[Characteristics of patients admitted from emergency units in 18 internal medicine departments and organisation of these departments: A cross sectional study from SNFMI (SiFMI study group) in 2015]. / Caractéristiques des patients admis en médecine interne dans 18 hôpitaux français en aval des urgences et organisation de ces services : enquête transversale de la SNFMI (groupe d'étude SiFMI) en 2015.

INTRODUCTION: Patients admitted from emergency units represent a large portion of the population in internal medicine departments. The aim of this study is to identify characteristics of patients and organization of these departments. METHODS: Between June 29th and July 26th 2015, voluntary internal medicine departments from the SiFMI group prospectively filled anonymized internet forms to collect data of each patients admitted in their ward from emergency units, during seven consecutive days. RESULTS: Three hundred and sixty-five patients from emergency departments were admitted in 18 internal medicine inpatients departments, totalling 1100 beds and 33,530 annual stays, 56% of them for emergency units inpatients. Mean age was 68 years, 54% were women, mean Charlson score was 2.6 and 44% of the patients took at least three drugs. Main causes of hospitalization were infectious (29%) and neurological (17%) diseases. Mean length of stay was 9.2 days. The medical team was composed by a median value of 4,5 [2,75-6,25] senior full-time equivalents, 86% were internists. Each department except one received residents, two third of them were from general medicine. CONCLUSION: This study highlights a high organizational variability among internal medicine departments and patients, and sets internal medicine as a specialty with a great capacity to achieve an integrative/comprehensive management of patients and to offer a comprehensive basis for physicians in training.

Prospective study comparing the conventional and same-day strategies to diagnose pulmonary tuberculosis.

OBJECTIVE: The WHO recommends same-day sputum smear microscopy for the diagnosis of smear-positive tuberculosis (TB) in countries with high TB burden for earlier diagnosis and treatment, a cornerstone to prevent air-borne transmission. We aimed to compare the conventional strategy (sputum collection on three consecutive days) and the same-day strategy (hour h, h+1, h+2) in France, a country with low TB burden. PATIENTS AND METHODS: Over a six-month period, all adult individuals presenting with presumptive smear-positive TB were eligible for the study, registered in https://clinicaltrials.gov/ ID (NCT02961569). Sputum specimens were collected three times the first day, then once on the second day and once on the third day. The concordance between the two strategies regarding smears and cultures were assessed. RESULTS: Of the 131 eligible individuals, 34 were given a TB treatment. Smears from hour h, h+1, h+2, day two and three were negative in 19 of these 34 patients. Positive smears were obtained in 15, 14, 15, 14, and 14 patients at hour h, h+1, h+2, on day two and three, respectively. Concordance regarding smear or culture was good, with Kappa 0.69 and 0.64, respectively. CONCLUSION: The same-day strategy seems to be a good alternative to the conventional strategy.

What Is the most Important for Elite Control: Genetic Background of Patient, Genetic Background of Partner, both or neither? Description of Complete Natural History within a Couple of MSM.

BACKGROUND: We describe a homosexual man who strongly controlled HIV-1 for ten years despite lack of protective genetic background. METHODS: HIV-1 DNA was measured in blood and other tissues. Cell susceptibility was evaluated with various strains. HIV-1-specific (CD4 and CD8 activation markers and immune check points) and NK cells responses were assessed; KIRs haplotypes and HLA alleles were determined. FINDINGS: Two HIV-1 RNA copies/mL of plasma were detected in 2009, using an ultra-sensitive assay. HIV-DNA was detected at 1.1 and 2 copies/106 PBMCs in 2009 and 2015 respectively, at 1.2 copies/106 cells in rectal cells in 2011. WBs showed weak reactivity with antibodies to gp160, p55 and p25 from 2007 to 2014, remaining incomplete in 2017. CD4 T cells were susceptible to various strains including HIVKON, a primary isolate of his own CRF02_AG variant. CD8 T cells showed a strong poly-functional response against HIV-Gag, producing mainly IFN-γ; a robust capacity of antibody-dependant cell cytotoxicity (ADCC) was observed in NK cells. Case patient was group B KIR haplotype. Neutralizing antibodies were not detected. CD4 and CD8 blood T cells showed normal proportions without increased activation markers. Phylogenetic analyses identified the same CRF02_AG variant in his partner. The patient and his partner were heterozygous for the CCR5ΔD32 deletion and shared HLA-B*07, C*07 non-protective alleles. INTERPRETATION: This thorough description of the natural history of an individual controlling HIV-1 in various compartments for ten years despite lack of protective alleles, and of his partner, may have implications for strategies to cure HIV-1 infection.

