RESUMEN

BACKGROUND: Prior to introducing pneumococcal conjugate vaccines (PCVs), Streptococcus pneumoniae was most commonly isolated from middle ear fluid of children with acute otitis media (AOM). Reducing nasopharyngeal colonisation of this bacterium by PCVs may lead to a decline in AOM. The effects of PCVs deserve ongoing monitoring since studies from the post-PCV era report a shift in causative otopathogens towards non-vaccine serotypes and other bacteria. This updated Cochrane Review was first published in 2002 and updated in 2004, 2009, and 2014. The review title was changed (to include the population, i.e. children) for this update. OBJECTIVES: To assess the effect of PCVs in preventing AOM in children up to 12 years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, Web of Science, and trials registers (ClinicalTrials.gov and WHO ICTRP) to 29 March 2019. SELECTION CRITERIA: Randomised controlled trials of PCV versus placebo or control vaccine. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. The primary outcomes were frequency of all-cause AOM and adverse effects. Secondary outcomes included frequency of pneumococcal AOM and frequency of recurrent AOM (defined as three or more AOM episodes in six months or four or more in one year). We used GRADE to assess the quality of the evidence. MAIN RESULTS: We included 14 publications of 11 trials (60,733 children, range 74 to 37,868 per trial) of 7- to 11-valent PCVs versus control vaccines (meningococcus type C vaccine in three trials, and hepatitis A or B vaccine in eight trials). We included two additional trials for this update. We did not find any relevant trials with the newer 13-valent PCV. Most studies were funded by pharmaceutical companies. Overall, risk of bias was low. In seven trials (59,415 children) PCVs were administered in early infancy, while four trials (1318 children) included children aged one year and over who were either healthy or had a history of respiratory illness. There was considerable clinical heterogeneity across studies, therefore we did not perform meta-analyses.Adverse eventsNine trials reported on adverse effects (77,389 children; high-quality evidence). Mild local reactions and fever were common in both groups, and occurred more frequently in PCV than in control vaccine groups: redness (< 2.5 cm): 5% to 20% versus 0% to 16%; swelling (< 2.5 cm): 5% to 12% versus 0% to 8%; and fever (< 39 °C): 15% to 44% versus 8% to 25%. More severe redness (> 2.5 cm), swelling (> 2.5 cm), and fever (> 39 °C) occurred less frequently (0% to 0.9%, 0.1% to 1.3%, and 0.4% to 2.5%, respectively in children receiving PCV) and did not differ significantly between PCV and control vaccine groups. Pain or tenderness, or both was reported more frequently in PCV than in control vaccine groups: 3% to 38% versus 0% to 8%. Serious adverse events judged causally related to vaccination were rare and did not differ significantly between groups, and no fatal serious adverse event judged causally related to vaccination was reported.PCV administered in early infancyPCV7The effect of a licenced 7-valent PCV with CRM197 as carrier protein (CRM197-PCV7) on all-cause AOM varied from -5% (95% confidence interval (CI) -25% to 12%) relative risk reduction (RRR) in high-risk infants (1 trial; 944 children; moderate-quality evidence) to 6% (95% CI -4% to 16%; 1 trial; 1662 children) and 6% (95% CI 4% to 9%; 1 trial; 37,868 children) RRR in low-risk infants (high-quality evidence). PCV7 with the outer membrane protein complex of Neisseria meningitidis serogroup B as carrier protein (OMPC-PCV7), was not associated with a reduction in all-cause AOM (RRR -1%, 95% CI -12% to 10%; 1 trial; 1666 children; high-quality evidence).CRM197-PCV7 and OMPC-PCV7 were associated with 20% (95% CI 7% to 31%) and 25% (95% CI 11% to 37%) RRR in pneumococcal AOM, respectively (2 trials; 3328 children; high-quality evidence) and CRM197-PCV7 with 9% (95% CI -12% to 27%) to 10% (95% CI 7% to 13%) RRR in recurrent AOM (2 trials; 39,530 children; high-quality evidence).PHiD-CV10/11The effect of a licenced 10-valent PCV conjugated to protein D, a surface lipoprotein of Haemophilus influenzae, (PHiD-CV10) on all-cause AOM varied from 6% (95% CI -6% to 17%; 1 trial; 5095 children) to 15% (95% CI -1% to 28%; 1 trial; 7359 children) RRR in healthy infants (moderate-quality evidence). PHiD-CV11 was associated with 34% (95% CI 21% to 44%) RRR in all-cause AOM (1 trial; 4968 children; high-quality evidence).PHiD-CV10 and PHiD-CV11 were associated with 53% (95% CI 16% to 74%) and 52% (95% CI 37% to 63%) RRR in pneumococcal AOM (2 trials; 12,327 children; high-quality evidence) and PHiD-CV11 with 56% (95% CI -2% to 80%) RRR in recurrent AOM (1 trial; 4968 children; moderate-quality evidence).PCV administered at later agePCV7We found no evidence of a beneficial effect on all-cause AOM of administering CRM197-PCV7 in children aged 1 to 7 years with a history of respiratory illness or frequent AOM (2 trials; 457 children; high-quality evidence) and CRM197-PCV7 combined with a trivalent influenza vaccine in children aged 18 to 72 months with a history of respiratory tract infections (1 trial; 597 children; high-quality evidence).CRM197-PCV9In 1 trial including 264 healthy day-care attendees aged 1 to 3 years, CRM197-PCV9 was associated with 17% (95% CI -2% to 33%) RRR in parent-reported all-cause OM (low-quality evidence). AUTHORS' CONCLUSIONS: Administration of the licenced CRM197-PCV7 and PHiD-CV10 during early infancy is associated with large relative risk reductions in pneumococcal AOM. However, the effects of these vaccines on all-cause AOM is far more uncertain. We found no evidence of a beneficial effect on all-cause AOM of administering PCVs in high-risk infants, after early infancy (i.e. in children one year and above), and in older children with a history of respiratory illness. Compared to control vaccines, PCVs were associated with an increase in mild local reactions (redness, swelling), fever, and pain and/or tenderness. We found no evidence of a difference in more severe local reactions, fever, or serious adverse events judged causally related to vaccination.

