Prevalence and Antimicrobial Resistance of Bacteria in Children With Acute Otitis Media and Ear Discharge: A Systematic Review.

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

Acuut loopoor: niet laten lopen = Acute ear discharge, a reason for consultation

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

Effectiveness of analgesic ear drops as add-on treatment to oral analgesics in children with acute otitis media: study protocol of the OPTIMA pragmatic randomised controlled trial

INTRODUCTION: Ear 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 ANALYSIS: This 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 DISSEMINATION: The 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 REGISTRATION: The 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

Topical or oral antibiotics for children with acute otitis media presenting with ear discharge: study protocol of a randomised controlled non-inferiority trial

BACKGROUND: Around 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 ANALYSIS: A 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 DISSEMINATION: The 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 NUMBER: The Netherlands National Trial Register; NTR6723. Date of registration: 27 November 2017

A Strong Decline in the Incidence of Childhood Otitis Media During the COVID-19 Pandemic in the Netherlands

Introduction: Recent reports have highlighted the impact of the COVID-19 pandemic on the incidence of infectious disease illnesses and antibiotic use. This study investigates the effect of the pandemic on childhood incidence of otitis media (OM) and associated antibiotic prescribing in a large primary care-based cohort in the Netherlands. / Material and Methods: Retrospective observational cohort study using routine health care data from the Julius General Practitioners’ Network (JGPN). All children aged 0-12 registered in 62 practices before the COVID-19 pandemic (1 March 2019 - 29 February 2020) and/or during the pandemic (1 March 2020 - 28 February 2021) were included. Data on acute otitis media (AOM), otitis media with effusion (OME), ear discharge episodes and associated antibiotic prescriptions were extracted. Incidence rates per 1,000 child years (IR), incidence rate ratios (IRR) and incidence rate differences (IRD) were compared between the two study periods. / Results: OM episodes declined considerably during the COVID-19 pandemic: IR pre-COVID-19 vs COVID-19 for AOM 73.7 vs 27.1 [IRR 0.37]; for OME 9.6 vs 4.1 [IRR 0.43]; and for ear discharge 12.6 vs 5.8 [IRR 0.46]. The absolute number of AOM episodes in which oral antibiotics were prescribed declined accordingly (IRD pre-COVID-19 vs COVID-19: -22.4 per 1,000 child years), but the proportion of AOM episodes with antibiotic prescription was similar in both periods (47% vs 46%, respectively). / Discussion: GP consultation for AOM, OME and ear discharge declined by 63%, 57% and 54% respectively in the Netherlands during the COVID-19 pandemic. Similar antibiotic prescription rates before and during the pandemic indicate that the case-mix presenting to primary care did not considerably change. Our data therefore suggest a true decline as a consequence of infection control measures introduced during the pandemic

PROPHETIC EU: Prospective Identification of Pneumonia in Hospitalized Patients in the Intensive Care Unit in European and United States Cohorts

Background The prospective identification of patients at high risk for hospital-acquired/ventilator-associated bacterial pneumonia may improve clinical trial feasibility and foster antibacterial development. In a prior study conducted in the United States, clinical criteria were used to prospectively identify these patients; however, these criteria have not been applied in a European population. Methods Adults considered high risk for pneumonia (treatment with ventilation or high levels of supplemental oxygen) in the intensive care units of 7 European hospitals were prospectively enrolled from June 12 to December 27, 2017. We estimated the proportion of high-risk patients developing pneumonia according to US Food and Drug Administration guidance and a subset potentially eligible for antibacterial trial enrollment. We compared patient characteristics, treatment exposures, and pneumonia incidence in a European cohort and a previously described US cohort. Results Of 888 high-risk patients, 211/888 (24%) were treated for possible pneumonia, and 150/888 (17%) met the Food and Drug Administration definition for hospital-acquired/ventilator-associated bacterial pneumonia. A higher proportion of European patients treated for possible pneumonia met the pneumonia definition (150/211 [71%] vs 537/1464 [37%]; P < .001). Among patients developing pneumonia, a higher proportion of European patients met antibacterial trial eligibility criteria (124/150 [83%] vs 371/537 [69%]; P < .001). Conclusions Clinical criteria prospectively identified high-risk patients with high rates of pneumonia in the European cohort. Despite higher rates of established risk factors and incident pneumonia, European patients were significantly less likely to receive antibiotics for possible pneumonia than US patients. Different treatment practices may contribute to lower rates of antibacterial trial enrollment in the United States

The Necessity of Self-Employment Towards Retirement: Evidence from Labor Market Dynamics and Search Requirements for Unemployment Benefits

Hervorming Sociale Regelgevin

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707