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Background: Studies of see-and-treat management of cervical intraepithelial neoplasia (CIN) vary in their inclusion criteria, resulting in a broad range of overtreatment rates.Objectives: To determine overtreatment rates in see-and-treat management of women referred for colposcopy because of suspected CIN, in order to define circumstances supporting see-and-treat management.Search Strategy: MEDLINE, EMBASE, and the Cochrane Library were searched from inception up to 12 May 2014.Selection Criteria: Studies of see-and-treat management in women with a reported cervical smear result, colposcopic impression, and histology result were included.Data Collection and Analysis: Methodological quality was assessed with the Newcastle-Ottawa scale. We used the inverse variance method for pooling incidences, and a random-effects model was used to account for heterogeneity between studies. Overtreatment was defined as treatment in patients with no CIN or CIN1.Main Results: Thirteen studies (n = 4611) were included. The overall overtreatment rate in women with a high-grade cervical smear and a high-grade colposcopic impression was 11.6% (95% CI 7.8-15.3%). The overtreatment rate in women with a high-grade cervical smear and low-grade colposcopic impression was 29.3% (95% CI 16.7-41.9%), and in the case of a low-grade smear and high-grade colposcopic impression it was 46.4% (95% CI 15.7-77.1%). In women with a low-grade smear and low-grade colposcopic impression, the overtreatment rate was 72.9% (95% CI 68.1-77.7%).Author's Conclusions: The pooled overtreatment rate in women with a high-grade smear and high-grade colposcopic impression is at least comparable with the two-step procedure, which supports the use of see-and-treat management in this subgroup of women.Tweetable Abstract: See-and-treat management is justified in the case of a high-grade smear and a high-grade colposcopic impression. [ABSTRACT FROM AUTHOR]

SUMMARYThe burden of respiratory infections is mainly seen in primary healthcare. To evaluate the potential impact of new preventive strategies against respiratory infections, such as the implementation of pneumococcal conjugate vaccines for infants in 2006 in The Netherlands, we conducted a baseline retrospective cohort study of electronic primary-care patient records to assess consultation rates, comorbidities and antibiotic prescription rates for respiratory infections in primary care. We found that between 1995 and 2005, overall registered consultation rates for lower respiratory tract infections had increased by 42·4%, upper respiratory infections declined by 4·9%, and otitis media remained unchanged. Concomitantly, there was a steady rise in overall comorbidity (75·7%) and antibiotic prescription rates (67·7%). Since Dutch primary-care rates for respiratory infections changed considerably between 1995 and 2005, these changes must be taken into account to properly evaluate the effect of population-based preventive strategies on primary-care utilization. [ABSTRACT FROM AUTHOR]

OBJECTIVE: : To assess the attributable mortality of ventilator-associated pneumonia using results from randomized controlled trials on ventilator-associated pneumonia prevention. DATA SOURCES: : A systematic search was performed in PubMed, Embase, Web of Science, and Cochrane Library from their inception until July 2010. In addition, a reference and related article search was performed. STUDY SELECTION: : Randomized ventilator-associated pneumonia prevention studies in which all patients were mechanically ventilated and from which ventilator-associated pneumonia and mortality rates of intervention and control group could be extracted were included. DATA EXTRACTION/SYNTHESIS: : Fifty-three papers were identified describing 58 comparisons. Statistical significant reductions in ventilator-associated pneumonia incidences were reported in 20 of the 58 comparisons, whereas none of these trials reported a significant reduction of mortality. Pooled estimates of the relative risk reductions of both ventilator-associated pneumonia and mortality were calculated and the attributable mortality was estimated as the ratio between the relative risk reductions of mortality and ventilator-associated pneumonia. Effects of study quality, diagnostic methods used, and effectiveness of preventing ventilator-associated pneumonia on the mortality rate of ventilator-associated pneumonia were assessed in subgroup analyses. The overall attributable mortality of ventilator-associated pneumonia was estimated as 9%. In subgroup analyses, the attributable mortality varied between 3% and 17%. CONCLUSION: : Based on the results of 58 randomized studies on ventilator-associated pneumonia prevention, the attributable mortality rate of ventilator-associated pneumonia was estimated to be 9% and ranged between 3% and 17% in subgroup analyses. Together with the results of other recent studies, there is cumulative evidence that the attributable mortality resulting from ventilator-associated pneumonia is approximately 10%. [ABSTRACT FROM AUTHOR]