Asunto(s)

RESUMEN

OBJECTIVES: The prenatal diagnosis of oral clefts (OCs) by ultrasound can pose an ethical dilemma. The purpose of this study was to obtain insight into the psychosocial and moral considerations of prospective parents concerning OCs, the burden of OCs and parents' attitude toward possible termination of pregnancy (TOP) in order to improve counseling in the future. DESIGN: Between August 2011 and August 2014, a prospective cohort questionnaire study was administered. SETTING: Prenatal care clinic of the Wilhelmina's Children hospital, a Tertiary Care Centre. PARTICIPANTS: Parents expecting a child with an OC. MAIN OUTCOME MEASURES: Expectation of OCs in general and attitudes toward the impact and expected burden of the OC of their child. Furthermore, parents were asked if they had considered TOP. RESULTS: Most of the parents described an OC as a cosmetic disability (50.6%) or as "just a little different" (29.4%). These parents expected that the OC would not affect their own happiness and have only minor influence on the happiness of their future child. Health professionals had a considerable influence on parental opinion. A minority (6.4%, 5/85) of the respondents considered TOP, and none of the responders chose to terminate the pregnancy. CONCLUSIONS: This study suggests that future parents have very few negative perceptions of OC after prenatal counseling. Caregivers should be aware that their counseling is important for decision-making of parents.

RESUMEN

BACKGROUND: No consensus exists on the optimal treatment protocol for orofacial clefts or the optimal timing of cleft palate closure. This study investigated factors influencing speech outcomes after two-stage palate repair in adults with a non-syndromal complete unilateral cleft lip and palate (UCLP). METHODS: This was a retrospective analysis of adult patients with a UCLP who underwent two-stage palate closure and were treated at our tertiary cleft centre. Patients ≥17 years of age were invited for a final speech assessment. Their medical history was obtained from their medical files, and speech outcomes were assessed by a speech pathologist during the follow-up consultation. RESULTS: Forty-eight patients were included in the analysis, with a mean age of 21 years (standard deviation, 3.4 years). Their mean age at the time of hard and soft palate closure was 3 years and 8.0 months, respectively. In 40% of the patients, a pharyngoplasty was performed. On a 5-point intelligibility scale, 84.4% received a score of 1 or 2; meaning that their speech was intelligible. We observed a significant correlation between intelligibility scores and the incidence of articulation errors (P<0.001). In total, 36% showed mild to moderate hypernasality during the speech assessment, and 11%-17% of the patients exhibited increased nasalance scores, assessed through nasometry. CONCLUSIONS: The present study describes long-term speech outcomes after two-stage palatoplasty with hard palate closure at a mean age of 3 years old. We observed moderate long-term intelligibility scores, a relatively high incidence of persistent hypernasality, and a high pharyngoplasty incidence.

RESUMEN

OBJECTIVE: To identify early factors associated with disease course in patients with juvenile idiopathic inflammatory myopathies (IIMs). METHODS: Univariable and multivariable multinomial logistic regression analyses were performed in a large juvenile IIM registry (n = 365) and included demographic characteristics, early clinical features, serum muscle enzyme levels, myositis autoantibodies, environmental exposures, and immunogenetic polymorphisms. RESULTS: Multivariable associations with chronic or polycyclic courses compared to a monocyclic course included myositis-specific autoantibodies (multinomial odds ratio [OR] 4.2 and 2.8, respectively), myositis-associated autoantibodies (multinomial OR 4.8 and 3.5), and a documented infection within 6 months of illness onset (multinomial OR 2.5 and 4.7). A higher overall clinical symptom score at diagnosis was associated with chronic or monocyclic courses compared to a polycyclic course. Furthermore, severe illness onset was associated with a chronic course compared to monocyclic or polycyclic courses (multinomial OR 2.1 and 2.6, respectively), while anti-p155/140 autoantibodies were associated with chronic or polycyclic courses compared to a monocyclic course (multinomial OR 3.9 and 2.3, respectively). Additional univariable associations of a chronic course compared to a monocyclic course included photosensitivity, V-sign or shawl sign rashes, and cuticular overgrowth (OR 2.2-3.2). The mean ultraviolet index and highest ultraviolet index in the month before diagnosis were associated with a chronic course compared to a polycyclic course in boys (OR 1.5 and 1.3), while residing in the Northwest was less frequently associated with a chronic course (OR 0.2). CONCLUSION: Our findings indicate that myositis autoantibodies, in particular anti-p155/140, and a number of early clinical features and environmental exposures are associated with a chronic course in patients with juvenile IIM. These findings suggest that early factors, which are associated with poorer outcomes in juvenile IIM, can be identified.

