Morbidity and mortality associated with influenza exposure in long-term care facilities for dependent elderly people.

The purpose of this paper is to describe the impact of exposure to influenza on hospitalizations and deaths in the elderly residents of long-term care facilities (LTCFs). An observational, longitudinal, prospective, multicenter, cohort study collected influenza and influenza-like cases, diseases, hospitalizations, and deaths of dependent elderly residents of French LTCFs during the 2004-2005 seasonal influenza epidemic. A total of 8,041 residents of 98 participating LTCFs were included. The mean age was 85 +/- 9 years; 93% were vaccinated against influenza and 64% of the residents were exposed to influenza during the epidemic. Exposure to influenza increased both the all-cause risk of hospitalization (9.2% of the residents exposed vs. 7.4% of the residents not exposed) (relative risk, RR [95% confidence interval, CI] = 1.24 [1.05; 1.47]) and the all-cause risk of death (5.8% vs. 4.3%) (RR [95% CI] = 1.36 [1.10; 1.70]). Exposure to influenza increased the risks of death and hospitalization. Additional measures should be taken to avoid influenza exposure and apply recommendations more thoroughly in the particularly susceptible population of elderly LTCF residents.

[Cardiac tolerance of moxifloxacin: Clinical experience from a large observational French study in usual medical practice (IMMEDIAT study)]. / Tolérance cardiaque de la moxifloxacine: expérience clinique issue d'une large étude observationnelle française en pratique médicale usuelle (étude IMMEDIAT).

BACKGROUND: Moxifloxacin (Izilox) is prescribed for bacterial respiratory tract infections. ECG analysis done in clinical trials showed a mean QT prolongation at 6 ms that could lead to Torsades de Pointe. However, Izilox was well tolerated during clinical trials. To confirm the correct safety profile of Izilox in a large sample of patients, a French PMS study - MMEDIAT - was carried out in usual medical practice. METHODS: This prospective observational uncontrolled and monitored study was conducted in 13,578 patients with respiratory tract infection and treated with moxifloxacin 400 mg daily (duration: 5 to 10 days in accordance to the Market Authorization). Any clinical event being potentially a surrogate of a ventricular rhythm disorder ("critical event") were collected and analyzed by a Scientific Committee in charge to determine the potential cardiac origin of the reported event and to establish a causal relationship with the treatment. RESULTS: Among 13,578 patients, 1046 adverse events (678 patients [5%]) were reported, including 854 drug related events (564 patients [4.15%]). Of these 1046 adverse events, 95 (62 patients [0.46%]) were serious. A total of 189 critical adverse events (159 patients [1.2%]) were reviewed by the Scientific Committee. After analysis, 34 adverse events (28 patients [0.21%]) were assessed from potential cardiac origin. Of these 34 adverse events, 25 (19 patients [0.14%]) were assessed as drug-related: palpitations [13 patients], tachycardia [4 patients], malaise [4 patients], vertigo [3 patients] and pallor [1 patient]. All adverse events were transient and had favourable outcome. CONCLUSION: This PMS study confirmed that Izilox is well-tolerated in usual medical practice, in adequation with the safety data obtained in clinical trials.

[Efficacy of levofloxacin in the treatment of acute exacerbation of chronic bronchitis in patients with risk factors]. / Efficacité de la lévofloxacine dans le traitement des exacerbations aiguës de bronchite chronique chez les patients avec facteurs de risque.

