Qualitative study on shared decision making in cystitis management in general practice.

BACKGROUND: Cystitis are commonly treated with antibiotics, although non-antibiotic options could be considered for healthy non-pregnant women. Shared decision making (SDM) can be used in cystitis management to discuss the various treatment options but is not frequently applied in general practice. AIM: Identifying barriers and facilitators for applying SDM in cystitis management in general practice. DESIGN & SETTING: Qualitative explorative research in general practice with healthcare professionals (HCPs; general practitioners (GPs) and GP assistants) and healthy non-pregnant women with a recent history of cystitis (patients). METHOD: Individual semi-structured interviews were conducted between May and October 2022. We applied a combination of thematic and framework analysis. RESULTS: Ten GPs, seven GP assistants, and fifteen patients were interviewed. We identified three main barriers and one key facilitator: 1) applying SDM is deemed inefficient; 2) HCPs presume that patients expect antibiotic treatment and some HCPs consider non-antibiotic treatment inferior; 3) Patients are largely unaware of the various non-antibiotic treatment options for cystitis; 4) HCPs recognise some benefits of applying SDM in cystitis management, including reduced antibiotic use and improved patient empowerment, and patients appreciate involvement in treatment decisions, but preferences for SDM vary. CONCLUSION: SDM is infrequently applied in cystitis treatment in general practice due to the current efficient cystitis management, HCPs' perceptions, and patient unawareness. Nevertheless, both HCPs and patients recognise the long-term benefits of applying SDM in cystitis management. Our findings facilitate the development of tailored interventions to increase the application of SDM which should be co-created with HCPs and patients and fit into the current efficient cystitis management.

Accuracy of urgency allocation in patients with shortness of breath calling out-of-hours primary care: a cross-sectional study.

BACKGROUND: In out-of-hours primary care (OHS-PC), semi-automatic decision support tools are often used during telephone triage. In the Netherlands, the Netherlands Triage Standard (NTS) is used. The NTS is mainly expert-based and evidence on the diagnostic accuracy of the NTS' urgency allocation against clinically relevant outcomes for patients calling with shortness of breath (SOB) is lacking. METHODS: We included data from adults (≥18 years) who contacted two large Dutch OHS-PC centres for SOB between 1 September 2020 and 31 August 2021 and whose follow-up data about final diagnosis could be retrieved from their own general practitioner (GP). The diagnostic accuracy (sensitivity and specificity with corresponding 95% confidence intervals (CI)) of the NTS' urgency levels (high (U1/U2) versus low (U3/U4/U5) and 'final' urgency levels (including overruling of the urgency by triage nurses or supervising general practitioners (GPs)) was determined with life-threatening events (LTEs) as the reference. LTEs included, amongst others, acute coronary syndrome, pulmonary embolism, acute heart failure and severe pneumonia. RESULTS: Out of 2012 eligible triage calls, we could include 1833 adults with SOB who called the OHS-PC, mean age 53.3 (SD 21.5) years, 55.5% female, and 16.6% showed to have had a LTE. Most often severe COVID-19 infection (6.0%), acute heart failure (2.6%), severe COPD exacerbation (2.1%) or severe pneumonia (1.9%). The NTS urgency level had a sensitivity of 0.56 (95% CI 0.50-0.61) and specificity of 0.61 (95% CI 0.58-0.63). Overruling of the NTS' urgency allocation by triage nurses and/or supervising GPs did not impact sensitivity (0.56 vs. 0.54, p = 0.458) but slightly improved specificity (0.61 vs. 0.65, p < 0.001). CONCLUSIONS: The semi-automatic decision support tool NTS performs poorly with respect to safety (sensitivity) and efficiency (specificity) of urgency allocation in adults calling Dutch OHS-PC with SOB. There is room for improvement of telephone triage in patients calling OHS-PC with SOB. TRIAL REGISTRATION: The Netherlands Trial Register, number: NL9682 .

Within-episode repeat antibiotic prescriptions in patients with respiratory tract infections: A population-based cohort study.

BACKGROUND: Antimicrobial stewardship interventions mainly focus on initial antibiotic prescriptions, with few considering within-episode repeat prescriptions. We aimed to describe the magnitude, type and determinants of within-episode repeat antibiotic prescriptions in patients presenting to primary care with respiratory tract infections (RTIs). METHODS: We conducted a population-based cohort study among 530 sampled English general practices within the Clinical Practice Research Datalink (CPRD). All individuals with a primary care RTI consultation for which an antibiotic was prescribed between March 2018 and February 2022. Main outcome measurement was repeat antibiotic prescriptions within 28 days of a RTI visit stratified by age (children vs. adults) and RTI type (lower vs. upper RTI). Multivariable logistic regression and principal components analyses were used to identify risk factors and patient clusters at risk for within-episode repeat prescriptions. FINDINGS: 905,964 RTI episodes with at least one antibiotic prescription were identified. In adults, 19.9% (95% CI 19.3-20.5%) had at least one within-episode repeat prescription for a lower RTI, compared to 10.5% (95% CI 10.3-10.8%) for an upper RTI. In children, this was around 10% irrespective of RTI type. The majority of repeat prescriptions occurred a median of 10 days after the initial prescription and was the same antibiotic class in 48.3% of cases. Frequent RTI related GP visits and prior within-RTI-episode repeat antibiotic prescriptions were main factors associated with repeat prescriptions in both adults and children irrespective of RTI type. Young (<2 years) and older (65+) age were associated with repeat prescriptions. Among those aged 2-64 years, allergic rhinitis, COPD and oral corticosteroids were associated with repeat prescriptions. INTERPRETATIONS: Repeat within-episode antibiotic use accounts for a significant proportion of all antibiotics prescribed for RTIs, with same class antibiotics unlikely to confer clinical benefit and is therefore a prime target for future antimicrobial stewardship interventions.