Asunto(s)

RESUMEN

OBJECTIVE: Our aim is to introduce and validate a new oral cleft classification system based on prenatal ultrasound for use by professionals in daily practice. METHODS: During a 3-year period (2011-2014), all cases of prenatal oral cleft diagnosed by ultrasound were retrospectively reviewed. A new prenatal ultrasound classification system was introduced. For the purpose of validation, prenatal ultrasound images of oral cleft types were described according to the new classification system and were compared with postnatal findings by reviewing medical records. RESULTS: A total of 103 fetuses with oral cleft were identified by ultrasound. The mean gestation time at detection was 20.4 weeks (95% confidence intervals: 20.0-20.7). The association between oral cleft and other anomalies varied by cleft type; types 2b/3b and 4 were most frequently associated with other anomalies. The measure of agreement between the prenatal and postnatal findings showed a Kappa value of 0.63 (95% confidence intervals: 0.52-0.75), demonstrating the accuracy of this new classification system. CONCLUSION: A new prenatal oral cleft classification system is presented. This system appears to be accurate, and it shows the variation in the risk of associated anomalies for each cleft type. We expect that ultrasonographers will be able to use the new classification in daily practice.

Asunto(s)

RESUMEN

OBJECTIVE: The aim of this study was to assess the opinion of obstetric care providers who perform prenatal ultrasounds to screen for anomalies and who advise women about their options, including termination of pregnancy, when an oral cleft is detected. We compared providers' opinions about pregnancy termination for isolated oral cleft in The Netherlands, where the number of terminations is low, and in Israel, where the number is high. METHODS: Online questionnaires were used. The questions assessed the providers' views regarding the estimated burden of treatment, the functioning ability, and the level of happiness of children with an oral cleft and their parents. Additionally, we assessed providers' opinions on pregnancy termination for isolated oral cleft. RESULTS: In The Netherlands, more professionals considered oral cleft a disability (rate differences 17.8%, 95% confidence interval: 0.5-33.1%) than in Israel. In the Netherlands, 10.6% of respondents (compared with 11.1% in Israel) thought that an isolated cleft was a reason for terminations of pregnancy (TOP) (rate differences 0.6%, 95% confidence interval: -12% to 10.9%). CONCLUSIONS: Prenatal care providers in The Netherlands and Israel do not differ in their opinions about the severity of oral cleft and the acceptability of TOP for an isolated oral cleft. This study shows that prenatal care providers' attitudes do therefore not explain the dramatic difference between these countries in the number of TOP for isolated oral cleft.

Asunto(s)

RESUMEN

Childhood immune thrombocytopenia (ITP) is a rare autoimmune bleeding disorder. Most children recover within 6 to 12 months, but individual course is difficult to predict. We performed a systematic review and meta-analysis to identify predictors of chronic ITP. We found 1399 articles; after critical appraisal, 54 studies were included. The following predictors of chronic ITP in children, assessed in at least 3 studies, have been identified: female gender (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.04-1.31), older age at presentation (age ≥11 years; OR 2.47, 95% CI 1.94-3.15), no preceding infection or vaccination (OR 3.08, 95 CI 2.19-4.32), insidious onset (OR 11.27, 95% CI 6.27-20.27), higher platelet counts at presentation (≥20 × 10(9)/L: OR 2.15, 95% CI 1.63-2.83), presence of antinuclear antibodies (OR 2.87, 95% 1.57-5.24), and treatment with a combination of methylprednisolone and intravenous immunoglobulin (OR 2.67, 95% CI 1.44-4.96). Children with mucosal bleeding at diagnosis or treatment with intravenous immunoglobulin alone developed chronic ITP less often (OR 0.39, 95% CI 0.28-0.54 and OR 0.71, 95% CI 0.52-0.97, respectively). The protective effect of intravenous immunoglobulin is remarkable and needs confirmation in prospective randomized trials as well as future laboratory studies to elucidate the mechanism of this effect.

