurrent comorbidities on severe IPD. Vaccine serotypes were more likely to induce severe IPD among risk groups. The missed opportunities for vaccination underscore the need to enhance vaccination in risk groups.
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http://dx.doi.org/10.1093/ofid/ofz510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918451PMC
December 2019

Behavior of nurses and nurse aides toward influenza vaccine: the impact of the perception of occupational working conditions.

Hum Vaccin Immunother 2020 05 6;16(5):1125-1131. Epub 2019 Dec 6.

Service de Maladies Infectieuses, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France.

Although influenza vaccination of hospital healthcare workers (HCWs) has been associated with a reduction in patient mortality and morbidity, HCW vaccine coverage is low in France. Previous studies identified the role of perceptions of vaccine efficacy and safety as well as practical issues (e.g., limited time). We aimed to determine whether HCW behavior toward influenza vaccine was associated with occupation-related psycho-social issues and perceptions of management. Between February and August 2018, an anonymous online questionnaire explored the perceptions and behavior of nurses and nurse aides regarding the influenza vaccine, as well as the perceived quality of professional management, perceived psychological contract breach, perceived workload, and compassion fatigue using previously validated scales. Among the 791 respondents (mean age 36.9 ± 10 years, female 85.0%; nurses 76.4%), 28.6% had been vaccinated during the current year (i.e., the study year) and 13.0% during the previous year. Among those not vaccinated during the study year, their vaccination intention for the coming year on a 1-5 scale was 1/5 for 68.5% and 5/5 for 15.4%. Positive behavior/intention regarding the influenza vaccine (recent vaccination and/or high future intention) was positively correlated with perceptions of management and negatively correlated with feelings of a psychological contract breach and compassion fatigue. In multivariate analysis, this positive behavior/intention was correlated with management perception independently of the perceptions of vaccination itself. Among nurses and nurse aides, the propensity to be vaccinated appears to depend closely on the perceived working conditions. These factors should be addressed when promoting vaccination among these populations.
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http://dx.doi.org/10.1080/21645515.2019.1694328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227720PMC
May 2020

Perception of mandatory infant vaccines and trust in vaccination among first-year healthcare students: An opportunity window for the training of future healthcare workers.

Vaccine 2020 01 7;38(4):794-799. Epub 2019 Nov 7.

Infectious and Tropical Diseases Unit, Grenoble-Alpes University Hospital, Grenoble, France; Fédération d'Infectiologie Multidisciplinaire de l'Arc Alpin, Université Grenoble Alpes, Grenoble, France. Electronic address:

Introduction: A high level of vaccine hesitancy is observed in France; to maintain a high level of vaccine coverage, a policy of mandatory vaccines has been applied since January 2019. As vaccine hesitancy has been described among healthcare workers, we aimed to assess the adhesion to vaccination in students enrolled in the first common year of healthcare studies (PACES), and their perceptions regarding the mandatory vaccine policy.

Methods: We elaborated an anonymous online questionnaire and asked the 35 French universities offering PACES studies to diffuse it to their students; 26 accepted.

Results: Overall, 4326 participants completed the questionnaire (age 18.7 ± 1.5 years, female 76.1%). They evaluated vaccine usefulness and harmfulness at a median of 90 [IQT:80-100] and 25 [IQT:10-50], respectively; on the same scale, their median trust in vaccines was 82 [IQT:70-94]. Among the five main age classes (17 to 21 years), the positive perceptions of vaccination declined with age. A majority declared that making vaccines mandatory was morally and scientifically justified (65.7% and 84.7%, respectively); in response to the questionnaire showing a blatant anti-mandatory vaccine billboard, 52.3% and 28.6%, respectively, strongly disagreed or rather disagreed with it. Again, these proportions declined between 17 and 21 years. Participants were asked whether the mandatory vaccine policy would improve their perceptions of vaccination; those with poorer perceptions were less likely to answer this question positively.

