Chronic suppurative otitis media.

Chronic suppurative otitis media (CSOM) is a leading global cause of potentially preventable hearing loss in children and adults, associated with socioeconomic deprivation. There is an absence of consensus on the definition of CSOM, which complicates efforts for prevention, treatment, and monitoring. CSOM occurs when perforation of the tympanic membrane is associated with severe or persistent inflammation in the middle ear, leading to hearing loss and recurrent or persistent ear discharge (otorrhoea). Cholesteatoma, caused by the inward growth of the squamous epithelium of the tympanic membrane into the middle ear, can also occur. The optimal treatment of discharge in CSOM is topical antibiotics. In resource-limited settings where topical antibiotics might not be available, topical antiseptics are an alternative. For persistent disease, surgery to repair the tympanic membrane or remove cholesteatoma might offer long-term resolution of otorrhoea and potential improvement to hearing. Recent developments in self-fitted air-conduction and bone-conduction hearing aids offer promise as new options for rehabilitation.

A Geometrically Flexible Three-Dimensional Nanocarbon.

The development of architecturally unique molecular nanocarbons by bottom-up organic synthesis is essential for accessing functional organic materials awaiting technological developments in fields such as energy, electronics, and biomedicine. Herein, we describe the design and synthesis of a triptycene-based three-dimensional (3D) nanocarbon, GFN-1, with geometrical flexibility on account of its three peripheral π-panels being capable of interconverting between two curved conformations. An effective through-space electronic communication among the three π-panels of GFN-1 has been observed in its monocationic radical form, which exhibits an extensively delocalized spin density over the entire 3D π-system as revealed by electron paramagnetic resonance and UV-vis-NIR spectroscopies. The flexible 3D molecular architecture of GFN-1, along with its densely packed superstructures in the presence of fullerenes, is revealed by microcrystal electron diffraction and single-crystal X-ray diffraction, which establish the coexistence of both propeller and tweezer conformations in the solid state. GFN-1 exhibits strong binding affinities for fullerenes, leading to host-guest complexes that display rapid photoinduced electron transfer within a picosecond. The outcomes of this research could pave the way for the utilization of shape and electronically complementary nanocarbons in the construction of functional coassemblies.

Hearing loss in Australian First Nations children at 6-monthly assessments from age 12 to 36 months: Secondary outcomes from randomised controlled trials of novel pneumococcal conjugate vaccine schedules.

BACKGROUND: In Australian remote communities, First Nations children with otitis media (OM)-related hearing loss are disproportionately at risk of developmental delay and poor school performance, compared to those with normal hearing. Our objective was to compare OM-related hearing loss in children randomised to one of 2 pneumococcal conjugate vaccine (PCV) formulations. METHODS AND FINDINGS: In 2 sequential parallel, open-label, randomised controlled trials (the PREVIX trials), eligible infants were first allocated 1:1:1 at age 28 to 38 days to standard or mixed PCV schedules, then at age 12 months to PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S) (1:1). Here, we report prevalence and level of hearing loss outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. From March 2013 to September 2018, 261 infants were enrolled and 461 hearing assessments were performed. Prevalence of hearing loss was 78% (25/32) in the +P group and 71% (20/28) in the +S group at baseline, declining to 52% (28/54) in the +P groups and 56% (33/59) in the +S group at age 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% (9/42) in the +P group and 41% (20/49) in the +S group (difference -19%; (95% confidence interval (CI) [-38, -1], p = 0.07) and prevalence of no hearing loss was 36% (15/42) in the +P group and 16% (8/49) in the +S group (difference 19%; (95% CI [2, 37], p = 0.05). At subsequent time points, prevalence of moderate hearing loss remained lower in the +P group: differences -3%; (95% CI [-23, 18], p = 1.00 at age 24 months), -12%; (95% CI [-30, 6], p = 0.29 at age 30 months), and -9%; (95% CI [-23, 5], p = 0.25 at age 36 months). A major limitation was the small sample size, hence low power to reach statistical significance, thereby reducing confidence in the effect size. CONCLUSIONS: In this study, we observed a high prevalence and persistence of moderate (disabling) hearing loss throughout early childhood. We found a lower prevalence of moderate hearing loss and correspondingly higher prevalence of no hearing loss in the +P group, which may have substantial benefits for high-risk children, their families, and society, but warrant further investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01735084 and NCT01174849.

Recurrent otitis media and behaviour problems in middle childhood: A longitudinal cohort study.

