Paracetamol (acetaminophen) or non-steroidal anti-inflammatory drugs, alone or combined, for pain relief in acute otitis media in children.

BACKGROUND: Acute otitis media (AOM) is one of the most common childhood infectious diseases. Pain is the key symptom of AOM and central to children's and parents' experience of the illness. Because antibiotics provide only marginal benefits, analgesic treatment including paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs (NSAIDs) is regarded as the cornerstone of AOM management. This is an update of a review first published in 2016. OBJECTIVES: Our primary objective was to assess the effectiveness of paracetamol (acetaminophen) or NSAIDs, alone or combined, compared with placebo or no treatment in relieving pain in children with AOM. Our secondary objective was to assess the effectiveness of NSAIDs as compared with paracetamol in children with AOM. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 5, April 2023; MEDLINE (Ovid, from 1946 to May 2023), Embase (from 1947 to May 2023), CINAHL (from 1981 to May 2023), LILACS (from 1982 to May 2023), and Web of Science Core Collection (from 1955 to May 2023). We searched the WHO ICTRP and ClinicalTrials.gov for completed and ongoing trials (23 May 2023). SELECTION CRITERIA: We included randomised controlled trials comparing the effectiveness of paracetamol or NSAIDs, alone or combined, for pain relief in non-hospitalised children aged six months to 16 years with AOM. We also included trials of paracetamol or NSAIDs, alone or combined, for children with fever or upper respiratory tract infections if we were able to extract subgroup data on pain relief in children with AOM either directly or after obtaining additional data from study authors. We extracted and summarised data for the following comparisons: paracetamol versus placebo, NSAIDs versus placebo, NSAIDs versus paracetamol, and NSAIDs plus paracetamol versus paracetamol alone. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We rated the overall certainty of evidence for each outcome of interest using the GRADE approach. MAIN RESULTS: We included four trials (411 children) which were assessed at low to high risk of bias. Paracetamol versus placebo Data from one trial (148 children) informed this comparison. Paracetamol may be more effective than placebo in relieving pain at 48 hours (proportion of children with pain 10% versus 25%, risk ratio (RR) 0.38, 95% confidence interval (CI) 0.17 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) 7; low-certainty evidence). The evidence is very uncertain about the effects of paracetamol on fever at 48 hours (RR 1.03, 95% CI 0.07 to 16.12; very low-certainty evidence) and adverse events (RR 1.03, 95% CI 0.21 to 4.93; very low-certainty evidence). No data were available for our other outcomes of interest. NSAIDs versus placebo Data from one trial (146 children) informed this comparison. Ibuprofen may be more effective than placebo in relieving pain at 48 hours (proportion of children with pain 7% versus 25%, RR 0.28, 95% CI 0.11 to 0.70; NNTB 6; low-certainty evidence). The evidence is very uncertain about the effect of ibuprofen on fever at 48 hours (RR 1.06, 95% CI 0.07 to 16.57; very low-certainty evidence) and adverse events (RR 1.76, 95% CI 0.44 to 7.10; very low-certainty evidence). No data were available for our other outcomes of interest. NSAIDs versus paracetamol Data from four trials (411 children) informed this comparison. The evidence is very uncertain about the effect of ibuprofen versus paracetamol in relieving ear pain at 24 hours (RR 0.83, 95% CI 0.59 to 1.18; 2 RCTs, 39 children; very low-certainty evidence); 48 to 72 hours (RR 0.91, 95% CI 0.54 to 1.54; 3 RCTs, 183 children; low-certainty evidence); and four to seven days (RR 0.74, 95% CI 0.17 to 3.23; 2 RCTs, 38 children; very low-certainty evidence). The evidence is very uncertain about the effect of ibuprofen versus paracetamol on mean pain score at 24 hours (0.29 lower, 95% CI 0.79 lower to 0.20 higher; 3 RCTs, 111 children; very low-certainty evidence); 48 to 72 hours (0.25 lower, 95% CI 0.66 lower to 0.16 higher; 3 RCTs, 108 children; very low-certainty evidence); and four to seven days (0.30 higher, 95% CI 1.78 lower to 2.38 higher; 2 RCTs, 31 children; very low-certainty evidence). The evidence is very uncertain about the effect of ibuprofen versus paracetamol in resolving fever at 24 hours (RR 0.69, 95% CI 0.24 to 2.00; 2 RCTs, 39 children; very low-certainty evidence); 48 to 72 hours (RR 1.18, 95% CI 0.31 to 4.44; 3 RCTs, 182 children; low-certainty evidence); and four to seven days (RR 2.75, 95% CI 0.12 to 60.70; 2 RCTs, 39 children; very low-certainty evidence). The evidence is very uncertain about the effect of ibuprofen versus paracetamol on adverse events (RR 1.71, 95% CI 0.43 to 6.90; 3 RCTs, 281 children; very low-certainty evidence); reconsultations (RR 1.13, 95% CI 0.92 to 1.40; 1 RCT, 53 children; very low-certainty evidence); and delayed antibiotic prescriptions (RR 1.32, 95% CI 0.74 to 2.35; 1 RCT, 53 children; very low-certainty evidence). No data were available on time to resolution of pain. NSAIDs plus paracetamol versus paracetamol alone Data on the effectiveness of ibuprofen plus paracetamol versus paracetamol alone came from two trials that provided crude subgroup data for 71 children with AOM. The small sample provided imprecise effect estimates, therefore we were unable to draw any firm conclusions (very low-certainty evidence). AUTHORS' CONCLUSIONS: Despite explicit guideline recommendations on the use of analgesics in children with AOM, the current evidence on the effectiveness of paracetamol or NSAIDs, alone or combined, in children with AOM is limited. Paracetamol and ibuprofen as monotherapies may be more effective than placebo in relieving short-term ear pain in children with AOM. The evidence is very uncertain for the effect of ibuprofen versus paracetamol on relieving short-term ear pain in children with AOM, as well as for the effectiveness of ibuprofen plus paracetamol versus paracetamol alone, thereby preventing any firm conclusions. Further research is needed to provide insights into the role of ibuprofen as adjunct to paracetamol, and other analgesics such as anaesthetic eardrops, for children with AOM.