Conclusion: The perceptions of vaccination and the recent mandatory vaccine policy are positive in first-year students but better in younger ones, thus suggesting that vaccination should be taught early, during this study year. The mandatory vaccine policy may not improve the perceptions of those with a high level of vaccine hesitancy.
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http://dx.doi.org/10.1016/j.vaccine.2019.10.099DOI Listing
January 2020

A successful antibiotic treatment by a new administration route: a case report of a subcutaneous administration of ceftazidime and tobramycin.

Fundam Clin Pharmacol 2019 Dec 24;33(6):703-706. Epub 2019 May 24.

Pôle Pharmacie, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble 38000, France.

When intramuscular or intravenous administrations of parenteral drugs are not possible, the use of other routes (e.g., subcutaneous route) should be considered. We report a patient with Duchenne muscular dystrophy, who was hospitalized for acute pneumonia due to antibiotic-resistant strains of bacteria. Our patient was successfully recovered with antimicrobial therapy by subcutaneous administration of ceftazidime and tobramycin, for which no safety and efficacy data are available in humans. To the best of our knowledge, this case is the first supporting the subcutaneous administration safety and potential efficacy of both ceftazidime and tobramycin in humans.
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http://dx.doi.org/10.1111/fcp.12477DOI Listing
December 2019

Hepatic Brucelloma Diagnosis and Long-Term Treatment, France.

Emerg Infect Dis 2019 05;25(5):1021-1023

We report a case of hepatic brucelloma in France. This diagnosis may be suspected in any patient who has a liver abscess after traveling to a brucellosis-endemic area. Brucella spp. may be detected by PCR in the liver tissue or suppuration. Abscess drainage and prolonged antimicrobial therapy help achieve healing.
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http://dx.doi.org/10.3201/eid2505.180613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478221PMC
May 2019

Calprotectin discriminates septic arthritis from pseudogout and rheumatoid arthritis.

Rheumatology (Oxford) 2019 09;58(9):1644-1648

Infectious Diseases Unit, Centre Hospitalier Universitaire Grenoble Alpes.

Objective: We aimed to determine whether calprotectin and α-defensins could discriminate septic from other inflammatory arthritides.

Methods: Synovial fluids with a predominance of neutrophils from patients with septic arthritis, pseudogout and RA were prospectively collected. Neutrophil-related proteins calprotectin and human neutrophil α-defensins levels were assessed in synovial fluids. Demographic parameters and biomarkers with P-value ⩽0.05 for differentiating septic from non-septic arthritis were included in a multivariable model. Multivariable logistic regression with stepwise selection was performed to build the final combined model.

Results: A total of 74 patients were included: septic arthritis (n = 26), pseudogout (n = 28) and RA (n = 20). Patients with septic arthritis were more likely to be male and young, and to display higher synovial neutrophil count. Calprotectin was significantly increased in patients with septic arthritis. The multivariable model included calprotectin, synovial fluid neutrophil count and gender. Calprotectin was the only biomarker that discriminated septic arthritis from non-septic inflammatory arthritides, with 76% sensitivity, 94% specificity and a positive likelihood ratio = 12.2 at the threshold for calprotectin of 150 mg/l.

Conclusion: Synovial fluid calprotectin is a relevant biomarker to discriminate septic arthritis from other inflammatory arthritides. This biomarker should be tested in an independent cohort.
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http://dx.doi.org/10.1093/rheumatology/kez098DOI Listing
September 2019

Hypereosinophilia: Biological investigations and etiologies in a French metropolitan university hospital, and proposed approach for diagnostic evaluation.

PLoS One 2018 26;13(9):e0204468. Epub 2018 Sep 26.

Infectious Diseases Unit, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France.

Objectives: We aimed to evaluate the usefulness of biological investigations in cases of eosinophilia in our area (French Alps).

Methods: We retrospectively included all adult patients attending the infectious disease and internal medicine units between 2009 and 2015 with eosinophilia ≥1 G/l.