AIM: To investigate the long-term effects of early-life recurrent otitis media (OM) and subsequent behavioural problems in children at the age of 10 years. METHODS: Data from the Raine Study, a longitudinal pregnancy cohort, were used to categorise children into those with three or more episodes of OM (rOM group) and those without a history of recurrent OM in the first 3 years of life (reference group). The parent report Strengths and Difficulties Questionnaire was used to assess child behaviour at the age of 10 years. Parental questionnaires were used to report past and present diagnoses of various mental health and developmental conditions, including attention, anxiety, depression, learning, and speech-language problems. Multiple linear and logistic models were used to analyse the data and were adjusted for a fixed set of key confounding variables. RESULTS: The linear regression analysis revealed significant, independent associations between a history of recurrent OM and higher Strengths and Difficulties Questionnaire scores, including total, internalising, externalising, emotional, attention/hyperactivity and peer problems subscales. Logistic regression analyses revealed an independent increased likelihood for children in the rOM group to have a diagnosis of attention, anxiety, learning and speech-language problems. CONCLUSION: Children at 10 years of age with an early history of recurrent OM are more likely to exhibit attentional and behavioural problems when compared to children without a history of recurrent OM. These findings highlight the association between early-life recurrent OM and later behavioural problems that may require professional allied health-care interventions.

Do parent-reported early indicators predict later developmental language disorder? A Raine Study investigation.

BACKGROUND: Developmental language disorder (DLD) is one of the most common neurodevelopmental conditions. Due to variable rates of language growth in children under 5 years, the early identification of children with DLD is challenging. Early indicators are often outlined by speech pathology regulatory bodies and other developmental services as evidence to empower caregivers in the early identification of DLD. AIMS: To test the predictive relationship between parent-reported early indicators and the likelihood of children meeting diagnostic criteria for DLD at 10 years of age as determined by standardized assessment measures in a population-based sample. METHODS: Data were leveraged from the prospective Raine Study (n = 1626 second-generation children: n = 104 with DLD; n = 1522 without DLD). These data were transformed into 11 predictor variables that reflect well-established early indicators of DLD from birth to 3 years, including if the child does not smile or interact with others, does not babble, makes only a few sounds, does not understand what others say, says only a few words, says words that are not easily understood, and does not combine words or put words together to make sentences. Family history (mother and father) of speech and language difficulties were also included as variables. Regression analyses were planned to explore the predictive relationship between this set of early indicator variables and likelihood of meeting DLD diagnostic criteria at 10 years. RESULTS: No single parent-reported indicator uniquely accounted for a significant proportion of children with DLD at 10 years of age. Further analyses, including bivariate analyses testing the predictive power of a cumulative risk index of combined predictors (odds ratio (OR) = 0.95, confidence interval (CI) = 0.85-1.09, p = 0.447) and the moderating effect of sex (OR = 0.89, CI = 0.59-1.32, p = 0.563) were also non-significant. CONCLUSIONS: Parent reports of early indicators of DLD are well-intentioned and widely used. However, data from the Raine Study cohort suggest potential retrospective reporting bias in previous studies. We note that missing data for some indicators may have influenced the results. Implications for the impact of using early indicators as evidence to inform early identification of DLD are discussed. WHAT THIS PAPER ADDS: What is already known on the subject DLD is a relatively common childhood condition; however, children with DLD are under-identified and under-served. Individual variability in early childhood makes identification of children at risk of DLD challenging. A range of 'red flags' in communication development are promoted through speech pathology regulatory bodies and developmental services to assist parents to identify if their child should access services. What this paper adds to the existing knowledge No one parent-reported early indicator, family history or a cumulation of indicators predicted DLD at 10 years in the Raine study. Sex (specifically, being male) did not moderate an increased risk of DLD at 10 years in the Raine study. Previous studies reporting on clinical samples may be at risk of retrospective reporting bias. What are the potential or actual clinical implications of this work? The broad dissemination and use of 'red flags' is well-intentioned; however, demonstrating 'red flags' alone may not reliably identify those who are at later risk of DLD. Findings from the literature suggest that parent concern may be complemented with assessment of linguistic behaviours to increase the likelihood of identifying those who at risk of DLD. Approaches to identification and assessment should be considered alongside evaluation of functional impact to inform participation-based interventions.

Impact of ventilation tube insertion on long-term language outcomes at 6 and 10 years of age: A prospective pregnancy cohort study.

