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.

[Impact of influenza rapid diagnostic tests (IRDT) on the diagnosis of influenza and on the management of influenza in children in ambulatory pediatric setting]. / Impact des tests de diagnostic rapide de la grippe dans la prise en charge des enfants en période d'épidémie en pédiatrie de ville.

OBJECTIVE: Several studies have highlighted the assets of the influenza rapid diagnostic tests (IRDT) for the emergency department management of febrile children. The objective of this study was to determine in ambulatory pediatric setting impact of IRDT on the management of febrile children during an epidemic, especially on other diagnostic testing performed, antibiotic and antiviral treatments. METHODS: During an influenza epidemic, 37 paediatricians in three different areas of France included all children presenting fever with respiratory illnesses; they performed IRDT (test QuickVue for Influenza A and B, Quidel). Data collected were antiflu vaccination, previous asthma, symptoms, clinical signs, other diagnostic testing performed, and a follow-up two weeks later. RESULTS: Between December, 2006 and April, 2007, 695 children entered the program. The average age of those children was 4.1 years old (SD 3.4), median 3.2 (0.07-17.5). In 41.6% of the cases, the tests proved positive. Among 13 symptoms of influenza, only five were significantly more present in the group IRDT+: shiver (68.1% versus 57.4%), asthenia (87% versus 79.9%), cough (87.5% versus 70.1%), rhinorrhea (93.4% versus 83.3%), and sleepiness (54.2% versus 43.4%). The number of laboratory tests and radiographs ordered were less frequent in group IRDT+ than in group IRDT-: respectively 0.7% versus 11.6%, and 0.7% versus 8.6% (p<0.0001). IRDT+ group received antibiotics in 7.6% of cases (22 patients, 20 for OMA) and antiviral in 64.7%. IRDT- group received respectively 18.5% antibiotics, and no antiviral (p<0.0001). CONCLUSION: This study confirms the difficulty of clinical influenza diagnosis, and suggests the assets of IRDT to diagnose influenza and to improve the management of influenza in ambulatory paediatric setting.

[Impact of the rapid diagnosis downtown in the assumption of responsibility of the children in period of influenza]. / Impact des tests de diagnostic rapide en ville dans la prise en charge des enfants en période de grippe.

Several studies in children showed at the paediatric emergency hospital the interest of influenza rapid diagnostic tests (IRDT) in this disease for which the clinical diagnosis is difficult in children. The purpose of this prospective study carried out in ambulatory paediatric setting was to evaluate impact of the IRDT in the assumption of responsibility of children suspected of Influenza infection. Thirty paediatricians (14 without IRDT, 16 with IRDT) included 602 children between 2004 and 2005. The influenza was confirmed by IRDT in 54% of the cases. Among the 13 symptoms or signs recorded, only 4 - chills (61.6 vs 48.4%), cough (89.8 vs 71.1%), rhinorrhea (97.9 vs 86.2%), and anorexia (50.3 vs 34.8%) - were significantly more frequent (P

[Neuraminidase inhibitors in the general practice management of influenza: who prescribe them, when and with which results?]. / Les inhibiteurs de la neuraminidase dans la grippe en médecine générale: qui prescrit, quand et avec quels résultats?

OBJECTIVE: To describe in real-life conditions the flu therapeutic management, motivations to prescribe or not NAI (General Practitioners' (GPs) characteristics, decisional factors) and treated patients' course. DESIGN: A prospective, longitudinal, pharmacoepidemiological study involved 305 GPs in France during 2002-2003 winter epidemic peak. All patients>or=1 year old, with a clinical diagnostic of flu were included. RESULTS: One hundred and eighty-five GPs (150 NAI prescribing and 30 non-prescribing physicians) have included at least 1 patient. Prescribing physicians were the best informed on flu and NAI. 660 patients were analysed (250 NAI+ and 410 NAI-). 66% of NAI+ and 40% of NAI- attended to a consultation within 24 h (P<0.001). 31% of NAI+ and 20% of NAI- had a visit at home (P=0.002). Among the patients without complication at inclusion (N=585), 3% of NAI+ received an antibiotherapy vs 13% of NAI- (P<0.001). 43% of the patients had a sick leave, shorter for the NAI+ than NAI- (respectively, 3.7+/-1.7 vs 4.2+/-1.7 days, p=0.017). NAI was taken within 3 hours (median) after prescription by the 78% of the patients who returned their diary cards. The NAI+ patients had a faster improvement of symptoms than NAI- (within 24 h, respectively: 18 vs 5%, P<0.001) and they returned faster to routine activities (within 48 h, respectively: 27 vs 11%, P<0.001). CONCLUSIONS: This study evidenced the good use of NAI by the physicians. It confirms their therapeutic efficacy in real-life conditions and suggests their prescription allows decreasing antibiotic co-prescriptions and sick leaves duration, profits to consider in NAI benefit/risk ratio.