BACKGROUND: Closed suction systems (CSS) are increasingly replacing open suction systems (OSS) to perform endotracheal toilet in mechanically ventilated intensive care unit patients. Yet effectiveness regarding patient safety and costs of these systems has not been carefully analyzed. OBJECTIVE: To review effectiveness of CSS and OSS, with respect to patient outcome, bacterial contamination, and costs in adult intensive care unit patients. DATA SOURCE: Search of MEDLINE, CINAHL, EMBASE, and Cochrane databases and a manual review of article bibliographies. STUDY SELECTION: Randomized controlled trials comparing CSS and OSS in adult intensive care unit patients were retrieved. DATA EXTRACTION/SYNTHESIS: Assessment of abstracts and study quality was performed by two reviewers. Data were combined in meta-analyses by random effect models. Fifteen trials were identified. No significant differences were found in incidences of ventilator-associated pneumonia (eight studies, 1,272 patients) and mortality (four studies, 1,062 patients). No conclusions could be drawn with respect to arterial oxygen saturation (five studies, 109 patients), arterial oxygen tension (two studies, 19 patients), and secretion removal (two studies, 37 patients). Compared with OSS, endotracheal suctioning with CSS significantly reduced changes in heart rate (four studies, 85 patients; weighted mean difference, -6.33; 95% confidence interval, -10.80 to -1.87) and changes in mean arterial pressure (three studies, 59 patients; standardized mean difference, -0.43; 95% confidence interval, -0.87 to 0.00) but increased colonization (two studies, 126 patients; relative risk, 1.51; 95% confidence interval, 1.12-2.04). CSS seems to be more expensive than OSS. CONCLUSIONS: Based on the results of this meta-analysis, there is no evidence to prefer CSS more than OSS. [ABSTRACT FROM AUTHOR]

The article discusses a study, which reports that penicillin V (PCV) did not shorten symptoms in children with sore throat. Among all children combined and in children without group A streptococci (GAS), PCV did not differ from placebo for duration of symptoms (DOS). In the subgroup of children with GAS, the mean DOS was greater in the PCV3 group than in the placebo group, but the PCV7 group did not differ from the placebo group. The rate of GAS eradication was greater in the PCV7 group than in the placebo group. In children 4- 15 years of age with a sore throat, penicillin V for 3 or 7 days was not better than placebo for reducing the duration of symptoms.

Background: As a result of recent advances in the development of small microelectromechanical system mirrors, a novel forward-looking optical coherence tomography (OCT) probe with a uniquely large field of view is being commercially developed. The aim of this study is to prospectively assess the feasibility of this advanced OCT probe in interpreting ex vivo images of colorectal polyp tissue and to identify necessary steps for further development., Methods: A total of 13 colorectal lesions from 9 patients, removed during endoscopic resection, were imaged ex vivo with the OCT device and compared with histopathological images that served as the gold standard for diagnostics. Normal tissue from one patient, removed during the endoscopic procedure, was imaged as a negative control. We assessed the presence of features indicative for polyp type and degree of dysplasia, by comparing OCT images to histopathological images and by evaluating the presence of OCT-specific features identified by previous studies, such as effacement (loss of layered tissue structure), a hyperreflective epithelial layer, and irregularity of the surface., Results: As verified by corresponding histological images, tissue structures such as blood vessels and tissue layers could be distinguished in OCT images of the normal tissue sample. Detailed structures on histological images such as crypts and cell nuclei could not be identified in the OCT images. However, we did identify OCT features specific for colorectal lesions, such as effacement and a hyperreflective epithelial layer. In general, the imaging depth was about 1 mm., Conclusion: Some relevant tissue structures could be observed in OCT images of the novel device. However, some adaptations, such as increasing imaging depth using a laser with a longer central wavelength, are required to improve its clinical value for the imaging of colorectal lesions., (© 2024. The Author(s).)

