{"id":10537,"date":"2026-04-09T13:26:11","date_gmt":"2026-04-09T13:26:11","guid":{"rendered":"https:\/\/www.proefschriftmaken.nl\/portfolio\/saskia-hullegie\/"},"modified":"2026-04-23T07:25:25","modified_gmt":"2026-04-23T07:25:25","slug":"saskia-hullegie","status":"publish","type":"us_portfolio","link":"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/saskia-hullegie\/","title":{"rendered":"Saskia Hullegie"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"","protected":false},"author":8,"featured_media":12612,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"us_portfolio_category":[45],"class_list":["post-10537","us_portfolio","type-us_portfolio","status-publish","has-post-thumbnail","hentry","us_portfolio_category-new-template"],"acf":{"naam_van_het_proefschift":"Incidence, microbiology and management of acute otitis media and ear discharge in primary care","samenvatting":"Otitis media acuta (OMA), ofwel acute middenoorontsteking, is \u00e9\u00e9n van de meest voorkomende kinderinfecties en een belangrijke oorzaak van doktersbezoeken en antibioticumvoorschriften wereldwijd. Ongeveer 15-20% van de kinderen met een OMA presenteert zich met een acuut loopoor door een spontane perforatie van het trommelvlies. In tegenstelling tot wat vaak gedacht wordt, is een acuut ontstaan loopoor geen teken dat een OMA episode op zijn retour is. Kinderen met een OMA en een acuut loopoor hebben dezelfde mate van oorpijn en voelen zich bij de eerste presentatie vaak slechter dan kinderen zonder een loopoor. Ook hebben kinderen met OMA en een loopoor een hogere ziektelast met meer oorpijn en\/of koorts na 3-7 dagen en meer OMA-recidieven en gehoorproblemen na 3 maanden vergeleken met kinderen zonder een loopoor. Er is weinig literatuur beschikbaar over de meest voorkomende otopathogenen en de meest optimale behandeling van kinderen met OMA en een loopoor. Het hoofddoel van dit proefschrift was daarom om inzicht te krijgen in de incidentie, microbiologie en behandeling van OMA met een loopoor in de eerste lijn.\n\nIn hoofdstuk 2.1 worden de resultaten beschreven van een groot retrospectief cohortonderzoek in de eerste lijn naar de impact van de COVID-19-pandemie op de incidentie van otitis media bij kinderen in Nederland. Daartoe is routine zorgdata verzameld over OMA, otitis media met effusie (OME), looporen en bijbehorende antibioticumvoorschriften van alle kinderen in de leeftijd van 0-12 jaar die v\u00f3\u00f3r (1 maart 2019 - 29 februari 2020) en tijdens de COVID-19-pandemie (1 maart 2020 - 28 februari 2021) ingeschreven waren bij huisartsenpraktijken verbonden aan het Julius Huisartsen Netwerk (JHN). Huisartsbezoeken voor OMA, OME en looporen bij kinderen daalden tijdens de COVID-19 pandemie met respectievelijk 63%, 57% en 54%. Het aantal antibioticumvoorschriften voor otitis media was tijdens de pandemie vergelijkbaar met voorheen, wat erop wijst dat de mix van pati\u00ebnten in de eerstelijnszorg niet substantieel was veranderd. Dit suggereert dat de tijdens de COVID-19 pandemie ingevoerde maatregelen om besmettingen te voorkomen resulteerden in een daadwerkelijke daling van de otitis media incidentie bij kinderen.\n\nHoofdstuk 2.2 beschrijft een onderzoek naar de incidentie en de behandeling van OMA bij volwassenen in de eerste lijn. Hiertoe werd gebruikt gemaakt van de routine zorgdata van alle pati\u00ebnten van 15 jaar en ouder die van 2015 tot 2018 ingeschreven waren bij huisartsenpraktijken verbonden aan JHN. We hebben gegevens verzameld over OMA-episodes, OMA-gerelateerde consulten, co-morbiditeiten en antibioticumvoorschriften. In totaal werden 6.667 OMA-episodes bij 5.358 volwassen pati\u00ebnten (gemiddeld 1.2 OMA-episode per pati\u00ebnt) ge\u00efdentificeerd, resulterend in een totale OMA-incidentie van 5.3\/1000 persoonsjaren. Dit incidentiecijfer was redelijk stabiel over de bestudeerde jaren.","summary":"Topical or oral antibiotics in childhood AOMd: a randomised controlled non-inferiority trial\n\nDiscussion\n\nDue to early termination of the trial non-inferiority of antibiotic-corticosteroid eardrops to oral antibiotics could not be determined in children with AOMd. In our small group of 58 children, we found that those assigned to eardrops had lower resolution rates of ear pain and fever at 3 days, longer parent-reported ear discharge, and slightly higher mean ear pain scores over days 1-3 compared to those receiving oral antibiotics, but they received fewer oral antibiotic courses in three months and had less GI upset and rash.