Prognostic factors and prediction models for hospitalisation and all-cause mortality in adults presenting to primary care with a lower respiratory tract infection: a systematic review.

OBJECTIVE: To identify and synthesise relevant existing prognostic factors (PF) and prediction models (PM) for hospitalisation and all-cause mortality within 90 days in primary care patients with acute lower respiratory tract infections (LRTI). DESIGN: Systematic review. METHODS: Systematic searches of MEDLINE, Embase and the Cochrane Library were performed. All PF and PM studies on the risk of hospitalisation or all-cause mortality within 90 days in adult primary care LRTI patients were included. The risk of bias was assessed using the Quality in Prognostic Studies tool and Prediction Model Risk Of Bias Assessment Tool tools for PF and PM studies, respectively. The results of included PF and PM studies were descriptively summarised. RESULTS: Of 2799 unique records identified, 16 were included: 9 PF studies, 6 PM studies and 1 combination of both. The risk of bias was judged high for all studies, mainly due to limitations in the analysis domain. Based on reported multivariable associations in PF studies, increasing age, sex, current smoking, diabetes, a history of stroke, cancer or heart failure, previous hospitalisation, influenza vaccination (negative association), current use of systemic corticosteroids, recent antibiotic use, respiratory rate ≥25/min and diagnosis of pneumonia were identified as most promising candidate predictors. One newly developed PM was externally validated (c statistic 0.74, 95% CI 0.71 to 0.78) whereas the previously hospital-derived CRB-65 was externally validated in primary care in five studies (c statistic ranging from 0.72 (95% CI 0.63 to 0.81) to 0.79 (95% CI 0.65 to 0.92)). None of the PM studies reported measures of model calibration. CONCLUSIONS: Implementation of existing models for individualised risk prediction of 90-day hospitalisation or mortality in primary care LRTI patients in everyday practice is hampered by incomplete assessment of model performance. The identified candidate predictors provide useful information for clinicians and warrant consideration when developing or updating PMs using state-of-the-art development and validation techniques. PROSPERO REGISTRATION NUMBER: CRD42022341233.

Substantial Burden of Nonmedically Attended RSV Infection in Healthy-Term Infants: An International Prospective Birth Cohort Study.

BACKGROUND: During the first year of life, 1 in 4 infants develops a symptomatic respiratory syncytial virus (RSV) infection, yet only half seek medical attention. The current focus on medically attended RSV therefore underrepresents the true societal burden of RSV. We assessed the burden of nonmedically attended RSV infections and compared with medically attended RSV. METHODS: We performed active RSV surveillance until the age of 1 year in a cohort (n = 993) nested within the Respiratory Syncytial Virus Consortium in EUrope (RESCEU) prospective birth cohort study enrolling healthy term-born infants in 5 European countries. Symptoms, medication use, wheezing, and impact on family life were analyzed. RESULTS: For 97 of 120 (80.1%) nonmedically attended RSV episodes, sufficient data were available for analysis. In 50.5% (49/97), symptoms lasted ≥15 days. Parents reported impairment in usual daily activities in 59.8% (58/97) of episodes; worries, 75.3% (73/97); anxiety, 34.0% (33/97); and work absenteeism, 10.8% (10/93). Compared with medically attended RSV (n = 102, 9 hospital admissions), Respiratory Syncytial Virus NETwork (ReSViNET) severity scores were lower (3.5 vs 4.6, P < .001), whereas duration of respiratory symptoms and was comparable. CONCLUSIONS: Even when medical attendance is not required, RSV infection poses a substantial burden to infants, families, and society. These findings are important for policy makers when considering the implementation of RSV immunization. Clinical Trials Registration. ClinicalTrials.gov (NCT03627572).

Home-based management of hypoxaemic COVID-19 patients: design of the Therapy@Home pilot study.

INTRODUCTION: During the COVID-19 pandemic, hospital capacity was strained. Home-based care could relieve the hospital care system and improve patient well-being if safely organised.We designed an intervention embedded in a regional collaborative healthcare network for the home-based management of acutely ill COVID-19 patients requiring oxygen treatment. Here, we describe the design and pilot protocol for the evaluation of the feasibility of this complex intervention. METHODS AND ANALYSIS: Following a participatory action research approach, the intervention was designed in four consecutive steps: (1) literature review and establishment of an expert panel; (2) concept design of essential intervention building blocks (acute medical care, acute nursing care, remote monitoring, equipment and technology, organisation and logistics); (3) safety assessments (prospective risk analysis and a simulation patient evaluation) and (4) description of the design of the pilot (feasibility) study aimed at including approximately 15-30 patients, sufficient for fine-tuning for a large-scale randomised intervention. ETHICS AND DISSEMINATION: All patients will provide written, informed consent. The study was approved by the Medical Ethics Review Committee of the University Medical Center Utrecht, the Netherlands (protocol NL77421.041.21). The preparatory steps (1-4) needed to perform the pilot are executed and described in this paper. The findings of the pilot will be published in academic journals. If we consider the complex intervention feasible, we aim to continue with a large-scale randomised controlled study evaluating the clinical effectiveness, safety and implementation of the complex intervention.

ISOM 2023 Research Panel 5: Interventions- Vaccines and prevention, medical and surgical treatment, and impact of COVID-19 pandemic.