Absolute bioavailability of midazolam after subcutaneous administration to healthy volunteers.

AIMS: Midazolam is given intravenously for induction of anaesthesia and conscious sedation and by subcutaneous infusion in patients in palliative care units. The objective of the present study was to determine the absolute bioavailability of subcutaneous midazolam and its pharmacokinetics in young, healthy, male volunteers. METHODS: Eighteen volunteers were given single doses of 0.1 mg kg-1 midazolam i.v. and s.c. after a wash-out period of 7-15 days in an open-label, randomized, cross-over study. Blood samples were collected up to 12 h post-infusion. Plasma concentrations of midazolam and of its two metabolites, 1'-OHM and 4-OHM, were assessed using an h.p.l.c.-MS method (LOQ 0.5 ng ml-1 for each analyte). Vital signs, cardiac parameters and oximetry were monitored. Local tolerance was determined and adverse events were also monitored. RESULTS: After s.c. infusion t(max) and C(max) were 0.51 +/- 0.18 h and 127.8 +/- 29.3 ng ml-1 (mean +/- s.d.), respectively. No statistically significant difference was detected in AUC(0, infinity ) after i.v. and s.c. administration. The mean (+/- s.d.) absolute bioavailability of subcutaneous midazolam was 0.96 (+/- 0.14) (CI 0.84, 1.03). Mean (+/- s.d.) t1/2 was similar after s.c. (3.2 (+/- 1.0) h) and i.v. infusion (2.9 (+/- 0.7) h), although a statistically significant difference was reached (P < 0.05). Mean CL and V of i.v. midazolam were 4.4 +/- 1.0 ml min-1 kg-1 and 1.1 +/- 0.2 l kg-1 (mean +/- s.d.), respectively. Plasma concentrations of 1'-OHM were higher than those of 4-OHM. Few mild and transient adverse events were noted and there were no clinically significant effects on EEG, blood pressure and laboratory parameters. CONCLUSIONS: This study has shown that subcutaneous midazolam has excellent bioavailability and that administration of midazolam by this route could be preferable when the intravenous route is inappropriate.

Penetration of ceftriaxone (1 or 2 grams intravenously) into mediastinal and cardiac tissues in humans.

Penetration of ceftriaxone into heart tissues (valves, myocardium, auricles, and pericardium) and mediastinal tissues (fat and sternal bone) was evaluated after two regimens of ceftriaxone administration. Ten patients (group 1) were given 1,000 mg of ceftriaxone intravenously 30 min before anesthesia. Ten other patients (group 2) received the same dose and then a second 1,000-mg dose at the time of initiation of cardiopulmonary bypass. Similar and very satisfactory penetrations of ceftriaxone into tissue were observed for both groups. During opening and closure of the thorax, mean ceftriaxone concentration was in excess of the MIC at which 90% of the potential pathogens were inhibited (> or = 4 micrograms/g) in the thoracic fat, the sternal bone, and the pericardium. No significant differences between the two administration regimens in penetration of ceftriaxone into tissue were observed. During cardiopulmonary bypass, the ceftriaxone concentration was > or = 4 micrograms/g in the myocardium, the endocardium, and the auricle. The regimen of ceftriaxone administration did not significantly influence penetration of the drug into heart tissues. However, for some patients in the two groups and mainly in the sternal bone at the time of thorax closure (6 patients in group 1 and 5 patients in group 2), ceftriaxone levels in tissues were less than the MICs (4 micrograms/g) for some potential pathogens (methicillin-susceptible Staphylococcus aureus and methicillin-susceptible Staphylococcus epidermidis). During the different steps of the surgical procedures, all (10 of 10) patients in each group had tissue ceftriaxone levels greater than the MICs for gram-negative aerobic bacilli (0.1 microgram/g), except for Pseudomonas spp.

