Search

BackgroundNitrofurantoin is the first-choice antibiotic treatment for uncomplicated urinary tract infections (UTIs) in males according to the Dutch primary care UTI guideline. However, prostate involvement may be undetected and renders this treatment less suitable.AimTo compare the nitrofurantoin failure fraction with that found with use of other antibiotics in adult males diagnosed by their GP with an uncomplicated UTI, as well as GP adherence to the Dutch primary care UTI guideline.Design and settingRetrospective observational cohort study using routine healthcare data for males seeking care at GP practices participating in the Julius GP Network from 2014 to 2020.MethodMedical records were screened for signs and symptoms of complicated UTIs, antibiotic prescriptions, and referrals. Treatment failure was defined as prescription of a different antibiotic within 30 days after initiation of antibiotic therapy and/or acute hospital referral. The effects of age and comorbidities on failure were assessed using multivariable logistic regression.ResultsMost UTI episodes in males were uncomplicated (n = 6805/10 055 episodes, 68%). Nitrofurantoin was prescribed in 3788 (56%) of uncomplicated UTIs, followed by ciprofloxacin (n= 1887, 28%), amoxicillin/clavulanic acid (n= 470, 7%), and trimethoprim/sulfamethoxazole (n= 285, 4%). Antibiotic failure occurred in 25% (95% confidence interval [CI] = 23 to 26), 10% (95% CI = 9 to 12), 20% (95% CI = 16 to 24), and 14% (95% CI = 10 to 19) of episodes, respectively. The nitrofurantoin failure fraction increased with age. Comorbidities, adjusted for age, were not associated with nitrofurantoin failure.ConclusionNitrofurantoin failure was common in males with uncomplicated UTI and increased with age.

BackgroundPulse oximetry as a home or remote monitoring tool accelerated during the pandemic for patients with COVID-19, but evidence on its use is lacking.AimTo assess the feasibility of home monitoring by pulse oximetry of patients aged ≥40 years with cardiovascular comorbidity and moderate-to-severe COVID-19.Design and settingA primary care-based, open, pilot randomised controlled trial, with nested process evaluation, was undertaken in the Netherlands.MethodFrom November 2020 to June 2021, eligible patients presenting to one of 14 participating Dutch general practices were randomly allocated to regular measurement of peripheral oxygen saturation (at least three SpO2measurements per day for 14 days) with a validated pulse oximeter or usual care.ResultsAll 41 participants (21 intervention, 20 usual care) completed the 45-day follow-up period. Overall, the intervention group performed 97.6% of protocolised measurements; the median daily measurement per participant was 2.7 (interquartile range 1–4). Hypoxemia (SpO2P= 0.09). Primary care consultations were similar across groups: 50 for the intervention versus 51 for the control. Eleven visits by 10 participants were made to the emergency department (eight from the intervention group versus three from usual care), of which six participants were hospitalised (five intervention versus one usual care). No participants were admitted to the intensive care unit or died during follow-up.ConclusionHome monitoring of patients with moderate-to-severe COVID-19 by pulse oximetry appeared feasible; adherence was high, patients reported a high feeling of safety, while the number of primary care consultations remained similar to usual care.

It is often thought that acute ear discharge as a presenting symptom of acute otitis media (AOM) means that the infection is petering out. However, children with AOM presenting with ear discharge due to a spontaneous perforation of the eardrum (AOMd) have a poorer prognosis (i.e. higher rates of ear pain and/or fever at 3-7 days) than those without ear discharge. In this article we emphasize the importance of physical examination and early treatment of children and adults who present with acute ear discharge.

ObjectiveTo assess the performance of rapid antigen tests with unsupervised nasal and combined oropharyngeal and nasal self-sampling during the omicron period.DesignProspective cross sectional diagnostic test accuracy study.SettingThree public health service covid-19 test sites in the Netherlands, 21 December 2021 to 10 February 2022.Participants6497 people with covid-19 symptoms aged ≥16 years presenting for testing.InterventionsParticipants had a swab sample taken for reverse transcription polymerase chain reaction (RT-PCR, reference test) and received one rapid antigen test to perform unsupervised using either nasal self-sampling (during the emergence of omicron, and when omicron accounted for >90% of infections, phase 1) or with combined oropharyngeal and nasal self-sampling in a subsequent (phase 2; when omicron accounted for >99% of infections). The evaluated tests were Flowflex (Acon Laboratories; phase 1 only), MPBio (MP Biomedicals), and Clinitest (Siemens-Healthineers).Main outcome measuresThe main outcomes were sensitivity, specificity, and positive and negative predictive values of each self-test, with RT-PCR testing as the reference standard.ResultsDuring phase 1, 45.0% (n=279) of participants in the Flowflex group, 29.1% (n=239) in the MPBio group, and 35.4% ((n=257) in the Clinitest group were confirmatory testers (previously tested positive by a self-test at own initiative). Overall sensitivities with nasal self-sampling were 79.0% (95% confidence interval 74.7% to 82.8%) for Flowflex, 69.9% (65.1% to 74.4%) for MPBio, and 70.2% (65.6% to 74.5%) for Clinitest. Sensitivities were substantially higher in confirmatory testers (93.6%, 83.6%, and 85.7%, respectively) than in those who tested for other reasons (52.4%, 51.5%, and 49.5%, respectively). Sensitivities decreased from 87.0% to 80.9% (P=0.16 by χ2test), 80.0% to 73.0% (P=0.60), and 83.1% to 70.3% (P=0.03), respectively, when transitioning from omicron accounting for 29% of infections to >95% of infections. During phase 2, 53.0% (n=288) of participants in the MPBio group and 44.4% (n=290) in the Clinitest group were confirmatory testers. Overall sensitivities with combined oropharyngeal and nasal self-sampling were 83.0% (78.8% to 86.7%) for MPBio and 77.3% (72.9% to 81.2%) for Clinitest. When combined oropharyngeal and nasal self-sampling was compared with nasal self-sampling, sensitivities were found to be slightly higher in confirmatory testers (87.4% and 86.1%, respectively) and substantially higher in those testing for other reasons (69.3% and 59.9%, respectively).ConclusionsSensitivities of three rapid antigen tests with nasal self-sampling decreased during the emergence of omicron but was only statistically significant for Clinitest. Sensitivities appeared to be substantially influenced by the proportion of confirmatory testers. Sensitivities of MPBio and Clinitest improved after the addition of oropharyngeal to nasal self-sampling. A positive self-test result justifies prompt self-isolation without the need for confirmatory testing. Individuals with a negative self-test result should adhere to general preventive measures because a false negative result cannot be ruled out. Manufacturers of MPBio and Clinitest may consider extending their instructions for use to include combined oropharyngeal and nasal self-sampling, and other manufacturers of rapid antigen tests should consider evaluating this as well.