OBJECTIVE: Investigating the impact of early childhood ventilation tube insertion (VTI) on long-term language outcomes. DESIGN: Longitudinal cohort study. SETTING: A total of 2900 pregnant women participated in the Raine Study between 1989 and 1991 in Western Australia, and 2868 children have been followed up. PARTICIPANTS: Based on parental reports, 314 children had a history of recurrent otitis media but did not undergo VTI (rOM group); another 94 received VTI (VTI group); while 1735 had no history of rOM (reference group) in the first 3 years of childhood. Children with data on outcomes and confounders were included in analyses of PPVT-R at ages 6 (n = 1567) and 10 years (n = 1313) and CELF-III at 10 years (n = 1410) (approximately 5% in the VTI group and 15% in the rOM group). MAIN OUTCOME MEASURES: Peabody Picture Vocabulary Test-Revised edition and Clinical Evaluation of Language Fundamentals® Preschool-3. RESULTS: At 6 years, mean PPVT-R scores were significantly lower in the VTI group than the reference group (ß = -3.3; 95% CI [-6.5 to -0.04], p = .047). At 10 years, while the difference between the VTI and reference groups was less pronounced for PPVT-R scores, there was a small but consistent trend of lower measures, on average, across CELF-III scores (expressive: ß = -3.4 [-7.1 to 0.27], p = .069; receptive: ß = -4.1 [-7.9 to -0.34], p = .033; total: ß = -3.9 [-7.5 to -0.21], p = .038). There was no evidence to suggest that language outcomes in the rOM group differed from the reference group. CONCLUSION: Lower scores of language outcomes in school-aged children who received VTI in early childhood may suggest a long-term risk which should be considered alongside the potential benefits of VTI.

Gas-Induced Electrical and Magnetic Modulation of Two-Dimensional Conductive Metal-Organic Framework.

Controlled modulation of electronic and magnetic properties in stimuli-responsive materials provides valuable insights for the design of magnetoelectric or multiferroic devices. This paper demonstrates the modulation of electrical and magnetic properties of a semiconductive, paramagnetic metal-organic framework (MOF) Cu3(C6O6)2 with small gaseous molecules, NH3, H2S, and NO. This study merges chemiresistive and magnetic tests to reveal that the MOF undergoes simultaneous changes in electrical conductance and magnetization that are uniquely modulated by each gas. The features of response, including direction, magnitude, and kinetics, are modulated by the physicochemical properties of the gaseous molecules. This study advances the design of multifunctional materials capable of undergoing simultaneous changes in electrical and magnetic properties in response to chemical stimuli.

Early onset of otitis media is a strong predictor of subsequent disease in urban Aboriginal infants: Djaalinj Waakinj cohort study.

AIM: Australian Aboriginal and/or Torres Strait Islander children in rural/remote areas suffer high rates of persistent otitis media (OM) from early infancy. We aimed to determine the proportion of Aboriginal infants living in an urban area who have OM and investigate associated risk factors. METHODS: Between 2017 and 2020, the Djaalinj Waakinj cohort study enrolled 125 Aboriginal infants at 0-12 weeks of age in the Perth South Metropolitan region, Western Australia. Proportion of children with OM based on tympanometry at ages 2, 6 and 12 months was evaluated, type B tympanogram indicating middle ear effusion. Potential risk factors were investigated by logistic regression with generalised estimating equations. RESULTS: The proportion of children with OM was 35% (29/83) at 2 months, 49% (34/70) at 6 months and 49% (33/68) at 12 months of age. About 70% (16/23) of those with OM at ages 2 and/or 6 months had OM at 12 months compared with 20% (3/15) if no prior OM (relative risk = 3.48, 95% confidence interval (CI): 1.22-40.1). On multivariate analysis, infants living in houses with ≥1 person/room were at increased risk of OM (odds ratio = 1.78, 95% CI: 0.96-3.32). CONCLUSION: Approximately half of Aboriginal infants enrolled into the South Metropolitan Perth project have OM by the age of 6 months and early onset of disease strongly predicts subsequent OM. Early surveillance for OM in urban areas is needed for early detection and management to reduce the risk of long-term hearing loss which can have serious developmental, social, behavioural, educational and economic consequences.

The use of patient-report measures and intervention strategies for children and adolescents with chronic tinnitus: a scoping review.

