Patterns of non steroidal anti-inflammatory drug use in ambulatory care

The aim of this study was to discuss the patterns of non steroidal anti-inflammatory drug (NSAID) use in general population. We identified NSAID's users from the French Health Insurance System claims database covering more of the population in the Midi-Pyrenees area (southwest of France), if they have received at least one NSAID in June 2003. We discussed this population according to the NSAID used, to their demographic characteristics and to other drugs delivered in the period. Our study shows different patterns of use according to each NSAID. For example, users of ibuprofen or tiaprofenic acid were younger and less frequently exposed to "gastroprotective" drugs, users of coxibs were older and more frequently exposed to drugs increasing the risk of bleeding. This study confirms the wide use of NSAIDs and describes their target population. It underlines the interest of Health Insurance System Database for better knowledge of drug use in ambulatory care in France.     

Albumin administration improves organ function in critically ill hypoalbuminemic patients: A prospective, randomized, controlled, pilot study

OBJECTIVE: To test the hypothesis that administration of albumin to correct hypoalbuminemia might have beneficial effects on organ function in a mixed population of critically ill patients. DESIGN:: Prospective, controlled, randomized study. SETTING: Thirty-one-bed, mixed medicosurgical department of intensive care. PATIENTS: All adult patients with a serum albumin concentration < or =30 g/L were assessed for eligibility. Principal exclusion criteria were expected length of stay <72 hrs, life expectancy <3 months or a do-not-resuscitate order, albumin administration in the preceding 24 hrs, or evidence of fluid overload. INTERVENTIONS: The 100 patients were randomized to receive 300 mL of 20% albumin solution on the first day, then 200 mL/day provided their serum albumin concentration was <31 g/dL (albumin group), or to receive no albumin (control group). MEASUREMENTS AND MAIN RESULTS: The primary outcome was the effect of albumin administration on organ function as assessed by a delta Sequential Organ Failure Assessment score from day 1 to day 7 (or the day of intensive care discharge or death, whichever came first). The two groups of 50 patients were comparable at baseline for age, gender, albumin concentration, and Acute Physiology and Chronic Health Evaluation II score. Albumin concentration did not change over time in the control group but increased consistently in the albumin group (p < .001). Organ function improved more in the albumin than in the control group (p = .026), mainly due to a difference in respiratory, cardiovascular, and central nervous system components of the Sequential Organ Failure Assessment score. Diuretic use was identical in both groups, but mean fluid gain was almost three times higher in the control group (1679 +/- 1156 vs. 658 +/- 1101 mL, p = .04). Median daily calorie intake was higher in the albumin than in the control group (1122 [935-1158] vs. 760 [571-1077] kcal, p = .05). CONCLUSIONS: Albumin administration may improve organ function in hypoalbuminemic critically ill patients. It results in a less positive fluid balance and a better tolerance to enteral feeding.     

Neuromuscular blocking agents decrease inflammatory response in patients presenting with acute respiratory distress syndrome