BackgroundAntibiotics are overused in patients with acute rhinosinusitis (ARS) as it is difficult to identify those who benefit from antibiotic treatment.AimTo develop prediction models for computed tomography (CT)-confirmed ARS and culture-confirmed acute bacterial rhinosinusitis (ABRS) in adults presenting to primary care with symptoms suggestive of ARS.Design and settingThis was a systematic review and individual participant data meta-analysis.MethodCT-confirmed ARS was defined as the presence of fluid level or total opacification in any maxillary sinuses, whereas culture-confirmed ABRS was defined by culture of fluid from antral puncture. Prediction models were derived using logistic regression modelling.ResultsAmong 426 patients from three studies, 140 patients (32.9%) had CT-confirmed ARS. A model consisting of seven variables: previous diagnosis of ARS, preceding upper respiratory tract infection, anosmia, double sickening, purulent nasal discharge on examination, need for antibiotics as judged by a physician, and C-reactive protein (CRP) showed an optimism-corrected c-statistic of 0.73 (95% confidence interval [CI] = 0.69 to 0.78) and a calibration slope of 0.99 (95% CI = 0.72 to 1.19). Among 225 patients from two studies, 68 patients (30.2%) had culture-confirmed ABRS. A model consisting of three variables: pain in teeth, purulent nasal discharge, and CRP showed an optimism-corrected c-statistic of 0.70 (95% CI = 0.63 to 0.77) and a calibration slope of 1.00 (95% CI = 0.66 to 1.52). Clinical utility analysis showed that both models could be useful to rule out the target condition.ConclusionSimple prediction models for CT-confirmed ARS and culture-confirmed ABRS can be useful to safely reduce antibiotic use in adults with ARS in high-prescribing countries.

ObjectivesTo assess the performances of three commonly used rapid antigen diagnostic tests (Ag-RDTs) used as self-tests in asymptomatic individuals in the Omicron period.DesignCross-sectional diagnostic test accuracy study.SettingThree public health service COVID-19 test sites in the Netherlands.Participants3,600 asymptomatic individuals aged ≥16 years presenting for SARS-CoV-2 testing for any reason except confirmatory testing after a positive self-test.InterventionsParticipants were sampled for RT-PCR (reference test) and received one self-test (either Acon Flowflex (Flowflex), MP Biomedicals (MPBio), or Siemens-Healthineers Clinitest (Clinitest)) to perform unsupervised at home within three hours and blinded to the RT-PCR result.Main Outcome(s) and Measures(s)Diagnostic accuracies (sensitivity, specificity, positive and negative predictive values) of each self-test compared to RT-PCR.ResultsOverall sensitivities of the three self-tests were 27.5% (95% CI: 21.3-34.3%) for Flowflex, 20.9% (13.9-29.4%) for MPBio, and 25.6% (19.1-33.1%) for Clinitest. After applying a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL), sensitivities increased to 48.3% (95% CI: 37.6-59.2%), 37.8% (22.5-55.2%), and 40.0% (29.5-51.2%), respectively. No consistent differences were found in sensitivities by COVID-19 vaccination status, having had a prior SARS-CoV-2 infection, gender or age across the three self-tests. Specificities were >99% for all tests in most analyses.ConclusionsThe sensitivities of three commonly used SARS-CoV-2 Ag-RDTs when used as self-tests in asymptomatic individuals in the Omicron period, were very low. Our findings indicate that Ag-RDT self-testing in asymptomatic individuals may only detect the minority of infections at that point in time and may not be sufficient to prevent the spreading of the virus to other (vulnerable) persons. Repeated self-testing in case of a negative self-test is advocated to improve the diagnostic yield of the self-tests, and individuals should certainly be advised to re-test when symptoms develop.Summary boxWhat is already known on this topicIf sufficiently reliable, SARS-CoV-2 self-testing by asymptomatic persons prior to admission in places where groups gather could have a huge public health impact by lowering the reproduction number or keep it below one for longer periods.Current evidence suggests that SARS-CoV-2 rapid antigen diagnostic tests (Ag-RDTs) when used as self-tests by asymptomatic individuals perform suboptimal, but sample sizes of the previous studies were too small to draw robust conclusions, and also empirical data on the accuracy of Ag-RDT self-tests in asymptomatic individuals during the Omicron period are scarce.What this study addsCompared to RT-PCR testing, overall sensitivities of three commercially available SARS-CoV-2 Ag-RDTs when used as self-tests by asymptomatic individuals (primary analysis population of non-confirmatory testers; n= 3600, 87% of full analysis population) in the Omicron period, were very low: 27.5% (95% CI: 21.3-34.3%) for the Acon Flowflex test, 20.9% (13.9-29.4%) for the MP Biomedicals test, and 25.6% (19.1-33.1%) for the Siemens Healthineers Clinitest Ag-RDT, which increased to 48.3% (95% CI: 37.6-59.2%), 37.8% (22.5-55.2%), and 40.0% (29.5-51.2%), respectively, when applying a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL).Our findings indicate that Ag-RDT self-testing in asymptomatic individuals may only detect the minority of infections at that point in time and may not be sufficient to prevent the spreading of the virus to other (vulnerable) persons. Repeated self-testing in case of a negative self-test is advocated to improve the diagnostic yield of the self-tests, and individuals should certainly be advised to re-test when symptoms develop.

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.

Objectives: To assess the performances of three commonly used antigen rapid diagnostic tests used as self-tests in asymptomatic individuals in the Omicron period. Methods: We performed a cross-sectional diagnostic test accuracy study in the Omicron period in three public health service COVID-19 test sites in the Netherlands, including 3600 asymptomatic individuals aged ≥ 16 years presenting for SARS-CoV-2 testing for any reason except confirmatory testing after a positive self-test. Participants were sampled for RT-PCR (reference test) and received one self-test (either Acon Flowflex [Flowflex], MP Biomedicals (MPBio), or Siemens-Healthineers CLINITEST [CLINITEST]) to perform unsupervised at home. Diagnostic accuracies of each self-test were calculated. Results: Overall sensitivities were 27.5% (95% CI, 21.3–34.3%) for Flowflex, 20.9% (13.9–29.4%) for MPBio, and 25.6% (19.1–33.1%) for CLINITEST. After applying a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL), sensitivities increased to 48.3% (37.6–59.2%), 37.8% (22.5–55.2%), and 40.0% (29.5–51.2%), respectively. Specificities were >99% for all tests in most analyses. Discussion: The sensitivities of three commonly used SARS-CoV-2 antigen rapid diagnostic tests when used as self-tests in asymptomatic individuals in the Omicron period were very low. Antigen rapid diagnostic test self-testing in asymptomatic individuals may only detect a minority of infections at that point in time. Repeated self-testing in case of a negative self-test is advocated to improve the diagnostic yield, and individuals should be advised to re-test when symptoms develop.