Pneumococcal conjugate vaccines for preventing acute otitis media in children.

BACKGROUND: Prior to introducing pneumococcal conjugate vaccines (PCVs), Streptococcus pneumoniae was most commonly isolated from the middle ear fluid of children with acute otitis media (AOM). Reducing nasopharyngeal colonisation of this bacterium by PCVs may lead to a decline in AOM. The effects of PCVs deserve ongoing monitoring since studies from the post-PCV era report a shift in causative otopathogens towards non-vaccine serotypes and other bacteria. This updated Cochrane Review was first published in 2002 and updated in 2004, 2009, 2014, and 2019. OBJECTIVES: To assess the effect of PCVs in preventing AOM in children up to 12 years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, Web of Science, and two trials registers, ClinicalTrials.gov and WHO ICTRP, to 11 June 2020. SELECTION CRITERIA: Randomised controlled trials of PCV versus placebo or control vaccine. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. The primary outcomes were frequency of all-cause AOM and adverse effects. Secondary outcomes included frequency of pneumococcal AOM and frequency of recurrent AOM (defined as three or more AOM episodes in six months or four or more in one year). We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included 15 publications of 11 trials (60,733 children, range 74 to 37,868 per trial) of 7- to 11-valent PCVs versus control vaccines (meningococcus type C vaccine in three trials, and hepatitis A or B vaccine in eight trials). We included one additional publication of a previously included trial for this 2020 update. We did not find any relevant trials with the newer 13-valent PCV. Most studies were funded by pharmaceutical companies. Overall, risk of bias was low. In seven trials (59,415 children), PCVs were administered in early infancy, whilst four trials (1318 children) included children aged one year and over who were either healthy or had a history of respiratory illness. There was considerable clinical heterogeneity across studies, therefore we reported results from individual studies. PCV administered in early infancy PCV7 The licenced 7-valent PCV with CRM197 as carrier protein (CRM197-PCV7) was associated with a 6% (95% confidence interval (CI) -4% to 16%; 1 trial; 1662 children) and 6% (95% CI 4% to 9%; 1 trial; 37,868 children) relative risk reduction (RRR) in low-risk infants (moderate-certainty evidence), but was not associated with a reduction in all-cause AOM in high-risk infants (RRR -5%, 95% CI -25% to 12%). PCV7 with the outer membrane protein complex of Neisseria meningitidis serogroup B as carrier protein (OMPC-PCV7) was not associated with a reduction in all-cause AOM (RRR -1%, 95% CI -12% to 10%; 1 trial; 1666 children; low-certainty evidence). CRM197-PCV7 and OMPC-PCV7 were associated with 20% (95% CI 7% to 31%) and 25% (95% CI 11% to 37%) RRR in pneumococcal AOM, respectively (2 trials; 3328 children; high-certainty evidence), and CRM197-PCV7 with 9% (95% CI -12% to 27%) and 10% (95% CI 7% to 13%) RRR in recurrent AOM (2 trials; 39,530 children; moderate-certainty evidence). PHiD-CV10/11 The effect of a licenced 10-valent PCV conjugated to protein D, a surface lipoprotein of Haemophilus influenzae, (PHiD-CV10) on all-cause AOM in healthy infants varied from 6% (95% CI -6% to 17%; 1 trial; 5095 children) to 15% (95% CI -1% to 28%; 1 trial; 7359 children) RRR (low-certainty evidence). PHiD-CV11 was associated with 34% (95% CI 21% to 44%) RRR in all-cause AOM (1 trial; 4968 children; moderate-certainty evidence). PHiD-CV10 and PHiD-CV11 were associated with 53% (95% CI 16% to 74%) and 52% (95% CI 37% to 63%) RRR in pneumococcal AOM (2 trials; 12,327 children; high-certainty evidence), and PHiD-CV11 with 56% (95% CI -2% to 80%) RRR in recurrent AOM (1 trial; 4968 children; low-certainty evidence). PCV administered at a later age PCV7 We found no evidence of a beneficial effect on all-cause AOM of administering CRM197-PCV7 in children aged 1 to 7 years with a history of respiratory illness or frequent AOM (2 trials; 457 children; moderate-certainty evidence) and CRM197-PCV7 combined with a trivalent influenza vaccine in children aged 18 to 72 months with a history of respiratory tract infections (1 trial; 597 children; moderate-certainty evidence). CRM197-PCV9 In 1 trial including 264 healthy daycare attendees aged 1 to 3 years, CRM197-PCV9 was associated with 17% (95% CI -2% to 33%) RRR in parent-reported all-cause otitis media (very low-certainty evidence). Adverse events Nine trials reported on adverse effects (77,389 children; high-certainty evidence). Mild local reactions and fever were common in both groups, and occurred more frequently in PCV than in control vaccine groups: redness (< 2.5 cm): 5% to 20% versus 0% to 16%; swelling (< 2.5 cm): 5% to 12% versus 0% to 8%; and fever (< 39 °C): 15% to 44% versus 8% to 25%. More severe redness (> 2.5 cm), swelling (> 2.5 cm), and fever (> 39 °C) occurred less frequently (0% to 0.9%, 0.1% to 1.3%, and 0.4% to 2.5%, respectively) in children receiving PCV, and did not differ significantly between PCV and control vaccine groups. Pain or tenderness, or both, was reported more frequently in PCV than in control vaccine groups: 3% to 38% versus 0% to 8%. Serious adverse events judged to be causally related to vaccination were rare and did not differ significantly between groups, and no fatal serious adverse event judged causally related to vaccination was reported. AUTHORS' CONCLUSIONS: Administration of the licenced CRM197-PCV7 and PHiD-CV10 during early infancy is associated with large relative risk reductions in pneumococcal AOM. However, the effects of these vaccines on all-cause AOM is far more uncertain based on low- to moderate-certainty evidence. We found no evidence of a beneficial effect on all-cause AOM of administering PCVs in high-risk infants, after early infancy, and in older children with a history of respiratory illness. Compared to control vaccines, PCVs were associated with an increase in mild local reactions (redness, swelling), fever, and pain and/or tenderness. There was no evidence of a difference in more severe local reactions, fever, or serious adverse events judged to be causally related to vaccination.