[Penetration of ceftriaxone (1 or 2 gr intravenous) into mediastinal and cardiac tissues in man]. / Pénétration de la ceftriaxone (1 ou 2 g intraveineux) dans les tissus médiastinaux et cardiaques chez l'homme.

Ceftriaxone penetration into heart tissues (valves, myocardium, auricles and pericardium) and mediastinal tissues (fat and sternal bone) was evaluated after two regimens of ceftriaxone administration. Ten patients were given 1,000 g intravenously of ceftriaxone 30 min. before anesthesia. Ten other patients received the same dose and then a second 1,000 mg dose at the time of initiation of cardiopulmonary bypass. Similar and very satisfactory ceftriaxone tissue penetrations were observed in both groups. However, for some patients in the two groups and mainly in the sternal bone at the time of thorax closure, ceftriaxone levels in tissues were less than the MICs for some potential pathogens (Methicillin susceptible Staphylococcus aureus and Staphylococcus epidermidis). During the different steps of the surgical procedures all patients in both groups had tissue levels greater than the MICs for Gram negative aerobic bacilli, except for Pseudomonas spp.

Pharmacokinetics and tissue penetration of a single dose of ceftriaxone (1,000 milligrams intravenously) for antibiotic prophylaxis in thoracic surgery.

The pharmacokinetics and tissue penetration of ceftriaxone after a single intravenous injection of 1,000 mg to 17 patients for antibiotic prophylaxis in thoracic surgery were studied. The patients were scheduled for elective noncardiac thoracic surgery. Adequate levels in serum (higher than or equal to the MIC for 90% of isolates of Staphylococcus aureus, Streptococcus spp., Escherichia coli, Haemophilus influenzae, and Klebsiella pneumoniae) were found for all patients throughout the surgical procedures. Mean maximal (5-min) and final (24-h) ceftriaxone levels in serum were 157 +/- 42 and 8.6 +/- 4.5 mg/liter, respectively. The beta-phase elimination half-life was 8.6 +/- 3 h, the plasma clearance was 18.4 +/- 6.25 ml/min, and the apparent volume of distribution at steady state was 0.21 +/- 0.07 liters/kg. At the time of the thoracotomy, the ceftriaxone concentrations were 13.5 +/- 7.8 micrograms/g in thoracic wall fat and 27 +/- 9 micrograms/g in lung tissue. At the time of closure, the ceftriaxone concentration was 15 +/- 9 micrograms/g in thoracic wall fat. During the different steps of the surgical procedures, 100% of patients had adequate levels in tissue (higher than or equal to the MIC for 90% of isolates of Streptococcus spp., E. coli, H. influenzae, and K. pneumoniae). For S. aureus, 90 to 100% of patients had adequate tissue ceftriaxone levels.

[Lymphatic and lymph node diffusion of ceftriaxone. Incidence in the treatment of typhoid fever]. / Diffusion lymphatique et ganglionnaire de la ceftriaxone. Incidence dans le traitement des fièvres typhoïdes.

Following intravenous administration of 2 g ceftriaxone, concentrations of the drug were assayed in serum, in thoracic duct lymph from dogs, and in mesenteric lymph nodes in patients. Antibacterial activity of lymph against S. typhi was also studied. Results show that ceftriaxone concentrations in serum and lymph are comparable; with a satisfactory antibacterial activity of both fluids against S. typhi. In mesenteric lymph nodes, mean ceftriaxone concentration was approximately 1000 times the MIC for S. typhi. Our data contribute to explain the successful clinical results achieved with ceftriaxone in patients with typhoid fever.