Maxime Hentzien

Impact of age-related comorbidities on five-year overall mortality among elderly HIV-infected patients in the late HAART era — Role of chronic renal disease

ObjectivesTo identify main prognostic factors for 5-year mortality among age-related comorbidities (ARCs) in older people living with HIV (PLHIV).DesignA prospective, multicentre cohort study with a 5-year follow-up period in the late HAART era (from January 2008 to December 2012).SettingThe Dat’AIDS cohort involving 12 French hospitals.ParticipantsAll actively followed HIV-1 infected patients aged 60 or older.MeasurementsThe study endpoint was all-cause five-year mortality. The following ARCs were considered: chronic renal disease, cardiovascular diseases, cancer, chronic pulmonary disease, cirrhosis, diabetes and nutritional status. Hepatitis C (HCV), hepatitis B (HBV) co-infection and sociodemographic characteristics were also evaluated. Cox’s Proportional Hazards model was used for multivariate analysis.ResultsAmong 1415 PLHIV aged 60 or more patients included, mean age was 66±5.5 years; 154 died (mortality rate 2.47/100 patientyears). The most prevalent ARCs were chronic renal disease (20.1%), diabetes (14.2%) and cardiovascular diseases (12.2%). By multivariate analysis, chronic renal disease (adjusted hazard ratio (aHR)=2.25; 95% confidence interval (CI) [1.58-2.21]; p<10-4), cardiovascular diseases (aHR=2.40; 95%CI[1.64-3.52]; p<10-4), non-HIV related cancer (aHR=1.91; 95%CI[1.20-3.05]; p=0.007), cirrhosis (aHR=2.99; 95%CI[1.68-5.33]; p<10-3), HCV co-infection (aHR=2.00; 95%CI[1.18-3.38]; p=0.009), low body mass index (aHR=2.42; 95%CI[1.46-4.01]; p<10-3) and CD4 cell count < 200cells/μl (aHR=2.23; 95%CI[1.36-3.65]; p=0.002) were independently associated with 5 year mortality.ConclusionDue to a high prevalence, chronic renal disease and cardiovascular disease are main prognostic factors for 5-year mortality among aged PLHIV.

Poor knowledge among French travellers of the risk of acquiring multidrug-resistant bacteria during travel

Since it is not routine practice in France to raise public awareness about the risk of acquiring multidrug-resistant Enterobacteriaceae (MRE) during international travel, we aimed to determine, among French travellers attending a consultation for travel medicine, their level of knowledge about the risk of acquiring MRE. Among 191 adults enrolled in the study, only 10% of travellers were aware of the risk of becoming a carrier of MRE during travel, and 87% did not understand the difference between being colonized with MRE, and having a clinical infection with MRE. Consultations for travel medicine could be an opportunity to deliver specific information about the risks of acquiring MRE. Antibiotic resistance among Gram-negative bacteria is an emerging problem worldwide, mainly with the diffusion of extended spectrum beta-lactamase, plasmid-encoded cephalosporinases and carbapenemases-producing Enterobacteriaceae. These strains often show multi-resistance and are now diffusing worldwide in the community setting, outside of the hospital. Travel in areas endemic for multidrug-resistant Enterobacteriaceae (MRE) has been identified as a risk factor for the acquisition of MRE.1–5 Faecal colonization with MRE is very frequent among travellers to tropical regions, with a risk ranging from 20 to 70%, especially among those visiting the South Asian continent.2,3,5 Moreover, antibiotic use could favour proliferation of MRE by disrupting the intestinal microbiota balance, and the use of antibiotics for travel diarrhoea was associated with a 4-fold increase in the risk of acquiring MRE, whereas travel diarrhoea itself was only associated with a 2-fold increase in risk.2,3,6 Taken together, these elements suggest that informing the public about the risk of acquiring MRE during international travel could represent a preventive measure against the spread of MRE in France. The French public has been made aware of multidrug-resistant (MDR) bacteria through a media campaign conducted …

Macroscopic amoxicillin crystalluria.