Studies of acute exacerbations of chronic bronchitis (EXCB) included in the approval documents of levofloxacin (LVF) were reviewed in light of the good conditions of use defined by the French marketing approval and the AFSSAPS recommendations. The approval documents included two American studies comparing LVF 500 mg/d for 5-7 days with cefaclor 750 mg/d for 7-10 days or cefuroxime axetil (CXM) 500 mg/d for 7-10 days. A new descriptive analysis of efficacy was performed on a population meeting the recommendation criteria for antibiotic treatment in patients with clinical signs of obstruction. This analysis was stratified by number of risk factors (RF) for the following aggravating conditions: age above 65 years, diabetes or corticosteroid therapy. In the American studies, clinical efficacy, measured by rate of success in the total population, in the EXCB population requiring antibiotic therapy with or without risk factors, and in the EXCB population with at least one and at least two of the above-cited risk factors was 93.4% (351/376), 93.0% (268/288), 90.4% (122/135) and 94.4% (34/36) respectively with LVF and 92.2% (354/384), 92.5% (273/295), 87.7% (128/146) and 79.3% (23/29) respectively with the compared drugs. In the European study, the clinical efficacy in the total population, in the EXCB population requiring antibiotic therapy with or without risk factors, and in the EXCB population with at least one and at least two of the above-cited risk factors was 81.9% (195/238), 82.4% (182/221), 78.9% (112/142) and 75.0% (27/36) respectively with LVF and 72.5% (166/229), 74.0% (154/208), 73.1% (95/130) and 58.3% (21/36) respectively with the compared drugs. The efficacy of levofloxacin is thus confirmed for EXCB with signs of obstruction. When stratifying for RF, the efficacy of LVG persists with increasing numbers of RF, a result not observed with the compared drugs.

Valaciclovir as a single dose during prodrome of herpes facialis: a pilot randomized double-blind clinical trial.

BACKGROUND: Randomized clinical trials of valaciclovir in recurrent herpes labialis are lacking. OBJECTIVES: To determine whether a single course of valaciclovir, i.e. 500, 1000 or 2000 mg, administered during the prodrome of herpes facialis, could be beneficial. METHODS: Three hundred and forty-five out-patients with herpes labialis were screened and randomized for a multicentre, double-blind clinical trial. Ninety-six patients had no recurrence after 6 months of follow-up; 249 patients were finally included in the intent-to-treat (ITT) population. The main outcome measure was the rate of aborted episodes at day 3. The three treatment groups were similar at baseline. RESULTS: There was no statistically significant difference between the groups in rates of aborted lesions at day 3 in the ITT population, in particular between the 500 mg and 2000 mg treatment groups. CONCLUSIONS: Although a placebo group was not included in this pilot study, a single dose of valaciclovir was not considered beneficial in patients with recurrent herpes facialis.

[Levofloxacine for the treatment of pneumococcal pneumonia: results of a meta-analysis]. / La lévofloxacine dans le traitement des pneumonies à pneumocoques. Résultats d'une méta-analyse.

Levofloxacine is a fluoroquinolone presenting good anti-pneumococcal activity, including against strains with reduced sensitivity to penicillin. Four randomized controlled studies have compared the efficacy of levofloxacine versus other antibiotics (amoxacillin-clavulanic acid, amoxicillin, ceftriaxone, ceftriaxone plus cefuroxime +/- erythromycin) for the treatment of acute community-acquired pneumonia in adults. Grouping the 1,738 analyzable patients in these four studies, a meta-analysis was performed on the sub-group of 275 patients with documented pneumococcal infection (86 with bacteriemia) in order to compare the efficacy of levofloxacine with that of the comparer antibiotics. The trials were homogeneous, allowing the meta-analysis. The overall rate of clinical success was 88.6% in the levofloxacine group and 86.7% in the comparer group. The interval of confidence for the difference in the rate of estimated clinical success was between -5.65% and +9.39%. Bacteriologically, the rate of eradication was 90.2% and 90.4% respectively with an interval of confidence for the difference between -7.83% and +7.36%. The results of this meta-analysis confirmed that the efficacy of levofloxacine for the treatment of acute community-acquired pneumococcal pneumonia is not inferior to that of the comparers; the interval of confidence for the difference in the estimated rate of success did not include the breaking point of non-inferiority (-10% set for the clinical studies) and included zero.

