Literature Alerts
This section informs healthcare professionals of the latest medical information via daily news articles on respiratory disorders and other related areas.
Recent Headlines
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Modifying clinical practices to manage influenza in children effectively.
Pediatr Infect Dis J. 2008 Aug; 27(8): 738-43
Glezen WPChildren less than 5 years of age are at increased risk of morbidity from influenza infection compared with older children and adults aged 18-54 years. Although much of the disease burden can be prevented by annual vaccination, the misperception that influenza does not result in serious illness in children, including schoolchildren, contributes to ongoing low vaccination rates. In conjunction with community surveillance of influenza activity, rapid diagnostic tests can help identify influenza patients who may benefit from initiation of antiviral therapy. Antiviral therapy is most effective when started within at least 48 hours of the onset of symptoms, the earlier the better. The neuraminidase inhibitors oseltamivir and zanamivir are safe and effective as first-line treatments and prophylaxis for influenza in children. These agents have been shown to decrease symptoms and shorten the duration of illness, as well as to curb the spread of influenza infection. The neuraminidase inhibitors also have shown efficacy against influenza B infection and exhibit less viral resistance than the older adamantane antiviral class.
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Update on universal childhood immunizations.
Curr Opin Pediatr. 2008 Aug; 20(4): 483-9
Hamlin J, Senthilnathan S, Bernstein HHPURPOSE OF REVIEW: To provide an update of research findings and recommendations regarding immunizations. RECENT FINDINGS: New research has examined the efficacy of the 2007-2008 influenza vaccine, the transmission and incidence of human papillomavirus, the increased prevalence of pneumococcal serotypes not included in the 7-valent pneumococcal conjugate vaccine, the emergence of a drug-resistant strain of Streptococcus pneumoniae, febrile seizure rates following measles-mumps-rubella-varicella vaccination, and the 2006 mumps outbreak in the American Midwest. The Food and Drug Administration has approved the expansion of live attenuated influenza virus vaccine and quadrivalent meningococcal conjugate vaccine for use in children no younger than 2 years of age. The Advisory Committee on Immunization Practices now recommends immunization with quadrivalent meningococcal conjugate vaccine for all previously unvaccinated 11-18-year-old children and has revised its recommendations for Streptococcus pneumoniae catch-up vaccinations. The Advisory Committee on Immunization Practices no longer expresses a preference for the use of the combination measles-mumps-rubella-varicella vaccine over separate measles-mumps-rubella and varicella administration. Because of a notable recall of Haemophilus influenzae type B vaccines by Merck & Co Inc, Whitehouse Station, New Jersey, USA, the Advisory Committee on Immunization Practices recommends that pediatric providers conserve available Haemophilus influenzae type B vaccines by delaying the administration of the booster dose of the vaccine in healthy children. SUMMARY: New vaccine recommendations continue to be made, and research continues on infectious diseases, vaccine safety, and vaccine efficacy.
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Vaccine. 2008 Aug 5; 26(33): 4210-7
Levin MJ, Song LY, Fenton T, Nachman S, Patterson J, Walker R, Kemble G, Allende M, Hultquist M, Yi T, Nowak B, Weinberg AHIV-infected children (N=243), >or=5 to <18 years old, receiving stable antiretroviral therapy, were stratified by immunologic status and randomly assigned to receive intranasal live attenuated influenza vaccine (LAIV) or intramuscular trivalent inactivated influenza vaccine (TIV). The safety profile after LAIV or TIV closely resembled the previously reported tolerability to these vaccines in children without HIV infection. Post-vaccination hemagglutination inhibition (HAI) antibody responses and shedding of LAIV virus were also similar, regardless of immunological stratum, to antibody responses and shedding previously reported for children without HIV infection. LAIV should be further evaluated for a role in immunizing HIV-infected children.
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Update on immunizations in children and adolescents.
