Early Health Economic Modeling of Novel Therapeutics in Age-Related Hearing Loss.

Background: Health systems face challenges to accelerate access to innovations that add value and avoid those unlikely to do so. This is very timely to the field of age-related sensorineural hearing loss (ARHL), where a significant unmet market need has been identified and sizeable investments made to promote the development of novel hearing therapeutics (NT). This study aims to apply health economic modeling to inform the development of cost-effective NT. Methods: We developed a decision-analytic model to assess the potential costs and effects of using regenerative NT in patients ≥50 with ARHL. This was compared to the current standard of care including hearing aids and cochlear implants. Input data was collected from systematic literature searches and expert opinion. A UK NHS healthcare perspective was adopted. Three different but related analyses were performed using probabilistic modeling: (1) headroom analysis, (2) scenario analyses, and (3) threshold analyses. Results: The headroom analysis shows an incremental net monetary benefit (iNMB) of £20,017[£11,299-£28,737] compared to the standard of care due to quality-adjusted life-years (QALY) gains and cost savings. Higher therapeutic efficacy and access for patients with all degrees of hearing loss yields higher iNMBs. Threshold analyses shows that the ceiling price of the therapeutic increases with more severe degrees of hearing loss. Conclusion: NT for ARHL are potentially cost-effective under current willingness-to-pay (WTP) thresholds with considerable room for improvement in the current standard of care pathway. Our model can be used to help decision makers decide which therapeutics represent value for money and are worth commissioning, thereby paving the way for urgently needed NT.

Observational retrospective study calculating health service costs of patients receiving surgery for chronic rhinosinusitis in England, using linked patient-level primary and secondary care electronic data.

OBJECTIVES: Chronic rhinosinusitis (CRS) symptoms are experienced by an estimated 11% of UK adults, and symptoms have major impacts on quality of life. Data from UK and elsewhere suggest high economic burden of CRS, but detailed cost information and economic analyses regarding surgical pathway are lacking. This paper estimates healthcare costs for patients receiving surgery for CRS in England. DESIGN: Observational retrospective study examining cost of healthcare of patients receiving CRS surgery. SETTING: Linked electronic health records from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics databases in England. PARTICIPANTS: A phenotyping algorithm using medical ontology terms identified 'definite' CRS cases who received CRS surgery. Patients were registered with a general practice in England. Data covered the period 1997-2016. A cohort of 13 462 patients had received surgery for CRS, with 9056 (67%) having confirmed nasal polyps. OUTCOME MEASURES: Information was extracted on numbers and types of primary care prescriptions and consultations, and inpatient and outpatient hospital investigations and procedures. Resource use was costed using published sources. RESULTS: Total National Health Service costs in CRS surgery patients were £2173 over 1 year including surgery. Total costs per person-quarter were £1983 in the quarter containing surgery, mostly comprising surgical inpatient care costs (£1902), and around £60 per person-quarter in the 2 years before and after surgery, of which half were outpatient costs. Outpatient and primary care costs were low compared with the peak in inpatient costs at surgery. The highest outpatient expenditure was on CT scans, peaking in the quarter preceding surgery. CONCLUSIONS: We present the first study of costs to the English healthcare system for patients receiving surgery for CRS. The total aggregate costs provide a further impetus for trials to evaluate the relative benefit of surgical intervention.

Cost of childhood acute otitis media in primary care in the Netherlands: economic analysis alongside a cluster randomised controlled trial.