Lower limb giant cell arteritis and temporal arteritis: followup of 8 cases.

Among 8 patients with giant cell arteritis (GCA) (6 women, 2 men) whose clinical presentations were compatible with temporal arteritis (TA), 6 were followed for 37-105 (mean 74.9) months, one died shortly after treatment onset, and the last was asymptomatic (10 mg steroids/day) when lost to followup at 29 months. All 8 patients had bilateral leg claudication of recent onset; for 6 patients, this was the first symptom. All leg angiograms showed multiple, bilateral, long and smooth stenoses, thromboses, or both. Biopsies of diseased leg arteries from 4 patients provided histological proof of GCA; another case was histologically proven post mortem. Among the 5 patients who met at least 3 American College of Rheumatology criteria of GCA or TA, 3 without histologically documented leg GCA also had biopsy proven temporal GCA (n = 1), or headaches and claudication and angiographic inflammatory arteritis of the arms (n = 2). All patients received steroids; 3 had bypasses, one with endarterectomy. Five are asymptomatic after 24-100 months of steroids (mean 50.6). Revascularization was not successful; one amputation was necessary. Large artery involvement in GCA can affect the legs. Bilateral and rapidly progressive intermittent claudication of recent onset is the most common symptom, even in the absence of headaches or the presence of a silent inflammatory syndrome. Early diagnosis allows rapid initiation of steroid therapy, which is usually able to generate a sufficiently good response to avoid vascular surgery.

Mortality among human immunodeficiency virus-infected patients with cirrhosis or hepatocellular carcinoma due to hepatitis C virus in French Departments of Internal Medicine/Infectious Diseases, in 1995 and 1997.

Several studies have suggested that the progression of hepatitis C virus (HCV) infection is more severe in patients infected by the human immunodeficiency virus (HIV). Two national retrospective multicenter cohort surveys were performed in France that included 17,487 HIV-infected patients during 1995 and 26,497 during 1997. The following data was evaluated: total number of deaths; number of deaths linked to AIDS, cirrhosis, or hepatocellular carcinoma (HCC); and number of deaths related to other (non-HCV--linked) causes. In 1995, the causes of death were as follows: AIDS, 1307 (7.47%); cirrhosis or HCC, 21 (0.12%); and other (non-HCV--linked) causes, 99 (0.56%). In 1997, the causes of deaths were as follows: AIDS, 459 (1.73%); cirrhosis or HCC 36 (0.13%); and other (non-HCV--linked) causes, 48 (0.18%). Comparative results between the 1995 and 1997 surveys showed a dramatic decrease in AIDS-related mortality rates (7.47% vs. 1.73%; P<.001) but not in HCV-related mortality rates (0.06% vs. 0.07%; P=.79). In France, despite the high prevalence of HCV infection in HIV-positive patients, the mortality rate in 1995 and 1997 caused by HCV-related cirrhosis or HCC was low.

[Epidemiology and management of suspected pneumonia in nursing home residents]. / Epidémiologie et prise en charge des pneumopathies suspectées en maison de retraite.