OBJECTIVES: To identify and synthesize key research advances from the literature published between 2019 and 2023 on the advances in preventative measures, and medical and surgical treatment of uncomplicated otitis media (OM) including the impact of the COVID-19 pandemic on OM management. DATA SOURCES: Medline (PubMed), Embase, and the Cochrane Library. REVIEW METHODS: All relevant original articles published in English between June 2019 and February 2023 were identified. Studies related to guideline adherence, impact of treatment on immune response and/or microbiology, tympanoplasty, Eustachian tube balloon dilatation, mastoidectomy procedures, and those focusing on children with Down's syndrome or cleft palate were excluded. MAIN FINDINGS: Of the 9280 unique records screened, 64 were eligible for inclusion; 23 studies related to medical treatment, 20 to vaccines, 13 to surgical treatment, 6 to prevention (excl. vaccines) and 2 to the impact of COVID-19 on OM management. The level of evidence was judged 2 in 11 studies (17.2 %) and 3 or 4 in the remaining 53 studies (82.8 %) mainly due to the observational design, study limitations or low sample sizes. Some important advances in OM management have been made in recent years. Video discharge instructions detailing the identification and management of pain and fever for parents of children with acute otitis media (AOM) was more effective than paper instructions in reducing symptomatology; compared to placebo, levofloxacin solution was more effective for treating chronic suppurative otitis media, whereas AOM recurrences during two years of follow-up did not differ between children with recurrent AOM who received tympanostomy tube (TT) insertion or medical management. Further, novel pneumococcal conjugate vaccines (PCV) schedules for preventing OM in Aboriginal children appeared ineffective, and a protein-based pneumococcal vaccine had no added value over PCV13 for preventing AOM in native American infants. During the COVID-19 pandemic, a decline in OM and TT case volumes and complications was observed. IMPLICATION FOR PRACTICE AND FUTURE RESEARCH: Whether the observed impact of the COVID-19 pandemic on OM management extends to the post-pandemic era is uncertain. Furthermore, the impact of the pandemic on the conduct of urgently needed prospective methodologically rigorous interventional studies aimed at improving OM prevention and treatment remains to be elucidated since the current report consisted of studies predominantly conducted in the pre-pandemic era.

Shortness of breath as a diagnostic factor for acute coronary syndrome in male and female callers to out-of-hours primary care.

OBJECTIVE: Chest discomfort and shortness of breath (SOB) are key symptoms in patients with acute coronary syndrome (ACS). It is, however, unknown whether SOB is valuable for recognising ACS during telephone triage in the out-of-hours primary care (OHS-PC) setting. METHODS: A cross-sectional study performed in the Netherlands. Telephone triage conversations were analysed of callers with chest discomfort who contacted the OHS-PC between 2014 and 2017, comparing patients with SOB with those who did not report SOB. We determine the relation between SOB and (1) High urgency allocation, (2) ACS and (3) ACS or other life-threatening diseases. RESULTS: Of the 2195 callers with chest discomfort, 1096 (49.9%) reported SOB (43.7% men, 56.3% women). In total, 15.3% men (13.2% in those with SOB) and 8.4% women (9.2% in those with SOB) appeared to have ACS. SOB compared with no SOB was associated with high urgency allocation (75.9% vs 60.8%, OR: 2.03; 95% CI 1.69 to 2.44, multivariable OR (mOR): 2.03; 95% CI 1.69 to 2.44), but not with ACS (10.9% vs 12.0%; OR: 0.90; 95% CI 0.69 to 1.17, mOR: 0.91; 95% CI 0.70 to 1.19) or 'ACS or other life-threatening diseases' (15.0% vs 14.1%; OR: 1.07; 95% CI 0.85 to 1.36, mOR: 1.09; 95% CI 0.86 to 1.38). For women the relation with ACS was 9.2% vs 7.5%, OR: 1.25; 95% CI 0.83 to 1.88, and for men 13.2% vs 17.4%, OR: 0.72; 95% CI 0.51 to 1.02. For 'ACS or other life-threatening diseases', this was 13.0% vs 8.5%, OR: 1.60; 95% CI 1.10 to 2.32 for women, and 7.5% vs 20.8%, OR: 0.81; 95% CI 0.59 to 1.12 for men. CONCLUSIONS: Men and women with chest discomfort and SOB who contact the OHS-PC more often receive high urgency than those without SOB. This seems to be adequate in women, but not in men when considering the risk of ACS or other life-threatening diseases.

Outpatient respiratory syncytial virus infections and novel preventive interventions.

PURPOSE OF REVIEW: With interventions to prevent respiratory syncytial virus (RSV) infection within reach, this review aims to provide healthcare professionals with the latest information necessary to inform parents and assess the potential impact of RSV prevention on everyday practice. We address frequently asked questions for parental counseling. RECENT FINDINGS: Numerous studies emphasize the major burden of RSV on young children, parents, healthcare and society. In the first year of life, about 14% of healthy term infants visit a doctor and 2% require hospitalization due to RSV. In older children (1--5 years), RSV infections and associated morbidity (wheeze, acute otitis media) are major drivers of outpatient visits. A novel maternal RSV vaccine and long-acting mAb can provide protection during infants' first months of life. This maternal vaccine showed 70.9% efficacy against severe RSV infection within 150 days after birth; the mAb nirsevimab reduces medically attended RSV infections by 79.5% within 150 days after administration. Both gained regulatory approval in the USA (FDA) and Europe (EMA). SUMMARY: Novel RSV immunizations hold promise to reduce the RSV burden in infants, with substantial impact on everyday practice. Tailored parental guidance will be instrumental for successful implementation. Awaiting pediatric vaccines, RSV infections beyond infancy will still pose a significant outpatient burden.