A 62-year-old woman was referred to our hospital in September, 2013, with fever, arthralgia, and dyspnoea lasting for 6 days. Her medical history was uneventful apart from hypertension and active tobacco use. Her glomerular fi ltration rate at admission was 82 mL/min per 1·73 m2 (normal range ≥90 mL/min per 1·73 m2). Blood cultures on admission grew Strepto coccus agalactiae and acute aortic infective endocarditis was rapidly diagnosed with transoesophageal echocardiography. She was immediately started on highdose intravenous amoxicillin (200 mg/kg per day) with intravenous gentamicin (240 mg once-daily). After 4 days, we noticed cloudy urine, with a thin granular appearance (fi gure). Her urine pH was 5·5. Direct examination of the urine showed amoxicillin crystalluria with large, typically aggregated needle-shaped crystals (fi gure) that were birefringent under polarised light microscopy. Her clinical condition worsened with oliguria, acute renal failure, and pulmonary oedema within 24 h. An aortic ring abscess was evident on a second echocardiography. After emergency valve replacement surgery and renal replacement therapy, she recovered well and was discharged home in October, 2013, without further renal replacement therapy, and with improving renal function. Her last glomerular fi ltration rate was 45 mL/min per 1·73 m2 in March, 2014. At last follow-up, in September, 2014, the patient was asymptomatic. Amoxicillin is known to cause urine crystallisation, although its incidence is unknown. Amoxicillin crystalluria usually occurs with high-dose amoxicillin therapy, in urines that have a low pH and are highdensity (mainly due to insuffi cient fl uid intakes). Amoxicillin crystalluria can be microscopic or macroscopic. The typical microscopic appearance described here is usually suffi cient for diagnosis in a compatible context but the amoxicillin composition of these crystals can be confi rmed by infrared spectroscopy if needed. Amoxicillin crystalluria can be asymptomatic or can be responsible for haematuria or acute renal failure attributable to intratubular precipitation or urinary tract obstruction. In our patient, acute renal failure was multifactorial, but we speculate that amoxicillin crystalluria could have played a part. Physicians should be aware of such a complication of amoxicillin because high intravenous doses are frequently prescribed worldwide and because urine alkalinisation and increased fl uid intake might prevent crystalluria.

Epidemiology of autoimmune and inflammatory diseases in a French nationwide HIV cohort

Background: HIV infection and inflammatory and autoimmune diseases (IADs) are both related to immune dysfunction. Epidemiological data on IAD in patients living with HIV (PLHIV) are scarce. The aim of this study was thus to estimate the prevalence of 26 IAD among PLHIV followed in a large French multicenter cohort in the combination antiretroviral therapy (cART) era (from January 2000 to July 2013), and to describe their occurrence according to cART onset, the immuno-virological status of patients and hepatitis C virus (HCV) and/or hepatitis B virus coinfection. Method and results: During the study period, 33 403 PLHIV were included in the Dat’AIDS cohort; 1381 patients with an IAD were identified. The most prevalent IADs were psoriasis, sarcoidosis, rheumatoid arthritis, ankylosing spondyloarthritis, Graves disease, autoimmune hemolytic anemia, immune thrombocytopenia and chronic inflammatory bowel disease. In contrast, the prevalence of systemic lupus erythematosus and multiple sclerosis were low. Most patients (59%) developed IAD after HIV infection with a mean delay of 10.6 ± 6.4 years. Compared with the entire cohort, HCV coinfection was significantly more frequent in patients with psoriasis, Graves disease and immune thrombocytopenia, and chronic hepatitis B in patients was more frequent in those with immune thrombocytopenia and autoimmune hemolytic anemia. Among patients developing IAD after the diagnosis of HIV infection, 572 (70%) were on antiretroviral therapy and 419 of them (73%) had undetectable HIV viral load. Conclusion: Our study showed that some IAD are not rare among PLHIV and occur mostly in patients with immuno-virological control under cART. The higher frequency of HCV or hepatitis B virus coinfection for some IAD is also confirmed.

A comparison between intravascular and traditional cooling for inducing and maintaining temperature control in patients following cardiac arrest

Therapeutic temperature control has been widely used during the last decade to improve clinical outcomes. We conducted this retrospective observational study to compare traditional cooling with endovascular cooling in post-cardiac arrest comatose survivors and to compare results with current guidelines. PATIENTS AND METHODS All patients admitted to our ICU for cardiac arrest and for whom temperature control was performed were included. Traditional cooling included cold infusions, ice packs and cooling blankets. Endovascular cooling consisted in the insertion of a catheter in which cold fluid circulates in a closed circuit provided by a heat exchanger. Temperature control was started at a target temperature of 32°C to 34°C. Rewarming was performed passively in the traditional group and via computer-assistance in endovascular group. We evaluated the delay prior to and speed of cooling, thermic stability during the maintenance phase and the speed of rewarming. RESULTS Thirty-four patients were included. The speed of cooling was faster with the endovascular (-0.66±0.35°C/h) compared to the traditional (-0.35±0.38°C/h, P=0.006) technique, with target temperatures reached in 4.0 and 6.0h, respectively (P=0.14). Temperatures were more stable with the endovascular technique (0.03±0.05°C2) than with the traditional technique (0.26±0.16°C2, P<10-4). There were more deviations from the guideline target range in the traditional group (64.7% versus 17.6%, P=0.008). Rewarming was faster in the traditional group (+0.64±0.33°C/h, versus +0.36±0.12°C/h, P=0.01). No significant difference was found concerning mortality or length of stay in the ICU. CONCLUSION Temperature control with a cooling catheter was associated with faster cooling, improved thermic stability in the target range, less overcooling or overheating and slower rewarming in comparison with traditional techniques.