Am Fam Physician. 2008 Jun 1; 77(11): 1561-8
Ackerman LKOver the past few years, there have been many changes to the recommendations for children and adolescents by the Advisory Committee on Immunization Practices. These include dividing the immunization schedule into two parts (i.e., ages birth to six years and seven to 18 years, with catch-up schedules for each group); expanding the recommendations for influenza vaccine to children ages six months to 18 years without risk factors; expanding coverage for hepatitis A vaccine to include all children at one year of age; initiating routine immunization with oral rotavirus vaccine given at ages two, four, and six months; and adding a booster dose of varicella vaccine at four to six years of age. The tetanus and diphtheria toxoids and acellular pertussis vaccine (Tdap), quadrivalent meningococcal conjugate vaccine (MCV4), and quadrivalent human papillomavirus (HPV) vaccine are routinely recommended for adolescents 11 to 12 years of age. Tdap provides pertussis immunity in addition to the tetanus and diphtheria immunity provided by the tetanus and diphtheria toxoids vaccine (Td). MCV4 has improved immunogenicity compared with the older meningococcal vaccine. HPV vaccine protects against serotypes 6, 11, 16, and 18, and is given in three doses, ideally at 11 to 12 years of age; the effectiveness increases when the vaccine is given before the onset of sexual activity. Family physicians play an integral role in implementing new immunization recommendations and properly educating patients and families in the increasingly complex armamentarium of prevention.
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Bull World Health Organ. 2008 May; 86(5): 390-398C
Dherani M, Pope D, Mascarenhas M, Smith KR, Weber M, Bruce NReduction of indoor air pollution (IAP) exposure from solid fuel use is a potentially important intervention for childhood pneumonia prevention. This review updates a prior meta-analysis and investigates whether risk varies by etiological agent and pneumonia severity among children aged less than 5 years who are exposed to unprocessed solid fuels. Searches were made of electronic databases (including Africa, China and Latin America) without language restriction. Search terms covered all sources of IAP and wide-ranging descriptions of acute lower respiratory infections, including viral and bacterial agents. From 5317 studies in the main electronic databases (plus 307 African and Latin American, and 588 Chinese studies, in separate databases), 25 were included in the review and 24 were suitable for meta-analysis. Due to substantial statistical heterogeneity, random effects models were used. The overall pooled odds ratio was 1.78 (95% confidence interval, CI: 1.45-2.18), almost unchanged at 1.79 (95% CI: 1.26-2.21) after exclusion of studies with low exposure prevalence (< 15%) and one high outlier. There was evidence of publication bias, and the implications for the results are explored. Sensitivity subanalyses assessed the impact of control selection, adjustment for confounding, exposure and outcome assessment, and age, but no strong effects were identified. Evidence on respiratory syncytial virus was conflicting, while risk for severe or fatal pneumonia was similar to or higher than that for all pneumonia. Despite heterogeneity, this analysis demonstrated sufficient consistency to conclude that risk of pneumonia in young children is increased by exposure to unprocessed solid fuels by a factor of 1.8. Greater efforts are now required to implement effective interventions.
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J Acquir Immune Defic Syndr. 2008 Jul 1; 48(3): 289-96
Viganò A, Zuccotti GV, Pacei M, Erba P, Castelletti E, Giacomet V, Amendola A, Pariani E, Tanzi E, Clerici MOBJECTIVE: It is unclear whether the ability to respond to vaccines is restored by antiretroviral therapy. We evaluated the influenza-specific immune responses elicited by a virosomal vaccine in HIV-infected children on long-term successful highly active antiretroviral therapy (HAART). METHODS: This was an observational, prospective, open-label study enrolling 24 HIV-infected, HAART-treated (85 months' mean exposure), vaccine-naive children (median age=11.9 years) and 14 age- and gender-matched healthy controls. Mean CD4 T-cell counts (>900 cells/microL) and percentages (>37%) were comparable. The HIV RNA level was <50 copies/mL in all patients. Children received a single dose of trivalent virosome-adjuvanted influenza vaccine. A/H3N2-, A/H1N1-, and B-antigen-specific antibody (Ab) titers and subclasses and vaccine-specific interferon-gamma (IFNgamma)- and interleukin (IL)-2-producing T lymphocytes were analyzed at baseline and 1 and 6 months after immunization. RESULTS: Seroconversion (>or=4-fold Ab titer raise in >40% of patients) and seroprotection (Ab titer>or=1:40 in >70% of patients) was achieved at 1 month in both groups; however, fewer HIV-infected children fulfilled these criteria. The A/H3N2- and A/H1N1-specific Ab geometric mean titers were lower in HIV-infected children compared with healthy controls at 1 and 6 months; interestingly, a boost in vaccine-specific IgG3 T helper 1 type Ab was seen in healthy controls alone. Finally, vaccine specific-IFNgamma- and IL-2-producing T lymphocytes were reduced at both time points in HIV-infected children compared with healthy controls. CONCLUSIONS: One injection of virosomal-adjuvanted influenza vaccine stimulates good immune responses, although the humoral and cellular immune responses are reduced in HIV-infected children compared to healthy children. This indicates that immunologic function impairments may persist upon HIV infection even if HIV-positive viremia is suppressed and immune recovery seems to be achieved.