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.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects (benefits and harms) of autoinflation for otitis media with effusion (OME) in children.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects (benefits and harms) of topical and oral steroids for otitis media with effusion (OME) in children.

BackgroundPerformances of rapid antigen diagnostic tests (Ag-RDTs) with nasal self-sampling, and oropharyngeal plus nasal (OP-N) self-sampling, in the Omicron period are unknown.MethodsProspective diagnostic accuracy study among 6,497 symptomatic individuals aged >16 years presenting for SARS-CoV-2 testing at three test-sites. Participants were sampled for RT-PCR (reference test) and received one Ag-RDT to perform unsupervised with either nasal self-sampling (during the emergence of Omicron, and after Omicron share was >90%, phase-1) or with OP-N self-sampling (in a subsequent phase-2; Omicron share >99%). The evaluated tests were Acon Flowflex (Flowflex; phase-1 only), MP Biomedicals (MPBio), and Siemens-Healthineers Clinitest (Clinitest).FindingsDuring phase-1, 45% of Flowflex, 29% of MPBio, and 35% of Clinitest participants were confirmatory testers (previously tested positive by a self-test at own initiative). Overall sensitivities with nasal self-sampling were 79.0% (95% CI: 74.7-82.8%) for Flowflex, 69.9% (65.1-74.4%) for MPBio, and 70.2% (65.6-74.5%) for Clinitest. Sensitivities were substantially higher in confirmatory testers (93.6%, 83.6%, and 85.7%, respectively) than in those who tested for other reasons (52.4%, 51.5%, and 49.5%, respectively). Sensitivities decreased by 6.1 (p=0.16 by Chi-square test), 7.0 (p=0.60), and 12.8 (p=0.025) percentage points, respectively, when transitioning from 29% to >95% Omicron. During phase-2, 53% of MPBio, and 44% of Clinitest participants were confirmatory testers. Overall sensitivities with OP-N self-sampling were 83.0% (78.8%-86.7%) for MPBio and 77.3% (72.9%-81.2%) for Clinitest. Comparing OP-N to nasal sampling, sensitivities were slightly higher in confirmatory testers (87.4% and 86.1%, respectively), and substantially higher in those testing for other reasons (69.3% and 59.9%, respectively).InterpretatioSensitivities of three Ag-RDTs with nasal self-sampling decreased during Omicron emergence but was only statistically significant for Clinitest. Sensitivities were substantially influenced by the proportion of confirmatory testers. Addition of oropharyngeal to nasal self-sampling improved sensitivities of MPBio and Clinitest.FundingDutch Ministry of Health, Welfare, and Sport.Research into contextEvidence before this studySARS-CoV-2 rapid antigen diagnostic tests (Ag-RDTs) require no or minimal equipment, provide a result within 15-30 minutes, and can be used in a range of settings including for self-testing at home. Self-testing may potentially lower the threshold to testing and allows individuals to obtain a test result quickly and at their own convenience, which could support the early detection of infectious cases and reduce community transmission. Real world evidence on the performance of unsupervised nasal and oropharyngeal plus nasal (OP-N) self-sampling in the Omicron variant period is needed to accurately inform end-users and policymakers. Therefore, we conducted a large prospective diagnostic accuracy study of three commercially available Ag-RDTs with self-sampling (the Acon Flowflex test, the MP Biomedicals test, and the Siemens-Healthineers Clinitest) during and after the emergence of Omicron using RT-PCR as the reference standard. Our aims were to evaluate whether the accuracies of Ag-RDTs with nasal self-sampling changed over time with the emergence of Omicron; and to determine whether addition of oropharyngeal to nasal self-sampling with the same swab yielded higher diagnostic accuracies.What this study addsThe large comprehensive study was conducted in almost 6,500 participants with symptoms when presenting for routine SARS-CoV-2 testing at three public health service COVID-19 test-sites in the Netherlands. During the study, conducted between 21 December 2021 and 10 February 2022, the percentage of the Omicron variant in samples from the national SARS-CoV-2 pathogen surveillance increased from 29% in the first week to 99% in the last week of the study. The period during which the Omicron variant was dominant was divided into a nasal sampling phase (phase-1; Omicron present in >90% of surveillance samples) and an OP-N sampling phase (phase-2; Omicron share was >99%). In phase-1, 45% of Flowflex, 29% of MPBio, and 35% of Clinitest participants visited the test-site because of a positive self-test (confirmatory testers). Overall sensitivities with nasal self-sampling were 79.0% (95% CI: 74.7-82.8%) for the Flowflex, 69.9% (65.1-74.4%) for the MPBio, and 70.2% (65.6-74.5%) for the Clinitest Ag-RDT. Sensitivities were 94%, 84%, and 86%, respectively, for confirmatory testers, and 52%, 52%, and 50%, respectively, for those who had other reasons for getting tested. Sensitivities were 87.0% (79.7-92.4%), 83.1% (72.9-90.7%), and 80.0% (51.9-95.7%), respectively, in the first week, and decreased by 6.1 (p=0.16 by Chi-square test), 7.0 (p=0.60), and 12.8 (p=0.025) percentage points in the final week of the study. In Phase-2, 53% of MPBio and 44% of Clinitest participants were confirmatory testers. Overall sensitivities with OP-N self-sampling were 83.0% (78.8%-86.7%) for MPBio and 77.3% (72.9%-81.2%) for Clinitest. When comparing OP-N to nasal sampling, sensitivities were slightly higher in confirmatory testers (87.4% and 86.1%, respectively), and substantially higher in those testing for other reasons (69.3% and 59.9%).Implications of all the available evidenceThe sensitivities of three commercially available Ag-RDTs performed with nasal self-sampling decreased during the emergence of Omicron, but this trend was only statistically significant for Clinitest. Addition of oropharyngeal to nasal self-sampling improved the sensitivity of the MPBio and Clinitest, most notably in individuals who visited the test-site for other reasons than to confirm a positive self-test. Based on these findings, the manufacturers of MPBio and Clinitest may consider extending their instructions for use to include combined oropharyngeal and nasal sampling, and other manufacturers may consider evaluating this as well.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects (benefits and harms) of ventilation tubes (grommets) for otitis media with effusion in children.