\n\nStrengths and limitations\nThis is the first report on the comparative effectiveness evidence of antibiotic-corticosteroid eardrops versus oral antibiotic treatment in children with AOM presenting with ear discharge. The pragmatic design of the trial and high rate of data-completeness support applicability of its findings to routine daily practice.\n\nSome limitations deserve further attention. Accrual to our trial was affected by a temporary closure due to study medication supply issues. When this was resolved the COVID-19 pandemic complicated trial recruitment and accrual did not recover after the pandemic restrictions were lifted. This phenomenon has affected many trials worldwide. Further, our non-blinded design could potentially have introduced detection bias. However, detection bias is unlikely to have significantly impacted our findings since we compared two active treatments and \u2013 based on our parent panel input \u2013 parents do not have strong preferences for one over the other treatment. Also, a double dummy design would have hampered the applicability of trial results to everyday practice.\n\nWe chose hydrocortisone-bacitracin-colistin eardrops because they are widely used in the Netherlands and France, do not contain a potentially ototoxic aminoglycoside, cover the most important pathogens involved in AOM and have been proven effective in children with ventilation tubes who present with acute ear discharge. They are however not available in many countries. Despite absence of evidence, we believe that any combination of antibiotic-corticosteroid eardrops with a similar antimicrobial profile, like a quinolone-containing eardrops plus dexamethasone, would have yielded comparable results.\n\nComparison with existing literature\nWe initiated this trial after establishing superiority of antibiotic-corticosteroid eardrops over oral antibiotics in children with ventilation tubes who present with acute ear discharge. Our current findings in a small sample of children without ventilation tubes who present with AOMd indicate that these findings cannot be extrapolated to this patient population. While there is a patent passage between ear canal and the middle ear in children with ventilation tubes, the spontaneous eardrum perforation in children with AOMd may close too early to allow antibiotic-corticosteroid eardrops to completely resolve the middle ear inflammation.\n\nDuring the preparation of our trial we collaborated with the UK based team developing the REST (Runny Ear Study, trial registry number ISRCTN287PS92) addressing the same topic. We harmonised design and outcomes to enable future meta-analysis. This trial however was also terminated early due to issues with its electronic health record system platform and no formal statistical analysis was performed on its sample of 22 children.\n\nImplications for research and practice\nWe were unable to determine non-inferiority of antibiotic-corticosteroid eardrops to oral antibiotics, but our findings in a small group of children, requiring confirmation, suggest that oral antibiotics may be more effective in resolving symptoms and shortening the duration of ear discharge than antibiotic-corticosteroid eardrops in children with AOMd. That must be balanced against the findings that eardrops are associated with reasonable symptom control, fewer total oral antibiotic courses and less systemic side effects in case there is non-inferiority. Since we were unable to demonstrate non-inferiority of antibiotic-corticosteroid eardrops to oral antibiotics in children with AOMd, current guidelines\u2019 recommendation that clinicians can consider oral antibiotics in this group of children are not unreasonable, but must be balanced against the major public health threat of antibiotic resistance.