BACKGROUND: Acute otitis media (AOM) is among the most common paediatric conditions managed in primary care. Most recent estimates of the cost of AOM date from a decade ago and lack a full societal perspective. We therefore explored the societal cost of childhood AOM in the Netherlands within the setting of a trial comparing the effectiveness of an intervention aimed at educating general practitioners (GPs) about pain management in AOM compared to usual care. METHODS: Economic analysis alongside a cluster randomised controlled trial conducted between February 2015 and May 2018 in 37 practices (94 GPs). In total, 224 children with AOM were included of which 223 (99%) completed the trial (intervention: n = 94; control: n = 129). The cost of AOM due to health care costs, patient and family costs, and productivity losses by parent caregivers were retrieved from study diaries and primary care electronic health records, during 28-day follow-up. We calculated mean cost (€ and $) per AOM episode per patient with standard deviations (SD, in €) regardless of study group assignment because there was no clinical effect of the trial intervention. In sensitivity analysis, we calculated cost in the intervention and usual care group, after exclusion of extreme outliers. RESULTS: Mean total AOM cost per patient were €565.93 or $638.78 (SD €1071.01); nearly 90% of these costs were due to productivity losses experienced by parents. After exclusion of outliers, AOM cost was €526.70 or $594.50 (SD €987.96) and similar in the intervention and usual care groups: €516.10 or $582.53 (SD €949.69) and €534.55 or $603.36 (SD €920.55) respectively. CONCLUSIONS: At €566 or $639 per episode, societal cost of AOM is higher than previously known and mainly driven by productivity losses by children's parents. Considering its high incidence, AOM poses a significant economic burden that extends beyond direct medical costs. TRIAL REGISTRATION: Netherlands Trial Register no. NTR4920: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4920 .

Incidence and management of acute otitis media in adults: a primary care-based cohort study.

BACKGROUND: Although primarily considered a childhood disease, acute otitis media (AOM) also occurs in adults. Data on the burden of this condition in adults are, however, scarce. OBJECTIVE: To explore the primary care incidence and current management of AOM in adults. METHODS: All patients aged 15 and older included in the routine health care database of the Julius General Practitioners' Network were followed from 2015 to 2018 (contributing to a total of 1 261 575 person-years). We extracted data on AOM episodes, AOM-related consultations, comorbidities, and antibiotic and analgesic prescriptions. RESULTS: Five thousand three hundred and fifty-eight patients experienced one or more AOM episodes (total number of AOM episodes: 6667; mean 1.2 per patient). The overall AOM incidence was 5.3/1000 person-years and was fairly stable over the study period. Incidence was particularly high in atopic patients (7.3/1000 person-years) and declined with age (from 7.1 in patients 15-39 years of age to 2.7/1000 person-years in those aged 64 years and older). Oral antibiotics, predominantly amoxicillin, were prescribed in 46%, and topical antibiotics in 21% of all episodes. CONCLUSION: Over the past years, the incidence of AOM in adults in primary care has been stable. Oral antibiotic prescription rates resemble those in children with AOM, whereas a remarkably high topical antibiotic prescription rate was observed. Future prognostic research should inform on the need and feasibility of prospective studies into the best management strategy in this condition.

Effect of antibiotics in preventing hospitalizations from respiratory tract infections in children with Down syndrome.

BACKGROUND: Children with Down syndrome (DS) are at high risk of respiratory tract infections (RTIs) due to anatomical variations, comorbidities, and immune system immaturity. Evidence on interventions to reduce this risk is incomplete. This study aims to quantify the effect of antibiotics prescribed for RTIs in primary care on the subsequent risk of RTI-related hospitalization for children with DS versus controls. METHODS: We conducted a retrospective cohort study of 992 children with DS and 4874 controls managed by UK National Health Service General Practitioners (GPs) and hospitals as identified in CALIBER (Clinical disease research using LInked Bespoke studies and Electronic health Records), 1997-2010. Univariate and multivariate logistic regression were undertaken. RESULTS: In children with DS, the prescription of antibiotics following an RTI-related GP consultation did not significantly reduce the risk of RTI-related hospitalization in the subsequent 28 days (risk with antibiotics, 1.8%; without, 2.5%; risk ratio, 0.699; 95% confidence interval, 0.471-1.036). Subgroup analyses showed a risk reduction only in infants with DS, after adjustment for covariates. There was no reduction in risk for controls, overall or across subgroups. CONCLUSIONS: In conclusion, while prescription of antibiotics following RTI-related GP consultations were effective for infants with DS in reducing subsequent RTI-related hospitalization, this was not the case for older children with DS. We would encourage further high-quality cohort and randomized controlled trials to interrogate this finding, and to examine the impact of antibiotics on other endpoints, including symptom duration.