High prevalence of measles seronegativity in adults with HIV infection born in the era of measles vaccination in Northern France.

We investigated measles humoral immunity levels in a cohort of HIV-infected adult patients in France and attempted to identify risk factors for antimeasles antibodies seronegativity. Being born after 1983 [odds ratio (OR) 4.40; 95% confidence interval (95% CI) 1.26–14.09; P = 0.0013] and a nadir CD4+ cell count below 100 cells/&mgr;l (OR 4.79; 95% CI 1.61–14.82; P = 0.0048) were the two factors independently associated with measles seronegativity. Systematic measles antibody screening should be performed in HIV-infected individuals born in the era of measles vaccination (after 1983 in France).

Screening for Chikungunya virus infection in aged people: Development and internal validation of a new score

Background This study aimed to derive and validate a score for Chikungunya virus (CHIKV) infection screening in old people admitted to acute care units. Methods This study was performed in the Martinique University Hospitals from retrospective cases. Patients were aged 65+, admitted to acute care units for suspected CHIKV infection in 2014, with biological testing using Reverse Transcription Polymerase Chain Reaction (RT-PCR). RT-PCR was used as the gold standard. A screening score was created using adjusted odds ratios of factors associated with positive RT-PCR derived from a multivariable logistic regression model. A ROC curve was used to determine the best cut-off of the score. Bootstrap analysis was used to evaluate its internal validity. Results In all, 687 patients were included, 68% with confirmed CHIKV infection, and 32% with laboratory-unconfirmed CHIKV infection. Mean age was 80±8 years, 51% were women. Four variables were found to be independently associated with positive RT-PCR (fever: 3 points; arthralgia of the ankle: 2 points; lymphopenia: 6 points; absence of neutrophil leucocytosis: 10 points). The best cut-off was score ≥12; sensitivity was 87% (83%-90%) and specificity was 70% (63%-76%). Conclusion This score shows good diagnostic performance and good internal validation and could be helpful to screen aged people for CHIKV infection.

Derivation and internal validation of a mortality risk index for aged people living with HIV: The Dat'AIDS score

Objective The objective was to develop a multivariable prognostic index for overall mortality over a five-year span integrating classical HIV biomarkers and comorbidities in people living with HIV (PLHIV) aged 60 or older. Design Prospective multicenter cohort study from the French Dat’AIDS cohort. Methods All HIV-1 infected patients aged 60 years or older on 1st January 2008 were included. Sociodemographic data, CD4 cell count, CD4 nadir, HIV viral load, history of comorbidities, hepatitis co-infections and laboratory parameters at baseline were considered as potential prognostic variables. Primary outcome was all-cause mortality. Results Among 1415 patients included, we derived a score comprising the following predictors: Age (65–74: 1 point; ≥75: 8 points), CD4 cell count (200–349: 3 points; <200: 6 points), non-HIV related cancer (6 points), cardiovascular disease (8 points), estimated glomerular filtration rate (30–59 mL/min/1.73m2: 5 points; <30mL/min/1.73m2: 16 points), cirrhosis (13 points), low body mass index (<18.5 kg/m2, 10 points), anemia (6 points). Mean observed score was 7.0 ± 8.0 and ranged from 0 to 45. Score categories defined 4 risk groups for mortality: low, moderate, high and very high risk (5-year survival probability 0.95 (95%CI[0.93–0.97]), 0.90 (95%CI[0.87–0.92]), 0.77 (95%CI[0.68–0.84]) and 0.54 (95%CI[0.43–0.63]) respectively). The score showed good discrimination (C-statistic = 0.76) and calibration. Conclusions We propose a multivariable prognostic score for mortality among PLHIV aged 60 or over, who will become the predominant population in future years in western populations. It could be a useful tool for research, for developing preventive and treatment strategies according to risk group, and for risk assessment by clinicians.