Once versus twice daily enoxaparin for the initial treatment of acute venous thromboembolism.

Essentials In venous thromboembolism (VTE), it is uncertain if enoxaparin should be given twice or once daily. We compared the 15- and 30-day outcomes in VTE patients on enoxaparin twice vs. once daily. Patients on enoxaparin once daily had fewer major bleeds and deaths than those on twice daily. The rate of VTE recurrences was similar in both subgroups. SUMMARY: Background In patients with acute venous thromboembolism (VTE), it is uncertain whether enoxaparin should be administered twice or once daily. Methods We used the RIETE Registry data to compare the 15- and 30-day rates of VTE recurrence, major bleeding and death between patients receiving enoxaparin twice daily and those receiving it once daily. We used propensity score matching to adjust for confounding variables. Results The study included 4730 patients: 3786 (80%) received enoxaparin twice daily and 944 once daily. During the first 15 days, patients on enoxaparin once daily had a trend towards more VTE recurrences (odds ratio [OR], 1.79; 95% confidence interval [CI], 0.55-5.88), fewer major bleeds (OR, 0.42; 95% CI, 0.17-1.08) and fewer deaths (OR, 0.32; 95% CI, 0.13-0.78) than those on enoxaparin twice daily. At day 30, patients on enoxaparin once daily had more VTE recurrences (OR, 2.5; 95% CI, 1.03-5.88), fewer major bleeds (OR, 0.40; 95% CI, 0.17-0.94) and fewer deaths (OR, 0.58; 95% CI, 0.33-1.00). On propensity analysis, patients on enoxaparin once daily had fewer major bleeds at 15 (hazard ratio [HR], 0.30; 95% CI, 0.10-0.88) and at 30 days (HR, 0.16; 95% CI, 0.04-0.68) and also fewer deaths at 15 (HR, 0.37; 95% CI, 0.14-0.99) and at 30 days (HR, 0.19; 95% CI, 0.07-0.54) than those on enoxaparin twice daily. Conclusions Our findings confirm that enoxaparin prescribed once daily results in fewer major bleeds than enoxaparin twice daily, as suggested in a meta-analysis of controlled clinical trials.

[Central nervous system lymphoma revealed by lymphocytic meningitis in a patient with systemic lupus erythematosus: An unusual association]. / Méningite lymphocytaire chez une patiente lupique révélant un lymphome cérébral primitif : une association rare.

INTRODUCTION: We report an unusual observation of central nervous system (CNS) lymphoma in a 60-year-old woman with systemic lupus erythematosus and fatal outcome. OBSERVATION: The patient had systemic erythematosus lupus for 7 years, treated with mycophenolate mofetil and developed lymphocytic meningitis in 2015 associated to the presence of EBV in the cerebrospinal fluid and a necrotic vermis' lesion. Diagnosis of large B-cell lymphoma was histologically confirmed from stereotaxic biopsy, shortly before she died from neurological complications. CONCLUSION: Even though the current association is unusual, lymphocytic meningitis with hypoglycorrachia in patients with systemic lupus erythematosus may reveal CNS lymphoma and diagnosis confirmation requires stereotaxic biopsy in order not to delay specific therapeutic management.

Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John's Wort?