The Potential Added Value of Novel Hearing Therapeutics: An Early Health Economic Model for Hearing Loss.

OBJECTIVE: To construct an early health economic model to assess the potential added value of novel hearing therapeutics, compared with the current standard of care. We use idiopathic sudden sensorineural hearing loss (ISSNHL) as a case example, because it is a lead indication for several emerging hearing therapeutics. METHODS: A decision analytic model was developed to assess the costs and effects of using novel hearing therapeutics for patients with ISSNHL. This was compared to the current standard of care. Input data were derived from literature searches and expert opinion. The study adopted a healthcare perspective of the UK National Health Service. Four analyses were conducted: 1) headroom, 2) scenario, 3) threshold, 4) sensitivity. RESULTS: The decision analytic model showed that novel therapeutics for ISSNHL have potential value both in terms of improved patient outcomes, as well as incremental net monetary benefit (iNMB). The base case analysis revealed an iNMB of £39,032 for novel therapeutics compared with the current standard of care. Results of the threshold and scenario analysis revealed that age of treatment and severity of ISSNHL are major determinants of iNMB for novel therapeutics. CONCLUSION: This article describes the first health economic model for novel therapeutics for hearing loss; and shows that novel hearing therapeutics can be cost-effective under NICE's cost-effectiveness threshold, with considerable room for improvement in the current standard of care. Our model can be used to inform the development of cost-effective hearing therapeutics; and help decision makers decide which therapeutics represent value for money.

Hearing Protection, Restoration, and Regeneration: An Overview of Emerging Therapeutics for Inner Ear and Central Hearing Disorders.

OBJECTIVE: To provide an overview of biotechnology and pharmaceutical companies active in the field of inner ear and central hearing disorders and their therapeutic approaches. METHODS: Scientific and grey literature was searched using broad search terms to identify companies and their hearing-related therapeutic approaches. For each approach its lead indication, product, therapeutic modality, target, mechanism of action and current phase of clinical development was collated. RESULTS: A total of 43 biotechnology and pharmaceutical companies have been identified that are developing therapeutics for inner ear and central hearing disorders. Their therapeutics include drug-, cell- and gene-based approaches to prevent hearing loss or its progression, restore hearing, and regenerate the inner ear. Their therapeutic targets and specific mechanisms of action are wide-ranging, reflecting the complexity of the hearing pathways and the diversity of mechanisms underlying inner ear disorders. While none of the novel products under investigation have yet made it to the clinical market, and a large proportion are still at preclinical phase, many therapeutics have already entered clinical testing with more expected to do so in the next few years. CONCLUSION: A wide range of novel therapeutics targeting different hearing, balance and tinnitus pathways, and patient populations are approaching the clinical domain. It is important that clinicians involved in the care of patients with hearing loss prepare for what may become a radically different approach to the management of hearing disorders, and develop a true understanding of the new therapies' mechanisms of action, applications, and indications.

Impact of Repeated Influenza Immunization on Respiratory Illness in Children With Preexisting Medical Conditions.

PURPOSE: Annual influenza immunization in medical risk groups is recommended in many countries. Recent evidence suggests that repeated inactivated influenza vaccine (IIV) immunization throughout childhood may impair long-term immunity against influenza. We assessed whether prior immunization altered the effect of IIV in children with preexisting medical conditions on primary care-diagnosed respiratory illness (RI) episodes during the influenza season. METHODS: Electronic records of IIV-immunized children who met the criteria for annual IIV immunization according to Dutch guidelines were extracted from a primary care database from 2004 to 2015. For each year, we collected information on IIV immunization status, primary care-attended RI episodes (including influenza-like illness, acute RI, and asthma exacerbation), and potential confounders. Generalized estimating equations were used to model the association between prior IIV and occurrence of at least one RI episode during the influenza season, with "current year immunized but without IIV history" as reference group. RESULTS: A total of 4,183 children (follow-up duration: 11,493 child-years) were IIV immunized at least once. Adjusted estimates showed lower odds for RI in current year-immunized children with prior IIV compared with those without (odds ratio [OR] = 0.61; 95% CI, 0.47-0.78 for "current year immunized and one IIV in previous 2 years"; OR = 0.85; 95% CI, 0.68-1.07 for "current year immunized and ≥2 IIVs in previous 3 years, including prior year"). CONCLUSION: Repeated IIV immunization in children with preexisting medical conditions has no negative impact on, and may even increase, long-term protection against RI episodes diagnosed during the influenza season in primary care.