Microgels show advantages over bulk hydrogels due to convenient control over microgel size and composition, and the ability to use microgels to modularly construct larger hierarchical scaffold hydrogel materials. Here, supramolecular chemistry is used to formulate supramolecular polymer, dynamic microgels solely held together by non-covalent interactions. Four-fold hydrogen bonding ureido-pyrimidinone (UPy) monomers with different functionalities are applied to precisely tune microgel properties in a modular way, via variations in monomer concentration, bifunctional crosslinker ratio, and the incorporation of supramolecular dyes and peptides. Functionalization with a bioactive supramolecular cell-adhesive peptide induced selectivity of cells toward the bioactive microgels over non-active, non-functionalized versions. Importantly, the supramolecular microgels can also be applied as microscale building blocks into supramolecular bulk macrogels with tunable dynamic behavior: a robust and weak macrogel, where the micro- and macrogels are composed of similar molecular building blocks. In a robust macrogel, microgels act as modular micro-building blocks, introducing multi-compartmentalization, while in a weak macrogel, microgels reinforce and enhance mechanical properties. This work demonstrates the potential to modularly engineer higher-length-scale structures using small molecule supramolecular monomers, wherein microgels serve as versatile and modular micro-building units., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Purpose: Brachytherapy is associated with improved overall survival in cervical cancer patients, but the utilization seems hindered by high costs and relatively low reimbursement, particularly in the US. A one-room brachytherapy suite with CT (ORBT) could optimize the treatment workflow. By eliminating transport and waiting times, limiting applicator movement, and providing real-time applicator placement feedback, treatment time and costs could potentially be reduced. This study assesses the potential value of implementing ORBT in cervical cancer treatment., Methods and Materials: A variable cost model was developed to compare current (multi-room) brachytherapy workflows (MBRT) to ORBT, taking into account staff utilization, staff, equipment and consumables costs and room expenses. Two current care scenarios were simulated; applicator placement performed in the operating room (S1), and applicator placement performed in a brachytherapy suite (S2). For both scenarios literature reported fraction times of MBRT were compared to a range of ORBT times. Sensitivity analyses were performed to determine the influence of input parameters., Results: In scenario one, the results showed yearly savings of $45,572 up to $339,439 (USD), assuming a 5% and 20% reduction in fraction duration, respectively, in ORBT compared to MRBT. In scenario two, ORBT does not result in costs savings at 5% to 15% improvement. Therefore, only when ORBT results in a >20% improvement of fraction time, cost will be saved., Conclusions: The results indicate that reducing procedure time (using ORBT) can lead to cost savings, depending on the current workflow. Savings seem to depend mostly on applicator placement location, number of patients per year, and involved personnel., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Low molecular weight gels are formed via the self-assembly of small molecules into fibrous structures. In the case of hydrogels, these networks entrap large volumes of water, yielding soft materials. Such gels tend to have weak mechanical properties and a high permeability for cells, making them particularly appealing for regenerative medicine applications. Ureido-pyrimidinone (UPy) supramolecular gelators are self-assembling systems that have demonstrated excellent capabilities as biomaterials. Here, we combine UPy-gelators with another low molecular weight gelator, the functionalized dipeptide 2NapFF. We have successfully characterized these multicomponent systems on a molecular and bulk scale. The addition of 2NapFF to a crosslinked UPy hydrogel significantly increased hydrogel stiffness from 30 Pa to 1300 Pa. Small-angle X-ray scattering was used to probe the underlying structures of the systems and showed that the mixed UPy and 2NapFF systems resemble the scattering data produced by the pristine UPy systems. However, when a bifunctional UPy-crosslinker was added, the scattering was close to that of the 2NapFF only samples. The results suggest that the crosslinker significantly influences the assembly of the low molecular weight gelators. Finally, we analysed the biocompatibility of the systems using fibroblast cells and found that the cells tended to spread more effectively when the crosslinking species was incorporated. Our results emphasise the need for thorough characterisation at multiple length scales to finely control material properties, which is particularly important for developing novel biomaterials.