Pneumococcal conjugate vaccines for preventing acute otitis media in children.

BACKGROUND: Prior to introducing pneumococcal conjugate vaccines (PCVs), Streptococcus pneumoniae was most commonly isolated from middle ear fluid of children with acute otitis media (AOM). Reducing nasopharyngeal colonisation of this bacterium by PCVs may lead to a decline in AOM. The effects of PCVs deserve ongoing monitoring since studies from the post-PCV era report a shift in causative otopathogens towards non-vaccine serotypes and other bacteria. This updated Cochrane Review was first published in 2002 and updated in 2004, 2009, and 2014. The review title was changed (to include the population, i.e. children) for this update. OBJECTIVES: To assess the effect of PCVs in preventing AOM in children up to 12 years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, Web of Science, and trials registers (ClinicalTrials.gov and WHO ICTRP) to 29 March 2019. SELECTION CRITERIA: Randomised controlled trials of PCV versus placebo or control vaccine. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. The primary outcomes were frequency of all-cause AOM and adverse effects. Secondary outcomes included frequency of pneumococcal AOM and frequency of recurrent AOM (defined as three or more AOM episodes in six months or four or more in one year). We used GRADE to assess the quality of the evidence. MAIN RESULTS: We included 14 publications of 11 trials (60,733 children, range 74 to 37,868 per trial) of 7- to 11-valent PCVs versus control vaccines (meningococcus type C vaccine in three trials, and hepatitis A or B vaccine in eight trials). We included two additional trials for this update. We did not find any relevant trials with the newer 13-valent PCV. Most studies were funded by pharmaceutical companies. Overall, risk of bias was low. In seven trials (59,415 children) PCVs were administered in early infancy, while four trials (1318 children) included children aged one year and over who were either healthy or had a history of respiratory illness. There was considerable clinical heterogeneity across studies, therefore we did not perform meta-analyses.Adverse eventsNine trials reported on adverse effects (77,389 children; high-quality evidence). Mild local reactions and fever were common in both groups, and occurred more frequently in PCV than in control vaccine groups: redness (< 2.5 cm): 5% to 20% versus 0% to 16%; swelling (< 2.5 cm): 5% to 12% versus 0% to 8%; and fever (< 39 °C): 15% to 44% versus 8% to 25%. More severe redness (> 2.5 cm), swelling (> 2.5 cm), and fever (> 39 °C) occurred less frequently (0% to 0.9%, 0.1% to 1.3%, and 0.4% to 2.5%, respectively in children receiving PCV) and did not differ significantly between PCV and control vaccine groups. Pain or tenderness, or both was reported more frequently in PCV than in control vaccine groups: 3% to 38% versus 0% to 8%. Serious adverse events judged causally related to vaccination were rare and did not differ significantly between groups, and no fatal serious adverse event judged causally related to vaccination was reported.PCV administered in early infancyPCV7The effect of a licenced 7-valent PCV with CRM197 as carrier protein (CRM197-PCV7) on all-cause AOM varied from -5% (95% confidence interval (CI) -25% to 12%) relative risk reduction (RRR) in high-risk infants (1 trial; 944 children; moderate-quality evidence) to 6% (95% CI -4% to 16%; 1 trial; 1662 children) and 6% (95% CI 4% to 9%; 1 trial; 37,868 children) RRR in low-risk infants (high-quality evidence). PCV7 with the outer membrane protein complex of Neisseria meningitidis serogroup B as carrier protein (OMPC-PCV7), was not associated with a reduction in all-cause AOM (RRR -1%, 95% CI -12% to 10%; 1 trial; 1666 children; high-quality evidence).CRM197-PCV7 and OMPC-PCV7 were associated with 20% (95% CI 7% to 31%) and 25% (95% CI 11% to 37%) RRR in pneumococcal AOM, respectively (2 trials; 3328 children; high-quality evidence) and CRM197-PCV7 with 9% (95% CI -12% to 27%) to 10% (95% CI 7% to 13%) RRR in recurrent AOM (2 