Optimising pain management in children with acute otitis media through a primary care-based multifaceted educational intervention: study protocol for a cluster randomised controlled trial.

BACKGROUND: Whilst current guidelines highlight the importance of pain management for children with acute otitis media (AOM), there is evidence to suggest that this is not implemented in everyday practice. We have developed a primary care-based multifaceted educational intervention to optimise pain management in children with AOM, and we trial its clinical and cost effectiveness. METHODS: This cluster randomised controlled trial aims to recruit 250 children aged 6 months to 10 years presenting with AOM to general practitioners (GPs) in 30 primary care centres (PCCs) across the Netherlands. GPs in the PCCs allocated to the intervention group receive a blended GP educational programme (online and face-to-face training). The intervention asks GPs to proactively discuss pain management with parents using an information leaflet, and to prescribe paracetamol and ibuprofen according to current guidelines. GPs in both groups complete an online module illustrating various otoscopic images to standardise AOM diagnosis. GPs in the PCCs allocated to the control group do not receive any further training and provide 'care as usual'. During the 4-week follow-up, parents complete a symptom diary. The primary outcome is the difference in parent-reported mean earache scores over the first 3 days. Secondary outcomes include both number of days with earache and fever, GP re-consultations for AOM, antibiotic prescriptions, and costs. Analysis will be by intention-to-treat. DISCUSSION: The optimal use of analgesics through the multifaceted intervention may provide symptom relief and thereby reduce re-consultations and antibiotic prescriptions in children with AOM. TRIAL REGISTRATION: Netherlands Trial Register, NTR4920 . Registered on 19 December 2014.

Cost-effectiveness of treatment of acute otorrhea in children with tympanostomy tubes.

BACKGROUND: Acute otorrhea is a common problem in children with tympanostomy tubes. We recently demonstrated that treatment with antibiotic-glucocorticoid eardrops is clinically superior to oral antibiotics and initial observation. The aim of this study was to assess the cost-effectiveness of these three common treatment strategies for this condition. METHODS: We performed an open-label pragmatic trial in which 230 children with acute uncomplicated tympanostomy-tube otorrhea were randomly allocated to receive 1 of 3 treatments: hydrocortisone-bacitracin-colistin eardrops, oral amoxicillin-clavulanate suspension, and initial observation (no assigned medication prescription to fill). Parents kept a daily diary capturing ear-related symptoms, health care resource use, and non-health care costs for 6 months. At 2 weeks and 6 months, the study doctor visited the children at home performing otoscopy. Using a societal perspective, treatment failure (otoscopic presence of otorrhea at 2 weeks) and number of days with otorrhea as reported in the daily diary were balanced against the costs. RESULTS: Antibiotic-glucocorticoid eardrops were clinically superior to oral antibiotics and initial observation both at 2 weeks and 6 months. At 2 weeks, mean total cost per patient was US$42.43 for antibiotic-glucocorticoid eardrops, US$70.60 for oral antibiotics, and US$82.03 for initial observation. At 6 months, mean total cost per patient was US$368.20, US$420.73, and US$640.44, respectively. Because of the dominance of eardrops, calculating incremental cost-effectiveness ratios was redundant. CONCLUSIONS: Antibiotic-glucocorticoid eardrops are clinically superior and cost less than oral antibiotics and initial observation in children with tympanostomy tubes who develop otorrhea.