OBJECTIVE: To evaluate the effects of neuromuscular blocking agents (NMBAs) on pulmonary and systemic inflammation in patients with acute respiratory distress syndrome ventilated with a lung-protective strategy. DESIGN: Multiple-center, prospective, controlled, and randomized trial. SETTING: One medical and two medical-surgical intensive care units. PATIENTS: A total of 36 patients with acute respiratory distress syndrome (Pao2/Fio2 ratio of < or =200 at a positive end-expiratory pressure of > or =5 cm H2O) were included within 48 hrs of acute respiratory distress syndrome onset. INTERVENTIONS: Patients were randomized to receive conventional therapy plus placebo (n = 18) or conventional therapy plus NMBAs (n = 18) for 48 hrs. Both groups were ventilated with a lung-protective strategy (tidal volume between 4 and 8 mL/kg ideal body weight, plateau pressure of < or =30 cm H2O). MEASUREMENTS AND MAIN RESULTS: Bronchoalveolar lavages and blood samples were performed, before randomization and at 48 hrs, to determine the concentrations of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and IL-8. Pao2/Fio2 ratio was evaluated before randomization and at 24, 48, 72, 96, and 120 hrs. A decrease over time in IL-8 concentrations (p = .034) was observed in the pulmonary compartment of the NMBA group. At 48 hrs after randomization, pulmonary concentrations of IL-1beta (p = .005), IL-6 (p = .038), and IL-8 (p = .017) were lower in the NMBA group as compared with the control group. A decrease over time in IL-6 (p = .05) and IL-8 (p = .003) serum concentrations was observed in the NMBA group. At 48 hrs after randomization, serum concentrations of IL-1beta (p = .037) and IL-6 (p = .041) were lower in the NMBA group as compared with the control group. A sustained improvement in Pao2/Fio2 ratio was observed and was reinforced in the NMBA group (p < .001). CONCLUSION: Early use of NMBAs decrease the proinflammatory response associated with acute respiratory distress syndrome and mechanical ventilation.     

Variation in Gamma Interferon Responses to Different Infecting Strains of Mycobacterium tuberculosis in Acid-Fast Bacillus Smear-Positive Patients and Household Contacts in Antananarivo,Madagascar

The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop tuberculosis (TB), though many may become latently infected. More precise measurement of the human immune response to M. tuberculosis infection may help us understand this difference and potentially identify those subjects most at risk of developing active disease. Gamma interferon (IFN-γ) production has been widely used as a proxy marker to study infection and to examine the human immune response to specific M. tuberculosis antigens. It has been suggested that genetically distinct M. tuberculosis strains may invoke different immune responses, although how these differences influence the immune responses and clinical outcome in human tuberculosis is still poorly understood. We therefore evaluated the antigen-specific IFN-γ production responses in peripheral blood mononuclear cells from two cohorts of subjects recruited in Antananarivo, Madagascar, from 2004 to 2006 and examined the influence of the infecting M. tuberculosis strains on this response. The cohorts were sputum-positive index cases and their household contacts. Clinical strains isolated from the TB patients were typed by spoligotyping. Comparison of the IFN-γ responses with the spoligotype of the infecting clinical strains showed that “modern” M. tuberculosis strains, like Beijing and Central Asian (CAS) strains, tended to induce lower IFN-γ responses than “ancient” strains, like East African-Indian (EAI) strains, in index cases and their household contacts. These results suggest that new strains may have evolved to induce a host response different from that of ancient strains. These findings could have important implications in the development of therapeutic and diagnostic strategies.Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a major cause of global morbidity and mortality throughout the world. It is estimated that there are in excess of new 8 million cases of TB each year, and this represents just the tip of the iceberg. Infection with M. tuberculosis leads to clinically active TB in about 5 to 10% of exposed individuals. A much higher proportion of exposed individuals apparently become latently infected, and these individuals may remain noninfectious and symptom free for years. Approximately one-third of the world population is thought to be latently infected with M. tuberculosis. However, under some circumstances (in about 5% of the latently infected people), the host immune response is perturbed and latent M. tuberculosis infection may develop into clinically active TB (52). This process is most prominent in individuals coinfected with human immunodeficiency virus (HIV), but it can also occur with impairment of the immune system associated with old age, malnutrition, anti-inflammatory drug treatment, etc. Reactivation of latent disease is thought to contribute roughly half of all TB cases, and thus, understanding the factors controlling the development of acute primary TB or latent infection is crucial to TB control (64).Gamma interferon (IFN-γ) production has been widely used to study infection and to examine the human immune response to specific M. tuberculosis antigens. The 6-kDa early secreted antigenic target (ESAT-6) antigen, encoded by genes located within region of difference 1 (RD1) of the M. tuberculosis genome, is much more specific for M. tuberculosis than purified protein derivative (PPD), as these genes were deleted from M. bovis in the development of BCG substrains or are not found in most environmental mycobacteria (29, 53). Some studies showed that the level of IFN-γ release in response to ESAT-6 could identify TB contacts at risk of developing active disease after recent infection (3, 18, 30). CFP7 or TB10.4 is an immunodominant antigen recognized by TB patients and M. bovis BCG-vaccinated subjects, while ESAT-6 is specific to TB patients and induces a strong IFN-γ response (51). Moreover, since CFP7 induces strong protection against infection by M. tuberculosis, it was proposed to be a TB vaccine candidate (1, 19).There is a growing number of observations indicating that TB cases resulting from infection with epidemic strains, such as the W-Beijing strains (22, 35, 39, 44), may display a more severe pathology or more severe symptoms. Beijing strains were also found to induce higher fevers in pulmonary TB patients than other strains (62). In addition, the Beijing genotype, which is responsible for more than 80% of TB cases in China, was associated with virulence and high transmissibility (7, 28). The same has been found more recently with the RD(Rio) strains belonging to the Latin America-Mediterranean (LAM) family (38). Despite the fact that other epidemiological and clinical studies have failed to confirm any association between the mycobacterial genotype and the clinical presentation (8, 41, 43), the immunological aspects of infection with these strains is still of interest and poorly described.Epidemiological studies carried out in Madagascar showed no association between IS6110 patterns and clinical tuberculosis presentation (47), but they did reveal a heterologous population of M. tuberculosis strains, including the existence of a high frequency of unusual genotypes, such as the shared type 109 from the EAI8-MDG family (SpolDB4) (10) or strains with a single copy of IS6110 (24, 46). Since there are limited data on the correlation of the strain genotype with clinical features or the host immune response in patients and their contacts (57, 59), we investigated the IFN-γ response to the ESAT-6, CFP7, and PPD antigens in pulmonary TB patients and their household contacts (as this is commonly used as a biomarker to identify M. tuberculosis infection) and examined the influence of the M. tuberculosis genotype on this response.     