Asunto(s)

RESUMEN

BACKGROUND: Serum thymus and activation-regulated chemokine (sTARC) levels reflect disease severity of atopic dermatitis (AD) in small study populations. It remains unclear whether sTARC is a reliable outcome measurement for AD severity in heterogeneous AD populations in daily practice. OBJECTIVE: We sought to assess the utility of sTARC as a biomarker for monitoring AD severity in adults in daily practice. METHODS: sTARC, clinical skin score (Six Area, Six Sign AD [SASSAD]), and body surface area measurements were collected from all adult patients with AD visiting our clinic between March 2009 and March 2012, at first visit or exacerbation (baseline). In addition, data from short-term and long-term follow-up visits were collected. RESULTS: At baseline sTARC levels ranged widely (n = 320; minimum-maximum: 3-50,400 pg/mL) and sTARC and SASSAD or body surface area correlated moderately. In the majority of patients, sTARC and SASSAD or body surface area changed congruently during follow-up. LIMITATIONS: Data were collected retrospectively. CONCLUSION: sTARC may represent a suitable biomarker for monitoring of AD severity in daily practice.

Asunto(s)

RESUMEN

BACKGROUND: Acute otitis media (AOM) is a very common respiratory infection in early infancy and childhood. The marginal benefits of antibiotics for AOM in low-risk populations in general, the increasing problem of bacterial resistance to antibiotics and the huge estimated direct and indirect annual costs associated with otitis media (OM) have prompted a search for effective vaccines to prevent AOM. OBJECTIVES: To assess the effect of pneumococcal conjugate vaccines (PCVs) in preventing AOM in children up to 12 years of age. SEARCH METHODS: We searched CENTRAL (2013, Issue 11), MEDLINE (1995 to November week 3, 2013), EMBASE (1995 to December 2013), CINAHL (2007 to December 2013), LILACS (2007 to December 2013) and Web of Science (2007 to December 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) of PCVs to prevent AOM in children aged 12 years or younger, with a follow-up of at least six months after vaccination. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: We included 11 publications of nine RCTs (n = 48,426 children, range 74 to 37,868 per study) of 7- to 11-valent PCV (with different carrier proteins). Five trials (n = 47,108) included infants, while four trials (n = 1318) included children aged one to seven years that were either healthy (one study, n = 264) or had a previous history of upper respiratory tract infection (URTI), including AOM. We judged the methodological quality of the included studies to be moderate to high. There was considerable clinical diversity between studies in terms of study population, type of conjugate vaccine and outcome measures. We therefore refrained from pooling the results.In three studies, the 7-valent PCV with CRM197 as carrier protein (CRM197-PCV7) administered during early infancy was associated with a relative risk reduction (RRR) of all-cause AOM ranging from -5% in high-risk children (95% confidence interval (CI) -25% to 12%) to 7% in low-risk children (95% CI 4% to 9%). Another 7-valent PCV with the outer membrane protein complex of Neisseria meningitidis (N. meningitidis) serogroup B as carrier protein, administered in infancy, did not reduce overall AOM episodes, while a precursor 11-valent PCV with Haemophilus influenzae (H. influenzae) protein D as carrier protein was associated with a RRR of all-cause AOM episodes of 34% (95% CI 21% to 44%).A 9-valent PCV (with CRM197 carrier protein) administered in healthy toddlers was associated with a RRR of (parent-reported) OM episodes of 17% (95% CI -2% to 33%). CRM197-PCV7 followed by 23-valent pneumococcal polysaccharide vaccination administered after infancy in older children with a history of AOM showed no beneficial effect on first occurrence and later AOM episodes. In a study in older children with a previously diagnosed respiratory tract infection, performed during the influenza season, a trivalent influenza vaccine combined with placebo (TIV/placebo) led to fewer all-cause AOM episodes than vaccination with TIV and PCV7 (TIV/PCV7) when compared to hepatitis B vaccination and placebo (HBV/placebo) (RRR 71%, 95% CI 30% to 88% versus RRR 57%, 95% CI 6% to 80%, respectively) indicating that CRM197-PCV7 after infancy may even have negative effects on AOM. AUTHORS' CONCLUSIONS: Based on current evidence of the effects of PCVs for preventing AOM, the licensed 7-valent CRM197-PCV7 has modest beneficial effects in healthy infants with a low baseline risk of AOM. Administering PCV7 in high-risk infants, after early infancy and in older children with a history of AOM, appears to have no benefit in preventing further episodes. Currently, several RCTs with different (newly licensed, multivalent) PCVs administered during early infancy are ongoing to establish their effects on AOM. Results of these studies may provide a better understanding of the role of the newly licensed, multivalent PCVs in preventing AOM. Also the impact on AOM of the carrier protein D, as used in certain pneumococcal vaccines, needs to be further established.