BACKGROUND: Chronic tinnitus during childhood/adolescence can be associated with impaired quality of life. Guidelines for managing paediatric tinnitus recommend assessment and interventions are often based upon the experiences and opinions of guideline committee members. OBJECTIVE: To examine patient response tools used for the assessment and management of childhood tinnitus and how interventions had been evaluated. DESIGN: A structured scoping review (i) identifying and critically appraising patient response measures (PRMs) assessing tinnitus in children/adolescents, and (ii) critically appraising evidence supporting reported interventions. Original papers written in English, involving paediatric participants ≤19 years, reporting (i) application of established PRMs to assess the experience of chronic tinnitus or (ii) application and evaluation of tinnitus interventions were included. STUDY SAMPLE: Papers written in English, identifying, or assessing the experience of chronic tinnitus (>3 months) as a primary complaint during childhood/adolescence in participants ≤19 years of age using a PRM and studies evaluating the application of non-pharmaceutical interventions for tinnitus in children/adolescents. RESULTS: Six studies involving the assessment of tinnitus during childhood/adolescence using a PRM were identified and evaluated. Three established (previously named, described, and published) PRMs were applied of which none were developed specifically for children/adolescents. Three behavioural tinnitus interventions and three combination intervention strategies (coupling of psychological intervention with sound enrichment) had been applied to and evaluated within paediatric populations. CONCLUSIONS: Although clinicians are seeing children/adolescents with tinnitus, they are evaluating and managing children's distress without appropriate PRMs, and little evidence exists to support clinical interventions.

Ear and hearing outcomes in Aboriginal infants living in an urban Australian area: the Djaalinj Waakinj birth cohort study.

OBJECTIVE: Describe the ear and hearing outcomes in Aboriginal infants in an Australian urban area. DESIGN: Aboriginal infants enrolled in the Djaalinj Waakinj prospective cohort study had ear health screenings at ages 2-4, 6-8 and 12-18 months and audiological assessment at ∼12 months of age. Sociodemographic, environmental characteristics, otoscopy, otoacoustic emissions, tympanometry and visual reinforcement audiometry data were collected. STUDY SAMPLE: 125 infants were enrolled in the study; 67 completed audiological assessment, 62, 54, and 58 of whom attended ear screenings at 2-4, 6-8 and 12-18 months. RESULTS: Of the children that attended the audiological assessment, 36.5%, 50% and 64.3% of infants had otitis media (OM) at 2-4, 6-8 and 12-18 months. Using a 10 dB correction factor, 44.8% of infants had hearing loss (HL) (≥ 25 dB HL) at ∼ 12 months of age. More males (X2=5.4 (1df, p = 0.02)) and infants with OM at audiological assessment (X2=5.8 (1df, p = 0.02)) had HL. More infants that used a pacifier at 12-18 months of age had HL (X2=4.7 (1df, p = 0.03)). CONCLUSION: Aboriginal infants in an urban area have high rates of HL and OM, which requires early surveillance and timely treatment to reduce the medical and developmental impacts of OM and HL.

The prevalence of and potential risk factors for Developmental Language Disorder at 10 years in the Raine Study.

AIM: This study sought to determine the prevalence of Developmental Language Disorder (DLD) in Australian school-aged children and associated potential risk factors for DLD at 10 years. METHODS: This study used a cross-sectional design to estimate the prevalence of DLD in Generation 2 of the prospective Raine Study. Participants included 1626 children aged 10 years with available language data. Primary outcomes included variables matching diagnostic criteria for DLD. Associations of other potential prenatal and environmental variables were analysed as secondary outcomes. RESULTS: The prevalence of DLD in this sample was 6.4% (n = 104) at 10 years. This sub-cohort comprised 33.7% (n = 35) with expressive language deficits, 20.2% (n = 21) with receptive language deficits, and 46.2% (n = 48) with receptive-expressive deficits. No significant difference in sex distribution was observed (52.9% male, p = 0.799). Children who were exposed to smoke in utero at 18 weeks gestation were at increased risk of DLD at 10 years (OR = 2.56, CI = 1.23-5.35, p = 0.012). CONCLUSIONS: DLD is a relatively prevalent condition in Australian children, even when assessed in middle childhood years. These findings can inform future research priorities, and public health and educational policy which account for the associations with potential risk factors.

The reliability of video otoscopy recordings and still images in the asynchronous diagnosis of middle-ear disease.