An interaction of drug with food, herbs, and dietary supplements is usually the consequence of a physical, chemical or physiologic relationship between a drug and a product consumed as food, nutritional supplement or over-the-counter medicinal plant. The current educational review aims at reminding to the prescribing physicians that the most clinically relevant drug-food interactions may not be strictly limited to those with grapefruit juice and with the Saint John's Wort herbal extract and may be responsible for changes in drug plasma concentrations, which in turn decrease efficacy or led to sometimes life-threatening toxicity. Common situations handled in clinical practice such as aging, concomitant medications, transplant recipients, patients with cancer, malnutrition, HIV infection and those receiving enteral or parenteral feeding may be at increased risk of drug-food or drug-herb interactions. Medications with narrow therapeutic index or potential life-threatening toxicity, e.g., the non-steroidal anti-inflammatory drugs, opioid analgesics, cardiovascular medications, warfarin, anticancer drugs and immunosuppressants may be at risk of significant drug-food interactions to occur. Despite the fact that considerable effort has been achieved to increase patient' and doctor's information and ability to anticipate their occurrence and consequences in clinical practice, a thorough and detailed health history and dietary recall are essential for identifying potential problems in order to optimize patient prescriptions and drug dosing on an individual basis as well as to increase the treatment risk/benefit ratio.

Disrupted trabecular bone micro-architecture in middle-aged male HIV-infected treated patients.

OBJECTIVES: HIV-infected individuals are at increased risk of incident fractures. Evaluation of trabecular bone micro-architecture is an important tool to assess bone strength, but its use has not yet been reported in middle-aged HIV-infected male individuals. The aim of the study was to compare bone micro-architecture between HIV-infected and HIV-uninfected men. METHODS: In this cross-sectional study, 53 HIV-infected male individuals with a mean (± standard deviation) age of 49 ± 9 years who had been receiving antiretroviral therapy including tenofovir disoproxil fumarate (DF) for at least 60 months were compared with 50 HIV-uninfected male controls, matched for age and ethnic origin. We studied the volumetric bone density and micro-architecture of the radius and tibia using high-resolution peripheral quantitative computed tomography (HR-p QCT). RESULTS: Volumetric trabecular bone density was 17% lower in the tibia (P < 10(-4) ) and 16% lower in the radius (P < 10(-3) ) in HIV-infected patients compared with controls. By contrast, the cortical bone density was normal at both sites. The tibial trabecular micro-architecture differed markedly between patients and controls: bone volume/total volume (BV/TV) and trabecular number were each 13% lower (P < 10(-4) for both). Trabecular separation and inhomogeneity of the network were 18% and 24% higher in HIV-infected patients than in controls, respectively. The radial BV/TV and trabecular thickness were each 13% lower (P < 10(-3) and 10(-2) , respectively). Cortical thickness was not different between the two groups. CONCLUSIONS: The findings of lower volumetric trabecular bone density and disrupted trabecular micro-architectural parameters in middle-aged male HIV-infected treated patients help to explain bone frailty in these patients.

[Prevalence of granulomatous lesions in minor salivary gland biopsy in a case series of 65 patients with tuberculosis]. / Étude de la prévalence des granulomes à la biopsie des glandes salivaires accessoires chez 65 patients atteints de tuberculose.

PURPOSE: The distinction between tuberculosis (TB), a worldwide infectious granulomatosis requiring specific antibiotic therapy, and sarcoidosis, a rare granulomatous disease that may require corticosteroids is not straightforward and may result in diagnostic and therapeutic delay. METHODS: We prospectively and consecutively evaluated the presence of epithelioid granulomas in minor salivary gland biopsy of 65 consecutive patients with TB. RESULTS: In our study, 10.8 % of our TB patients had epithelioid granulomas without caseous necrosis identified in their minor salivary gland biopsy, regardless of the location of TB, HIV status and whether or not the sputum examination was positive for tuberculous bacilli. CONCLUSION: The presence of epithelioid granulomas in minor salivary gland biopsy may not be helpful to the clinician to rule out TB in a patient with suspected sarcoidosis.

Acute pain Factors predictive of post-operative pain and opioid requirement in multimodal analgesia following knee replacement.