Predicting adverse outcomes in adults with a community-acquired lower respiratory tract infection: a protocol for the development and validation of two prediction models for (i) all-cause hospitalisation and mortality and (ii) cardiovascular outcomes.

BACKGROUND: Community-acquired lower respiratory tract infections (LRTI) are common in primary care and patients at particular risk of adverse outcomes, e.g., hospitalisation and mortality, are challenging to identify. LRTIs are also linked to an increased incidence of cardiovascular diseases (CVD) following the initial infection, whereas concurrent CVD might negatively impact overall prognosis in LRTI patients. Accurate risk prediction of adverse outcomes in LRTI patients, while considering the interplay with CVD, can aid general practitioners (GP) in the clinical decision-making process, and may allow for early detection of deterioration. This paper therefore presents the design of the development and external validation of two models for predicting individual risk of all-cause hospitalisation or mortality (model 1) and short-term incidence of CVD (model 2) in adults presenting to primary care with LRTI. METHODS: Both models will be developed using linked routine electronic health records (EHR) data from Dutch primary and secondary care, and the mortality registry. Adults aged ≥ 40 years with a GP-diagnosis of LRTI between 2016 and 2019 are eligible for inclusion. Relevant patient demographics, medical history, medication use, presenting signs and symptoms, and vital and laboratory measurements will be considered as candidate predictors. Outcomes of interest include 30-day all-cause hospitalisation or mortality (model 1) and 90-day CVD (model 2). Multivariable elastic net regression techniques will be used for model development. During the modelling process, the incremental predictive value of CVD for hospitalisation or all-cause mortality (model 1) will also be assessed. The models will be validated through internal-external cross-validation and external validation in an equivalent cohort of primary care LRTI patients. DISCUSSION: Implementation of currently available prediction models for primary care LRTI patients is hampered by limited assessment of model performance. While considering the role of CVD in LRTI prognosis, we aim to develop and externally validate two models that predict clinically relevant outcomes to aid GPs in clinical decision-making. Challenges that we anticipate include the possibility of low event rates and common problems related to the use of EHR data, such as candidate predictor measurement and missingness, how best to retrieve information from free text fields, and potential misclassification of outcome events.

Topical and oral steroids for otitis media with effusion (OME) in children.

BACKGROUND: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. Although most episodes of OME in children resolve spontaneously within a few months, when persistent it may lead to behavioural problems and a delay in expressive language skills. Management of OME includes watchful waiting, medical, surgical and other treatments, such as autoinflation. Oral or topical steroids are sometimes used to reduce inflammation in the middle ear. OBJECTIVES: To assess the effects (benefits and harms) of topical and oral steroids for OME in children. SEARCH METHODS: We searched the Cochrane ENT Register, CENTRAL, Ovid MEDLINE, Ovid Embase, Web of Science, ClinicalTrials.gov, ICTRP and additional sources for published and unpublished studies on 20 January 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-randomised trials in children aged 6 months to 12 years with unilateral or bilateral OME. We included studies that compared topical or oral steroids with either placebo or watchful waiting (no treatment). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes, determined by a multi-stakeholder prioritisation exercise, were: 1) hearing, 2) OME-specific quality of life and 3) systemic corticosteroid side effects. Secondary outcomes were: 1) presence/persistence of OME, 2) other adverse effects (including local nasal effects), 3) receptive language skills, 4) speech development, 5) cognitive development, 6) psychosocial outcomes, 7) listening skills, 8) generic health-related quality of life, 9) parental stress, 10) vestibular function and 11) episodes of acute otitis media. We used GRADE to assess the certainty of evidence. Although we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method to assess hearing, due to challenges in interpreting the results of mean hearing thresholds. MAIN RESULTS: We included 26 studies in this review (2770 children). Most studies of oral steroids used prednisolone for 7 to 14 days. Studies of topical (nasal) steroids used various preparations (beclomethasone, fluticasone and mometasone) for between two weeks and three months. All studies had at least some concerns regarding risk of bias. Here we report our primary outcomes and main secondary outcome, at the longest reported follow-up. Oral steroids compared to placebo Oral steroids probably result in little or no difference in the proportion of children with normal hearing after 12 months (69.7% of children with steroids, compared to 61.1% of children receiving placebo, risk ratio (RR) 1.14, 95% confidence interval (CI) 0.97 to 1.33; 1 study, 332 participants; moderate-certainty evidence). There is probably little or no difference in OME-related quality of life (mean difference (MD) in OM8-30 score 0.07, 95% CI -0.2 to 0.34; 1 study, 304 participants; moderate-certainty evidence). Oral steroids may reduce the number of children with persistent OME at 6 to 12 months, but the size of the effect was uncertain (absolute risk reduction ranging from 13.3% to 45%, number needed to treat (NNT) of between 3 and 8; low-certainty evidence). The evidence was very uncertain regarding the risk of systemic corticosteroid side effects, and we were unable to conduct any meta-analysis for this outcome. Oral steroids compared to no treatment Oral steroids may result in little or no difference in the persistence of OME after three to nine months (74.5% children receiving steroids versus 73% of those receiving placebo; RR 1.02, 95% CI 0.89 to 1.17; 2 studies, 258 participants; low-certainty evidence). The evidence on adverse effects was very uncertain. We did not identify any evidence on hearing or disease-related quality of life. Topical (intranasal) steroids compared to placebo We did not identify data on the proportion of children who returned to normal hearing. However, the mean change in hearing threshold after two months was -0.3 dB lower (95% CI -6.05 to 5.45; 1 study, 78 participants; very low-certainty evidence). The evidence suggests that nasal steroids make little or no difference to disease-specific quality of life after nine months (OM8-30 score, MD 0.05 higher, 95% CI -0.36 to 0.46; 1 study, 82 participants; low-certainty evidence). The evidence is very uncertain regarding the effect of nasal steroids on persistence of OME at up to one year. Two studies reported this: one showed a potential benefit for nasal steroids, the other showed a benefit with placebo (2 studies, 206 participants). The evidence was also very uncertain regarding the risk of corticosteroid-related side effects, as we were unable to provide a pooled effect estimate. Topical (intranasal) steroids compared to no treatment We did not identify data on the proportion of children who returned to normal hearing. However, the mean difference in final hearing threshold after four weeks was 1.95 dB lower (95% CI -3.85 to -0.05; 1 study, 168 participants; low-certainty evidence). Nasal steroids may reduce the persistence of OME after eight weeks, but the evidence was very uncertain (58.5% of children receiving steroids, compared to 81.3% of children without treatment, RR 0.72, 95% CI 0.57 to 0.91; 2 studies, 134 participants). We did not identify any evidence on disease-related quality of life or adverse effects. AUTHORS' CONCLUSIONS: Overall, oral steroids may have little effect in the treatment of OME, with little improvement in the number of children with normal hearing and no effect on quality of life. There may be a reduction in the proportion of children with persistent disease after 12 months. However, this benefit may be small and must be weighed against the potential for adverse effects associated with oral steroid use. The evidence for nasal steroids was all low- or very low-certainty. It is therefore less clear if nasal steroids have any impact on hearing, quality of life or persistence of OME. Evidence on adverse effects was very limited. OME is likely to resolve spontaneously for most children. The potential benefit of treatment may therefore be small and should be balanced with the risk of adverse effects. Future studies should aim to determine which children are most likely to benefit from treatment, rather than offering interventions to all children.