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The treatment of bronchiolitis.
Arch Dis Child. 2008 Sep; 93(9): 793-8
Yanney M, Vyas HBronchiolitis is the commonest reason for hospital admission in infancy and the most frequent cause of acute respiratory failure in children admitted to paediatric intensive care units in the UK and North America. The respiratory syncytial virus accounts for most cases of bronchiolitis, however, new virus isolation techniques have led to the discovery of previously unrecognised viruses, including the human metapneumovirus and bocavirus which also play a significant role. The main developments in bronchiolitis management in recent years relate to the use of immunoprophylaxis; a number of other therapies such as the use of heliox are currently being investigated. Supportive therapy remains the mainstay of management with limited or no evidence of benefit for most other pharmacological treatments. This article summarises the current understanding of the different bronchiolitis phenotypes, with a brief description of outcomes and a review of the evidence for the various therapeutic interventions.
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Poor immune responses to a birth dose of diphtheria, tetanus, and acellular pertussis vaccine.
J Pediatr. 2008 Sep; 153(3): 327-32
Halasa NB, O'Shea A, Shi JR, LaFleur BJ, Edwards KMOBJECTIVES: To evaluate the safety and immunogenicity of an additional birth dose of diphtheria, tetanus, and acellular pertussis vaccine (DTaP). STUDY DESIGN: Fifty infants between 2 to 14 days of age were randomly assigned to receive either DTaP and hepatitis B vaccines (experimental) or hepatitis B alone (control) at birth. At 2, 4, 6, and 17 months of age, DTaP and routine vaccines were administered to both groups. Safety data were collected after each dose, and sera were obtained at birth, 6, 7, 17, and 18 months. Immune responses to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae were measured by enzyme-linked immunosorbent assay; responses to other vaccines were assessed. RESULTS: No differences were seen between the 2 groups in either local or systemic reactions; all vaccines were well tolerated. Compared with the control group, infants in the experimental group demonstrated significantly lower geometric mean antibody concentrations for pertussis toxin and pertactin 6, 7, and 18 months, for fimbrae at 6, 7, 17, and 18 months, and for FHA at 18 months, and lower geometric mean antibody concentrations for diphtheria at 7 months. Immune responses to all other vaccine antigens were comparable. CONCLUSION: Administration of an additional dose of DTaP at birth was safe but was associated with a significantly lower response to diphtheria and 3 of 4 pertussis antigens compared with controls.
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Pediatrics. 2008 Jun; 121(6): e1555-62
Sandora TJ, Shih MC, Goldmann DABACKGROUND: Students often miss school because of gastrointestinal and respiratory illnesses. We assessed the effectiveness of a multifactorial intervention, including alcohol-based hand-sanitizer and surface disinfection, in reducing absenteeism caused by gastrointestinal and respiratory illnesses in elementary school students. METHODS: We performed a school-based cluster-randomized, controlled trial at a single elementary school. Eligible students in third to fifth grade were enrolled. Intervention classrooms received alcohol-based hand sanitizer to use at school and quaternary ammonium wipes to disinfect classroom surfaces daily for 8 weeks; control classrooms followed usual hand-washing and cleaning practices. Parents completed a preintervention demographic survey. Absences were recorded along with the reason for absence. Swabs of environmental surfaces were evaluated by bacterial culture and polymerase chain reaction for norovirus, respiratory syncytial virus, influenza, and parainfluenza 3. The primary outcomes were rates of absenteeism caused by gastrointestinal or respiratory illness. Days absent were modeled as correlated Poisson variables and compared between groups by using generalized estimating equations. Analyses were adjusted for family size, race, health status, and home sanitizer use. We also compared the presence of viruses and the total bacterial colony counts on several classroom surfaces. RESULTS: A total of 285 students were randomly assigned; baseline demographics were similar in the 2 groups. The adjusted absenteeism rate for gastrointestinal illness was significantly lower in the intervention-group subjects compared with control subjects. The adjusted absenteeism rate for respiratory illness was not significantly different between groups. Norovirus was the only virus detected and was found less frequently on surfaces in intervention classrooms compared with control classrooms (9% vs 29%). CONCLUSIONS: A multifactorial intervention including hand sanitizer and surface disinfection reduced absenteeism caused by gastrointestinal illness in elementary school students. Norovirus was found less often on classroom surfaces in the intervention group. Schools should consider adopting these practices to reduce days lost to common illnesses.