BACKGROUND: Despite the development of multimodal analgesia for postoperative pain management, opioids are still required for effective pain relief after knee arthroplasty. We aimed to identify the determinants of post-operative pain intensity and post-operative opioid requirement in this context. METHODS: In this observational prospective study, we recorded patient characteristics, pre-operative pain intensity, anxiety and depression levels, sensitivity and pain thresholds in response to an electrical stimulus, and mu-opioid receptor (OPRM1) and catechol-O-methyltransferase (COMT) single-nucleotide polymorphisms. Multivariate linear regression models were used to identify predictors of post-operative pain at rest and opioid requirement. RESULTS: We included 109 patients. Pre-operative pain at rest (p = 0.047), anxiety level (p = 0.001) and neuropathic pain symptoms (p = 0.030) were independently and positively associated with mean post-operative pain intensity adjusted for mean post-operative morphine equivalent dose (MED). Mean post-operative pain intensity at rest was lower (p = 0.006) in patients receiving celecoxib and pregabalin in the post-operative period, with all other variables constant. Mean post-operative MED over 5 days was low, but highly variable (78.2 ± 32.1 mg, from 9.9 to 170 mg). Following adjustment for mean post-operative pain intensity, it was independently negatively correlated with age (p = 0.004), and positively correlated with associated paracetamol treatment (p = 0.031). No genetic effect was detected in our sample. CONCLUSIONS: Our findings suggest that clinicians could use the pre-operative pain profile, in terms of anxiety levels, neuropathic pain symptoms, and chronic pre-operative pain intensity, to improve the efficacy of pain management after knee surgery.

[Drug-food interactions in internal medicine: What physicians should know?]. / Interactions médicaments-aliments en médecine interne: quels messages pour le clinicien?

Orally administered medications may interact with various fruits, vegetables, herbal medicines, functional foods or dietary supplements. Drug-food interactions, which are mostly unknown from prescribers, including internists, may be responsible for changes in drug plasma concentrations, which may decrease efficacy or led to sometimes life-threatening toxicity. Aging, concomitant medications, transplant recipients, patients with cancer, malnutrition, HIV infection and those receiving enteral or parenteral feeding are at increased risk of drug-food interactions. This review focused on the most clinically relevant drug-food interactions, including those with grapefruit juice, Saint-John's Wort, enteral or parenteral nutrition, their respective consequences in the clinical setting in order to provide thoughtful information for internists in their routine clinical practice. Specific clinical settings are also detailed, such as the Ramadan or multiple medications especially in elderly patients. Drug-food interactions are also presented with respect to the main therapeutic families, including the non-steroidal anti-inflammatory drugs, analgesics, cardiovascular medications, warfarin as well as new oral anticoagulants, anticancer drugs and immunosuppressant medications. Considerable effort has been achieved to a better understanding of food-drug interactions and increase clinicians' ability to anticipate their occurrence and consequences in clinical practice. Describing the frequency of relevant food-drug interactions in internal medicine is paramount in order to optimize patient care and drug dosing on an individual basis as well as to increase patients and doctors information.

[What happens to therapeutic changes decided during hospitalization in an internal medicine ward? A two-month single-centre prospective study in France]. / Que deviennent les modifications thérapeutiques décidées au cours d'une hospitalisation en médecine interne ? Étude prospective française monocentrique sur 2 mois.

PURPOSE: During a hospitalization in an internal medicine department, drug prescriptions are frequently modified. We studied the course of these therapeutic changes after patients' discharge. METHODS: Eighty-four patients with a long-term drug prescription and a registered general practitioner were included on the day of their discharge from an internal medicine department in Paris. Their medications before and after the hospitalization were established according to the discharge letter, and patients were contacted two months after discharge in order to assess the modifications that could have occurred during these two months after discharge. RESULTS: Medications prescribed before the admission were often preserved, 17.7% were withdrawn, and 7% were switched to another medication. Two months after discharge, 85% of the modifications were maintained, the discharge drug prescription was renewed without a change for 77% of the patients. The drug classes that were the more frequently modified during the hospital stay were the antihypertensive therapies, with 65% of sustained modifications at two months, and analgesics, with 75% of sustained modifications. Therapeutic changes that were explained in the discharge letter were more frequently preserved at two months than those that were not explained (100% versus 79%, 95%CI of the difference [0.09-0.27]; P<0.0001). CONCLUSION: Therapeutic changes decided during a hospitalization in an internal medicine unit and prescribed at discharge are mostly preserved in outpatients two months after discharge, especially when the modifications are explained in the discharge letter.