Predicting sepsis-related mortality and ICU admissions from telephone triage information of patients presenting to out-of-hours GP cooperatives with acute infections: A cohort study of linked routine care databases.

BACKGROUND: General practitioners (GPs) often assess patients with acute infections. It is challenging for GPs to recognize patients needing immediate hospital referral for sepsis while avoiding unnecessary referrals. This study aimed to predict adverse sepsis-related outcomes from telephone triage information of patients presenting to out-of-hours GP cooperatives. METHODS: A retrospective cohort study using linked routine care databases from out-of-hours GP cooperatives, general practices, hospitals and mortality registration. We included adult patients with complaints possibly related to an acute infection, who were assessed (clinic consultation or home visit) by a GP from a GP cooperative between 2017-2019. We used telephone triage information to derive a risk prediction model for sepsis-related adverse outcome (infection-related ICU admission within seven days or infection-related death within 30 days) using logistic regression, random forest, and neural network machine learning techniques. Data from 2017 and 2018 were used for derivation and from 2019 for validation. RESULTS: We included 155,486 patients (median age of 51 years; 59% females) in the analyses. The strongest predictors for sepsis-related adverse outcome were age, type of contact (home visit or clinic consultation), patients considered ABCD unstable during triage, and the entry complaints"general malaise", "shortness of breath" and "fever". The multivariable logistic regression model resulted in a C-statistic of 0.89 (95% CI 0.88-0.90) with good calibration. Machine learning models performed similarly to the logistic regression model. A "sepsis alert" based on a predicted probability >1% resulted in a sensitivity of 82% and a positive predictive value of 4.5%. However, most events occurred in patients receiving home visits, and model performance was substantially worse in this subgroup (C-statistic 0.70). CONCLUSION: Several patient characteristics identified during telephone triage of patients presenting to out-of-hours GP cooperatives were associated with sepsis-related adverse outcomes. Still, on a patient level, predictions were not sufficiently accurate for clinical purposes.

Incomplete and possibly selective recording of signs, symptoms, and measurements in free text fields of primary care electronic health records of adults with lower respiratory tract infections.

OBJECTIVES: To assess the completeness of recording of relevant signs, symptoms, and measurements in Dutch free text fields of primary care electronic health records (EHR) of adults with lower respiratory tract infections (LRTI). STUDY DESIGN AND SETTING: Retrospective cohort study embedded in a prediction modeling project using routine health care data of the Julius General Practitioners' Network of adult patients with LRTI. Free text fields of 1,000 primary care consultations of LRTI episodes between 2016 and 2019 were manually annotated to retrieve data on the recording of sixteen relevant signs, symptoms, and measurements. RESULTS: For 12/16 (75%) of the relevant signs, symptoms, and measurements, more than 50% of the values was not recorded. The patterns of recorded values indicated selective recording of positive or abnormal values. Recording rates varied across consultation type (physical consultation vs. home visit), diagnosis (acute bronchitis vs. pneumonia), antibiotic prescription issued (yes vs. no), and between practices. CONCLUSION: In EHR of primary care LRTI patients, recording of signs, symptoms, and measurements in free text fields is incomplete and possibly selective. When using free text data in EHR-based research, careful consideration of its recording patterns and appropriate missing data handling techniques is therefore required.

The epidemiological impact of digital and manual contact tracing on the SARS-CoV-2 epidemic in the Netherlands: Empirical evidence.