\n\nSupplementary Table 1. Disease specific quality of life assessed with the otitis media-6 questionnaire at baseline, at 2 weeks and 3 months follow up\n\nDifference in change score \u00b1 Eardrops vs oral Abx \u0394 T2-T3 (p): 0.76 (p =0.207), -0.57 (p= 0.234), -0.08 (p = 0.793), -0.01 (p = 0.988), 0.15 (p = 0.764), 0.29 (p = 0.581), 0.11 (p= 0.773), 0.42 (p = 0.864), -0.78 (p = 0.283)\n\nOral Abx \u0394 T2-T3 (SD): 2.6 (2.39), 1.7 (1.69), 0.6 (0.97), 2.4 (1.72), 2.2 (1.73), 1.8 (1.92), 1.9 (1.47), 11.2 (8.80), 3.8 (2.23)\n\nChange score * Eardrops \u0394 T2-T3 (SD): 3.4 (1.66), 1.1 (1.52), 0.5 (1.07), 2.4 (1.64), 2.3 (1.69), 2.1 (1.59), 2.0 (1.22), 11.6 (7.63), 3.0 (2.56)\n\nDifference in change score \u00b1 Eardrops vs oral Abx \u0394 T0-T2 (p): -1.19 (p=0.006), 0.71 (p = 0.127), 0.07 (p = 0.831), -0.63 (p= 0.097), -0.33 (p= 0.385), -0.55 (p = 0.149), -0.36 (p = 0.164), -1.73 (p = 0.246), -0.32 (p = 0.585)\n\nOral Abx \u0394 T0-T2 (SD): 1.3 (1.39), -0.7 (1.69), -0.2 (1.43), 1.1 (1.14), 0.8 (1.42), 0.9 (1.54), 0.54 (0.91), 3.3 (5.49), 0.7 (1.92)\n\nChange score * Eardrops \u0394 T0-T2 (SD): 0.1 (1.68), 0.0 (1.71), -0.2 (0.82), 0.5 (1.6), 0.5 (1.42), 0.4 (1.29), 0.19 (0.98), 1.5 (5.50), 0.4 (2.32)\n\nMonth 3 (n=48)\nOral Abx mean (SD): 2.2 (1.44), 2.1 (1.37), 1.6 (0.69), 1.9 (1.03), 1.9 (0.93), 2.1 (1.20), 2.0 (0.99), 11.7 (5.96), 7.8 (2.09)\nEardrops mean (SD): 1.9 (1.29), 2.0 (1.40), 1.7 (1.34), 1.9 (0.97), 1.9 (1.09), 2.1 (1.45), 1.9 (1.11), 11.4 (6.68), 7.8 (2.09)\n\nOral Abx; oral antibiotics; \u00b01-7: higher scores indicating more of a problem. *Change score between time points, a positive score indicates deterioration. A score < 0.5 indicates trivial change; 0.5 - 0.9 small change, 1.0 - 1.4 moderate change; and > 1.5 large change; \u00b1 using independent t-test.\n\nWeek 2 (n=56)\nOral Abx mean (SD): 4.6 (1.63), 3.7 (1.8), 2.0 (1.13), 4.3 (1.3), 3.9 (1.3), 3.8 (1.4), 3.7 (1.11), 22.2 (6.67), 5.1 (1.92)\nEardrops mean (SD): 5.1 (1.68), 3.1 (1.90), 2.2 (1.41), 4.3 (1.67), 4.1 (1.62), 4.1 (1.3), 3.9 (1.33), 22.8 (7.54), 4.8 (1.55)\n\nBaseline (n=57)\nOral Abx mean (SD): 5.9 (1.26), 3.0 (2.05), 1.8 (1.20), 5.4 (1.23), 4.7 (1.42), 4.7 (1.37), 4.3 (0.95), 25.5 (5.68), 4.4 (1.89)\nEardrops mean (SD): 5.2 (1.68), 3.2 (1.83), 2.1 (1.23), 4.8 (1.77), 4.6 (1.79), 4.7 (1.42), 4.1 (1.24), 24.3 (7.43), 4.4 (2.21)\n\nRange of scores: 1 to 7, 1 to 7, 1 to 7, 1 to 7, 1 to 7, 1 to 7, 1 to 7, 6 to 42, 0 to 10\nQuestionnaire items: Physical suffering, Hearing loss, Speech impairment, Emotional distress, Activity limitations, Caregivers concerns, Mean symptom score, Total score, Visual analog score","auteur":"Saskia Hullegie","auteur_slug":"saskia-hullegie","publicatiedatum":"18 september 2024","taal":"NL","url_flipbook":"https:\/\/ebook.proefschriftmaken.nl\/ebook\/saskiahullegie?iframe=true","url_download_pdf":"","url_epub":"","ordernummer":"FTP-202604091322","isbn":"978-94-6510-020-3","doi_nummer":"","naam_universiteit":"Universiteit Utrecht","afbeeldingen":12612,"naam_student:":"","binnenwerk":"","universiteit":"Universiteit Utrecht","cover":"","afwerking":"","cover_afwerking":"","design":""},"_links":{"self":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/10537","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio"}],"about":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/types\/us_portfolio"}],"author":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/comments?post=10537"}],"version-history":[{"count":1,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/10537\/revisions"}],"predecessor-version":[{"id":10540,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/10537\/revisions\/10540"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media\/12612"}],"wp:attachment":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media?parent=10537"}],"wp:term":[{"taxonomy":"us_portfolio_category","embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio_category?post=10537"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}