Evolutionary dynamics of hepatitis C virus NS3 protease domain during and following treatment with narlaprevir, a potent NS3 protease inhibitor.

Narlaprevir, a hepatitis C virus (HCV) NS3/4A serine protease inhibitor, has demonstrated robust antiviral activity in a placebo-controlled phase 1 study. To study evolutionary dynamics of resistant variants, the NS3 protease sequence was clonally analysed in thirty-two HCV genotype 1-infected patients following treatment with narlaprevir. Narlaprevir monotherapy was administered for one week (period 1) followed by narlaprevir/pegylated interferon-alpha-2b combination therapy with or without ritonavir (period 2) during two weeks, interrupted by a washout period of one month. Thereafter, all patients initiated pegylated interferon-alpha-2b/ribavirin combination therapy. Longitudinal clonal analysis was performed in those patients with NS3 mutations. After narlaprevir re-exposure, resistance-associated mutations at position V36, T54, R155 and A156 were detected in five patients in >95% of the clones. Narlaprevir retreatment resulted in a 2.58 and 5.06 log10 IU/mL viral load decline in patients with and without mutations, respectively (P=<0.01). After treatment, resistant variants were replaced with wild-type virus within 2-24 weeks in three patients. However, the R155K mutation was still observed 3.1 years after narlaprevir dosing in two patients in 5% and 45% of the viral population. Resistant variants could be detected early during treatment with narlaprevir. A slower viral load decline was observed in those patients with resistance-associated mutations detectable by direct population sequencing. These mutations disappeared within six months following treatment with the exception of R155K mutation, which persisted in two patients.

[Off-label use of recombinant factor VII (rFVIIa) in teaching hospitals in Paris in 2010]. / Utilisation hors AMM du facteur VII activé recombinant (Novoseven®) à l'AP-HP en 2010.

INTRODUCTION: Recombinant activated factor VII (rFVIIa) (Novoseven(®)) was initially developed as a substitutive treatment in haemophiliacs but has then been used in situations of major haemorrhage in non-haemophiliacs (off-label use). The goal of the present study was to assess the practice patterns when rFVIIa is used in off-label indications in major teaching hospitals of Paris in 2010. METHODS: We retrospectively identified files of patients in whom rFVIIa had been used. Physicians in charge of these patients (or the most proxy physician available) were contacted and files analysed with one of the authors. Quality of rFVIIa used in these off-label situations was determined based on either French or European guidelines or the available literature when no guidelines could be found. Three categories were defined for indication, dosage, timing, associated biological factors and overall use: adequate, acceptable (mainly adequate but lacking some characteristics of an "ideal" prescription) and inadequate (lacking most of the necessary characteristics of an "ideal" prescription). RESULTS: Among 59 patients who had an off-label prescription of rFVIIa, 49 prescriptions could be analysed. Indication for use and timing of administration were adequate in 100% of multiple trauma cases and 83% of obstetrical cases. Biological criteria associated with an improved efficacy were found in two thirds of prescriptions analysed. Overall, prescriptions were adequate or acceptable in 82% of cases. CONCLUSION: In the vast majority of patients who received rFVIIa for off-label indications in teaching hospitals of the Paris area in 2010, prescriptions were in line with recommendations.

Challenges in the optimisation of post-operative pain management with opioids in obese patients: a literature review.