Results: We identified 298 cases (129 women and 169 men). In 139 patients, eosinophilia had not been addressed. In the 159 others, the cause of eosinophilia was identified in 118 (74.2%). The main identified causes at the time were drug reactions (24.5%, mostly β-lactams and allopurinol), infectious diseases (17.0%), vasculitis (8.2%), autoimmune diseases (6.9%), and malignant diseases (6.2%). In patients with a skin rash, eosinophilia was significantly more often investigated, and a diagnosis significantly more often made. Helminthosis were mainly diagnosed in tropical travelers (18/24) excepting toxocariasis (3 non-travelers). Stool examination for helminthosis was positive in 5/76 patients (6.6%) (all tropical travelers); 391 helminth serologies were performed in 91 patients, with 7.9% being positive (all but 3 positive cases were travelers). Anti-neutrophil cytoplasmic antibodies (ANCA) were positive in 26/112 patients (23.2%), with 9 cases of vasculitis identified.

Conclusions: Drug-related eosinophilia is the main etiology. Search for helminthosis is not recommended among non-travelers (excepting toxocariasis). ANCA should be performed early so as not to overlook vasculitis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204468PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157892PMC
March 2019

Midwives' perceptions of vaccines and their role as vaccinators: The emergence of a new immunization corps.

Vaccine 2018 08 30;36(34):5204-5209. Epub 2018 Jun 30.

Department of Infectious Diseases - Centre Hospitalier Universitaire Grenoble-Alpes, Grenoble, France; Fédération d'Infectiologie Multidisciplinaire de l'Arc Alpin - Université Grenoble-Alpes, Grenoble, France. Electronic address:

Background: In France, midwives have recently been authorized to administer various vaccines to women (including pregnant women), newborns, and their family members. This is expected to enhance vaccine coverage. However, the French high level of vaccine hesitancy is also observed in some healthcare workers. We thus aimed to determine the perceptions of French midwives concerning vaccines.

Methods: We distributed an anonymous online questionnaire between September and December 2017, targeting midwives who were still in training or working in the public or private sector.

Results: A total of 917 questionnaires were analyzed (median age 26 years). Almost half of participants (44.5%) were students. On a scale of 0-100, the median perception of the usefulness, safety, and trust of vaccinations were 92, 80, and 85, respectively. The mean scores of students were significantly higher for each perception, whereas in professional midwives, age and perceptions were negatively correlated. When asked whether there were scientific, philosophical, or religious arguments not to vaccinate, 83.2%, 69.8%, and 77.8% of participants disagreed, respectively. The vast majority (91.6%) was very or mostly favorable to the pertussis vaccine after delivery, but only around half (51.5%) to the influenza vaccine during pregnancy; those favorable to the pertussis vaccine were younger. A high proportion of participants (88.3%) considered that midwives were in a good position to vaccinate, with this proportion being even higher among students.

Conclusions: These results suggest that the recent authorization regarding vaccine administration will result in better vaccine coverage of pregnant women and their families by midwives. The better perceptions of younger participants are also encouraging. However, the level of trust in vaccinations (only 80.1%) and the low number of participants favorable to the influenza vaccine during pregnancy suggest that initial and continuous training should be reinforced.
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http://dx.doi.org/10.1016/j.vaccine.2018.06.050DOI Listing
August 2018

Perceptions of and intentions to use a recently introduced blood-based HIV self-test in France.

AIDS Care 2018 10 10;30(10):1223-1227. Epub 2018 Jun 10.

a Comité de Coordination de la Lutte contre le VIH (COREVIH) Arc Alpin , Grenoble , France.