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Can Fam Physician. 2008 May; 54(5): 742-3
Worrall G -
Pediatrics. 2008 Jun; 121(6): e1591-8
Carbajal R, Biran V, Lenclen R, Epaud R, Cimerman P, Thibault P, Annequin D, Gold F, Fauroux BOBJECTIVE: Palivizumab (Synagis [Abbot Laboratories, Kent, United Kingdom]) is recommended for the prevention of severe lower respiratory tract infections caused by respiratory syncytial virus in infants at high risk. These injections are very painful, and currently the use of analgesics is not systematic. The objective of this study was to compare the efficacy of EMLA with premixed 50% nitrous oxide/oxygen, used alone or combined with EMLA, for pain alleviation during palivizumab injections. METHODS: This randomized, double-blind, multicenter study included children who were younger than 24 months. Each child randomly received during the first 3 monthly injections 3 different analgesic interventions: (1) EMLA: application of EMLA plus air inhalation; (2) nitrous oxide/oxygen: inhalation of 50/50 nitrous oxide/oxygen plus application of a placebo cream; and (3) nitrous oxide/oxygen plus EMLA: inhalation of 50/50 nitrous oxide/oxygen plus application of EMLA. Each child was his or her own control. Procedural pain was assessed through videotapes with the Modified Behavioral Pain Scale. The procedure itself was subdivided in 2 periods: (1) injection and (2) recovery (first 30 seconds after the removal of the needle). Modified Behavioral Pain Scale scores over time (injection and recovery periods) and among treatments were compared by repeated-measures analysis of variance. RESULTS: Fifty-five children were included. Mean +/- SD Modified Behavioral Pain Scale pain scores for EMLA, nitrous oxide/oxygen, and nitrous oxide/oxygen plus EMLA were, respectively, 9.3 +/- 1.0, 8.8 +/- 1.2, and 8.2 +/- 1.8 during the injection and 7.8 +/- 1.7, 7.4 +/- 1.9, and 6.9 +/- 2.4 during the recovery period. A significant time and treatment effect in favor of the combined nitrous oxide/oxygen plus EMLA was observed. CONCLUSIONS: The administration of 50/50 nitrous oxide/oxygen to infants and young children is effective in decreasing the pain associated with palivizumab intramuscular injections. The combined nitrous oxide/oxygen plus EMLA cream was more effective than either EMLA cream or nitrous oxide/oxygen alone.
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Clin Vaccine Immunol. 2008 Jul; 15(7): 1042-53
Forrest BD, Pride MW, Dunning AJ, Capeding MR, Chotpitayasunondh T, Tam JS, Rappaport R, Eldridge JH, Gruber WCThe highly sensitive gamma interferon (IFN-gamma) enzyme-linked immunosorbent spot (ELISPOT) assay permits the investigation of the role of cell-mediated immunity (CMI) in the protection of young children against influenza. Preliminary studies of young children confirmed that the IFN-gamma ELISPOT assay was a more sensitive measure of influenza memory immune responses than serum antibody and that among seronegative children aged 6 to <36 months, an intranasal dose of 10(7) fluorescent focus units (FFU) of a live attenuated influenza virus vaccine (CAIV-T) elicited substantial CMI responses. A commercial inactivated influenza virus vaccine elicited CMI responses only in children with some previous exposure to related influenza viruses as determined by detectable antibody levels prevaccination. The role of CMI in actual protection against community-acquired, culture-confirmed clinical influenza by CAIV-T was investigated in a large randomized, double-blind, placebo-controlled dose-ranging efficacy trial with 2,172 children aged 6 to <36 months in the Philippines and Thailand. The estimated protection curve indicated that the majority of infants and young children with >or=100 spot-forming cells/10(6) peripheral blood mononuclear cells were protected against clinical influenza, establishing a possible target level of CMI for future influenza vaccine development. The ELISPOT assay for IFN-gamma is a sensitive and reproducible measure of CMI and memory immune responses and contributes to establishing requirements for the future development of vaccines against influenza, especially those used for children.