Asunto(s)

RESUMEN

BACKGROUND: Otitis media (OM) is a leading cause of medical consultations, antibiotic prescription and surgery in children. The surgical procedures offered to children with recurrent or persistent OM are insertion of grommets, adenoidectomy or a combination of the two. There is clear National Institute for Health and Care Excellence guidance for the use of grommets in subgroups of children with persistent OM with effusion (OME), but similar guidance is not available for adenoidectomy, either in persistent OME or in recurrent acute OM (AOM). OBJECTIVES: (1) To develop a model to predict the risk of children referred for adenoidectomy having a prolonged duration of their OM. Then, (2a) to evaluate the overall effect of adenoidectomy, with or without grommets, on OM using individual patient data (IPD) and (2b) to identify those subgroups of children who are most likely to benefit from adenoidectomy with or without grommets. DATA SOURCES: A number of electronic databases were searched from their inception including the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), metaRegister of Current Controlled Trials (mRCT), ClinicalTrials.gov, International Clinical Trials Registry Platform (ICTRP), ClinicalStudyResults.org and Google. REVIEW METHODS: Studies eligible for inclusion in this IPD meta-analysis were randomised controlled trials (RCTs) in children up to 12 years of age diagnosed with recurrent AOM and/or persistent OME in which adenoidectomy (with or without grommets) was compared with non-surgical treatment or grommets alone. The final selection of eligible studies and the quality assessment were carried out according to standard methods and disagreement was resolved by discussion. RESULTS: A total of 503 articles were identified of which 10 trials were included in the meta-analysis; eight of these were at a low risk of bias and two were at moderate risk. The primary outcome was failure at 12 months, defined by a set of persisting symptoms and signs. In the prognostic analysis 56% of those children referred for adenoidectomy (but randomised to the non-surgical group) failed to improve (38% of the children with recurrent AOM and 89% of the children with persistent OME). Children who had adenoidectomy had a greater chance of clinical improvement. The size of that effect is, in general, small but persists for at least 2 years. Two subgroups of children are most likely to benefit from adenoidectomy: first, children aged < 2 years with recurrent AOM - 16% of those who had adenoidectomy failed at 12 months whereas 27% of those who did not have adenoidectomy failed [rate difference (RD) 12%, 95% confidence interval (Cl) 6% to 18%; number needed to treat (NNT) = 9]; second, children aged ≥ 4 years with persistent OME - 51% of those who had adenoidectomy failed at 12 months whereas 70% of those who did not have adenoidectomy failed (RD 19%, 95% Cl 12% to 26%; NNT = 6). No significant benefit of adenoidectomy was found in children aged ≥ 2 years with recurrent AOM and children aged < 4 years with persistent OME. LIMITATIONS: The need to use a composite end point and the limited number of subgroup variables that could be studied are factors that reduce the robustness of these results; however, we do not believe that this reduces the validity of the conclusions. CONCLUSIONS: Adenoidectomy is most beneficial in children with persistent OME aged ≥ 4 years. A smaller beneficial effect was found in children with recurrent AOM aged < 2 years. Consideration must be given to the balance between benefits and harms. Future research is required in a number of key areas, including defining the best methods of selecting, developing and administering patient-reported outcome measures to assess the value of treatments for children with persistent OME and recurrent AOM and upper respiratory infections; investigating the clinical effectiveness and cost-effectiveness of hearing aids (air or bone conduction) and the use of interventions to improve classroom acoustics for children with different degrees of persistence and severity of hearing loss associated with OME; and investigating why professionals' and parents'/carers' treatment preferences vary so much both nationally and internationally. We do not understand why adenoidectomy works in different subgroups at different ages, nor its effects in special populations, such as children with Down syndrome. We also need further research on the impact and optimal management of otitis media in these special situations and others, such as in children with a cleft palate or developmental problems. STUDY REGISTRATION: The study is registered as PROSPERO CRD42011001549. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Asunto(s)

RESUMEN

OBJECTIVE: To compare the costs associated with 2 clinical strategies in children with recurrent upper respiratory tract infections (URTIs): immediate adenoidectomy vs an initial watchful waiting strategy. DESIGN: A cost-minimization analysis from a societal perspective including both direct and indirect costs, alongside an open randomized controlled trial with a 2-year follow-up. SETTING: Multicenter study, including 11 general and 2 university hospitals in the Netherlands. PATIENTS: The study population comprised 111 children aged 1 through 6 years, selected for adenoidectomy for recurrent URTIs according to current clinical practice. INTERVENTION: A strategy of immediate adenoidectomy with or without myringotomy or a strategy of initial watchful waiting. MAIN OUTCOMES MEASURES: Difference in median costs during the 2-year follow-up. RESULTS: The median total of direct and indirect costs in the adenoidectomy and watchful waiting group were €1385 (US $1995) and €844 (US $1216) per patient, respectively. The extra costs in the adenoidectomy group are primarily attributable to surgery and visits to the otorhinolaryngologist. Other costs did not differ significantly between the groups. CONCLUSIONS: In children selected for adenoidectomy for recurrent URTIs, immediate adenoidectomy results in an increase in costs, whereas it confers no clinical benefit over an initial watchful waiting strategy. TRIAL REGISTRATION: trialregister.nl Identifier:NTR968; isrctn.org Identifier:ISRCTN03720485.