IntroductionEar pain is the most prominent symptom of childhood acute otitis media (AOM). To control the pain and reduce reliance on antibiotics, evidence of effectiveness for alternative interventions is urgently needed. This trial aims to investigate whether analgesic ear drops added to usual care provide superior ear pain relief over usual care alone in children presenting to primary care with AOM.Methods and analysisThis is a pragmatic, two-arm, individually randomised, open, superiority trial with cost-effectiveness analysis and nested mixed-methods process evaluation in general practices in the Netherlands. We aim to recruit 300 children aged 1–6 years with a general practitioner (GP) diagnosis of AOM and ear pain. Children will be randomly allocated (ratio 1:1) to either (1) lidocaine hydrochloride 5 mg/g ear drops (Otalgan) one to two drops up to six times daily for a maximum of 7 days in addition to usual care (oral analgesics, with/without antibiotics); or (2) usual care. Parents will complete a symptom diary for 4 weeks as well as generic and disease-specific quality of life questionnaires at baseline and 4 weeks. The primary outcome is the parent-reported ear pain score (0–10) over the first 3 days. Secondary outcomes include proportion of children consuming antibiotics, oral analgesic use and overall symptom burden in the first 7 days; number of days with ear pain, number of GP reconsultations and subsequent antibiotic prescribing, adverse events, complications of AOM and cost-effectiveness during 4-week follow-up; generic and disease-specific quality of life at 4 weeks; parents’ and GPs’ views and experiences with treatment acceptability, usability and satisfaction.Ethics and disseminationThe Medical Research Ethics Committee Utrecht, the Netherlands, has approved the protocol (21-447/G-D). All parents/guardians of participants will provide written informed consent. Study results will be submitted for publication in peer-reviewed medical journals and presented at relevant (inter)national scientific meetings.Trial registrationThe Netherlands Trial Register: NL9500; date of registration: 28 May 2021. At the time of publication of the study protocol paper, we were unable to make any amendments to the trial registration record in the Netherlands Trial Register. The addition of a data sharing plan was required to adhere to the International Committee of Medical Journal Editors guidelines. The trial was therefore reregistered in ClinicalTrials.gov (NCT05651633; date of registration: 15 December 2022). This second registration is for modification purposes only and the Netherlands Trial Register record (NL9500) should be regarded as the primary trial registration.

BackgroundAround 15%–20% of children with acute otitis media present with ear discharge due to a spontaneous tear or perforation of the eardrum (AOMd). Current guidance recommends clinicians to consider oral antibiotics as first-line treatment in this condition. The opening in the eardrum however should allow topical antibiotics to enter the middle ear directly. Local administration of antibiotics does not expose children to systemic side effects and may put less selective resistance pressure on bacteria. Evidence on the effectiveness of this approach in children with AOMd is lacking.Methods and analysisA primary care-based, open, individually randomised, controlled, non-inferiority trial. The trial aims to recruit 350 children aged 6 months to 12 years with AOMd and ear pain and/or fever. Participants will be randomised to 7 days of hydrocortisone-bacitracin-colistin eardrops five drops three times daily or amoxicillin oral suspension 50 mg/kg body weight per day, divided over three doses. Parents will keep a daily diary of AOM symptoms, adverse events and complications for 2 weeks. In addition, they will record AOM recurrences, healthcare utilisation and societal costs for 3 months. The primary outcome is the proportion of children without ear pain and fever at day 3. Secondary outcomes include ear pain and fever intensity/severity; days with ear discharge; eardrum perforation at 2 weeks; adverse events during first 2 weeks; costs; and cost effectiveness at 2 weeks and 3 months. The primary analyses will be intention-to-treat and per-protocol analyses will be conducted as well.Ethics and disseminationThe medical research ethics committee Utrecht, The Netherlands has given ethical approval (17-400/G-M). Parents/guardians of participants will provide written informed consent. Study results will be submitted for publication in peer-reviewed medical journals and presented at relevant (inter)national scientific meetings.Trial registration numberThe Netherlands National Trial Register; NTR6723. Date of registration: 27 November 2017.

BackgroundSARS-CoV-2 self-tests may lower the threshold of testing and produce a result quickly. This could support the early detection of infectious cases and reduce further community transmission. However, the diagnostic accuracy of (unsupervised) self-testing with rapid antigen diagnostic tests (Ag-RDTs) is mostly unknown. We therefore conducted a large-scale head-to-head comparison of the diagnostic accuracy of a self-performed SARS-CoV-2 saliva and nasal Ag-RDT, each compared to a molecular reference test, in the general population in the Netherlands.MethodsIn this cross-sectional study we consecutively included individuals aged 16 years and older presenting for SARS-CoV-2 testing at three Dutch public health service test sites irrespective of their indication for testing, vaccination status, and symptomatology. Participants were sampled for molecular testing at the test site and received two self-tests (the Hangzhou AllTest saliva self-test and the SD Biosensor nasal self-test by Roche Diagnostics) to perform at home within a few hours without knowledge of their molecular test result. Information on presence and type of symptoms, user experiences, and results of both self-tests were collected via an online questionnaire. For each self-test, sensitivity, specificity, positive and negative predictive values were determined with molecular testing as reference standard.FindingsThe SARS-CoV-2 molecular reference test positivity rate was 6.5% in the 2,819 participants. Overall sensitivities with 95% confidence intervals were 46.7% (85/182; 39.3%-54.2%) for the saliva Ag-RDT, and 68.9% (124/180; 61.6%-75.6%) for the nasal Ag-RDT. With a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL) as a proxy of infectiousness, sensitivities increased to 54.9% (78/142; 46.4%-63.3%) for the saliva Ag-RDT and 83.9% (120/143; 76.9%-89.5%) for the nasal Ag-RDT.For the nasal Ag-RDT, sensitivities were 78.5% [71.1%-84.8%] and 22.6% [9.6%-41.1%] in those with and without symptoms at the time of sampling, which increased to 90.4% (113/125; 83.8%-94.9%) and 38.9% (7/18; 17.3%-64.3%) after applying the viral load cut-off. In those with and without prior confirmed SARS-CoV-2, sensitivities were 36.8% [19/372; 16.3%-61.6%] and 72.7% [161/2437; 65.1%-79.4%] for the nasal Ag-RDT, which increased to 100% (7/7; 59.0%-100%) and 83.1% (113/126; 75.7%-89.0%) after applying the viral load cut-off.The diagnostic accuracy of the nasal Ag-RDT did not differ by COVID-19 vaccination status, sex, and age. Specificities were >99%, positive predictive values >70% and negative predictive values >95%, for the saliva Ag-RDT, and >99%, >90%, and >95% for the nasal Ag-RDT, respectively, in most analyses.Interpreting the results was considered (very) easy for both self-tests.InterpretationThe Hangzhou AllTest self-performed saliva Ag-RDT is not reliable for SARS-CoV-2 infection detection overall nor in the studied subgroups. The SD Biosensor self-performed nasal Ag-RDT had high sensitivity in individuals with symptoms and in those without a prior SARS-CoV-2 infection. The overall accuracy in individuals with symptoms was comparable to that found in previous studies with professional sampling for this Ag-RDT. The extremely low sensitivity of the nasal Ag-RDT in asymptomatic individuals and in individuals who had had a prior SARS-CoV-2 infection is an important finding and warrants further investigation.FundingDutch Ministry of Health, Welfare, and Sport.