trials; 39,530 children; high-quality evidence).PHiD-CV10/11The effect of a licenced 10-valent PCV conjugated to protein D, a surface lipoprotein of Haemophilus influenzae, (PHiD-CV10) on all-cause AOM varied from 6% (95% CI -6% to 17%; 1 trial; 5095 children) to 15% (95% CI -1% to 28%; 1 trial; 7359 children) RRR in healthy infants (moderate-quality evidence). PHiD-CV11 was associated with 34% (95% CI 21% to 44%) RRR in all-cause AOM (1 trial; 4968 children; high-quality evidence).PHiD-CV10 and PHiD-CV11 were associated with 53% (95% CI 16% to 74%) and 52% (95% CI 37% to 63%) RRR in pneumococcal AOM (2 trials; 12,327 children; high-quality evidence) and PHiD-CV11 with 56% (95% CI -2% to 80%) RRR in recurrent AOM (1 trial; 4968 children; moderate-quality evidence).PCV administered at later agePCV7We found no evidence of a beneficial effect on all-cause AOM of administering CRM197-PCV7 in children aged 1 to 7 years with a history of respiratory illness or frequent AOM (2 trials; 457 children; high-quality evidence) and CRM197-PCV7 combined with a trivalent influenza vaccine in children aged 18 to 72 months with a history of respiratory tract infections (1 trial; 597 children; high-quality evidence).CRM197-PCV9In 1 trial including 264 healthy day-care attendees aged 1 to 3 years, CRM197-PCV9 was associated with 17% (95% CI -2% to 33%) RRR in parent-reported all-cause OM (low-quality evidence). AUTHORS' CONCLUSIONS: Administration of the licenced CRM197-PCV7 and PHiD-CV10 during early infancy is associated with large relative risk reductions in pneumococcal AOM. However, the effects of these vaccines on all-cause AOM is far more uncertain. We found no evidence of a beneficial effect on all-cause AOM of administering PCVs in high-risk infants, after early infancy (i.e. in children one year and above), and in older children with a history of respiratory illness. Compared to control vaccines, PCVs were associated with an increase in mild local reactions (redness, swelling), fever, and pain and/or tenderness. We found no evidence of a difference in more severe local reactions, fever, or serious adverse events judged causally related to vaccination.

Facilitators and barriers to brokering between research and care by senior clinical-scientists in general practice and elderly care medicine.

BACKGROUND: Clinician-scientists (CSs) are physicians who work in daily care and have an academic role in research or education. They may act as knowledge brokers and help to connect research and clinical practice. There is no data available on CSs' brokering activities and the perceived barriers and facilitators to optimising their role in general practice (GP) and elderly care medicine (EM). AIM: To identify the brokering activities of CSs in these fields and the barriers and facilitators they come across whilst sharing knowledge and connecting people in research and frontline health care. DESIGN AND SETTING: Qualitative interview study among 17 Dutch senior CSs. METHOD: Interview data were audio recorded, transcribed verbatim and thematic interpretative analysis was used to identify themes. RESULTS: CSs facilitate collaboration between researchers and practitioners. They exchange knowledge on both sides, make use of extensive networks and constantly and actively involve care in research and research in care. CSs come across barriers as well as facilitators that influence their brokering activities. Some barriers and facilitators are at the individual level, other are related more to the job context and workplace. CONCLUSIONS: This study reveals barriers to overcome and facilitators to develop related to the brokering role of CSs. To make the best use of CSs, brokering activities and the added value of CSs should be recognised and supported. Awareness of what CSs need to function effectively in demanding work settings could be important for the future impact of the role on the fields of GP and EM.

Paracetamol (acetaminophen) or non-steroidal anti-inflammatory drugs, alone or combined, for pain relief in acute otitis media in children.