An estimated 28,000 French people infected with HIV remain undiagnosed, leading to HIV transmission and late-stage HIV infections. An over-the-counter HIV self-test has been available since September 2015. We thus aimed to explore people's perceptions of and intentions to use the test. An anonymous online questionnaire, targeting the general population and men who have sex with men (MSM) was distributed between November 2015 and January 2016. It explored at-risk sexual behavior, perceptions of the HIV self-test, and past and intended future use. A total of 1,082 participants completed ≥90% of the questionnaire (67.1% male, 32.4% female, 0.5% other; mean age 32.8 ± 12 years). 44.8% were MSM. 41.5% declared that they did not always use or make their partner use a condom in the case of penetration with someone other than their usual partner (if applicable). 9.9% had already used the HIV self-test, with this proportion being higher in multivariate analysis for individuals with a monthly income exceeding €1,000 and those declaring to be informed about HIV. 38.5% stated their intention to use the self-test in the coming month or year; in multivariate analysis, this proportion was lower for MSM and higher for those who did not always use or make their partner use a condom in the case of penetration with someone other than their usual partner. The majority (68.4%) underestimated the testing delay to rule out HIV infection. The most frequently cited concerns were that self-test does not test for other sexually transmitted infections (49.5%) and is not free of charge (44.4%), and that users are left alone with the result (41.0%). The HIV self-test was identified as a useful tool by different at-risk populations; it may therefore enhance the number of diagnoses. The test delay must be appropriately communicated to users, while a lower purchase price may increase usage.
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http://dx.doi.org/10.1080/09540121.2018.1485837DOI Listing
October 2018

Exogenous human herpesvirus 6 reinfection after tumor-infiltrating T-lymphocyte therapy.

Cytotherapy 2018 04 9;20(4):521-523. Epub 2018 Feb 9.

Laboratory of Virology, University Hospital of Grenoble, Grenoble, France; Institut de Biologie Structurale, CEA, CNRS, Univ. Grenoble Alpes, Grenoble, France. Electronic address:

Exogenous human herpes virus 6 (HHV-6) reinfection has never been reported in patients receiving tumor-infiltrating T lymphocytes therapy. We report an unusual case of HHV-6 infection following infusion of HHV-6 infected autologous T lymphocytes. HHV-6 infection could interfere with the tumor antigen immune recognition and the efficacy of immunotherapy.
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http://dx.doi.org/10.1016/j.jcyt.2017.12.006DOI Listing
April 2018

Ultradeep sequencing of B and non-B HIV-1 subtypes: Viral diversity and drug resistance mutations before and after one month of antiretroviral therapy in naive patients.

J Clin Virol 2017 10 25;95:13-19. Epub 2017 Jul 25.

Team "HIV and human persistent viruses", Institut de Biologie Structurale, UMR5075 CNRS-CEA-UGA, Grenoble, France; Fédération d'Infectiologie Multidisciplinaire de l'Arc Alpin, Université Grenoble Alpes, France; Virology Laboratory, Infectious Agents Department, Centre Hospitalier Universitaire Grenoble Alpes, CS10217, 38043 Grenoble Cedex 9, France.

Background: Ultradeep pyrosequencing technologies permit an assessment of the genetic diversity and the presence and frequency of minority variants in a viral population. The effect of these parameters on the outcome of highly active antiretroviral therapy (HAART) in HIV-infected patients is poorly understood.

Objectives: The present study used the pyrosequencing Roche 454 prototype assay to determine whether antiretroviral efficacy is correlated with viral diversity and minority drug resistance mutations in HIV-infected treatment-naive patients and to compare assay performance in B and non-B subtypes.

Study Design: The study included 30 HIV-1 infected naive patients (20 with subtype non-B and 10 with subtype B). Ultradeep pyrosequencing of protease and reverse transcriptase genes was performed at baseline and 1 month after HAART initiation. Plasma HIV VL was measured at 0 and after 1, 3, and 6 months of HAART.

Results: Pre-HAART minority drug resistance mutations were observed to NRTI in 4 patients, to NNRTI in 6 patients, and to PI in 1 patient; there was no difference in HAART-induced VL decay between patients. Pre-HAART diversity was significantly correlated with the time elapsed since HIV-1 infection diagnosis, but not with the subtype, VL, or CD4 count. Patients with an undetectable VL after 3 months of HAART had a higher pre-HAART diversity. Pre- and post-HAART diversities were not statistically different. There was no difference in assay performance between subtype B and non-B.