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Safety and immunogenicity of trivalent inactivated influenza vaccine in infants.
J Infect Dis. 2008 May 15; 197(10): 1448-54
Halasa NB, Gerber MA, Chen Q, Wright PF, Edwards KMBACKGROUND: Trivalent inactivated influenza vaccine (TIV) is not licensed for use in infants <6 months old, the group with the highest influenza hospitalization rates among children. METHODS: In this prospective, open-label study, 2 doses of TIV were administered to healthy infants aged 10-22 weeks. Adverse reactions were assessed, and hemagglutination inhibition (HAI) antibody titers were determined. Weekly telephone surveillance for influenza-like illness was conducted during the influenza season. RESULTS: A total of 42 infants were enrolled and completed the study. Mild local and systemic reactions were noted. In the first season (2004-2005), postvaccination HAI titers >1:32 were noted for 31.6%, 47.4%, and 21.1% of 19 subjects for H1N1, H3N2, and B strains included in the vaccine, respectively. In the second season (2005-2006), postvaccination HAI titers >1:32 were seen in 45.5%, 59.1%, and 0% of 23 subjects for H1N1, H3N2, and B strains included in the vaccine, respectively. Infants who were seronegative before vaccination (titers <1:8) were significantly more likely to have a 4-fold rise in antibody titer after vaccination, compared with infants who had prevaccination titers >1:8 (P<.001). CONCLUSION: Two doses of TIV were found to be safe and moderately immunogenic against some influenza strains. The presence of preexisting maternally derived antibody was associated with significantly lower seroresponse rates to vaccination. Whether vaccination with TIV will prevent influenza in these young children remains to be determined.
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Hum Vaccin. 2008 Jan-Feb; 4(1): 31-5
Meriste S, Jacquet JM, Willems P, Lutsar IThis open randomized study compared the immunogenicity and safety of a diphtheria-tetanus-acellular pertussis (DTPa) and H. influenzae polyribosylribitol phosphate conjugated to the tetanus toxoid (Hib-PRP-T) vaccine (mixed prior to administration) with separate injections of DTPa and Hib vaccines in toddlers aged two years. A total of 119 children (60 mixed; 59 separate administration), primed with DTPw, but not with Hib vaccine were enrolled. Prior to immunization only 10.3% of toddlers had anti-PRP antibody titres > or =1.0 microg/ml, compared with all children on Days 7 and 30. The anti-PRP and anti-tetanus antibody geometric mean concentrations were lower after the combined DTPa/Hib vaccine compared to separately administered vaccines (47.16 microg/ml vs 78.36 microg/ml and 24.95 IU/ml vs 40.63 IU/ml, respectively). One month after vaccination all children had anti-tetanus and anti-diphtheria antibody titres above the protective level of > or =0.1 IU/ml. The rates of recorded adverse events were similar and mostly mild or moderate in intensity whether the vaccines were combined as a single injection or given separately. We conclude that in 2-year old children, previously not immunized against Hib, a single dose of DTPa and Hib was safe and highly immunogenic irrespective of whether it was given as a combined vaccine or separate injections. Although the increase in anti-T and early (7-10 days after) anti-PRP concentrations was greater when the vaccine components were given separately than after combined administration, the DTPa/Hib combined vaccine would provide an effective method of delivering primary Hib vaccination in unprimed toddlers.
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Improved antibody responses in infants less than 1 year old using intradermal influenza vaccination.