Adenoidectomy with or without grommets for children with otitis media: an individual patient data meta-analysis.

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.

Immediate adenoidectomy vs initial watchful waiting strategy in children with recurrent upper respiratory tract infections: an economic evaluation.

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.

Good agreement between parents and physician in the assessment of ear discharge in children.

Physicians often rely on parental observation of ear discharge in the follow-up after its treatment, but little is known about the reliability of this assessment. Follow-up data of trial participants treated for acute or chronic ear discharge showed a good agreement between parents' and physician's assessment, with high positive predictive values, but lower negative predictive values.

A comparison of subgroup analyses in grant applications and publications.

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.

Cost effectiveness of pneumococcal conjugate vaccination against acute otitis media in children: a review.

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.

Interventions in health care professionals to improve treatment in children with upper respiratory tract infections.

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.

Trimethoprim-sulfamethoxazole in children with chronic otitis media: a randomized comparison of costs and effects.

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.

Adenotonsillectomy or watchful waiting in patients with mild to moderate symptoms of throat infections or adenotonsillar hypertrophy: a randomized comparison of costs and effects.

OBJECTIVE: To evaluate the cost-effectiveness of adenotonsillectomy compared with watchful waiting in Dutch children. DESIGN: Economic evaluation along with an open, randomized, controlled trial. SETTING: Multicenter, including 21 general and 3 university hospitals in the Netherlands. PARTICIPANTS: Three hundred children aged 2 to 8 years were selected for adenotonsillectomy according to routine medical practice. Excluded were children who had frequent throat infections and those with suspected obstructive sleep apnea. MAIN OUTCOME MEASURES: Incremental cost-effectiveness in terms of costs per episode of fever, throat infection, and upper respiratory tract infection avoided. RESULTS: Annual costs incurred in the adenotonsillectomy group were euro803 (the average exchange rate for the US dollar in 2002 was $1.00 = euro1.1, except toward the end of 2002 when $0.95 = euro100) and euro551 in the watchful waiting group (46% increase). During a median follow-up of 22 months, surgery compared with watchful waiting reduced the number of episodes of fever and throat infections by 0.21 per person-year (95% confidence interval, -0.12 to 0.54 and 0.06 to 0.36, respectively) and upper respiratory tract infections by 0.53 (95% confidence interval, 0.08 to 0.97) episodes. The incremental costs per episode avoided were euro1136, euro1187, and euro465, respectively. CONCLUSIONS: In children undergoing adenotonsillectomy because of mild to moderate symptoms of throat infections or adenotonsillar hypertrophy, surgery resulted in a significant increase in costs without realizing relevant clinical benefit. Subgroups of children in whom surgery would be cost-effective may be identified in further research. .

Evaluation of a new device for home cardiorespiratory recording in children.

OBJECTIVE: To evaluate the feasibility of using a new home cardiorespiratory recording device (HCRD) in children. DESIGN: Cross-sectional study. PATIENTS: Consecutive children scheduled for adenotonsillectomy to treat habitual snoring and/or apneas at otorhinolaryngology clinics in 2 academic and 7 general hospitals. INTERVENTION: Single-night unattended home cardiorespiratory recording prior to adenotonsillectomy using the HCRD. MAIN OUTCOME MEASURES: Number of technically acceptable recordings and successful recordings with artifact-free signals (respiration, saturation, and nasal flow) present for sufficient duration to allow scoring of the polysomnogram and to make a diagnosis. RESULTS: Of 53 eligible children, 24 participated in the study. The main reason for nonparticipation was refusal of caregivers (n = 16). Mean (SD) age of participants was 4.2 (1.6) years; median Brouillette obstructive sleep apnea score was 2.54. Technically acceptable recordings were obtained in 18 children (75%). Only 7 recordings (29%) were classified as successful. The poorest signal quality was obtained from the nasal cannula. CONCLUSION: Based on strict scoring criteria in this study, the results of single-night unattended recordings at home with the HCRD fell short of expectations.