ObjectiveTo assess the diagnostic accuracy of three rapid antigen tests (Ag-RDTs) for detecting SARS-CoV-2 infection in the general population.DesignCross-sectional study with follow-up using pseudonymised record linkage.SettingThree Dutch public health service COVID-19 test sites.ParticipantsConsecutively included individuals aged 16 years and older presenting for SARS-CoV-2 testing.Main outcome measuresSensitivity, specificity, positive and negative predictive values of BD-VeritortmSystem (Becton Dickinson), PanBio (Abbott), and SD-Biosensor (Roche Diagnostics), applying routinely used sampling methods (combined oropharyngeal and nasal [OP-N] or nasopharyngeal [NP] swab), with molecular testing as reference standard. For SD-Biosensor, the diagnostic accuracy with OP-N sampling was also assessed. A viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL) served as a proxy of infectiousness.ResultsSARS-CoV-2 prevalence and overall sensitivities with 95% confidence intervals were 188/1441 (13.0%) and 129/188 (68.6% [61.5%-75.2%]) for BD-Veritor, 173/2056 (8.4%) and 119/173 (68.8% [61.3%-75.6%]) for PanBio, and 215/1769 (12.2%) and 160/215 (74.4% [68.0%-80.1%]) for SD-Biosensor with routine sampling, and 164/1689 (9.7%) and 123/164 (75.0% [67.7%-81.4%]) for SD-Biosensor with OP-N sampling. In those symptomatic or asymptomatic at sampling, sensitivities were 72.2%-83.4% and 54.0%-55.9%, respectively. With a viral load cut-off, sensitivities were 125/146 (85.6% [78.9%-90.9%]) for BD-Veritor, 108/121 (89.3% [82.3%-94.2%]) for PanBio, 160/182 (87.9% [82.3%-92.3%]) for SD-Biosensor with routine sampling, and 118/141 (83.7% [76.5%-89.4%]) with OP-N sampling. Specificities were >99%, and positive and negative predictive values >95%, for all tests in most analyses. 61.3% of false negative Ag-RDT participants returned for testing within 14 days (median of 3 days, interquartile range 3) of whom 90.3% tested positive.ConclusionsThe overall sensitivities of the three Ag-RDTs were 68.6%-75.0%, increasing to at least 85.6% after the viral load cut-off was applied. For SD-Biosensor, the diagnostic accuracy with OP-N and NP sampling was comparable. Over 55% of false negative Ag-RDT participants tested positive during follow-up.

Background Acute otitis media is a painful infection of the middle ear that is commonly seen in children. In some children, the eardrum spontaneously bursts, discharging visible pus (otorrhoea) into the outer ear. Objective To compare the clinical effectiveness of immediate topical antibiotics or delayed oral antibiotics with the clinical effectiveness of immediate oral antibiotics in reducing symptom duration in children presenting to primary care with acute otitis media with discharge and the economic impact of the alternative strategies. Design This was a pragmatic, three-arm, individually randomised (stratified by age Setting A total of 44 English general practices. Participants Children aged ≥ 12 months and Interventions (1) Immediate ciprofloxacin (0.3%) solution, four drops given three times daily for 7 days, or (2) delayed ‘dose-by-age’ amoxicillin suspension given three times daily (clarithromycin twice daily if the child was penicillin allergic) for 7 days, with structured delaying advice. All parents were given standardised information regarding symptom management (paracetamol/ibuprofen/fluids) and advice to complete the course. Comparator Immediate ‘dose-by-age’ oral amoxicillin given three times daily (or clarithromycin given twice daily) for 7 days. Parents received standardised symptom management advice along with advice to complete the course. Main outcome measure Time from randomisation to the first day on which all symptoms (pain, fever, being unwell, sleep disturbance, otorrhoea and episodes of distress/crying) were rated ‘no’ or ‘very slight’ problem (without need for analgesia). Methods Participants were recruited from routine primary care appointments. The planned sample size was 399 children. Follow-up used parent-completed validated symptom diaries. Results Delays in software deployment and configuration led to small recruitment numbers and trial closure at the end of the internal pilot. Twenty-two children (median age 5 years; 62% boys) were randomised: five, seven and 10 to immediate oral, delayed oral and immediate topical antibiotics, respectively. All children received prescriptions as randomised. Seven (32%) children fully adhered to the treatment as allocated. Symptom duration data were available for 17 (77%) children. The median (interquartile range) number of days until symptom resolution in the immediate oral, delayed oral and immediate topical antibiotic arms was 6 (4–9), 4 (3–7) and 4 (3–6), respectively. Comparative analyses were not conducted because of small numbers. There were no serious adverse events and six reports of new or worsening symptoms. Qualitative clinician interviews showed that the trial question was important. When the platform functioned as intended, it was liked. However, staff reported malfunctioning software for long periods, resulting in missed recruitment opportunities. Troubleshooting the software placed significant burdens on staff. Limitations The over-riding weakness was the failure to recruit enough children. Conclusions We were unable to answer the main research question because of a failure to reach the required sample size. Our experience of running an electronic platform-supported trial in primary care has highlighted challenges from which we have drawn recommendations for the National Institute for Health Research (NIHR) and the research community. These should be considered before such a platform is used again. Trial registration Current Controlled Trials ISRCTN12873692 and EudraCT 2017-003635-10. Funding This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 67. See the NIHR Journals Library website for further project information.