Background: Robot-assisted minimally invasive gastrectomy (RAMIG) is increasingly used as a surgical approach for gastric cancer. This study assessed the effectiveness of RAMIG and studied which stages of the IDEAL-framework (1 = Idea, 2A = Development, 2B = Exploration, 3 = Assessment, 4 = Long-term follow-up) were followed., Methods: The Cochrane Library, Embase, Pubmed, and Web of Science were searched for studies on RAMIG up to January 2023. Data collection included the IDEAL-stage, demographics, number of participants, and study design. For randomized controlled trials (RCTs) and long-term studies, data on intra-, postoperative, and oncologic outcomes, survival, and costs of RAMIG were collected and summarized., Results: Of the 114 included studies, none reported the IDEAL-stage. After full-text reading, 18 (16%) studies were considered IDEAL-2A, 75 (66%) IDEAL-2B, 4 (4%) IDEAL-3, and 17 (15%) IDEAL-4. The IDEAL-stages were followed sequentially (2A-4), with IDEAL-2A studies still ongoing. IDEAL-3 RCTs showed lower overall complications (8.5-9.2% RAMIG versus 17.6-19.3% laparoscopic total/subtotal gastrectomy), equal 30-day mortality (0%), and equal length of hospital stay for RAMIG (mean 5.7-8.5 days RAMIG versus 6.4-8.2 days open/laparoscopic total/subtotal gastrectomy). Lymph node yield was similar across techniques, but RAMIG incurred significantly higher costs than laparoscopic total/subtotal gastrectomy ($13,423-15,262 versus $10,165-10,945). IDEAL-4 studies showed similar or improved overall/disease-free survival for RAMIG., Conclusion: During worldwide RAMIG implementation, the IDEAL-framework was followed in sequential order. IDEAL-3 and 4 long-term studies showed that RAMIG is similar or even better to conventional surgery in terms of hospital stay, lymph node yield, and overall/disease-free survival. In addition, RAMIG showed reduced postoperative complication rates, despite higher costs., (© 2024. The Author(s).)

Rationale and Objectives: Assess the feasibility of a prototype image reconstruction algorithm in correcting motion artifacts in cone-beam computed tomography (CBCT) scans of interventional instruments in the lung., Materials and Methods: First, phantom experiments were performed to assess the algorithm, using the Xsight lung phantom with custom inserts containing straight or curved catheters. During scanning, the inserts moved in a continuous sinusoidal or breath-hold mimicking pattern, with varying amplitudes and frequencies. Subsequently, the algorithm was applied to CBCT data from navigation bronchoscopy procedures. The algorithm's performance was assessed quantitatively via edge-sharpness measurements and qualitatively by three specialists., Results: In the phantom study, the algorithm improved sharpness in 13 out of 14 continuous sinusoidal motion and five out of seven breath-hold mimicking scans, with more significant effects at larger motion amplitudes. Analysis of 27 clinical scans showed that the motion corrected reconstructions had significantly sharper edges than standard reconstructions (2.81 (2.24-6.46) vs. 2.80 (2.16-4.75), p = 0.003). These results were consistent with the qualitative assessment, which showed higher scores in the sharpness of bronchoscope-tissue interface and catheter-tissue interface in the motion-corrected reconstructions. However, the tumor demarcation ratings were inconsistent between raters, and the overall image quality of the new reconstructions was rated lower., Conclusion: Our findings suggest that applying the new prototype algorithm for motion correction in CBCT images is feasible. The algorithm improved the sharpness of medical instruments in CBCT scans obtained during diagnostic navigation bronchoscopy procedures, which was demonstrated both quantitatively and qualitatively., Competing Interests: Declaration of Competing Interest J.J.F. and M.M.R. have received a research grant from Siemens Healthineers, which was paid to the institute, without restrictions regarding publications or data. R.L.J.V. declares that his department has a research contract with Siemens Healthineers. P.F. is an employee of Siemens Healthcare GmbH. His contribution to this research was primarily in providing technical expertise and ensuring the accuracy of the technical content in the paper. All other authors declare no conflict of interest that could have affected the work reported in this paper. Siemens Healthineers had no role in data collection, data analysis, interpretation of the results, or the decision to submit for publication., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: The increasing interest in early identification of people at risk of developing dementia, has led to the development of numerous models aimed at estimating the likelihood of progression from mild cognitive impairment (MCI) to dementia. It is important to study both the need for and possible outcomes related with such prediction models, including the impact of risk predictions on perceived quality of life (QoL)., Objective: This study aimed to quantify the impact that receiving a risk prediction on progression from MCI to dementia has on QoL., Methods: A Discrete Choice Experiment (DCE) and Time Trade Off (TTO) study were performed. Participants completed choice tasks related to dementia prognosis while imagining having MCI. We collected DCE data by an online survey, and TTO data via videoconferencing interviews. DCE data were analyzed using a mixed multinomial logit model and were anchored to a health state utility scale using mean observed TTO valuations., Results: 296 people participated in the DCE and 42 in the TTO. Moderate and high predicted dementia risks were associated with decrements in utility (-0.05 and -0.18 respectively), compared to no prognostic information. Low predicted risk was associated with an increase in utility (0.06), as well as the availability of medication or lifestyle interventions (0.05 and 0.13 respectively)., Conclusions: This study shows a significant impact of dementia risk predictions on QoL and highlights the importance of caution when sharing information about expected MCI disease courses.