Asunto(s)

RESUMEN

BACKGROUND: High rates of potentially pathogenic bacteria and respiratory viruses can be detected in the upper respiratory tract of healthy children. Investigating presence of and associations between these pathogens in healthy individuals is still a rather unexplored field of research, but may have implications for interpreting findings during disease. METHODOLOGY/PRINCIPAL FINDINGS: We selected 986 nasopharyngeal samples from 433 6- to 24-month-old healthy children that had participated in a randomized controlled trial. We determined the presence of 20 common respiratory viruses using real-time PCR. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus were identified by conventional culture methods. Information on risk factors was obtained by questionnaires. We performed multivariate logistic regression analyses followed by partial correlation analysis to identify the overall pattern of associations. S. pneumoniae colonization was positively associated with the presence of H. influenzae (adjusted odds ratio 1.60, 95% confidence interval 1.18-2.16), M. catarrhalis (1.78, 1.29-2.47), human rhinoviruses (1.63, 1.19-2.22) and enteroviruses (1.97, 1.26-3.10), and negatively associated with S. aureus presence (0.59, 0.35-0.98). H. influenzae was positively associated with human rhinoviruses (1.63, 1.22-2.18) and respiratory syncytial viruses (2.78, 1.06-7.28). M. catarrhalis colonization was positively associated with coronaviruses (1.99, 1.01-3.93) and adenoviruses (3.69, 1.29-10.56), and negatively with S. aureus carriage (0.42, 0.25-0.69). We observed a strong positive association between S. aureus and influenza viruses (4.87, 1.59-14.89). In addition, human rhinoviruses and enteroviruses were positively correlated (2.40, 1.66-3.47), as were enteroviruses and human bocavirus, WU polyomavirus, parainfluenza viruses, and human parechovirus. A negative association was observed between human rhinoviruses and coronaviruses. CONCLUSIONS/SIGNIFICANCE: Our data revealed high viral and bacterial prevalence rates and distinct bacterial-bacterial, viral-bacterial and viral-viral associations in healthy children, hinting towards the complexity and potential dynamics of microbial communities in the upper respiratory tract. This warrants careful consideration when associating microbial presence with specific respiratory diseases.

Asunto(s)

RESUMEN

In this paper, the authors compare subgroup analyses as outlined in grant applications and their related publications. Grants awarded by the Netherlands Organization for Health Research and Development (ZonMw) from 2001 onward that were finalized before March 1, 2010, were studied. Of the 79 grant proposals, 50 (63%) were intervention studies, 18 (23%) were diagnostic studies, and 6 (8%) were prognostic studies. Subgroups were mentioned in 49 (62%) grant applications and in 53 (67%) publications. In 20 of the 79 projects (25%), the publications were completely in agreement with the grant proposal; that is, subgroups that were prespecified in the grant proposal were reported and no new subgroup analyses were introduced in the publications. Of the 149 prespecified subgroups, 46 (31%) were reported in the final report or scientific publications, and 143 of the 189 (76%) reported subgroups were based on post-hoc findings. For 77% of the subgroup analyses in the publications, there was no mention of whether these were prespecified or post hoc. Justification for subgroup analysis and methods to study subgroups were rarely reported. The authors conclude that there is a large discrepancy between grant applications and final publications regarding subgroup analyses. Both nonreporting prespecified subgroup analyses and reporting post-hoc subgroup analyses are common. More guidance is clearly needed.

Asunto(s)

RESUMEN

While pneumococcal conjugate vaccines have shown to be highly effective against invasive pneumococcal disease, their potential effectiveness against acute otitis media (AOM) might become a major economic driver for implementing these vaccines in national immunization programmes. However, the relationship between the costs and benefits of available vaccines remains a controversial topic. Our objective is to systematically review the literature on the cost effectiveness of pneumococcal conjugate vaccination against AOM in children. We searched PubMed, Cochrane and the Centre for Reviews and Dissemination databases (Database of Abstracts of Reviews of Effects [DARE], NHS Economic Evaluation Database [NHS EED] and Health Technology Assessment database [HTA]) from inception until 18 February 2010. We used the following keywords with their synonyms: 'otitis media', 'children', 'cost-effectiveness', 'costs' and 'vaccine'. Costs per AOM episode averted were calculated based on the information in this literature. A total of 21 studies evaluating the cost effectiveness of pneumococcal conjugate vaccines were included. The quality of the included studies was moderate to good. The cost per AOM episode averted varied from &U20AC;168 to &U20AC;4214, and assumed incidence rates varied from 20,952 to 118,000 per 100,000 children aged 0-10 years. Assumptions regarding direct and indirect costs varied between studies. The assumed vaccine efficacy of the 7-valent pneumococcal CRM197-conjugate vaccine was mainly adopted from two trials, which reported 6-8% efficacy. However, some studies assumed additional effects such as herd immunity or only took into account AOM episodes caused by serotypes included in the vaccine, which resulted in efficacy rates varying from 12% to 57%. Costs per AOM episode averted were inversely related to the assumed incidence rates of AOM and to the estimated costs per AOM episode. The median costs per AOM episode averted tended to be lower in industry-sponsored studies. Key assumptions regarding the incidence and costs of AOM episodes have major implications for the estimated cost effectiveness of pneumococcal conjugate vaccination against AOM. Uniform methods for estimating direct and indirect costs of AOM should be agreed upon to reliably compare the cost effectiveness of available and future pneumococcal vaccines against AOM.