Objective To assess the diagnostic test accuracy of two rapid antigen tests in asymptomatic and presymptomatic close contacts of people with SARS-CoV-2 infection on day 5 after exposure. Design Prospective cross sectional study. Setting Four public health service covid-19 test sites in the Netherlands. Participants 4274 consecutively included close contacts (identified through test-and-trace programme or contact tracing app) aged 16 years or older and asymptomatic for covid-19 when requesting a test. Main outcome measures Sensitivity, specificity, and positive and negative predictive values of Veritor System (Beckton Dickinson) and Biosensor (Roche Diagnostics) rapid antigen tests, with reverse-transcriptase polymerase chain reaction (RT-PCR) testing as reference standard. The viral load cut-off above which 95% of people with a positive RT-PCR test result were virus culture positive was used as a proxy of infectiousness. Results Of 2678 participants tested with Veritor, 233 (8.7%) had a RT-PCR confirmed SARS-CoV-2 infection of whom 149 were also detected by the rapid antigen test (sensitivity 63.9%, 95% confidence interval 57.4% to 70.1%). Of 1596 participants tested with Biosensor, 132 (8.3%) had a RT-PCR confirmed SARS-CoV-2 infection of whom 83 were detected by the rapid antigen test (sensitivity 62.9%, 54.0% to 71.1%). In those who were still asymptomatic at the time of sampling, sensitivity was 58.7% (51.1% to 66.0%) for Veritor (n=2317) and 59.4% (49.2% to 69.1%) for Biosensor (n=1414), and in those who developed symptoms were 84.2% (68.7% to 94.0%; n=219) for Veritor and 73.3% (54.1% to 87.7%; n=158) for Biosensor. When a viral load cut-off was applied for infectiouness (≥5.2 log10 SARS-CoV-2 E gene copies/mL), the overall sensitivity was 90.1% (84.2% to 94.4%) for Veritor and 86.8% (78.1% to 93.0%) for Biosensor, and 88.1% (80.5% to 93.5%) for Veritor and 85.1% (74.3% to 92.6%) for Biosensor, among those who remained asymptomatic throughout. Specificities were >99%, and positive and negative predictive values were >90% and >95%, for both rapid antigen tests in all analyses. Conclusions The sensitivities of both rapid antigen tests in asymptomatic and presymptomatic close contacts tested on day 5 onwards after close contact with an index case were more than 60%, increasing to more than 85% after a viral load cut-off was applied as a proxy for infectiousness.

BACKGROUND: Of children with acute otitis media (AOM), 15%-20% present with acute onset ear discharge due to a spontaneous perforation of the tympanic membrane (AOMd). This review aims to quantify the prevalence and antimicrobial resistance (AMR) status of bacteria in children with AOMd in the pneumococcal conjugate vaccine (PCV) era.METHODS: Systematic searches were performed in PubMed, EMBASE and Cochrane Library from inception to June 7, 2019. Two reviewers extracted relevant data and assessed risk of bias independently. All English studies reporting any prevalence and/or AMR data of bacterial middle ear isolates from children with AOMd were included. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal checklist.RESULTS: Of 4088 unique records retrieved, 19 studies (10,560 children) were included. Overall quality was judged good. Streptococcus pneumoniae (median 26.1%, range 9.1%-47.9%), Haemophilus influenzae (median 18.8%, range 3.9%-55.3%), Staphylococcus aureus (median 12.3%, range 2.3%-34.9%) and Streptococcus pyogenes (median 11.8%, range 1.0%-30.9%) were the most prevalent bacteria. In 76.0% (median, range 48.7%-100.0%, 19 studies, 1,429 children) any bacterium was identified. AMR data were sparse and mainly limited to S. pneumoniae. We found no evidence of a clear shift in the prevalence of bacteria and AMR over time.CONCLUSIONS: In children with AOMd, S. pneumoniae and H. influenzae are the 2 predominant bacteria, followed by S. aureus and S. pyogenes in the post-PCV era. AMR data are sparse and no clearly change over time was observed. Ongoing surveillance of the microbiology profile in children with AOMd is warranted to guide antibiotic selection and to assess the impact of children's PCV status.

BackgroundPre-/asymptomatic close contacts of SARS-CoV-2 infected individuals were tested at day 5 after contact by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Diagnostic accuracy of antigen-detecting rapid diagnostic tests (Ag-RDT) in pre-/asymptomatic close contacts was up till now unknown.MethodsWe performed a prospective cross-sectional diagnostic test accuracy study. Close contacts (e.g. selected via the test-and-trace program or contact tracing app) aged ≥16 years and asymptomatic when requesting a test, were included consecutively and tested at day 5 at four Dutch public health service test sites. We evaluated two Ag-RDTs (BD Veritor™ System Ag-RDT (BD), and Roche/SD Biosensor Ag-RDT (SD-B)) with RT-PCR as the reference standard. Virus culture was performed in RT-PCR positive individuals to determine the viral load cut-off above which 95% was culture positive, as a proxy of infectiousness.ResultsOf 2,678 BD-tested individuals, 233 (8.7%) were RT-PCR positive and BD detected 149 (sensitivity 63.9%; 95% confidence interval 57.4%-70.1%). Out of 1,596 SD-B-tested individuals, 132 (8.3%) were RT-PCR positive and SD-B detected 83 (sensitivity 62.9%; 54.0%-71.1%). When applying an infectiousness viral load cut-off ≥ 5.2 log10 gene copies/mL, the sensitivity was 90.1% (84.2%-94.4%) for BD, 86.8% (78.1% to 93.0%) for SD-B overall, and 88.1% (80.5%-93.5%) for BD, 85.1% (74.3%-92.6%) for SD-B for those still asymptomatic at the actual time of sampling. Specificity was >99% for both Ag-RDTs in all analyses.ConclusionsThe sensitivity for detecting SARS-CoV-2 of both Ag-RDTs in pre-/asymptomatic close contacts is over 60%, increasing to over 85% after applying an infectiousness viral load cut-off.Trial registration numberNot applicable. A study protocol is available upon request.