Vaccine. 2008 May 23; 26(22): 2700-5
Sugimura T, Ito Y, Tananari Y, Ozaki Y, Maeno Y, Yamaoka T, Kudo YBACKGROUND: Antibody response to influenza vaccine is limited in early. Infants have poorer hemagglutination-inhibiting antibody responses than 12-month-old. Intradermal administration reportedly elicited immune responses similar to or better than a standard intramuscular dose. We hypothesized that intradermal injection could achieve a better response in infants than subcutaneous injection. METHODS: We randomized 34 healthy infants 6-12 months old to either intradermal immunization (0.1 ml of trivalent influenza vaccine containing at least 3 microg of hemagglutinin antigen per strain) or subcutaneous immunization (also 0.1 ml). Changes in hemagglutination inhibition titer were compared using Mann-Whitney U-test, changes in positivity rate, seroconversion, and seroprotection. Local and systemic adverse events were assessed. RESULTS: All 32 infants received both injections. Antibody titers on days at 42 after intradermal injection were significantly greater than subcutaneous injection (P=0.032 in A/New Caledonia (H1N1), 0.019 in A New York (H3N2) and 0.044 in B/Shanghai. Positive titers for A New York (H3N2) were attained significantly more often after intradermal (73.3%) than subcutaneous injection (23.5%) on day 28, and significantly more often 42 days after intradermal injection (93.3% for A/New Caledonia (H1N1) and 73.3% for B/Shanghai) than after subcutaneous injection. Positive rates for other stains were similar between groups on days 28 and 42. Seroconversion rates were similar between groups. Seroprotection on day 42 for A New York (H3N2) was significantly greater in the intradermal (86.7%) than in the subcutaneous group (35.3%). Seroprotection rates for other stains were similar. CONCLUSIONS: Intradermal administration to infants of two doses of influenza vaccine was more immunogenic than subcutaneous injection. Seroconversion and seroprotection rates remained insufficient. Further study of route, quantity, and frequency are needed to improve of responses in infants.
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The course of fever following influenza virus infection in children treated with oseltamivir.
J Med Virol. 2008 Jun; 80(6): 1065-71
Suzuki E, Ichihara KAlthough the effectiveness of oseltamivir against influenza virus infection is well known, there has been no report analyzing the detailed time course of fever following the drug treatment in children. Oseltamivir was prescribed for 4 days to every child with a positive result for rapid immunological test for influenza virus during 2002--2003, 2003--2004, and 2004--2005 epidemics. Only those who were 1-12 years of age and prescribed oseltamivir within 24 hr after the onset of fever were included in the analysis. The numbers of children with type A/H3N2 disease for the three seasons were 64, 77, and 33, and those with type B disease were 102, 4, and 86, for the respective seasons. The period until normalization of temperature was obtained from six-hourly recordings of body temperature. By multiple regression analysis, temperature periods were longer in type B than in type A/H3N2 disease, negatively associated with age, and positively with maximal body temperature (all: P < 0.001). The effectiveness of oseltamivir on body temperature in type B disease was less apparent in the 2004--2005 than in the 2002--2003 season, irrespective of age. No such between-season difference was observed for Type A/H3N2 disease. Frequencies of ineffective cases with biphasic fever (19.6% and 43.0% during 2002--2003 and 2004--2005 seasons) were significantly higher in type B than in type A/H3N disease (12.0% and 11.8%, respectively). The effectiveness of oseltamivir depends on a child's age, maximal body temperature and the virus type. This study confirmed recent reports indicating decreased effectiveness of oseltamivir against type B disease.
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Vaccines for preventing influenza in healthy children.
Cochrane Database Syst Rev. 2008; CD004879
Jefferson T, Rivetti A, Harnden A, Di Pietrantonj C, Demicheli VBACKGROUND: The consequences of influenza in children and adults are mainly absenteeism from school and work. However, the risk of complications is greatest in children and people over 65 years old. OBJECTIVES: To appraise all comparative studies evaluating the effects of influenza vaccines in healthy children; assess vaccine efficacy (prevention of confirmed influenza) and effectiveness (prevention of influenza-like illness) and document adverse events associated with influenza vaccines. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, issue 3); OLD MEDLINE (1950 to 1965); MEDLINE (1966 to September 2007); EMBASE (1974 to September 2007); Biological Abstracts (1969 to September 2007); and Science Citation Index (1974 to September 2007). SELECTION CRITERIA: Randomised controlled trials (RCTs), cohort and case-control studies of any influenza vaccine in healthy children under 16 years of age. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: Fifty-one studies with 294,159 observations were included. Sixteen RCTs and 18 cohort studies were included in the analysis of vaccine efficacy and effectiveness. From RCTs, live vaccines showed an efficacy of 82% (95% confidence interval (CI) 71% to 89%) and an effectiveness of 33% (95% CI 28% to 38%) in children older than two compared with placebo or no intervention. Inactivated vaccines had a lower efficacy of 59% (95% CI 41% to 71%) than live vaccines but similar effectiveness: 36% (95% CI 24% to 46%). In children under two, the efficacy of inactivated vaccine was similar to placebo. Variability in study design and presentation of data was such that a meta-analysis of safety outcome data was not feasible. Extensive evidence of reporting bias of safety outcomes from trials of live attenuated vaccines impeded meaningful analysis. AUTHORS' CONCLUSIONS: Influenza vaccines are efficacious in children older than two but little evidence is available for children under two. There was a marked difference between vaccine efficacy and effectiveness. No safety comparisons could be carried out, emphasizing the need for standardisation of methods and presentation of vaccine safety data in future studies. It was surprising to find only one study of inactivated vaccine in children under two years, given current recommendations to vaccinate healthy children from six months old in the USA and Canada. If immunisation in children is to be recommended as a public health policy, large-scale studies assessing important outcomes and directly comparing vaccine types are urgently required.