Asunto(s)

RESUMEN

OBJECTIVE: To analyse which strategies are used to promote evidence based interventions in the management of children with upper respiratory tract infections (URTIs) in daily practice. To assess the effectiveness of these interventions, and when more are effective--which works best. And to analyse the costs associated with these interventions. METHODS: We systematically searched Pubmed, Embase and CENTRAL bibliographies for studies on the effectiveness of strategies aimed at changing health care professionals' behavior in the management of children with URTIs. RESULTS: The search yielded 11,788 references, of which 18 studies were eligible, and 10 met the inclusion criteria. Most strategies were aimed at changing antibiotic prescribing behavior in children with acute otitis media. All strategies used (i.e. computer interventions, educational sessions with or without education materials, collaborative development of guidelines and a training video in combination with a risk factor checklist) were effective in changing health care professionals practice regarding children with URTIs. Multifaceted and computer strategies work best. Computer interventions reduced antibiotic prescribing by 4% and 34% and increased guideline compliance by 41%. Educational sessions combined with education materials reduced inappropriate antibiotic prescription by 2% and 17% and increased knowledge of compliance enhancing strategies by 28% and 29%. Collaborative guideline development combined with educational materials reduced inappropriate antibiotic prescription by 24% and 40%. Finally, by a combination of a training video and a risk factor checklist appropriate referrals by the GP to the otolaryngologist increased by 37%. Since the costs associated with the interventions were not explicitly mentioned in the articles, no conclusion on cost-effectiveness can be drawn. CONCLUSION: Multifaceted and computer strategies appear to be most effective to put evidence into practice in the area of URTIs in children.

Asunto(s)

RESUMEN

BACKGROUND: Adenoidectomy, surgical removal of the adenoids, is a common ENT operation worldwide in children with otitis media. A systematic review on the effectiveness of adenoidectomy in this specific group has not previously been performed. OBJECTIVES: To assess the effectiveness of adenoidectomy versus non-surgical management or tympanostomy tubes in children with otitis media. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; mRCT and additional sources for published and unpublished trials. The date of the most recent search was 30 March 2009. SELECTION CRITERIA: Randomised controlled trials comparing adenoidectomy, with or without tympanostomy tubes, versus non-surgical management or tympanostomy tubes only in children with otitis media. The primary outcome studied was the proportion of time with otitis media with effusion (OME). Secondary outcomes were mean number of episodes, mean number of days per episode and per year, and proportion of children with either acute otitis media (AOM) or otitis media with effusion (OME), as well as mean hearing level. Tertiary outcome measures included atrophy of the tympanic membrane, tympanosclerosis, retraction of the pars tensa and pars flaccid and cholesteatoma. DATA COLLECTION AND ANALYSIS: Two authors assessed trial quality and extracted data independently. MAIN RESULTS: Fourteen randomised controlled trials (2712 children) studying the effectiveness of adenoidectomy in children with otitis media were evaluated. Most of these trials were too heterogeneous to pool in a meta-analysis. Loss to follow up varied from 0% to 63% after two years.Adenoidectomy in combination with a unilateral tympanostomy tube has a beneficial effect on the resolution of OME (risk difference (RD) 22% (95% CI 12% to 32%) and 29% (95% CI 19% to 39%) for the non-operated ear at six and 12 months, respectively (n = 3 trials)) and a very small (< 5 dB) effect on hearing, compared to a unilateral tympanostomy tube only. The results of studies of adenoidectomy with or without myringotomy versus non-surgical treatment or myringotomy only, and those of adenoidectomy in combination with bilateral tympanostomy tubes versus bilateral tympanostomy tubes only, also showed a small beneficial effect of adenoidectomy on the resolution of the effusion. The latter results could not be pooled due to large heterogeneity of the trials.Regarding AOM, the results of none of the trials including this outcome indicate a significant beneficial effect of adenoidectomy. The trials were too heterogeneous to pool in a meta-analysis.The effects of adenoidectomy on changes of the tympanic membrane or cholesteatoma have not been studied. AUTHORS' CONCLUSIONS: Our review shows a significant benefit of adenoidectomy as far as the resolution of middle ear effusion in children with OME is concerned. However, the benefit to hearing is small and the effects on changes in the tympanic membrane are unknown. The risks of operating should be weighed against these potential benefits.The absence of a significant benefit of adenoidectomy on AOM suggests that routine surgery for this indication is not warranted.