Objective: Acute and chronic tonsillitis are frequently treated with antibiotics. This study aimed to understand the presence of pathogenic micro-organisms on the surface and core of chronically infected tonsils among Tanzanian children., Methods: The study enrolled children undergoing adenotonsillectomy. Surface and core tonsillar swabs were taken. Quantitative polymerase chain reaction was performed for Streptococcus pneumoniae , Haemophilus influenzae , Moraxella catarrhalis , Staphylococcus aureus , Neisseria meningitidis and Pseudomonas aeruginosa ., Results: Surface and core combined, isolated N meningitidis (86.1 per cent) was found the most, followed by H influenzae (74.9 per cent), S pneumoniae (42.6 per cent) and S aureus (28.7 per cent). M catarrhalis and P aeruginosa were only found in a few patients, 5.6 per cent and 0.8 per cent respectively., Conclusion: Colonisation of the tonsillar surface and core has been found. Potentially pathogenic micro-organisms are likely to be missed based on a throat swab. Hence, the practice of surface tonsillar swabbing may be misleading or insufficient.

Objectives: Identifying unmet needs for innovative solutions across disease contexts is challenging but important for directing funding and research efforts and informing early-stage decisions during the innovation process. Our aim was to study the merits of care pathway analysis to scope disease contexts and guide the development of innovative devices. We used oncologic surgery as a case study, for which many intraoperative imaging techniques are under development., Methods: Care pathway analysis is a mapping process, which produces graphical maps of clinical pathways using important outcomes and subsequent consequences. We performed care pathway analyses for glioblastoma, breast, bladder, prostate, renal, pancreatic, and oral cavity cancer. Differences between a "perfect" care pathway and the current care pathway in terms of percentage of inadequate margins, associated recurrences, quality of life, and 5-year overall survival were calculated to determine unmet needs. Data from The Netherlands Cancer Registry and literature were used., Results: Care pathway analysis showed that highest percentages of inadequate margins were found in oral cavity cancer (72.5%), glioblastoma (48.7%), and pancreatic cancer (43.9%). Inadequate margins showed the strongest increase in recurrences in cancer of oral cavity, and bladder (absolute increases of 43.5% and 41.2%, respectively). Impact on survival was largest for bladder and oral cavity cancer with positive margins., Conclusions: Care pathway analysis provides overviews of current clinical paths in multiple indications. Disease contexts can be compared via effectiveness gaps that show the potential need for innovative solutions. This information can be used as basis for stakeholder involvement processes to prioritize care pathways in need of innovation., Competing Interests: Author Disclosures Drs Scholte and Grutters reported receiving grants from Dutch Research Council during the conduct of the study. Dr. Rovers reported receiving grants from the Dutch Organization (Dutch Research Council) and Siemens Healthineers. No other disclosures were reported., (Copyright © 2023 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Concerns exist regarding the generalizability of results from randomized controlled trials (RCTs) evaluating arthroscopic partial meniscectomy (APM) to treat degenerative meniscus tears. It has been suggested that study populations are not representative of subjects selected for surgery in daily clinical practice. Therefore, we aimed to compare patients included in trials and prospective cohort studies that received APM for a degenerative meniscus tear., Patients and Methods: Individual participant data from 4 RCTs and 2 cohort studies undergoing APM were collected. 1,970 patients were analyzed: 605 patients included in RCTs and 1,365 included in the cohorts. We compared patient and disease characteristics, knee pain, overall knee function, and health-related quality of life at baseline between the RCT and cohort groups using standardized differences, ratios comparing the variance of continuous covariates, and graphical methods such as quantile-quantile plots, side-by-side boxplots, and non-parametric density plots., Results: Differences between RCT and the cohort were observed primarily in age (younger patients in the cohort; standardized difference: 0.32) and disease severity, with the RCT group having more severe symptoms (standardized difference: 0.38). While knee pain, overall knee function, and quality of life generally showed minimal differences between the 2 groups, it is noteworthy that the largest observed difference was in knee pain, where the cohort group scored 7 points worse (95% confidence interval 5-9, standardized difference: 0.29)., Conclusion: Patients in RCTs were largely representative of those in cohort studies regarding baseline scores, though variations in age and disease severity were observed. Younger patients with less severe osteoarthritis were more common in the cohort; however, trial participants still appear to be broadly representative of the target population.