Drugs and dilated cardiomyopathies: a case/noncase study in the French PharmacoVigilance Database

AIMS

To evaluate putative associations between drugs and dilated cardiomyopathy.

METHODS

We used the case/noncase method in the French PharmacoVigilance Database (FPVD). Cases were all the observations with dilated cardiomyopathy registered into the FPVD between 1 January 1990 and 30 June 2007. Noncases were all other reports other than those studied. Anthracyclines were used as positive controls. Data were expressed as reporting odds ratio (ROR) with their 95% confidence intervals.

RESULTS

Out of the 258 729 adverse drug reaction (ADR) reports recorded in the FPVD between 1 January 1990 and 30 June 2007, 47 (22 men, mean age 49 years) were defined as dilated cardiomyopathy. In these 47 patients, 67 drugs were ‘suspect’. A significant ROR was found with cytotoxic (epirubicin, mitoxantrone, cyclophosphamide, gemcitabine, fluorouracil) and antiretroviral (lamividune, zidovudine, abacavir) but also with isotretinoin, prednisone, appetite suppressant (clobenzorex) and psychotropic [antipsychotic (clozapine, olanzapine), lithium, antidepressant (clomipramine, amitriptyline, fluvoxamine)] drugs.

CONCLUSIONS

The present study describes an association between some drugs and reports of dilated cardiomyopathies. This relationship involves not only some already suspected drugs (anthracyclines, antiretrovirals), but also other drugs (antipsychotics, lithium, antidepressants, retinoids) less known to induce such an ADR. Despite the mandatory limits of this kind of study (underreporting, confounding factors …), these data represent a pharmacovigilance signal and could contribute to establish further prospective studies in order to confirm such signals.     

What was Montpellier's theriac

The long-lasting fame of Montpellier's theriac does not come from the originality of its composition. In the Middle Ages, its formula followed Antidotarium Nicolai's while, in the modern period, it copied Galen's. This fame is explained by the reputation of the medical University, by the dynamism of its apothecaries and by the strength of Montpellier's trade networks.