Asunto(s)

RESUMEN

BACKGROUND: Adenoidectomy, surgical removal of the adenoids, is a common ENT operation worldwide in children with recurrent or chronic nasal symptoms. A systematic review on the effectiveness of adenoidectomy in this specific group has not previously been performed. OBJECTIVES: To assess the effectiveness of adenoidectomy versus non-surgical management in children with recurrent or chronic nasal symptoms. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; mRCT and additional sources for published and unpublished trials. The date of the most recent search was 30 March 2009. SELECTION CRITERIA: Randomised controlled trials comparing adenoidectomy, with or without tympanostomy tubes, versus non-surgical management or tympanostomy tubes alone in children with recurrent or chronic nasal symptoms. The primary outcome studied was the number of episodes, days per episode and per year with nasal symptoms and the proportion of children with recurrent episodes of nasal symptoms. Secondary outcomes were mean number of episodes, mean number of days per episode and per year, and proportion of children with nasal obstruction alone. DATA COLLECTION AND ANALYSIS: Two authors assessed trial quality and extracted data independently. MAIN RESULTS: Only one study included children scheduled for adenoidectomy because of recurrent or chronic nasal symptoms or middle ear disease. In this study no beneficial effect of adenoidectomy was found. The numbers in this study were, however, small (n = 76) and the quality of the study was moderate. The outcome was improvement in episodes of common colds. The risk differences were non-significant, being 2% (95% CI -18% to 22%) and -11% (95% CI -28% to 7%) after 12 and 24 months, respectively.A second study included children with recurrent acute otitis media (n = 180). As otitis media is known to be associated with nasal symptoms, the number of days with rhinitis was studied as a secondary outcome measure. The risk difference was non-significant, being -4 days (95% CI -13 to 7 days). AUTHORS' CONCLUSIONS: Current evidence regarding the effect of adenoidectomy on recurrent or chronic nasal symptoms or nasal obstruction alone is sparse, inconclusive and has a significant risk of bias.High quality trials assessing the effectiveness of adenoidectomy in children with recurrent or chronic nasal symptoms should be initiated.

Asunto(s)

RESUMEN

BACKGROUND: Both treatment guidelines and the amount of antibiotics used for acute otitis media (AOM) vary across western countries. Parental expectations and their awareness of antimicrobial use and resistance, which may also be influenced by the guidelines, are not yet completely known. OBJECTIVE: To compare parental experiences and opinions regarding the management of AOM in children with AOM in Finland and The Netherlands. METHODS: We sent the questionnaires via public day care in Turku, Finland, and Utrecht, The Netherlands. We asked about family background, child's history of AOM and parental experiences and attitudes about AOM treatment and antimicrobial resistance. RESULTS: Of 1151 participants, 83% in Finland and 49% in The Netherlands had had at least one episode of AOM. Antibiotics were used more frequently in Finland than in The Netherlands, 99% versus 78%, respectively. More Finnish parents reported to believe that antibiotics are necessary in the treatment of AOM as compared to Dutch parents. Use of analgesics for AOM was similar (80% in Finland and 86% in The Netherlands). One-third of the parents had discussed resistance with their doctor. According to parental experiences, antimicrobial resistance had caused more problems in Finland than in The Netherlands (20% versus 2%). Finally, 88% of parents in Finland and 65% in The Netherlands were worried that bacteria could become resistant to antibiotics. CONCLUSIONS: Treatment practices and parental expectations seem to interact with each other. Therefore, if we aim to change AOM treatment practices, we have to modify both guidelines and parental expectations.

Asunto(s)

RESUMEN

OBJECTIVE: To study the cost-effectiveness of a 6- to 12-week course of high-dose oral trimethoprim-sulfamethoxazole in children with chronic active otitis media (COM). STUDY DESIGN: Cost-effectiveness study including both direct and indirect costs alongside a randomized placebo-controlled trial. SETTING: Tertiary care university hospital in the Netherlands. PATIENTS: One hundred one children aged 1 to 12 years with a documented history of COM for at least 3 months. INTERVENTION: Six to 12 weeks of oral trimethoprim-sulfamethoxazole 18 mg/kg twice daily versus placebo. MAIN OUTCOME MEASURES: Incremental cost-effectiveness in terms of costs per number needed to treat (NNT) to cure 1 patient (incremental cost-effectiveness ratio [ICER]). Curation was defined as no otomicroscopic signs of otorrhea in either ear. RESULTS: After 6 weeks of follow-up, the difference in mean cost per patient between the trimethoprim-sulfamethoxazole and placebo groups was Euro100 (US $126). The NNT was 4 (clinical effect), and the corresponding ICER was Euro400 (US $504), that is, the average extra costs to cure 1 child from otorrhea is Euro400 (US $504). After 12 weeks of follow-up, the difference in mean costs between both groups was Euro159 (US $201), the NNT was 7, and the corresponding ICER was Euro1,113 (US $1,407).The mean costs after 1 year of follow-up were Euro1,601 (US $2,021) in the trimethoprim-sulfamethoxazole group and Euro1,164 (US $1,469) in the placebo group. Because the clinical effect of trimethoprim-sulfamethoxazole disappeared after its discontinuation, we did not calculate an ICER at 1 year of follow-up. CONCLUSION: In children with active COM, direct and indirect costs of a 6- to 12-week course of high-dose oral trimethoprim-sulfamethoxazole are modest in the light of its short-term clinical benefit.

Asunto(s)