Background: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. It may cause hearing loss which, when persistent, may lead to developmental delay, social difficulty and poor quality of life. Management includes watchful waiting, autoinflation, medical and surgical treatment. Insertion of ventilation tubes has often been used as the preferred treatment., Objectives: To evaluate the effects (benefits and harms) of ventilation tubes (grommets) for OME in children., Search Methods: We searched the Cochrane ENT Register, CENTRAL, Ovid MEDLINE, Ovid Embase, Web of Science, ClinicalTrials.gov, ICTRP and additional sources for published and unpublished trials on 20 January 2023., Selection Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs in children (6 months to 12 years) with OME for ≥ 3 months. We included studies that compared ventilation tube (VT) insertion with five comparators: no treatment, watchful waiting (ventilation tubes inserted later, if required), myringotomy, hearing aids and other non-surgical treatments., Data Collection and Analysis: We used standard Cochrane methods. Our primary outcomes were determined following a multi-stakeholder prioritisation exercise and were: 1) hearing; 2) OME-specific quality of life; 3) persistent tympanic membrane perforation (as a severe adverse effect of the surgery). Secondary outcomes were: 1) persistence of OME; 2) other adverse effects (including tympanosclerosis, VT blockage and pain); 3) receptive language skills; 4) speech development; 5) cognitive development; 6) psychosocial skills; 7) listening skills; 8) generic health-related quality of life; 9) parental stress; 10) vestibular function; 11) episodes of acute otitis media. We used GRADE to assess the certainty of evidence for key outcomes. Although we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method, due to challenges in interpreting the results of mean hearing thresholds., Main Results: We included 19 RCTs (2888 children). We considered most of the evidence to be very uncertain, due to wide confidence intervals for the effect estimates, few participants, and a risk of performance and detection bias. Here we report our key outcomes at the longest reported follow-up. There were some limitations to the evidence. No studies investigated the comparison of ventilation tubes versus hearing aids. We did not identify any data on disease-specific quality of life; however, many studies were conducted before the development of specific tools to assess this in otitis media. Short-acting ventilation tubes were used in most studies and thus specific data on the use of long-acting VTs is limited. Finally, we did not identify specific data on the effects of VTs in children at increased risk of OME (e.g. with craniofacial syndromes). Ventilation tubes versus no treatment (four studies) The odds ratio (OR) for a return to normal hearing after 12 months was 1.13 with VTs (95% confidence interval (CI) 0.46 to 2.74; 54% versus 51%; 1 study, 72 participants; very low-certainty evidence). At six months, VTs may lead to a large reduction in persistent OME (risk ratio (RR) 0.30, 95% CI 0.14 to 0.65; 20.4% versus 68.0%; 1 study, 54 participants; low-certainty evidence). The evidence is very uncertain about the chance of persistent tympanic membrane perforation with VTs at 12 months (OR 0.85, 95% CI 0.38 to 1.91; 8.3% versus 9.7%; 1 RCT, 144 participants). Early ventilation tubes versus watchful waiting (six studies) There was little to no difference in the proportion of children whose hearing returned to normal after 8 to 10 years (i.e. by the age of 9 to 13 years) (RR for VTs 0.98, 95% CI 0.94 to 1.03; 93% versus 95%; 1 study, 391 participants; very low-certainty evidence). VTs may also result in little to no difference in the risk of persistent OME after 18 months to 6 years (RR 1.21, 95% CI 0.84 to 1.74; 15% versus 12%; 3 studies, 584 participants; very low-certainty evidence). We were unable to pool data on persistent perforation. One study showed that VTs may increase the risk of perforation after a follow-up duration of 3.75 years (RR 3.65, 95% CI 0.41 to 32.38; 1 study, 391 participants; very low-certainty