OBJECTIVE: To compare the asynchronous assessment of video otoscopic still images to recordings by an audiologist and ear, nose and throat surgeon (ENT) for diagnostic reliability and agreement in identifying middle-ear disease. DESIGN: A prospective cross-sectional study, asynchronously assessing video otoscopy, tympanometry and case history (Dx1). A subset was re-diagnosed (Dx2). STUDY SAMPLE: Video otoscopy and data from 146 children recruited at two public community events; a sub-set of 47 were re-assessed. RESULTS: The intra-rater diagnostic agreement between Dx1 and Dx2 was moderate (k = 0.445-0.552) for the ENT surgeon, and almost-perfect (k = 0.928) for the audiologist, in both procedures. The agreement between the two procedures was substantial (k = 0.624) and moderate (k = 0.416) for the ENT surgeon in Dx1 and Dx2 respectively, and almost-perfect for the audiologist (k = 0.854-0.978) in both rounds. In Dx1, the inter-rater agreement between the clinicians was substantial using still images (k = 0.672) and moderate using recordings (k = 0.593); in Dx2 it was moderate using both procedures (k = 0.477-0.488). CONCLUSION: Both video otoscopic procedures, in addition to tympanometry and case history information, can be reliably used for asynchronous diagnosis of childhood middle-ear disease. An audiologist has a potential role in triaging children with middle-ear abnormalities and, therefore, improving access to ear-health services.

Unraveling the Electrical and Magnetic Properties of Layered Conductive Metal-Organic Framework With Atomic Precision.

This paper describes structural elucidation of a layered conductive metal-organic framework (MOF) material Cu3 (C6 O6 )2 by microcrystal electron diffraction with sub-angstrom precision. This insight enables the first identification of an unusual π-stacking interaction in a layered MOF material characterized by an extremely short (2.73 Å) close packing of the ligand arising from pancake bonding and ordered water clusters within pores. Band structure analysis suggests semiconductive properties of the MOF, which are likely related to the localized nature of pancake bonds and the formation of a singlet dimer of the ligand. The spin of CuII within the Kagomé arrangement dominates the paramagnetism of the MOF, leading to strong geometrical magnetic frustration.

Enhanced Gearing Fidelity Achieved Through Macrocyclization of a Solvated Molecular Spur Gear.

Molecular spur gear dynamics with high gearing fidelity can be achieved through a careful selection of constituent molecular components that favorably position and maintain the two gears in a meshed configuration. Here, we report the synthesis of a new macrocyclic molecular spur gear with a bibenzimidazole stator combined with a second naphthyl bis-gold-phosphine gold complex stator to place two 3-fold symmetric 9,10-diethynyl triptycene cogs at the optimal distance of 8.1 Å for gearing. Micro electron diffraction (µED) analysis confirmed the formation of the macrocyclic structure and the proper alignment of the triptycene cogs. Gearing dynamics in solution are predicted to be extremely fast and, in fact, were too fast to be observed with variable-temperature 1H NMR using CD2Cl2 as the solvent. A combination of molecular dynamics and metadynamics simulations predict that the barriers for gearing and slippage are ca. 4 kcal mol-1 and ca. 9 kcal mol-1, respectively. This system is characterized by enhanced gearing fidelity compared to the acyclic analog. This is achieved by rigidification of the structure, locking the two triptycenes in the preferred gearing distance and orientation.

Otitis media guidelines for Australian Aboriginal and Torres Strait Islander children: summary of recommendations.

INTRODUCTION: The 2001 Recommendations for clinical care guidelines on the management of otitis media in Aboriginal and Torres Islander populations were revised in 2010. This 2020 update by the Centre of Research Excellence in Ear and Hearing Health of Aboriginal and Torres Strait Islander Children used for the first time the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. MAIN RECOMMENDATIONS: We performed systematic reviews of evidence across prevention, diagnosis, prognosis and management. We report ten algorithms to guide diagnosis and clinical management of all forms of otitis media. The guidelines include 14 prevention and 37 treatment strategies addressing 191 questions. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINES: A GRADE approach is used. Targeted recommendations for both high and low risk children. New tympanostomy tube otorrhoea section. New Priority 5 for health services: annual and catch-up ear health checks for at-risk children. Antibiotics are strongly recommended for persistent otitis media with effusion in high risk children. Azithromycin is strongly recommended for acute otitis media where adherence is difficult or there is no access to refrigeration. Concurrent audiology and surgical referrals are recommended where delays are likely. Surgical referral is recommended for chronic suppurative otitis media at the time of diagnosis. The use of autoinflation devices is recommended for some children with persistent otitis media with effusion. Definitions for mild (21-30 dB) and moderate (> 30 dB) hearing impairment have been updated. New "OMapp" enables free fast access to the guidelines, plus images, animations, and multiple Aboriginal and Torres Strait Islander language audio translations to aid communication with families.