BACKGROUND: Acute otitis media (AOM) is one of the most common childhood infectious diseases and a significant reason for antibiotic prescriptions in children worldwide. Pain from middle ear infection and pressure behind the eardrum is the key symptom of AOM. Ear pain is central to children's and parents' experience of the illness. Because antibiotics provide only marginal benefits, analgesic treatment including paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs (NSAIDs) is regarded as the cornerstone of AOM management in children. OBJECTIVES: Our primary objective was to assess the effectiveness of paracetamol (acetaminophen) or NSAIDs, alone or combined, compared with placebo or no treatment in relieving pain in children with AOM. Our secondary objective was to assess the effectiveness of NSAIDs compared with paracetamol in children with AOM. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 7, July 2016; MEDLINE (Ovid, from 1946 to August 2016), Embase (from 1947 to August 2016), CINAHL (from 1981 to August 2016), LILACS (from 1982 to August 2016) and Web of Science (from 1955 to August 2016) for published trials. We screened reference lists of included studies and relevant systematic reviews for additional trials. We searched WHO ICTRP, ClinicalTrials.gov, and the Netherlands Trial Registry (NTR) for completed and ongoing trials (search date 19 August 2016). SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the effectiveness of paracetamol or NSAIDs, alone or combined, for pain relief in children with AOM. We also included trials of paracetamol or NSAIDs, alone or combined, for children with fever or upper respiratory tract infections (URTIs) if we were able to extract subgroup data on pain relief in children with AOM either directly or after obtaining additional data from study authors. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed methodological quality of the included trials and extracted data. We used the GRADE approach to rate the overall quality of evidence for each outcome of interest. MAIN RESULTS: We included three RCTs (327 children) which were assessed at low to moderate risk of bias.One RCT included 219 children with AOM, and used a three-arm, parallel group, double-blind design to compare paracetamol versus ibuprofen versus placebo. All children also received antibiotics and those with fever > 39 °C could have received paracetamol (30 mg to 60 mg) additionally to the studied treatments.Another RCT involved 156 febrile children (26 of whom had AOM). The study design was a three-arm, parallel group, double-blind design and compared paracetamol versus ibuprofen versus ibuprofen plus paracetamol.The third RCT included 889 children with respiratory tract infections (82 of whom had AOM). This study applied a 3 x 2 x 2 factorial, open-label design and compared paracetamol versus ibuprofen versus ibuprofen plus paracetamol. Study participants were randomised to one of the three treatment groups as well as two dosing groups (regular versus as required) and two steam inhalation groups (steam versus no steam).Authors of two RCTs provided crude subgroup data on children with AOM. We used data from the remaining trial to inform comparison of paracetamol versus placebo (148 children) and ibuprofen versus placebo (146 children) assessments. Data from all included RCTs informed comparison of ibuprofen versus paracetamol (183 children); data from the two RCTs informed comparison of ibuprofen plus paracetamol versus paracetamol alone (71 children).We found evidence, albeit of low quality, that both paracetamol and ibuprofen as monotherapies were more effective than placebo in relieving pain at 48 hours (paracetamol versus placebo: proportion of children with pain 10% versus 25%, RR 0.38, 95% CI 0.17 to 0.85; number needed to treat to benefit (NNTB) 7; ibuprofen versus placebo: proportion of children with pain 7% versus 25%, RR 0.28, 95% CI 0.11 to 0.70; NNTB 6). Very low quality evidence suggested that adverse events did not significantly differ between children treated with either paracetamol, ibuprofen or placebo.We found insufficient evidence of a difference between ibuprofen and paracetamol in relieving ear pain at 24 hours (2 RCTs, 39 children; RR 0.83, 95% CI 0.59 to 1.18; very low quality evidence), 48 to 72 hours (3 RCTs, 183 children; RR 0.91, 95% CI 0.54 to 1.54; low quality evidence) and four to seven days (2 RCTs, 38 children; RR 0.74, 95% CI 0.17 to 3.23; very low quality evidence).Data on the effectiveness of ibuprofen plus paracetamol versus paracetamol alone came from two RCTs that provided crude subgroup data for 71 children with AOM. The small sample provided imprecise effect estimates and we were consequently unable to draw any firm conclusions (very low quality evidence). AUTHORS' CONCLUSIONS: Despite explicit guideline recommendations on its use, current evidence on the effectiveness of paracetamol or NSAIDs, alone or combined, in relieving pain in children with AOM is limited. Low quality evidence indicates that both paracetamol and ibuprofen as monotherapies are more effective than placebo in relieving short-term ear pain in children with AOM. There is insufficient evidence of a difference between ibuprofen and paracetamol in relieving short-term ear pain in children with AOM, whereas data on the effectiveness of ibuprofen plus paracetamol versus paracetamol alone were insufficient to draw any firm conclusions. Further research is needed to provide insights into the role of ibuprofen as adjunct to paracetamol, and other analgesics such as anaesthetic eardrops, for children with AOM.