evidence) but the actual number of children who develop persistent perforation may be low, as demonstrated by another study (1.26%; 1 study, 635 ears; very low-certainty evidence). Ventilation tubes versus non-surgical treatment (one study) One study compared VTs to six months of antibiotics (sulphisoxazole). No data were available on return to normal hearing, but final hearing thresholds were reported. At four months, the mean difference was -5.98 dB HL lower (better) for those receiving VTs, but the evidence is very uncertain (95% CI -9.21 to -2.75; 1 study, 125 participants; very low-certainty evidence). No evidence was identified regarding persistent OME. VTs may result in a low risk of persistent perforation at 18 months of follow-up (no events reported; narrative synthesis of 1 study, 60 participants; low-certainty evidence). Ventilation tubes versus myringotomy (nine studies) We are uncertain whether VTs may slightly increase the likelihood of returning to normal hearing at 6 to 12 months, since the confidence intervals were wide and included the possibility of no effect (RR 1.22, 95% CI 0.59 to 2.53; 74% versus 64%; 2 studies, 132 participants; very low-certainty evidence). After six months, persistent OME may be reduced for those who receive VTs compared to laser myringotomy, but the evidence is very uncertain (OR 0.27, 95% CI 0.19 to 0.38; 1 study, 272 participants; very low-certainty evidence). At six months, the risk of persistent perforation is probably similar with the use of VTs or laser myringotomy (narrative synthesis of 6 studies, 581 participants; moderate-certainty evidence)., Authors' Conclusions: There may be small short- and medium-term improvements in hearing and persistence of OME with VTs, but it is unclear whether these persist after longer follow-up. The RCTs included do not allow us to say when (or how much) VTs improve hearing in any specific child. However, interpretation of the evidence is difficult: many children in the control groups recover spontaneously or receive VTs during follow-up, VTs may block or extrude, and OME may recur. The limited evidence in this review also affects the generalisability/applicability of our findings to situations involving children with underlying conditions (e.g. craniofacial syndromes) or the use of long-acting tubes. Consequently, RCTs may not be the best way to determine whether an intervention is likely to be effective in any individual child. Instead, we must better understand the different OME phenotypes to target interventions to children who will benefit most, and avoid over-treating when spontaneous resolution is likely., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Acute otitis media (AOM) is one of the most common diseases in childhood for which antibiotics are commonly prescribed; a systematic review reported a pooled prevalence of 85.6% in high-income countries. This is an update of a Cochrane Review first published in the Cochrane Library in 1997 and updated in 1999, 2005, 2009, 2013 and 2015., Objectives: To assess the effects of antibiotics for children with AOM., Search Methods: We searched CENTRAL, MEDLINE, Embase, Current Contents, CINAHL, LILACS and two trial registers. The date of the search was 14 February 2023., Selection Criteria: We included randomised controlled trials comparing 1) antimicrobial drugs with placebo, and 2) immediate antibiotic treatment with expectant observation (including delayed antibiotic prescribing) in children with AOM., Data Collection and Analysis: Two review authors independently screened trials for inclusion and extracted data using the standard methodological procedures recommended by Cochrane. Our primary outcomes were: 1) pain at various time points (24 hours, two to three days, four to seven days, 10 to 14 days), and 2) adverse effects likely to be related to the use of antibiotics. Secondary outcomes were: 1) abnormal tympanometry findings, 2) tympanic membrane perforation, 3) contralateral otitis (in unilateral cases), 4) AOM recurrences, 5) serious complications related to AOM and 6) long-term effects (including the number of parent-reported AOM symptom episodes, antibiotic