Whole-cell pertussis vaccine in early infancy for the prevention of allergy in children.

BACKGROUND: Atopic diseases are the most common chronic conditions of childhood. The apparent rise in food anaphylaxis in young children over the past three decades is of particular concern, owing to the lack of proven prevention strategies other than the timely introduction of peanut and egg. Due to reported in vitro differences in the immune response of young infants primed with whole-cell pertussis (wP) versus acellular pertussis (aP) vaccine, we systematically appraised and synthesised evidence on the safety and the potential allergy preventive benefits of wP, to inform recommendation for future practice and research. OBJECTIVES: To assess the efficacy and safety of wP vaccinations in comparison to aP vaccinations in early infancy for the prevention of atopic diseases in children. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Embase, and grey literature. The date of the search was 7 September 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) that reported the occurrence of atopic diseases, and RCTs only to assess safety outcomes. To be included studies had to have at least six months follow-up, and involve children under 18 years old, who received a first dose of either wP (experimental intervention) or aP (comparator) before six months of age. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies for eligibility, extracted the data, and assessed risk of bias using standard Cochrane methods. We assessed the certainty of the evidence using GRADE. Our primary outcomes were diagnosis of IgE-mediated food allergy and all-cause serious adverse events (SAEs). Secondary outcomes included: diagnosis of not vaccine-associated anaphylaxis or urticaria, diagnosis of asthma, diagnosis of allergic rhinitis, diagnosis of atopic dermatitis and diagnosis of encephalopathy. Due to paucity of RCTs reporting on the atopic outcomes of interest, we assessed a broader outcome domain (cumulative incidence of atopic disease) as specified in our protocol. We summarised effect estimates as risk ratios (RR) and 95% confidence intervals (CI). Where appropriate, we pooled safety data in meta-analyses using fixed-effect Mantel-Haenszel methods, without zero-cell corrections for dichotomous outcomes. MAIN RESULTS: We identified four eligible studies reporting on atopic outcomes, representing 7333 children. Based on a single trial, there was uncertain evidence on whether wP vaccines affected the risk of overall atopic disease (RR 0.85, 95% CI 0.62 to 1.17) or asthma only (RR 1.04, 95% CI 0.59 to 1.82; 497 children) by 2.5 years old.Three NRSIs were judged to be at serious or critical risk of bias due to confounding, missing data, or both, and were ineligible for inclusion in a narrative synthesis.  We identified 21 eligible studies (137,281 children) that reported the safety outcomes of interest. We judged seven studies to be at high risk of bias and those remaining, at unclear risk.  The pooled RR was 0.94 for all-cause SAEs (95% CI 0.78 to 1.15; I2 = 0%; 15 studies, 38,072 children). For every 1000 children primed with a first dose of wP, 11 had an SAE. The corresponding risk with aP was 12 children (95% CI 9 to 13). The 95% CI around the risk difference ranged from three fewer to two more events per 1000 children, and the certainty of the evidence was judged as moderate (downgraded one level for imprecision). No diagnoses of encephalopathy following vaccination were reported (95% CI around the risk difference - 5 to 12 per 100,000 children; seven primary series studies; 115,271 children). The certainty of the evidence was judged as low, since this is a serious condition, and we could not exclude a clinically meaningful difference. AUTHORS' CONCLUSIONS: There is very low-certainty evidence that a first dose of wP given early in infancy, compared to a first dose of aP, affects the risk of atopic diseases in children. The incidence of all-cause SAEs in wP and aP vaccinees was low, and no cases of encephalopathy were reported. The certainty of the evidence was judged as moderate for all-cause SAEs, and low for encephalopathy. Future studies should use sensitive and specific endpoints of clinical relevance, and should be conducted in settings with high prevalence of IgE-mediated food allergy. Safety endpoints should prioritise common vaccine reactions, parental acceptability, SAEs and their potential relatedness to the dose administered.

Systemic antibiotics for chronic suppurative otitis media.