Impact of early daycare on healthcare resource use related to upper respiratory tract infections during childhood: prospective WHISTLER cohort study.

BACKGROUND: Daycare attendance is an established risk factor for upper respiratory tract infections (URTI) and acute otitis media (AOM). Whether this results in higher use of healthcare resources during childhood remains unknown. We aim to assess the effect of first year daycare attendance on the timing and use of healthcare resources for URTI and AOM episodes during early childhood. METHODS: In the Wheezing-Illnesses-STudy-LEidsche-Rijn birth cohort, 2,217 children were prospectively followed up to age six years. Children were categorized according to first-year daycare attendance (yes versus no) and age at entry when applicable (age 0 to 2 months, 3 to 5 months and 6 to 12 months). Information on general practitioner (GP) diagnosed URTI and AOM, GP consultations, antibiotic prescriptions and specialist referral was collected from medical records. Daycare attendance was recorded by monthly questionnaires during the first year of life. RESULTS: First-year daycare attendees and non-attendees had similar total six-year rates of GP-diagnosed URTI and AOM episodes (59/100 child-years, 95% confidence interval 57 to 61 versus 56/100 child-years, 53 to 59). Daycare attendees had more GP-diagnosed URTI and AOM episodes before the age of one year and fewer beyond the age of four years than non-attendees (Pinteraction <0.001). Daycare attendees had higher total six-year rates for GP consultation (adjusted rate ratio 1.15, 1.00 to 1.31) and higher risk for specialist referrals (hazard ratio: 1.43, 1.01 to 2.03). The number of antibiotic prescriptions in the first six years of life was only significantly increased among children who entered daycare between six to twelve months of age (rate ratio 1.32, 1.04 to 1.67). This subgroup of child-care attendees also had the highest overall URTI and AOM incidence rates, GP consultation rates and risk for specialist referral. CONCLUSIONS: Children who enter daycare in the first year of life, have URTI and AOM at an earlier age, leading to higher use of healthcare resources compared to non-attendees, especially when entering daycare between six to twelve months. These findings emphasize the need for improved prevention strategies in daycare facilities to lower infection rates at the early ages.

Panel 5: Impact of otitis media on quality of life and development.

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.

Accuracy of telephone triage in primary care patients with chest discomfort: a cross-sectional study.

OBJECTIVE: To assess the accuracy of semi-automatic assisted telephone triage in patients with acute chest discomfort against the diagnosis of acute coronary syndrome (ACS) or other life-threatening events (LTEs). METHODS: A cross-sectional study was performed of telephone conversations with 2023 patients with acute chest discomfort (pain, pressure, tightness or discomfort) who called out-of-hours services for primary care (OHS-PC) between 2014 and 2016. Sensitivity, specificity, positive and negative predicted values were calculated for a high urgency (patient seen within one hour) against the diagnoses of ACS and other LTEs. Diagnoses were retrieved from the patients' medical records in general practice, including hospital specialists' discharge letters. RESULTS: Of 2023 patients who called because of chest discomfort, 227 (11.2%) had an ACS (men 14.9%, women 8.2%) and 58 (2.9%) had another LTE (men 3.6%, women 2.3%). The sensitivity and specificity of a high Netherlands Triage System (NTS) urgency allocation against ACS/other LTEs were 0.73 (95% CI 0.68 to 0.78) and 0.43 (95% CI 0.40 to 0.45), respectively. In 13.2% of the calls the triage nurse overruled the NTS urgency, mostly by upscaling (11.0%). The sensitivity and specificity of the final urgency allocation were 0.86 (95% CI 0.81 to 0.90) and 0.34 (95% CI 0.32 to 0.37). The positive and negative predictive values of the final urgency were 0.18 (95% CI 0.17 to 0.19) and 0.94 (95% CI 0.92 to 0.95), respectively. CONCLUSIONS: The semi-automatic triage NTS tool underestimated the urgency in 27% of patients with ACS/other LTEs. Overruling by triage nurses improved safety, but still 14% of men and women with ACS/other LTEs received too low urgency, while efficiency remained poor. TRIAL REGISTRATION NUMBER: NTR7331.

Improving pain management in childhood acute otitis media in general practice: a cluster randomised controlled trial of a GP-targeted educational intervention.

BACKGROUND: Pain management in acute otitis media (AOM) is often suboptimal, potentially leading to unnecessary discomfort, GP reconsultation, and antibiotic prescribing. AIM: To assess the effectiveness of a GP-targeted educational intervention to improve pain management in children with AOM. DESIGN AND SETTING: Pragmatic, 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. METHOD: GPs 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. RESULTS: Mean 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). CONCLUSION: An 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.

Is the time of calling helpful for differentiating transient ischaemic attack and stroke from mimics in primary care out-of-hours services? A cross-sectional study.