The Dutch government introduced the CoronaMelder smartphone application for digital contact tracing (DCT) to complement manual contact tracing (MCT) by Public Health Services (PHS) during the 2020-2022 SARS-CoV-2 epidemic. Modelling studies showed great potential but empirical evidence of DCT and MCT impact is scarce. We determined reasons for testing, and mean exposure-testing intervals by reason for testing, using routine data from PHS Amsterdam (1 December 2020 to 31 May 2021) and data from two SARS-CoV-2 rapid diagnostic test accuracy studies at other PHS sites in the Netherlands (14 December 2020 to 18 June 2021). Throughout the study periods, notification of DCT-identified contacts was via PHS contact-tracers, and self-testing was not yet widely available. The most commonly reported reason for testing was having symptoms. In asymptomatic individuals, it was having been warned by an index case. Only around 2% and 2-5% of all tests took place after DCT or MCT notification, respectively. About 20-36% of those who had received a DCT or MCT notification had symptoms at the time of test request. Test positivity after a DCT notification was significantly lower, and exposure-test intervals after a DCT or MCT notification were longer, than for the above-mentioned other reasons for testing. Our data suggest that the impact of DCT and MCT on the SARS-CoV-2 epidemic in the Netherlands was limited. However, DCT impact might be enlarged if app use coverage is improved, contact-tracers are eliminated from the digital notification process to minimise delays, and DCT is combined with self-testing.

Antibiotics for acute otitis media in children.

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

Ventilation tubes (grommets) for otitis media with effusion (OME) in children.

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

Patients' and GPs' views and expectations of home monitoring with a pulse oximeter: a mixed-methods process evaluation of a pilot randomised controlled trial.

BACKGROUND: Research on how home monitoring with a pulse oximeter is executed and experienced by patients with an acute illness such as COVID-19 and their GPs is scarce. AIM: To examine the process of structured home monitoring with a pulse oximeter for patients with COVID-19, their caregivers, and their GPs. DESIGN AND SETTING: This was a mixed-method process evaluation alongside a pilot feasibility randomised controlled trial. Patients drawn from a general practice setting, with COVID-19, and aged ≥40 years with cardiovascular comorbidities were included. METHOD: Quantitative trial data from 21 intervention group participants (age 63.2 years) were used, plus qualitative data from semi-structured interviews with 15 patients (age 62.9 years), eight informal caregivers, and 10 GPs. RESULTS: Adherence to the intervention was very high; 97.6% of protocolised peripheral oxygen saturation (SpO2) measurements in the first 14 days until admission to hospital were recorded (677/694, median daily per patient 2.7). Three identified themes from the interviews were: (a) user-friendliness of home monitoring: easy use of the pulse oximeter and patient preference of a three times daily measurement scheme; (b) patient empowerment: pulse oximeter use enhanced patient self-assurance and empowered patients and informal caregivers in disease management; and (c) added value to current clinical decision making. GPs perceived the pulse oximeter as a useful diagnostic tool and did not experience any additional workload. They felt more secure with remote monitoring with a pulse oximeter than only phone-based monitoring, but emphasised the need to keep an overall view on the patient's condition. CONCLUSION: Structured home monitoring by pulse oximetry supports patients and their informal caregivers in managing, and GPs in monitoring, acute COVID-19 disease. It appears suitable for use in acutely ill patients in general practice.

Adenoidectomy for otitis media with effusion (OME) in children.