In 2020, the COVID-19 pandemic brought dramatic changes in the delivery of primary health care across the world, presumably changing the number of consultations for infectious diseases and antibiotic use. We aimed to assess the impact of the pandemic on infections and antibiotic prescribing in Dutch primary care. All patients included in the routine health care database of the Julius General Practitioners’ Network were followed from March through May 2019 (n = 389,708) and March through May 2020 (n = 405,688). We extracted data on consultations for respiratory/ear, urinary tract, gastrointestinal and skin infections using the International Classification of Primary Care (ICPC) codes. These consultations were combined in disease episodes and linked to antibiotic prescriptions. The numbers of infectious disease episodes (total and those treated with antibiotics), complications, and antibiotic prescription rates (i.e., proportion of episodes treated with antibiotics) were calculated and compared between the study periods in 2019 and 2020. Fewer episodes were observed during the pandemic months than in the same months in 2019 for both the four infectious disease entities and complications such as pneumonia, mastoiditis and pyelonephritis. The largest decline was seen for gastrointestinal infections (relative risk (RR), 0.54, confidence interval (CI), 0.51 to 0.58) and skin infections (RR, 0.71, CI, 0.67 to 0.75). The number of episodes treated with antibiotics declined as well, with the largest decrease seen for respiratory/ear infections (RR, 0.54, CI, 0.52 to 0.58). The antibiotic prescription rate for respiratory/ear infections declined from 21% to 13% (difference −8.0% (CI, −8.8 to −7.2)), yet the prescription rates for other infectious disease entities remained similar or increased slightly. The decreases in primary care infectious disease episodes and antibiotic use were most pronounced in weeks 15–19, mid-COVID-19 wave, after an initial peak in respiratory/ear infection presentation in week 11, the first week of lock-down. In conclusion, our findings indicate that the COVID-19 pandemic has had profound effects on the presentation of infectious disease episodes and antibiotic use in primary care in the Netherlands. Consequently, the number of infectious disease episodes treated with antibiotics decreased. We found no evidence of an increase in complications.

IntroductionAcute rhinosinusitis (ARS) is a prime reason for doctor visits and among the conditions with highest antibiotic overprescribing rates in adults. To reduce inappropriate prescribing, we aim to predict the absolute benefit of antibiotic treatment for individual adult patients with ARS by applying multivariable risk prediction methods to individual patient data (IPD) of multiple randomised placebo-controlled trials.Methods and analysisThis is an update and re-analysis of a 2008 IPD meta-analysis on antibiotics for adults with clinically diagnosed ARS. First, the reference list of the 2018 Cochrane review on antibiotics for ARS will be reviewed for relevant studies published since 2008. Next, the systematic searches of CENTRAL, MEDLINE and Embase of the Cochrane review will be updated to 1 September 2020. Methodological quality of eligible studies will be assessed using the Cochrane Risk of Bias 2 tool. The primary outcome is cure at 8–15 days. Regression-based methods will be used to model the risk of being cured based on relevant predictors and treatment, while accounting for clustering. Such model allows for risk predictions as a function of treatment and individual patient characteristics and hence gives insight into individualised absolute benefit. Candidate predictors will be based on literature, clinical reasoning and availability. Calibration and discrimination will be evaluated to assess model performance. Resampling techniques will be used to assess internal validation. In addition, internal–external cross-validation procedures will be used to inform on between-study differences and estimate out-of-sample model performance. Secondarily, we will study possible heterogeneity of treatment effect as a function of outcome risk.Ethics and disseminationIn this study, no identifiable patient data will be used. As such, the Medical Research Involving Humans Subject Act (WMO) does not apply and official ethical approval is not required. Results will be submitted for publication in international peer-reviewed journals.PROSPERO registration numberCRD42020220108.

What you need to know Acute middle ear infection, otherwise known as acute otitis media, affects children in their early years. One in two children has had three episodes by age 3.12 It is characterised by middle ear effusion and ear pain or fever.3 More than one third of preschool children consulted a doctor for earache or ear discharge in a large prospective cohort study in England (13 617 children).4 Accurate diagnosis of acute otitis media can be challenging in young children.5 It tends to be overdiagnosed in primary care and can lead to unnecessary use of antibiotics.678 Recent changes in the delivery of primary care, brought about because of covid-19,9 have shown that not all children with suspected acute otitis media need to be managed in a healthcare setting. Indeed, a multidisciplinary panel of UK nurses, general practitioners, and emergency department consultants agreed that systemically well children with ear pain could be managed at home initially without primary care input. …

BackgroundPain management in acute otitis media (AOM) is often suboptimal, potentially leading to unnecessary discomfort, GP reconsultation, and antibiotic prescribing.AimTo assess the effectiveness of a GP-targeted educational intervention to improve pain management in children with AOM.Design and settingPragmatic, cluster randomised controlled trial (RCT). GPs in 37 practices (intervention n = 19; control n = 18) across the Netherlands recruited 224 children with GP-confirmed AOM and ear pain (intervention n = 94; control n = 130) between February 2015 and May 2018.MethodGPs in practices allocated to the intervention group were trained (online and face-to-face) to discuss pain management with parents using an information leaflet, and prompted to prescribe weight-appropriate dosed paracetamol. Ibuprofen was additionally prescribed if pain control was still insufficient. GPs in the control group provided usual care.ResultsMean ear pain scores over the first 3 days were similar between groups (4.66 versus 4.36; adjusted mean difference = −0.05; 95% confidence intervals [CI] = −0.93 to 0.83), whereas analgesic use, in particular ibuprofen, was higher in the intervention group. The total number of antibiotic prescriptions during the 28-day follow-up was similar (mean rate 0.43 versus 0.47; adjusted rate ratio [aRR] 0.97; 95% CI = 0.68 to 1.38). Parents of children in the intervention group were more likely to reconsult for AOM-related complaints (mean rate 0.70 versus 0.41; aRR 1.73; 95% CI = 1.14 to 2.62).ConclusionAn intervention aimed at improving pain management for AOM increases analgesic use, particularly ibuprofen, but does not provide symptomatic benefit. GPs are advised to carefully weigh the potential benefits of ibuprofen against its possible harms.