OBJECTIVES: Telephone triage of patients suspected of transient ischaemic attack (TIA) or stroke is challenging. Both TIA and stroke more likely occur during daytime, with a peak in the morning hours. Thus, the time of calling might be a helpful determinant during telephone triage. We assessed the time of calling in patients with stroke-like symptoms who called the out-of-hours services in primary care (OHS-PC), and evaluated whether the time of calling differed between patients with TIA or stroke compared with those with mimics. DESIGN: Cross-sectional study. SETTING: Six OHS-PC locations in the Netherlands. PARTICIPANTS: 1269 telephone triage recordings of patients calling the OHS-PC because of stroke-like symptoms. We collected information on patient characteristics, symptoms, time of calling and urgency allocation. The final diagnosis related to each triage call was based on letters from the neurologist (retrieved from the patient's general practitioner). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measures were the time of calling hourly and 4 hourly, and the risk of TIA or stroke/hour. The secondary outcome measure was the risk ratio of TIA or stroke in the morning (08:00-12:00h) versus other hours. RESULTS: Mean age was 68.6 (SD±18.5) years, 56.9% were women and 50.0% had a TIA or stroke. The risk ratio of TIA or stroke among people calling with stroke-like symptoms between 08:00-12:00h versus other hours was 1.13 (95% CI 1.00 to 1.28, p=0.070). After correction for age and sex, the adjusted risk ratio was 0.94 (95% CI 0.80 to 1.10, p=0.434). CONCLUSION: In patients who called the OHS-PC because of stroke-like symptoms, the time of calling did not differ between patients with TIA or stroke and patients with mimics. TRIAL REGISTRATION NUMBER: The Netherlands National Trial Registry (NTR7331).

Optimisation of telephone triage of callers with symptoms suggestive of acute cardiovascular disease in out-of-hours primary care: observational design of the Safety First study.

INTRODUCTION: In the Netherlands, the 'Netherlands Triage Standard' (NTS) is frequently used as digital decision support system for telephone triage at out-of-hours services in primary care (OHS-PC). The aim of the NTS is to guarantee accessible, efficient and safe care. However, there are indications that current triage is inefficient, with overestimation of urgency, notably in suspected acute cardiovascular disease. In addition, in primary care settings the NTS has only been validated against surrogate markers, and diagnostic accuracy with clinical outcomes as the reference is unknown. In the Safety First study, we address this gap in knowledge by describing, understanding and improving the diagnostic process and urgency allocation in callers with symptoms suggestive of acute cardiovascular disease, in order to improve both efficiency and safety of telephone triage in this domain. METHODS AND ANALYSIS: An observational study in which 3000 telephone triage recordings (period 2014-2016) will be analysed. Information is collected from the recordings including caller and symptom characteristics and urgency allocation. The callers' own general practitioners are contacted for the final diagnosis of each contact. We included recordings of callers with symptoms suggestive of acute coronary syndrome (ACS) or transient ischaemic attack (TIA)/stroke. With univariable and multivariable logistic regression analyses the diagnostic accuracy of caller and symptom characteristics will be analysed in terms of predictive values with urgency level, and ACS and TIA/stroke as outcomes, respectively. To further improve our understanding of the triage process at OHS-PC, we will carry out additional studies applying both quantitative and qualitative methods: (i) case-control study on serious adverse events (SAE), (ii) conversation analysis study and (iii) interview study with triage nurses. ETHICS AND DISSEMINATION: The Medical Ethics Committee Utrecht, the Netherlands endorsed this study (National Trial Register identification: NTR7331). Results will be disseminated at scientific conferences, regional educational sessions and publication in peer-reviewed journals.

Challenges in measuring interprofessional-interorganisational collaboration with a questionnaire.

BACKGROUND: Collaboration between medical professionals from separate organisations is necessary to deliver good patient care. This care is influenced by professionals' perceptions about their collaboration. Until now, no instrument to measure such perceptions was available in the Netherlands. A questionnaire developed and validated in Spain was translated to assess perceptions about clinicians' collaboration in primary and secondary care in the Dutch setting. AIM: Validation in the Dutch setting of a Spanish questionnaire that aimed to assess perceptions of clinicians about interorganisational collaboration. DESIGN & SETTING: After translation, cultural adaptation, and pre-testing, the questionnaire was sent to GPs and secondary care clinicians (SCCs) in three regions in the Netherlands. The responses of 445 responders were used to assess the validity and reliability of the questionnaire. METHOD: A confirmatory factor analysis (CFA) and an exploratory factor analysis (EFA) were performed to study the construct validity of the hypothesised factor model underlying the questionnaire. Test-retest reliability was evaluated using weighted Kappa statistics. RESULTS: Results of the CFA indicated poor fit of the hypothesised factor structure. EFA, executed separately for each region, showed a highly unstable factor structure. The test-retest reliability analysis demonstrated low re-test reliability. CONCLUSION: The underlying factor structure of a Spanish questionnaire could not be reproduced. The construct validity and reliability of this questionnaire were insufficient to warrant use in the Dutch setting. This study demonstrates the need for evaluating validity and reliability of questionnaires in local settings.

Pain management in acute otitis media: a qualitative study exploring GPs' views and expectations parallel to a trial of an educational intervention.