BACKGROUND: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. When persistent, it may lead to developmental delay, social difficulty and poor quality of life. Management of OME includes watchful waiting, autoinflation, medical and surgical treatment. Adenoidectomy has often been used as a potential treatment for this condition. OBJECTIVES: To assess the benefits and harms of adenoidectomy, either alone or in combination with ventilation tubes (grommets), for OME in children. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 20 January 2023. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised trials in children aged 6 months to 12 years with unilateral or bilateral OME. We included studies that compared adenoidectomy (alone, or in combination with ventilation tubes) with either no treatment or non-surgical treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Primary outcomes (determined following a multi-stakeholder prioritisation exercise): 1) hearing, 2) otitis media-specific quality of life, 3) haemorrhage. SECONDARY OUTCOMES: 1) persistence of OME, 2) adverse effects, 3) receptive language skills, 4) speech development, 5) cognitive development, 6) psychosocial skills, 7) listening skills, 8) generic health-related quality of life, 9) parental stress, 10) vestibular function, 11) episodes of acute otitis media. We used GRADE to assess the certainty of evidence for each outcome. Although we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method to assess hearing, due to challenges in interpreting the results of mean hearing thresholds. MAIN RESULTS: We included 10 studies (1785 children). Many of the studies used concomitant interventions for all participants, including insertion of ventilation tubes or myringotomy. All included studies had at least some concerns regarding the risk of bias. We report results for our main outcome measures at the longest available follow-up. We did not identify any data on disease-specific quality of life for any of the comparisons. Further details of additional outcomes and time points are reported in the review. 1) Adenoidectomy (with or without myringotomy) versus no treatment/watchful waiting (three studies) After 12 months there was little difference in the proportion of children whose hearing had returned to normal, but the evidence was very uncertain (adenoidectomy 68%, no treatment 70%; risk ratio (RR) 0.97, 95% confidence interval (CI) 0.65 to 1.46; number needed to treat to benefit (NNTB) 50; 1 study, 42 participants). There is a risk of haemorrhage from adenoidectomy, but the absolute risk appears small (1/251 receiving adenoidectomy compared to 0/229, Peto odds ratio (OR) 6.77, 95% CI 0.13 to 342.54; 1 study, 480 participants; moderate certainty evidence). The risk of persistent OME may be slightly lower after two years in those receiving adenoidectomy (65% versus 73%), but again the difference was small (RR 0.90, 95% CI 0.81 to 1.00; NNTB 13; 3 studies, 354 participants; very low-certainty evidence). 2) Adenoidectomy (with or without myringotomy) versus non-surgical treatment No studies were identified for this comparison. 3) Adenoidectomy and bilateral ventilation tubes versus bilateral ventilation tubes (four studies) There was a slight increase in the proportion of ears with a return to normal hearing after six to nine months (57% adenoidectomy versus 42% without, RR 1.36, 95% CI 0.98 to 1.89; NNTB 7; 1 study, 127 participants (213 ears); very low-certainty evidence). Adenoidectomy may give an increased risk of haemorrhage, but the absolute risk appears small, and the evidence was uncertain (2/416 with adenoidectomy compared to 0/375 in the control group, Peto OR 6.68, 95% CI 0.42 to 107.18; 2 studies, 791 participants). The risk of persistent OME was similar for both groups (82% adenoidectomy and ventilation tubes compared to 85% ventilation tubes alone, RR 0.96, 95% CI 0.86 to 1.07; very low-certainty evidence). 4) Adenoidectomy and unilateral ventilation tube versus unilateral ventilation tube (two studies) Slightly more children returned to normal hearing after adenoidectomy, but the confidence intervals were wide (57% versus 46%, RR 1.24, 95% CI 0.79 to 1.96; NNTB 9; 1 study, 72 participants; very low-certainty evidence). Fewer children may have persistent OME after 12 months, but again the confidence intervals were wide (27.2% compared to 40.5%, RR 0.67, 95% CI 0.35 to 1.29; NNTB 8; 1 study, 74 participants). We did not identify any data on haemorrhage. 5) Adenoidectomy and ventilation tubes versus no treatment/watchful waiting (two studies) We did not identify data on the proportion of children who returned to normal hearing. However, after two years, the mean difference in hearing threshold for those allocated to adenoidectomy was -3.40 dB (95% CI -5.54 to -1.26; 1 study, 211 participants; very low-certainty evidence). There may be a small reduction in the proportion of children with persistent OME after two years, but the evidence was very uncertain (82% compared to 90%, RR 0.91, 95% CI 0.82 to 1.01; NNTB 13; 1 study, 232 participants). We noted that many children in the watchful waiting group had also received surgery by this time point. 6) Adenoidectomy and ventilation tubes versus non-surgical treatment No studies were identified for this comparison. AUTHORS' CONCLUSIONS: When assessed with the GRADE approach, the evidence for adenoidectomy in children with OME is very uncertain. Adenoidectomy may reduce the persistence of OME, although evidence about the effect of this on hearing is unclear. For patients and carers, a return to normal hearing is likely to be important, but few studies measured this outcome. We did not identify any evidence on disease-specific quality of life. There were few data on adverse effects, in particular postoperative bleeding. The risk of haemorrhage appears to be small, but should be considered when choosing a treatment strategy for children with OME. Future studies should aim to determine which children are most likely to benefit from treatment, rather than offering interventions to all children.

Immunoglobulin treatment for hospitalised infants and young children with respiratory syncytial virus infection.

BACKGROUND: Millions of children are hospitalised due to respiratory syncytial virus (RSV) infection every year. Treatment is supportive, and current therapies (e.g. inhaled bronchodilators, epinephrine, nebulised hypertonic saline, and corticosteroids) are ineffective or have limited effect. Respiratory syncytial virus immunoglobulin may be used prophylactically to prevent hospital admission from RSV-related illness. It may be considered for the treatment of established severe RSV infection or for treatment in an immunocompromised host, although it is not licensed for this purpose. It is unclear whether immunoglobulins improve outcomes when used as a treatment for established RSV infection in infants and young children admitted to hospital. This is an update of a review first published in 2019. OBJECTIVES: To assess the effects of immunoglobulins for the treatment of RSV-proven lower respiratory tract infections (LRTIs) in children aged up to three years, admitted to hospital. SEARCH METHODS: For this 2022 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Specialised Register, Ovid MEDLINE, Embase, CINAHL, and Web of Science (from inception to 2 December 2022) with no restrictions. We searched two trial registries for ongoing trials (to 2 December 2022) and checked the reference lists of reviews and included articles for additional studies. SELECTION CRITERIA: Randomised controlled trials comparing immunoglobulins with placebo in hospitalised infants and children aged up to three years with laboratory-diagnosed RSV lower respiratory tract infection. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed risk of bias, and extracted data. We assessed evidence certainty using GRADE. MAIN RESULTS: In total, we included eight trials involving 906 infants and children aged up to three years. We included one new trial in this update. The immunoglobulin preparations used in these trials included anti-RSV immunoglobulin and the monoclonal antibody preparations palivizumab and motavizumab. Five trials were conducted at single or multiple sites within a single high-income country (four in the USA, one in Qatar). Three trials included study sites in different countries. All three of these trials included study sites in one or more high-income countries (USA, Chile, New Zealand, Australia, Qatar), with two trials also including a study site in a middle-income country (Panama). Five of the eight trials were "supported" or "sponsored" by the trial drug manufacturers. The evidence is very uncertain about the effect of immunoglobulins on mortality (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.14 to 5.27; 4 studies, 309 participants). There were four deaths - two amongst 98 children receiving immunoglobulins, and two amongst 98 children receiving placebo. One additional death occurred in a fourth trial, however the study group of the child was not known and the data were not included in the analysis (very low-certainty evidence). The use of immunoglobulins in infants and children admitted to hospital with RSV proven LRTI probably results in little to no difference in the length of hospitalisation (mean difference (MD) -0.13 days, 95% CI -0.37 to 0.12; 6 studies, 737 participants; moderate-certainty evidence). Immunoglobulins may result in little to no difference in the number of children who experience one or more adverse events of any severity or seriousness compared to placebo (RR 1.18, 95% CI 0.78 to 1.78; 5 studies, 340 participants; low-certainty evidence) or the number of children who experience one or more adverse events judged by study investigators to be serious in nature, compared to placebo (RR 1.08, 95% CI 0.65 to 1.79; 4 studies, 238 participants; low-certainty evidence). Certainty of evidence for secondary outcomes was low. This evidence suggests that use of immunoglobulins results in little to no difference in the need for, or duration of, mechanical ventilation and the need for, or duration of, supplemental oxygen. The use of immunoglobulins does not reduce the need for admission to the intensive care unit (ICU) and when children are admitted to the ICU results in little to no difference in the duration of ICU stay. AUTHORS' CONCLUSIONS: We are very uncertain about the effect of immunoglobulins on mortality. We are moderately certain that use of immunoglobulins in hospitalised infants and children may result in little to no difference in the length of hospitalisation. Immunoglobulins may result in little to no difference in adverse events, the need for or duration of mechanical ventilation, supplemental oxygen, or admission to the intensive care unit, though we are less certain about this evidence and the true effect of immunoglobulins on these outcomes may differ markedly from the estimated effect observed in this review. All trials were conducted in high-income countries, and data from populations in which the rate of death from RSV infection is higher are lacking.