Conclusions: A high pre-HAART viral diversity might have a positive effect on the outcome of HAART. Pre-therapeutic minority drug resistance mutations are uncommon in naive patients.
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http://dx.doi.org/10.1016/j.jcv.2017.07.013DOI Listing
October 2017

Added Value of Next-Generation Sequencing for Multilocus Sequence Typing Analysis of a Pneumocystis jirovecii Pneumonia Outbreak1.

Emerg Infect Dis 2017 08;23(8):1237-1245

Pneumocystis jirovecii is a major threat for immunocompromised patients, and clusters of pneumocystis pneumonia (PCP) have been increasingly described in transplant units during the past decade. Exploring an outbreak transmission network requires complementary spatiotemporal and strain-typing approaches. We analyzed a PCP outbreak and demonstrated the added value of next-generation sequencing (NGS) for the multilocus sequence typing (MLST) study of P. jirovecii strains. Thirty-two PCP patients were included. Among the 12 solid organ transplant patients, 5 shared a major and unique genotype that was also found as a minor strain in a sixth patient. A transmission map analysis strengthened the suspicion of nosocomial acquisition of this strain for the 6 patients. NGS-MLST enables accurate determination of subpopulation, which allowed excluding other patients from the transmission network. NGS-MLST genotyping approach was essential to deciphering this outbreak. This innovative approach brings new insights for future epidemiologic studies on this uncultivable opportunistic fungus.
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http://dx.doi.org/10.3201/eid2308.161295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547796PMC
August 2017

Thrombosis and antiphospholipid antibody syndrome during acute Q fever: A cross-sectional study.

Medicine (Baltimore) 2017 Jul;96(29):e7578

URMITE, Aix Marseille Université, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU - Méditerranée Infection Aix Marseille Univ, APHM, INSERM, VRCM, UMR_S 1076, Laboratoire d'Immunologie, Marseille Service de médecine interne Service de maladies infectieuses, Centre Hospitalier Universitaire de Grenoble, Grenoble Service de médecine interne, Centre hospitalier d'Avignon, Avignon Service de médecine interne et tropicale, Hôpital d'Instruction des Armées Laveran, Marseille Service de neurologie, Hôpital de Valence, Valence Service de maladies infectieuses, Hôpital Bretonneau, Tours Centre Hospitalier Universitaire de Nice, Nice Service de médecine interne et maladies infectieuses, CHU de Poitiers, Inserm, Poitiers Service de maladies infectieuses, CHU de Montpellier, Montpellier Centre Hospitalier Andrée-Rosemon, Cayenne, Guyane Aix Marseille Univ, INSERM, UMR912 (SESSTIM), IRD ORS PACA Laboratoire d'Hématologie, CHU Timone, APHM, Marseille, France.