BACKGROUND: Chronic suppurative otitis media (CSOM) is a chronic inflammation and infection of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Systemic antibiotics are a commonly used treatment option for CSOM, which act to kill or inhibit the growth of micro-organisms that may be responsible for the infection. Antibiotics can be used alone or in addition to other treatments for CSOM. OBJECTIVES: To assess the effects of systemic antibiotics for people with CSOM. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 16 March 2020. SELECTION CRITERIA: We included randomised controlled trials comparing systemic antibiotics (oral, injection) against placebo/no treatment or other systemic antibiotics with at least a one-week follow-up period, involving patients with chronic (at least two weeks) ear discharge of unknown cause or due to CSOM. Other treatments were allowed if both treatment and control arms also received it. DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not, measured at between one week and up to two weeks, two weeks to up to four weeks, and after four weeks); health-related quality of life using a validated instrument; ear pain (otalgia) or discomfort or local irritation. Secondary outcomes included hearing, serious complications and ototoxicity measured in several ways. MAIN RESULTS: We included 18 studies (2135 participants) with unclear or high risk of bias. 1. Systemic antibiotics versus no treatment/placebo It is very uncertain if there is a difference between systemic (intravenous) antibiotics and placebo in the resolution of ear discharge at between one and two weeks (risk ratio (RR) 8.47, 95% confidence interval (CI) 1.88 to 38.21; 33 participants; 1 study; very low-certainty evidence). The study did not report results for resolution of ear discharge after two weeks. Health-related quality of life was not reported. The evidence is very uncertain for hearing and serious (intracranial) complications. Ear pain and suspected ototoxicity were not reported. 2. Systemic antibiotics versus no treatment/placebo (both study arms received topical antibiotics) Six studies were included of which five presented useable data. There may be little or no difference in the resolution of ear discharge at between one to two weeks for oral ciprofloxacin compared to placebo or no treatment when ciprofloxacin ear drops were used in both intervention arms (RR 1.02, 95% CI 0.93 to 1.12; 390 participants; low-certainty evidence). No results after two weeks were reported. Health-related quality of life was not reported. The evidence is very uncertain for ear pain, serious complications and suspected ototoxicity. 3. Systemic antibiotics versus no treatment/placebo (both study arms received other background treatments) Two studies used topical antibiotics plus steroids as background treatment in both arms. It is very uncertain if there is a difference in resolution of ear discharge between metronidazole and placebo at four weeks (RR 0.91, 95% CI 0.51 to 1.65; 40 participants; 1 study; very low-certainty evidence). This study did not report other outcomes. It is also very uncertain if resolution of ear discharge at six weeks was improved with co-trimoxazole compared to placebo (RR 1.54, 95% CI 1.09 to 2.16; 98 participants; 1 study; very low-certainty evidence). Resolution of ear discharge was not reported at other time points. From the narrative report there was no evidence of a difference between groups for health-related quality of life, hearing or serious complications (very low-certainty evidence). One study (136 participants) used topical antiseptics as background treatment in both arms and found similar resolution of ear discharge between the amoxicillin and no treatment groups at three to four months (RR 1.03, 95% CI 0.75 to 1.41; 136 participants; 1 study; very low-certainty evidence). The narrative report indicated no evidence of differences in hearing or suspected ototoxicity (both very low-certainty evidence). No other outcomes were reported. 4. Different types of systemic antibiotics This is a summary of four comparisons, where different antibiotics were compared to each other. Eight studies compared different types of systemic antibiotics against each other: quinolones against beta-lactams (four studies), lincosamides against nitroimidazoles (one study) and comparisons of different types of beta-lactams (three studies). It was not possible to conclude if there was one class or type of systemic antibiotic that was better in terms of resolution of ear discharge. The studies did not report adverse events well. AUTHORS' CONCLUSIONS: There was a limited amount of evidence available to examine whether systemic antibiotics are effective in achieving resolution of ear discharge for people with CSOM. When used alone (with or without aural toileting), we are very uncertain if systemic antibiotics are more effective than placebo or no treatment. When added to an effective intervention such as topical antibiotics, there seems to be little or no difference in resolution of ear discharge (low-certainty evidence). Data were only available for certain classes of antibiotics and it is very uncertain whether one class of systemic antibiotic may be more effective than another. Adverse effects of systemic antibiotics were poorly reported in the studies included. As we found very sparse evidence for their efficacy, the possibility of adverse events may detract from their use for CSOM.

Topical versus systemic antibiotics for chronic suppurative otitis media.