Objective To summarize recent advances in knowledge on otitis media (OM) and quality of life (QoL) and development by synthesizing relevant research in this field published between June 1., 2015 until June 1., 2019. Data sources Systematic searches of PubMed, Embase and the Cochrane Library using predefined database-specific syntaxes. Review methods Articles selected were randomized controlled trials and observational studies with an adequate control group estimating treatment effects of OM including acute OM (AOM), recurrent AOM (RAOM), OM with effusion (OME), chronic OM (COM) and chronic suppurative OM (CSOM). Items included were Health Status, Health Status Indicators, Quality of Life, Functional Status, Specific Learning Disorder, Developmental Disabilities, Language Development Disorders, and Problem Behavior. Results The electronic database searches yielded a total of 699 records. After screening titles and abstracts, we identified 34 potentially eligible articles. Of these, 18 were excluded. This left 15 articles suitable for inclusion. Conclusions Although evidence is accumulating that OM may significantly impair children's QoL and development as well as caregiver's QoL, studies on this topic are relatively scarce and vary substantially in terms of methodological quality and outcome measurement instruments (OMI) used. In this review, studies have used 10 different OMIs capturing a wide range of OM symptoms as well as generic and disease-specific QoL outcomes. OM was associated with negative effects on auditory processing, language and speech development, school readiness, social competence, psychosocial wellbeing, and sleep. We found only four relevant randomized controlled trials, which mostly failed to demonstrate superiority of interventions in terms of QoL improvement and reports on reversibility are lacking. This underpins the urgent need for high quality studies in this field using validated and uniform OMIs. To facilitate interpretation and harmonization of study findings, we suggest and support the development of a core outcome set for the various OM entities that should include the most reliable and meaningful QoL and developmental OMIs.

Background Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is a rare clinical syndrome of unknown cause usually identified in children. Tonsillectomy is considered a potential treatment option for this syndrome. This is an update of a Cochrane Review first published in 2010 and previously updated in 2014. Objectives To assess the effectiveness and safety of tonsillectomy (with or without adenoidectomy) compared with non‐surgical treatment in the management of children with PFAPA. Search methods The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2019, Issue 4); PubMed; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 15 October 2019. Selection criteria Randomised controlled trials comparing tonsillectomy (with or without adenoidectomy) with non‐surgical treatment in children with PFAPA. Data collection and analysis We used the standard methodological procedures expected by Cochrane. The primary outcomes were the proportion of children whose symptoms have completely resolved and complications of surgery (haemorrhage and number of days of postoperative pain). Secondary outcomes were: number of episodes of fever and the associated symptoms; severity of episodes; use of corticosteroids; absence or time off school; quality of life. We used GRADE to assess the certainty of the evidence for each outcome. Main results Two trials were included with a total of 67 children randomised (65 analysed); we judged both to be at low risk of bias. One trial of 39 participants recruited children with PFAPA syndrome diagnosed according to rigid, standard criteria. The trial compared adenotonsillectomy to watchful waiting and followed up patients for 18 months. A smaller trial of 28 children applied less stringent criteria for diagnosing PFAPA and probably also included participants with alternative types of recurrent pharyngitis. This trial compared tonsillectomy alone to no treatment and followed up patients for six months. Combining the trial results suggests that patients with PFAPA likely experience less fever and less severe episodes after surgery compared to those receiving no surgery. The risk ratio (RR) for immediate resolution of symptoms after surgery that persisted until the end of follow‐up was 4.38 (95% confidence interval (CI) 0.64 to 30.11); number needed to treat to benefit (NNTB) = 2, calculated based on an estimate that 156 in 1000 untreated children have a resolution) (moderate‐certainty evidence). Both trials reported that there were no complications of surgery. However, the numbers of patients randomly allocated to surgery (19 and 14 patients respectively) were too small to detect potentially important complications such as haemorrhage. Surgery probably results in a large overall reduction in the average number of episodes over the total length of follow‐up (rate ratio 0.08, 95% CI 0.05 to 0.13), reducing the average frequency of PFAPA episodes from one every two months to slightly less than one every two years (moderate‐certainty evidence). Surgery also likely reduces severity, as indicated by the length of PFAPA symptoms during these episodes. One study reported that the average number of days per PFAPA episode was 1.7 days after receiving surgery, compared to 3.5 days in the control group (moderate‐certainty evidence). The evidence suggests that the proportion of patients requiring corticosteroids was also lower in the surgery group compared to those receiving no surgery (RR 0.58, 95% CI 0.37 to 0.92) (low‐certainty evidence). Other outcomes such as absence from school and quality of life were not measured or reported. Authors' conclusions The evidence for the effectiveness of tonsillectomy in children with PFAPA syndrome is derived from two small randomised controlled trials. These trials reported significant beneficial effects of surgery compared to no surgery on immediate and complete symptom resolution (NNTB = 2) and a substantial reduction in the frequency and severity (length of episode) of any further symptoms experienced. However, the evidence is of moderate certainty (further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate) due to the relatively small sample sizes of the studies and some concerns about the applicability of the results. Therefore, the parents and carers of children with PFAPA syndrome must weigh the risks and consequences of surgery against the alternative of using medications. It is well established that children with PFAPA syndrome recover spontaneously and medication can be administered to try and reduce the severity of individual episodes. It is uncertain whether adenoidectomy combined with tonsillectomy adds any additional benefit to tonsillectomy alone.

Samenvatting Thuismeting van zuurstofsaturatie bij COVID-19-patiënten neemt momenteel een vlucht in de huisartsenpraktijk. Het is een praktisch middel om patiënten thuis te monitoren. De validiteit van de saturatiemetingen vormt echter een punt van zorg. Daarnaast verdient wetenschappelijke onderbouwing van de toegevoegde waarde van thuismeting van zuurstofsaturatie meer aandacht. Zeker met het oog op mogelijke klinische vervolgstappen naar substitutie van zorg in de thuisbehandeling van COVID-19-patiënten.

Background Despite recent clinical guideline development, the best pathway of care for children with symptoms of obstructive sleep-disordered breathing (oSDB) is still debated. This systematic review aims to map the research in childhood oSDB that has been conducted so far to support further guideline development, identify evidence gaps, and guide future research. Methods A systematic search was performed in PubMed, EMBASE, and the Cochrane Library from inception to November 26, 2015. All publications on childhood oSDB were included, irrespective of type and language. The annual number of publications in the field of oSDB was counted over all years; for those published since January 1, 2011 (ie, the date of the latest literature search of the American Academy of Pediatrics guideline), total and annual numbers of publications across main research themes and methodologies were calculated. Results Of the 7,637 unique records retrieved, 5,871 publications were eligible for inclusion. There was an increase in annual publications since 2000, with 46% published since 2011. Most publications (61%) focused on individual treatment modalities, incidence, or prognosis. Few publications (2.7%) focused on health service delivery, outcomes, and health economics. Observational studies composed 78.5% of publications, 2.4% were randomized controlled trials, and 0.4% used a qualitative approach as their main methodology. Conclusions A recent surge in research activity into childhood oSDB has improved the knowledge base for this condition; however, the lack of health services, health economics, and outcomes research impacts the applicability of evidence informing current guidance and leaves important questions for future research. Registration PROSPERO: registration number CRD42015029291