prescriptions and health care utilisation as assessed at least one year after randomisation). We used the GRADE approach to rate the overall certainty of evidence for each outcome of interest., Main Results: Antibiotics versus placebo We included 13 trials (3401 children and 3938 AOM episodes) from high-income countries, which we assessed at generally low risk of bias. Antibiotics do not reduce pain at 24 hours (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.78 to 1.01; 5 trials, 1394 children; high-certainty evidence), or at four to seven days (RR 0.76, 95% CI 0.50 to 1.14; 7 trials, 1264 children), but result in almost a third fewer children having pain at two to three days (RR 0.71, 95% CI 0.58 to 0.88; number needed to treat for an additional beneficial outcome (NNTB) 20; 7 trials, 2320 children; high-certainty evidence), and likely result in two-thirds fewer having pain at 10 to 12 days (RR 0.33, 95% CI 0.17 to 0.66; NNTB 7; 1 trial, 278 children; moderate-certainty evidence). Antibiotics increase the risk of adverse events such as vomiting, diarrhoea or rash (RR 1.38, 95% CI 1.16 to 1.63; number needed to treat for an additional harmful outcome (NNTH) 14; 8 trials, 2107 children; high-certainty evidence). Antibiotics reduce the risk of children having abnormal tympanometry findings at two to four weeks (RR 0.83, 95% CI 0.72 to 0.96; NNTB 11; 7 trials, 2138 children), slightly reduce the risk of experiencing tympanic membrane perforations (RR 0.43, 95% CI 0.21 to 0.89; NNTB 33; 5 trials, 1075 children) and halve the risk of contralateral otitis episodes (RR 0.49, 95% CI 0.25 to 0.95; NNTB 11; 4 trials, 906 children). However, antibiotics do not reduce the risk of abnormal tympanometry findings at six to eight weeks (RR 0.89, 95% CI 0.70 to 1.13; 3 trials, 953 children) and at three months (RR 0.94, 95% CI 0.66 to 1.34; 3 trials, 809 children) or late AOM recurrences (RR 0.94, 95% CI 0.79 to 1.11; 6 trials, 2200 children). Severe complications were rare, and the evidence suggests that serious complications do not differ between children treated with either antibiotics or placebo. Immediate antibiotics versus expectant observation We included six trials (1556 children) from high-income countries. The evidence suggests that immediate antibiotics may result in a reduction of pain at two to three days (RR 0.53, 95% CI 0.35 to 0.79; NNTB 8; 1 trial, 396 children; low-certainty evidence), but probably do not reduce the risk of pain at three to seven days (RR 0.75, 95% CI 0.50 to 1.12; 4 trials, 959 children; moderate-certainty evidence), and may not reduce the risk of pain at 11 to 14 days (RR 0.91, 95% CI 0.75 to 1.10; 1 trial, 247 children; low-certainty evidence). Immediate antibiotics increase the risk of vomiting, diarrhoea or rash (RR 1.87, 95% CI 1.39 to 2.51; NNTH 10; 3 trials, 946 children; high-certainty evidence). Immediate antibiotics probably do not reduce the proportion of children with abnormal tympanometry findings at four weeks and evidence suggests that immediate antibiotics may not reduce the risk of tympanic membrane perforation and AOM recurrences. No serious complications occurred in either group., Authors' Conclusions: This review reveals that antibiotics probably have no effect on pain at 24 hours, a slight effect on pain in the days following and only a modest effect on the number of children with tympanic perforations, contralateral otitis episodes and abnormal tympanometry findings at two to four weeks compared with placebo in children with AOM. In high-income countries, most cases of AOM spontaneously remit without complications. The benefits of antibiotics must be weighed against the possible harms: for every 14 children treated with antibiotics, one child experienced an adverse event (such as vomiting, diarrhoea or rash) that would not have occurred if antibiotics were withheld. For most children with mild disease in high-income countries, an expectant observational approach seems justified. Therefore, clinical management should emphasise advice about adequate analgesia and the limited role for antibiotics., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)