OBJECTIVE: We conducted a descriptive epidemiology study to examine the conditions of management of infectious lung disease in institutionalized elderly populations (population profile, diagnostic and therapeutic modalities) and to analyze the general and mental consequences in terms of independence (impact of the infectious event on the subject's life style). PATIENTS AND METHODS: A pragmatic survey was conducted by a multicentric observatory composed of 573 general practitioners, practicing in nursing homes. The series included 1790 patients aged over 70 years and residing in nursing homes who developed infectious lung disease over a 10-month period. The MMSE score was used to assess mental status and the Barthel index to assess functional handicap. Each patient was evaluated at the time of the final diagnosis (prescription of an antibiotic or decision for hospitalization) and at most 3 days after the end of this treatment or at discharge from hospital. RESULTS: The elderly population (84 +/- 7 years) was predominantly composed of women. The patients were treated for an acute respiratory infection considered in 30% of the cases to be acute lobar pneumonia. Subgroups of patients were identified for analysis: death (3.7%), x-ray confirmation of the diagnosis (11.5%), hospitalized patients (10.2%). In addition to major deterioration of the general health status, a consequence of the infection more than of the severity of the respiratory symptoms, the development of an acute episode coincided with reduced intellectual functions and onset of a state of confusion. In 70% of the cases, this resulted in a loss of independence of variable importance--simple difficulty for moving around to major functional handicap. The infectious episode was cured or improved (persistence of minor signs not requiring specific treatment) in 94.3% of the cases with appropriate antibiotics: single-drug regimen in 93.7% give per os (75%) or intravenously (25%) using aminopenicillin (with or without a beta lactamase inhibitor) in 80% of the cases. Antibiotic treatment was associated with physical therapy in more than half the cases, and with general conticosteroids in 40%. The treatment scheme was modified in 9.4% of the cases (change of antibiotic in 6%). CONCLUSION: This survey confirms the high risk related to general conditions in elderly institutionalized patients who develop respiratory infection. More than the infection itself, the rapid degradation of the general health status, or decompensation of comorbid states can create life-threatening situations or favor the development of irreversible handicaps.

Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d'Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l'Hepatite C.

From January 1996 to January 1997, 321 patients with an average age of 46 +/- 16 years and chronically infected with hepatitis C virus (HCV) were prospectively enrolled in a study designed to determine the prevalence of extrahepatic manifestations associated with HCV infection in a large cohort of HCV patients, to identify associations between clinical and biologic manifestations, and to compare the results obtained in human immunodeficiency virus (HIV)-positive versus HIV-negative subsets. In a cross-sectional study, clinical extrahepatic manifestations, viral coinfections with HIV and/or hepatitis B virus, connective tissue diseases, and a wide panel of autoantibodies were assessed. Thirty-eight percent (122/321) of patients presented at least 1 clinical extrahepatic manifestation including arthralgia (60/321, 19%), skin manifestations (55/321, 17%), xerostomia (40/321, 12%), xerophthalmia (32/321, 10%), and sensory neuropathy (28/321, 9%). Main biologic abnormalities were mixed cryoglobulins (110/196, 56%), thrombocytopenia (50/291, 17%), and the presence of the following autoantibodies: antinuclear (123/302, 41%), rheumatoid factor (107/280, 38%), anticardiolipin (79/298, 27%), antithyroglobulin (36/287, 13%) and antismooth muscle cell (27/288, 9%). At least 1 autoantibody was present in 210/302 (70%) of sera. By multivariate logistic regression analysis, 4 parameters were significantly associated with cryoglobulin positivity: systemic vasculitis (p = 0.01, odds ratio OR[ = 17.3), HIV positivity (p = 0.0006, OR = 10.2), rheumatoid factor positivity (p = 0.01, OR = 2.8), and sicca syndrome (p = 0.03, OR = 0.27). A definite connective tissue disease was noted in 44 patients (14%), mainly symptomatic mixed cryoglobulinemia and systemic vasculitis, HIV coinfection (23%) was associated with 3 parameters: anticardiolipin (p = 0.003, OR = 4.18), thrombocytopenia (p = 0.01, OR = 3.56), and arthralgia or myalgia (p = 0.017, OR = 0.23). HIV-positive patients presented more severe histologic lesions (p = 0.0004). Extrahepatic clinical manifestations in HCV patients involve primarily the skin and joints. The most frequent immunologic abnormalities include mixed cryoglobulins, rheumatoid factor, antinuclear, anticardiolipin, and antithyroglobulin antibodies. Cryoglobulin positivity is associated with systemic vasculitis and rheumatoid factor and HIV positivity. HIV coinfection is associated with arthralgia or myalgia, anticardiolipin antibodies, and thrombocytopenia.