Q fever is a neglected and potentially fatal disease. During acute Q fever, antiphospholipid antibodies are very prevalent and have been associated with fever, thrombocytopenia, acquired heart valve disease, and progression to chronic endocarditis. However, thrombosis, the main clinical criterion of the 2006 updated classification of the antiphospholipid syndrome, has not been assessed in this context. To test whether thrombosis is associated with antiphospholipid antibodies and whether the criteria for antiphospholipid syndrome can be met in patients with acute Q fever, we conducted a cross-sectional study at the French National Referral Center for Q fever.Patients included were diagnosed with acute Q fever in our Center between January 2007 and December 2015. Each patient's history and clinical characteristics were recorded with a standardized questionnaire. Predictive factors associated with thrombosis were assessed using a rare events logistic regression model. IgG anticardiolipin antibodies (IgG aCL) assessed by an enzyme-linked immunosorbent assay were tested on the Q fever diagnostic serum. A dose-dependent relationship between IgG aCL levels and thrombosis was tested using a receiver operating characteristic (ROC) analysis.Of the 664 patients identified for inclusion in the study, 313 (47.1%) had positive IgG aCL and 13 (1.9%) were diagnosed with thrombosis. Three patients fulfilled the antiphospholipid syndrome criteria. After multiple adjustments, only positive IgG aCL (relative risk, 14.46 [1.85-113.14], P = .011) were independently associated with thrombosis. ROC analysis identified a dose-dependent relationship between IgG aCL levels and occurrence of thrombosis (area under curve, 0.83, 95%CI [0.73-0.93], P < .001).During acute Q fever, antiphospholipid antibodies are associated with thrombosis, thrombocytopenia, and acquired valvular heart disease. Antiphospholipid antibodies should be systematically assessed in acute Q fever patients. Hydroxychloroquine, which has been previously shown to antagonize IgG aCL pathogenic properties, should be tested in acute Q fever patients with anticardiolipin antibodies to prevent antiphospholipid-associated complications.Key Point: In addition to fever, thrombocytopenia and acquired valvular heart disease, antiphospholipid antibodies are associated with thrombosis during acute Q fever.
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http://dx.doi.org/10.1097/MD.0000000000007578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5521934PMC
July 2017

Evolution of EBV seroprevalence and primary infection age in a French hospital and a city laboratory network, 2000-2016.

PLoS One 2017 17;12(4):e0175574. Epub 2017 Apr 17.

Infectious Disease Unit, Grenoble University Hospital, Grenoble, France.

Background: According to rare studies, the age at EBV primary infection (PI) has recently risen in some developed countries. A later age at infection is generally considered a risk factor for severe EBV PI, although few studies exist on this subject. Our investigation aimed to determine whether EBV seroprevalence and EBV PI epidemiology have evolved in France, and to what extent age and infection intensity (regarding biological parameters) are correlated.

Methods And Findings: We conducted a retrospective study of the following EBV serological tests databases: tests carried out at Grenoble University Hospital (2000-2016) (n = 53,553); and tests carried out by a network of city laboratories in Grenoble area (2008-2015) (n = 27,485). The hospital population showed a continuous, significant decrease in EBV seroprevalence over the studied period for patients aged 20 and over (p<0.01). The seroprevalence also decreased for different age classes (<10, 15-19, 20-30, and 30-40 years old) over the periods 2001-2005, 2006-2010, and 2011-2015. Consistently, the age at PI was significantly higher in the years 2008-2015 than in the years 2001-2007 (15.6±12.0 vs. 13.7±11.0; p = 0.03). The city laboratory population showed the same trend of decreasing seroprevalence (p = 0.06); no significant variations in age at PI were observed. The age at PI was positively correlated with ASAT, ALAT, γGT, and bilirubin blood levels (p<0.01) and negatively correlated with platelet counts (p<0.05).

Conclusion: In the last 15 years, the age at EBV PI has increased, whereas seroprevalence has decreased. Moreover, our findings confirm the positive correlation between age and biological abnormalities. Taken together, these results suggest that the incidence of severe EBV PI will increase in the future.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175574PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5393566PMC
April 2017

[Controversy surrounding the vaccine: what to do]?

Rev Prat 2017 01;67(1):17-19

Service de maladies infectieuses et médecine tropicale, CHU de Grenoble, Groupe VIH et virus humains persistants, institut de biologie structurale, Grenoble, France, Bureau de coordination du groupe vaccination et prévention de la Société de pathologie infectieuse de langue française, Paris, France.

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January 2017

Negative perceptions of hepatitis B vaccination among attendees of an urban free testing center for sexually transmitted infections in France.

Hum Vaccin Immunother 2017 05 12;13(5):998-1004. Epub 2016 Dec 12.

b Free testing center for sexually transmitted infections (CEGIDD) , Conseil Général de l'Isère , Grenoble , France.