Bioclinical Test to Predict Nephropathia Epidemica Severity at Hospital Admission

This test identifies patients at low, intermediate, and high risk for severe disease.

Clinical Forms of Chikungunya Virus Infection: The Challenge and Utility of a Consensus Definition

We read with great interest the recently published article by Dorléans et al. entitled “Outbreak of Chikungunya in the French Caribbean Islands of Martinique and Guadeloupe.” The authors provide useful and relevant data about this emerging disease, and the study had several strong points that deserve to be underlined. First, data collection was prospective, using a standardized questionnaire and, thus, of high quality. Second, cases of chikungunya virus infection (CVI) were prospectively identified by reverse transcriptase-polymerase chain reaction (RT-PCR) or by serology immunoglobulinM (IgM). Third, preliminary data were recorded using a specialized informatics system dedicated to priority infectious diseases in France. Fourth, additional datawere retrospectively recorded by specialized researchpersonnel.However,wewould like tomake some additional remarks specifically regarding the population of patients aged 65 years or older. In 2015, the World Health Organization (WHO) brought together anexpert group todevelopconsensusdefinitionsof the clinical forms of CVI. The resulting definitions described three clinical forms at the acute phase, based on clinical, epidemiological, and laboratory criteria. A confirmed typical case is defined by “fever AND joint pain with acute onset” AND “residing or visiting areas with local transmission of Chikungunya” OR “laboratory confirmation by immunoglobulin or RT-PCR.” Confirmed atypical cases are defined by the same criteria AND the presence of other clinical or biological manifestations (including neurological, cardiovascular, and hepatic findings). Confirmed severe cases are defined by the same criteria and dysfunction of at least one organ or system that threatens life and requires hospitalization. In their article, Dorléans et al. classified their patients according to three clinical forms (typical, atypical, and severe) based on signs observed at the acute phase but without reference to the WHOclassification. Indeed, the authors used the same terms as those described by the WHO, but the criteria are not the same, which could create confusion and may leave room for misinterpretation. For example, according to the definition proposed by Dorléans et al., tenosynovitis, rash, or diarrhea would each alone be considered as representative of typical CVI. Similarly, encephalitis, which can be life-threatening, was considered as a sign of atypical presentation, and not as severe disease. Several authors have already reported that the definition of the clinical forms of CVI is not applicable in infants or in older adults. In the study reported by Dorléans et al., 17% of subjects were aged less than 1 year and 40% were aged more than 60 years. Therefore, this raises the question of the validity of “one size fits all” definitions supposedly applicable to all populations. Regarding elderly subjects, the frequently atypical clinical profile of CVI in this population renders it difficult to unmask the diagnosis. Accordingly, Godaert et al. have reported that the rate of under-diagnosis of CVI in a population of patients attending the emergency department was more than 20% among those aged 65 years or more, compared with around 3% in younger patients. Indeed, the usual presentation of CVI is different in elderly subjects, and the screening tools used in 2014 performonlymoderately well in elderly subjects. In view of the inclusion criteria, and in particular, the hospital-based population included in the study by Dorléans et al., the frequency of each form of disease described in their article likely does not represent the true frequency observed in the general population. The authors underline that subjects aged 60 years and older represented 69.5% of patients with severe forms versus 33.6% of non-severe forms of CVI. The fact that severe forms of CVI are more common in hospitalized older adults has also been reported previously. Godaert et al. compared the frequency of clinical forms, as defined by the WHO, between subjects aged 65 years and older and their younger counterparts, among patients presenting from their home to the emergency department within 3 days of onset of symptoms of CVI. There was no statistically significant difference in the frequency of severe disease between the two populations, but older subjects more frequently presented atypical forms, as defined by the WHO. This finding suggests that there may be some selection bias among hospitalized patients. Regarding in-hospital mortality, Dorléans et al. report a death rate of 4% in the overall population. A previous study among patients aged 65 years and older reported a mortality of 9.1% in this group, and the predictors of death identified were the presence of cardiovascular, respiratory, neurological, or digestive disorders, and a history of alcoholism. Therefore, these should all be considered as signs of disease severity in this population and not signs of atypical presentation. Dorléans et al. reported that there were 74 deaths in their study, but it would have been interesting to specify the distribution of these deaths according to the clinical forms they described. All these points underline the importance of using consensus definitions for the clinical forms of disease that are applicable in each patient population. The use of standardized terms would greatly facilitate comparisons between studies. Secondly, the findings of Dorléans et al. underscore the fact that CVI takes a heavy toll on older subjects and, therefore, specific studies are warranted to improve diagnosis and provide adequate management in this population.