BACKGROUND: Optimal pain management is accepted as the cornerstone of acute otitis media (AOM) management, but analgesics are neither prescribed routinely nor explicitly recommended in day-to-day practice. AIM: To explore GPs views on and expectations regarding pain management in children with AOM, and how a multifaceted educational intervention aimed at optimising pain management shapes these perceptions. DESIGN & SETTING: Qualitative study conducted alongside a cluster randomised controlled trial (cRCT), the PIMPOM study, in the Netherlands. METHOD: Twelve GPs were purposefully sampled from primary care centres allocated to the intervention group and were interviewed, using semi-structured, audio-recorded interviews. The intervention comprised a blended GP educational programme (internet-based and face-to-face training) aimed at discussing pain management proactively with parents using a parent information leaflet, and prescribing paracetamol and ibuprofen according to current guidelines. Interviews were transcribed verbatim and analysed thematically by a multidisciplinary team. RESULTS: GPs considered AOM a very painful condition. Initially, GPs felt unable to offer adequate treatment for AOM-related ear pain. The intervention provided tools, such as knowledge, communication skills, and an information leaflet, which reduced their feelings of helplessness and empowered them to manage childhood AOM more adequately. GPs indicated that the intervention led to a shift in focus from treating the infection with antibiotics to treating symptoms with analgesics. There was a general lack of knowledge about the possibility of prescribing ibuprofen to children. GPs expressed mixed views on prescribing this drug to children. CONCLUSION: A primary-care based multifaceted educational intervention aimed at optimising pain management in childhood AOM offered GPs tools to optimise management of this condition and changed GPs perceptions, namely from treating the infection with antibiotics to treating symptoms.

Diagnostic delay of pulmonary embolism in primary and secondary care: a retrospective cohort study.

BACKGROUND: Delayed diagnosis of pulmonary embolism (PE) is common because symptoms can be non-specific. The few studies that have investigated diagnostic delay have not taken into account the role of primary care physicians in the diagnostic process. AIM: To document and quantify the stages of diagnostic delay of PE and to identify clinical factors associated with this delay. DESIGN AND SETTING: A retrospective cohort study conducted in Zwolle and its surroundings in the Netherlands. METHOD: Primary and secondary care records of all patients diagnosed with PE between January 2008 and December 2009 were reviewed for dates of symptom onset, date of presentation and diagnosis, and for clinical findings. Relationships between delay and clinical parameters were tested using multivariate regression analysis. RESULTS: The 261 patients enrolled in the study had an average total delay of 8.6 days. Patient delay (4.2 days average) and delay in primary care (3.9 days) were the major contributors to this delay. Chest pain (odds ratio [OR] 0.51, 95% confidence interval [CI] = 0.28 to 0.92, P = 0.03) and symptoms of deep venous thrombosis (calf pain) (OR 0.49, 95% CI = 0.24 to 0.98, P = 0.05) were associated with an early diagnosis. Patient delay was shorter in patients with chest pain (OR 0.49, 95% CI = 0.25 to 0.95, P = 0.03) and longer in patients with dyspnoea (OR 2.95, 95% CI = 0.99 to 8.85, P = 0.05). In primary care, chest pain (OR 0.37, 95% CI = 0.17 to 0.84, P = 0.02) and rales (OR 0.22, 95% CI = 0.06 to 0.83, P = 0.03) were associated with an early referral, whereas comorbidity led to a delayed referral. CONCLUSION: This study shows that the diagnostic delay of PE is substantial, especially patient delay and delay in primary care. There is room to reduce this delay by increasing the awareness of both patients and GPs. Further research is needed on clinical factors that raise suspicion of PE in primary care.

Poor Performance Among Trainees in a Dutch Postgraduate GP Training Program.

BACKGROUND AND OBJECTIVES: Poor performance among trainees is an important issue, for patient safety and economic reasons. While early identification might enhance remediation measures, we explored the frequency, nature, and risk factors of poor performance in a Dutch postgraduate general practitioner (GP) training program. METHODS: All trainees who started the GP training between 2005 and 2007 were included. Multivariate logistic regression analysis was applied to examine associations between individual characteristics; early assessments of competencies and knowledge, training process characteristics (eg, illness, maternal leave), and the outcome poor performance; sub-analyses were performed for each year. RESULTS: A total of 215 trainees started the 3-year GP program, and 49 (22.8%) exhibited poor performance (in one or more years). In the first and second years, problem areas among poor performers were equally distributed across the roles of "medical expert," "communicator," and "professional." In the third year, shortcomings in "professionalism" were the most common problem. Increasing age was a risk factor for poor performance as were insufficient scores in communication and knowledge. Poor performance in the previous year was a risk factor for poor performance in the second and third years; OR=4.20 (CI=1.31--13.47) and OR=5.40 (CI=1.58--18.47), respectively. CONCLUSIONS: Poor performance is prevalent but primarily occurring within a single training year. This finding suggests that trainees are capable of solving trainee problems. Increasing age, insufficient assessment scores early in the training, and poor performance in a previous year constitute risk factors for poor performance.