Antibiotics for otitis media with effusion (OME) in children.

BACKGROUND: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. When persistent, it may lead to developmental delay, social difficulty and poor quality of life. Management of OME includes watchful waiting, autoinflation, medical and surgical treatment. Antibiotics are sometimes used to treat any bacteria present in the effusion, or associated biofilms. OBJECTIVES: To assess the effects (benefits and harms) of oral antibiotics for otitis media with effusion (OME) in children. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register, CENTRAL, Ovid MEDLINE, Ovid Embase, Web of Science, ClinicalTrials.gov, ICTRP and additional sources for published and unpublished studies to 20 January 2023. SELECTION CRITERIA: We included randomised controlled trials and quasi-randomised trials in children aged 6 months to 12 years with unilateral or bilateral OME. We included studies that compared oral antibiotics with either placebo or no treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were determined following a multi-stakeholder prioritisation exercise and were: 1) hearing, 2) otitis media-specific quality of life and 3) anaphylaxis. Secondary outcomes were: 1) persistence of OME, 2) adverse effects, 3) receptive language skills, 4) speech development, 5) cognitive development, 6) psychosocial skills, 7) listening skills, 8) generic health-related quality of life, 9) parental stress, 10) vestibular function and 11) episodes of acute otitis media. We used GRADE to assess the certainty of evidence for each outcome. Although we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method to assess hearing, due to challenges in interpreting the results of mean hearing thresholds. MAIN RESULTS: We identified 19 completed studies that met our inclusion criteria (2581 participants). They assessed a variety of oral antibiotics (including penicillins, cephalosporins, macrolides and trimethoprim), with most studies using a 10- to 14-day treatment course. We had some concerns about the risk of bias in all studies included in this review. Here we report our primary outcomes and main secondary outcome, at the longest reported follow-up time. Antibiotics versus placebo We included 11 studies for this comparison, but none reported all of our outcomes of interest and limited meta-analysis was possible. Hearing One study found that more children may return to normal hearing by two months (resolution of the air-bone gap) after receiving antibiotics as compared with placebo, but the evidence is very uncertain (Peto odds ratio (OR) 9.59, 95% confidence interval (CI) 3.51 to 26.18; 20/49 children who received antibiotics returned to normal hearing versus 0/37 who received placebo; 1 study, 86 participants; very low-certainty evidence). Disease-specific quality of life No studies assessed this outcome. Presence/persistence of OME At 6 to 12 months of follow-up, the use of antibiotics compared with placebo may slightly reduce the number of children with persistent OME, but the confidence intervals were wide, and the evidence is very uncertain (risk ratio (RR) 0.89, 95% CI 0.68 to 1.17; 48% versus 54%; number needed to treat (NNT) 17; 2 studies, 324 participants; very low-certainty evidence). Adverse event: anaphylaxis No studies provided specific data on anaphylaxis. Three of the included studies (448 children) did report adverse events in sufficient detail to assume that no anaphylactic reactions occurred, but the evidence is very uncertain (very low-certainty evidence). Antibiotics versus no treatment We included eight studies for this comparison, but very limited meta-analysis was possible. Hearing One study found that the use of antibiotics compared to no treatment may result in little to no difference in final hearing threshold at three months (mean difference (MD) -5.38 dB HL, 95% CI -9.12 to -1.64; 1 study, 73 participants; low-certainty evidence). The only data identified on the return to normal hearing were reported at 10 days of follow-up, which we considered to be too short to accurately reflect the efficacy of antibiotics. Disease-specific quality of life No studies assessed this outcome. Presence/persistence of OME Antibiotics may reduce the proportion of children who have persistent OME at up to three months of follow-up, when compared with no treatment (RR 0.64, 95% CI 0.50 to 0.80; 6 studies, 542 participants; low-certainty evidence). Adverse event: anaphylaxis No studies provided specific data on anaphylaxis. Two of the included studies (180 children) did report adverse events in sufficient detail to assume that no anaphylactic reactions occurred, but the evidence is very uncertain (very low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for the use of antibiotics for OME is of low to very low certainty. Although the use of antibiotics compared to no treatment may have a slight beneficial effect on the resolution of OME at up to three months, the overall impact on hearing is very uncertain. The long-term effects of antibiotics are unclear and few of the studies included in this review reported on potential harms. These important endpoints should be considered when weighing up the potential short- and long-term benefits and harms of antibiotic treatment in a condition with a high spontaneous resolution rate.