Background: Official French health care policy recommends vaccinations against hepatitis B for all infants and at-risk adults. Attendees at our free testing center for sexually transmitted infections (FTC-STI) routinely express hepatitis B vaccine hesitancy. We aimed in this exposed population to explore the extent of knowledge concerning HBV infection, to quantify HBV vaccine refusal, and to identify the reasons for this refusal.

Methods: During a 3-month period in 2013, all attendees at the Grenoble FTC-STI were given an anonymous questionnaire exploring their knowledge of hepatitis B, perception of the hepatitis B vaccine, acceptance of free same-day hepatitis B vaccination, and reasons for refusing this offer (where applicable).

Results: The questionnaire was completed by 735 attendees (64.7% of those attending during the study period)(59.9% men; age 27.9 ± 9.2). Most respondents identified hepatitis B as a potentially severe, potentially lifelong illness existing in France. Concerning the hepatitis B vaccine, less than 50% totally or mostly agreed that it is safe; when asked whether the vaccine is dangerous, 44.2% answered "I don't know" and 14.0% agreed; when asked whether the vaccine is "not well characterized," 45.0%, answered "I don't know" and 26.5% agreed. When asked whether they mistrust the hepatitis B vaccine or all vaccines in general, 39.0% and 28.9% of those unvaccinated agreed, respectively. Two thirds refused to get vaccinated on the same day. When asked whether they were afraid of the adverse effects of this vaccine, only 18.7% disagreed.

Conclusion: Negative perceptions of the hepatitis B vaccine are widespread in this at-risk population. Consequently, a successful communication strategy must reassure this at-risk population of the vaccine's innocuous nature.
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http://dx.doi.org/10.1080/21645515.2016.1264549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443383PMC
May 2017

Grouped Cases of Pulmonary Pneumocystosis After Solid Organ Transplantation: Advantages of Coordination by an Infectious Diseases Unit for Overall Management and Epidemiological Monitoring.

Infect Control Hosp Epidemiol 2017 02 28;38(2):179-185. Epub 2016 Nov 28.

4Service de Maladies Infectieuses et Tropicales,CHU de Grenoble,France.

OBJECTIVE To determine the origin of grouped cases of Pneumocystis pneumonia in solid-organ transplant recipients at our institution. DESIGN A case series with clinical examinations, genotyping, and an epidemiological survey. SETTING A university hospital in France. PATIENTS We report 12 solid-organ transplant recipients with successive cases of Pneumocystis pneumonia that occurred over 3 years; 10 of these cases occurred in a single year. METHODS We used molecular typing of P. jirovecii strains by multilocus sequence typing and clinical epidemiological survey to determine potential dates and places of transmission. RESULTS Between May 2014 and March 2015, 10 solid-organ transplant recipients (5 kidney transplants, 4 heart transplants, and 1 lung transplant) presented with Pneumocystis pneumonia. Molecular genotyping revealed the same P. jirovecii strain in at least 6 patients. This Pneumocystis strain was not identified in control patients (ie, nontransplant patients presenting with pulmonary pneumocystosis) during this period. The epidemiological survey guided by sequencing results provided information on the probable or possible dates and places of contamination for 5 of these patients. The mobile infectious diseases unit played a coordination role in the clinical management (adaptation of the local guidelines) and epidemiological survey. CONCLUSION Our cardiac and kidney transplant units experienced grouped cases of pulmonary pneumocystosis. Genotyping and epidemiological surveying results suggested interhuman contamination, which was quickly eliminated thanks to multidisciplinary coordination. Infect Control Hosp Epidemiol 2017;38:179-185.
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http://dx.doi.org/10.1017/ice.2016.274DOI Listing
February 2017

Herpes simplex type 2 encephalitis and methotrexate medication: a fortuitous or causative association in a patient with spondyloarthritis?

Antivir Ther 2017 23;22(4):357-359. Epub 2016 Nov 23.

Laboratory of Virology, University Hospital of Grenoble, Grenoble, France.