[Levofloxacin in the treatment of community-acquired pneumococcal pneumonia]. / La lévofloxacine dans le traitement des pneumonies communautaires à pneumocoque.

OBJECTIVES: Levofloxacin is a new fluoroquinolone active against S. pneumoniae. Oral and intravenous administration is available. The aim of this study was to determine its efficacy in community-acquired pneumonia. PATIENTS AND METHODS: Five clinical trials included 1989 patients eligible for analysis. The dosage was 500 mg once or twice a day depending on the studies. Levofloxacin was compared with amoxicillin (3 g/d), amoxicillin/clavulanic acid (1500 mg/d), ceftriaxone (1-4 g/d combined or not with a macrolide and/or relay cefuroxime axetil). RESULTS: In these studies and among the patients eligible for analysis, microbiologically proven S. pneumoniae pneumonia occurred in 170 of the patients treated with levofloxacine and in 140 treated with the comparator. Bacteriemia was evidenced in 51/170 of the levofloxacin-treated patients (30%) and in 45/140 (32%) of the comparator-treated patients. At treatment end, clinical success rate was 93.5% (159/170) for levofloxacin and 90.7% (127/140) for comparators. S. pneumoniae eradication rate was comparable for levofloxacin (94.9%) and comparators (95.3%). In patients with bacteriemia, the clinical success rate was 86.2% (44/51) for levofloxacin and 84.4% (38/45) for comparators. DISCUSSION: These findings establish the efficacy of levofloxcin for the treatment of pneumococcal pneumonia, a major treatment challenge in community-acquired pneumonia. This compound has its place in the context of good use of antibiotics. Levofloxacin should be used in priority for patients with risk factors for complications with rapidly unfavorable course or as second intention treatment when re-evaluating insufficient therapeutic response.

[1977 mortality rate in HIV-infected patients presenting with hepatitis C cirrhosis. Results of the GERMIVC multicenter survey conducted in French departments of internal medicine or infectious disease]. / Mortalité par cirrhose virale C chez les patients infectés par le VIH dans les services de médecine interne et de pathologie infectieuse en 1997. Enquête multicentrique GERMIVIC. (Groupe d'étude sur le virus C). (Société nationale française de médecine interne). (Société de pathologie Infectieuse de langue française).

PURPOSE: Hepatitis C (HCV) has a high prevalence (10-30%) among human immunodeficiency virus (HIV)-infected patients. However, little information is available regarding the impact of hepatitis C on survival. The objective of our study was to determine the incidence of hepatitis C-related deaths in HIV-HCV co-infected patients. METHODS: The study was a retrospective (1-year), multicenter cohort survey conducted in 63 departments of either internal medicine or infectious diseases in France. It included 26,497 HIV-infected patients, of whom 4,465 (16.8%) presented coinfection due to the hepatitis C virus. The following parameters were studied for the year 1997: total number of deaths, number of deaths related to either AIDS, cirrhosis, hepatocellular carcinoma, or other causes. RESULTS: Among the 26,497 patients, 543 deaths (incidence: 2%) were observed in 1997; 543 deaths were due to AIDS (incidence: 1.7%), 36 to cirrhosis and/or hepatocellular carcinoma (incidence: 0.13%), and 48 (incidence: 0.18%) to another cause. In the subgroup including 4,465 HIV-HCV-coinfected patients, 29 deaths (incidence: 0.64%) were due to either HCV-related cirrhosis or hepatocellular carcinoma. These results were compared with those of a previous similar survey conducted in 1995, before the era of highly active antiretroviral therapy. The only significant difference is the dramatic regression of deaths due to AIDS. CONCLUSION: The impact of hepatitis C virus on the mortality among HIV-infected patients whose follow-up took place in departments of either internal medicine or infectious diseases in France was very low in 1997. The expected increase in the life span in these patients could modify these results in the future, due to recent improvements in the HIV infection treatment.