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Respiratory syncytial virus infection and recurrent wheezing: what next?
J Chemother. 2007 Oct; 19 Suppl 2: 8-11
Puddu M, Fanos VRecent literature has provided evidence of a link between early RSV infection and chronic respiratory morbidity (recurrent wheezing, reactive airway disease and asthma). The mechanism of this association is not well understood but both genetic and environmental factors are involved. The classical studies from Sweden, Tucson and Finland are briefly summarized. Moreover new data concerning a recent multi-center international study on this topic are presented. The study, which enrolled 191 preterm infants (
J Chemother. 2007 Oct; 19 Suppl 2: 5-7
Pelosi U, Porcu G, Chia L, Firinu D
Pediatrics. 2008 May; 121(5): e1190-5
Martinón-Torres F, Rodríguez-Núñez A, Martinón-Sánchez JMOBJECTIVE: The purpose of this work was to evaluate the effects of administering either heliox or air oxygen in combination with nasal continuous positive airway pressure in infants with refractory bronchiolitis. PATIENT AND METHODS: We conducted a prospective, interventional, single-center, crossover study in a teaching hospital including infants 1 month to 2 years of age, consecutively admitted to the PICU from February 2004 to February 2005 for treatment of severe acute bronchiolitis unresponsive to therapy. Patients with a clinical score (Modified Wood's Clinical Asthma Score) of >5, arterial oxygen saturation of <92%, or transcutaneous CO(2) pressure of >50 mmHg despite supportive therapy, nebulized L-epinephrine, and heliox therapy through a nonrebreathing reservoir face mask were eligible. During the study period, 40 infants with bronchiolitis were admitted to the PICU; 12 fulfilled inclusion criteria. A predetermined balanced sequential allocation to either 30 minutes of treatment with nasal continuous positive airway pressure with heliox or to air-oxygen nasal continuous positive airway pressure was performed. Measurements were taken at baseline and after 30 minutes of each treatment. RESULTS: Baseline mean values were as follows: nasal continuous positive airway pressure of 7.2 cmH(2)O; clinical score of 7.7 points; transcutaneous CO(2) pressure of 61.6 mmHg; and arterial oxygen saturation of 88.6%, with the fraction of inspired oxygen at 35.4%. Clinical score, transcutaneous CO(2) pressure, and arterial oxygen saturation improved during the study time with both heliox-nasal continuous positive airway pressure and air-oxygen-nasal continuous positive airway pressure: after 1 hour, the clinical score fell 1.7 points, transcutaneous CO(2) pressure decreased 8.2 mmHg, and arterial oxygen saturation increased by 7.7%. Improvement in clinical score was double with heliox-nasal continuous positive airway pressure compared with the air-oxygen-nasal continuous positive airway pressure (2.12 vs 1.08 points), and the fall in the transcutaneous CO(2) pressure was greater with heliox-nasal continuous positive airway pressure compared with air-oxygen-nasal continuous positive airway pressure (9.7 vs 5.4 mm Hg). There was no difference in arterial oxygen saturation between groups. No patients required endotracheal intubation. No adverse effects attributable to either of the study interventions were detected. CONCLUSIONS: Nasal continuous positive airway pressure improves the clinical score and the CO(2) elimination of infants with refractory bronchiolitis. These positive effects are significantly enhanced when nasal continuous positive airway pressure is combined with heliox instead of air oxygen. Both techniques are noninvasive, seem safe, and may reduce the need for endotracheal intubation.
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