An increasing number of obese patients are undergoing surgery, particularly bariatric and orthopaedic surgery. The physiological differences between obese and normal-weight subjects may modify not only anaesthetic requirements during surgery but also post-operative analgesic management, raising a number of challenges in a critical period. In this review, we analyse studies of post-operative pain management with opioids in obese subjects. We discuss the genetic factors common to pain and obesity and the factors potentially modifying opioid pharmacokinetics and pharmacodynamics in obese patients, and we analyse the overall efficacy and safety of opioids for pain management during the post-operative period in obese patients. Both modifications to surgical methods and additional analgesic treatments to decrease the requirement for opioids may improve early rehabilitation and quality of care and reduce adverse effects in obese patients.

[An atypical presentation of Kikuchi-Fujimoto disease]. / Maladie de Kikuchi-Fujimoto: une présentation atypique.

INTRODUCTION: Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) is a rare clinical entity characterized by the association of enlarged lymph nodes in the posterior cervical region and fever. The disease is more frequent in young women. CASE REPORT: We report a 41-year-old African patient who presented with atypical features of Kikuchi's disease including cutaneous lupus, haemophagocytosis, and lymphocytic meningitis. The ethnic origin and the clinical presentation were initially suggestive of tuberculous meningitis. However, microbiological analyses remained negative, histological findings were suggestive of Kikuchi's disease and HHV6 DNA integration was documented in our patient. CONCLUSION: Kikuchi's disease should be suspected in an African patient when lymphocytic meningitis is associated with enlarged cervical lymph nodes, hemophagocytosis and HHV6 DNA integration.

BK-virus infections: a literature review.

BK-virus is a very common polyomavirus in the global population, similar to the JC-virus responsible for Progressive Multifocal Leukoencephalopathy. BK-virus infections are an important diagnostic and therapeutic challenge in immuno-compromised patients, including: bone marrow transplant pediatric recipients in whom it may cause hemorrhagic cystitis, renal transplant recipients in whom it may cause interstitial nephropathy leading to graft loss, and in HIV infected patients in whom it may cause some types of encephalitis. Indeed, this poorly documented virus is responsible for infections with various clinical profiles, probably under-diagnosed, but could also be involved in the genesis of some cancers, especially cervix and prostate cancer. We reviewed the latest published data on this virus focusing on its possible pro-oncogenic properties. We also listed the diseases in which it is involved, with an emphasis on rare and insufficiently investigated entities. Finally, we studied the new tools available for diagnosis and treatment, and their importance in current practice.

Randomised clinical trial: anti-viral activity of ANA773, an oral inducer of endogenous interferons acting via TLR7, in chronic HCV.

BACKGROUND: The ANA773 is an oral prodrug of a small-molecule toll-like receptor (TLR)7 agonist. Preclinical and healthy volunteer clinical studies with ANA773 have demonstrated induction of endogenous interferon-α (IFN-α) of multiple subtypes, which supports the potential utility in the treatment of chronic hepatitis C virus (HCV) infection. AIM: To examine safety, tolerability, pharmacodynamics, pharmacokinetics and anti-viral activity of ANA773. METHODS: The ANA773 was investigated in a double-blind, placebo-controlled study in 34 patients chronically infected with HCV of any genotype. Patients were treatment-naïve or had relapsed following previous interferon-based treatment. This dose escalation study was composed of four dose groups (800, 1200, 1600 and 2000mg). In each group, six to eight patients received ANA773 and two received placebo. Patients were dosed with ANA773 every-other-day for either 28 days (800, 1200 or 1600mg) or 10days (2000mg). RESULTS: Mild to moderate adverse events were reported, with an increase in frequency and intensity with increasing dose. No serious AEs were reported and there were no early discontinuations. There were dose-related increases in various markers of IFN-α response. The mean maximum change in serum HCV RNA level from baseline was -0.34, -0.29, -0.40, -0.97 and -1.26log(10) in the placebo, 800, 1200, 1600 and 2000mg cohorts, respectively. At the 2000mg dose, ANA773 significantly (P=0.037) reduced serum HCV RNA levels (range: 0.14 to -3.10log(10) ). CONCLUSION: The ANA773 was generally well tolerated and resulted in a dose-related IFN-dependent response leading to a significant decrease in serum HCV RNA levels in the 2000mg dose group.