It is unclear whether immunosuppression is a risk factor for herpes encephalitis. Herein, we describe a rare case of herpes simplex virus type 2 encephalitis in a patient treated with low-dose methotrexate for HLA-B27-associated spondyloarthritis. The patient was successfully treated with acyclovir but presented sequelae of encephalitis. Here we discuss the possible role of low-dose methotrexate therapy as a risk factor of neurological herpes reactivation and severe disease. The host-related and viral risk factors are also addressed.
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http://dx.doi.org/10.3851/IMP3110DOI Listing
May 2018

Influence of the First Consultation on Adherence to Antiretroviral Therapy for HIV-infected Patients.

Open AIDS J 2016 7;10:182-189. Epub 2016 Sep 7.

Service des Maladies Infectieuses, Centre Hospitalier Universitaire de Grenoble, Grenoble, France; Université Grenoble Alpes, Grenoble,France; Team "HIV and other human persistent viruses", Institut de Biologie Structurale, UMR 5075 UGA-CEA-CNRS, Grenoble, France.

Background: Physician attitude influences the way patients cope with diagnosis and therapy in chronic severe diseases such as cancer. Previous studies showed that such an effect exists in HIV care; it is likely that it begins with the first contact with a physician.

Objective: We aimed to explore in HIV-infected persons their perception of the first consultation they had with an HIV specialist (PFC-H), and whether this perception correlates with adherence to antiretroviral therapy.

Method: The study was conducted in Grenoble University Hospital, France, a tertiary care center. Every antiretroviral-experienced patient was asked to freely complete a self-reported, anonymous questionnaire concerning retrospective PFC-H, present adherence (Morisky scale), and present perceptions and beliefs about medicine (BMQ scale).

Results: One hundred and fifty-one questionnaires were available for evaluation. PFC-H score and adherence were correlated, independently from age, gender, and numbers of pill(s) and of pill intake(s) per day. BMQ score also correlated with adherence; structural equation analysis suggested that the effect of PFC-H on adherence is mediated by positive beliefs.

Conclusion: These results suggest that for HIV-infected persons, the perceptions remaining from the first consultation with an HIV specialist physician influence important issues such as adherence and perception about medicine. Physicians must be aware of this potentially long-lasting effect.
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http://dx.doi.org/10.2174/1874613601610010182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037933PMC
September 2016

Dynamics of Epstein-Barr viral load after hematopoietic stem cell transplantation and effect of preemptive rituximab therapy.

Transpl Infect Dis 2016 Dec 24;18(6):889-895. Epub 2016 Nov 24.

Infectious Disease Unit, University Hospital, Grenoble, France.

Background: Epstein-Barr virus (EBV) displays oncogenic properties, particularly in the immunocompromised host. Notably, hematopoietic stem cell transplantation (HSCT) recipients with a detectable blood EBV viral load (BEBVL) are considered at higher risk of post-transplant lymphoproliferative diseases (PTLD). Therefore, BEBVL is monitored after HSCT, and preemptive rituximab may be used in patients with high values. However, little is known about post-HSCT BEBVL dynamics, and the threshold that should lead to anti-CD20 therapy is poorly defined.

Methods: We retrospectively analyzed the post-HSCT BEBVL of 332 adult HSCT recipients in our center from 2005 to 2013, including the effect of rituximab.

Results: Detection of BEBVL >100, 1000, 5000, 10 000, and 50 000 copies/mL occurred in, respectively, 77.7%, 69.6%, 37.0%, 27.1%, and 7.5% of the patients after a respective median time of 9, 14, 15, 16, and 14 weeks. No BEBVL threshold was associated with an overall survival difference. Seventy-eight patients received rituximab, with a BEBVL decrease in most. Among patients with detectable BEBVL, long-term survival did not differ in rituximab treated and non-treated, except for patients with BEBVL ≥50 000. Only one case of PTLD was observed.

Conclusions: BEBVL is frequently detectable after HSCT, but suggests no strong association with survival. Preemptive rituximab therapy threshold remains to be defined.
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http://dx.doi.org/10.1111/tid.12618DOI Listing
December 2016