BACKGROUND: Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and often polymicrobial infection (involving more than one micro-organism) of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Antibiotics are the most common treatment for CSOM, which act to kill or inhibit the growth of micro-organisms that may be responsible for the infection. Antibiotics can be administered both topically and systemically, and can be used alone or in addition to other treatments for CSOM such as ear cleaning (aural toileting). OBJECTIVES: To assess the effects of topical versus systemic antibiotics for people with CSOM. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 16 March 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with at least a one-week follow-up involving patients (adults and children) who had chronic ear discharge of unknown cause or CSOM, where the ear discharge had continued for more than two weeks. The studies compared topical antibiotics against systemic (oral, injection) antibiotics. We separated studies according to whether they compared the same type of antibiotic in both treatment groups, or different types of antibiotics. For each comparison we considered whether there was background treatment for both treatment groups, for example aural toileting (ear cleaning). DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not, measured at between one week and up to two weeks, two weeks up to four weeks, and after four weeks), health-related quality of life using a validated instrument, ear pain (otalgia) or discomfort or local irritation. Secondary outcomes included hearing, serious complications and ototoxicity measured in several ways. MAIN RESULTS: Six studies (445 participants), all with high risk of bias, were included. All but two studies included patients with confirmed CSOM, where perforation of the ear drum was clearly documented. None of the studies reported results for resolution of ear discharge after four weeks or health-related quality of life. 1. Topical versus systemic administration of the same type of antibiotics (quinolones) Four studies (325 participants) compared topical versus systemic (oral) administration of ciprofloxacin. Three studies reported resolution of ear discharge at one to two weeks and found that the topical administration may slightly increase resolution (risk ratio (RR) 1.48, 95% confidence interval (CI) 1.24 to 1.76; 285 participants; 3 studies; I2 = 0%; low-certainty evidence). In these studies, aural toileting was either not mentioned, or limited to the first visit. Three studies (265 participants) reported that they did not suspect ototoxicity in any participants, but it is unclear how this was measured (very low-certainty evidence). No studies reported the outcomes of ear pain or serious complications. No studies reported results for hearing, despite it being measured in three studies. 2. Topical versus systemic administration of different types of antibiotics (quinolones versus aminoglycosides) One study (60 participants) compared topical ciprofloxacin versus gentamicin injected intramuscularly. No aural toileting was reported. Resolution of ear discharge was not measured at one to two weeks. The study did not report any 'side effects' from which we assumed that no ear pain, suspected ototoxicity or serious complications occurred (very low-certainty evidence). The study stated that "no worsening of the audiometric function related to local or parenteral therapy was observed". 3. Topical versus systemic administration of different types of antibiotics (quinolones versus amoxicillin-clavulanic acid) One study compared topical ofloxacin with amoxicillin-clavulanic acid with all participants receiving suction ear cleaning at the first visit. It is uncertain if there is a difference between the two groups in resolution of ear discharge at one to two weeks due to study limitations and the very small sample size (RR 2.93, 95% CI 1.50 to 5.72; 56 participants; very low-certainty evidence). It is unclear if there is a difference between topical quinolone compared with oral amoxicillin-clavulanic acid with regards to ear pain, hearing or suspected ototoxicity (very low-certainty evidence). No studies reported the outcome of serious complications. AUTHORS' CONCLUSIONS: There was a limited amount of low-quality evidence available, from studies completed over 15 years ago, to examine whether topical or systemic antibiotics are more effective in achieving resolution of ear discharge for people with CSOM. However, amongst this uncertainty there is some evidence to suggest that the topical administration of antibiotics may be more effective than systemic administration of antibiotics in achieving resolution of ear discharge (dry ear). There is limited evidence available regarding different types of antibiotics. It is not possible to determine with any certainty whether or not topical quinolones are better or worse than systemic aminoglycosides. These two groups of compounds have different adverse effect profiles, but there is insufficient evidence from the included studies to make any comment about these. In general, adverse effects were poorly reported.

Teleaudiology hearing aid fitting follow-up consultations for adults: single blinded crossover randomised control trial and cohort studies.

OBJECTIVE: To evaluate and compare the effectiveness and quality of standard face-to-face and teleaudiology hearing aid fitting follow-up consultations and blended services for adult hearing aid users. DESIGN AND STUDY SAMPLE: Fifty-six participants were randomly allocated to two equal groups, with equal numbers of new and experienced users. One standard and one teleaudiology follow-up consultation were delivered by an audiologist, the latter assisted by a facilitator. The order was reversed for the second group. Outcome measurement tools were applied to assess aspects of participants' communication, fitting (physical, sensorial), quality of life, and service. Cross-sectional and longitudinal outcomes were analysed. RESULTS: Most participants presented with moderate, sloping, and symmetrical sensorineural hearing loss. The duration of teleaudiology (42.96 ± 2.73 min) was equivalent to face-to-face consultations (41.25 ± 2.61 min). All modes of service delivery significantly improved outcomes for communication, fitting, and quality of life (p > 0.05). Satisfaction for both consultation modes was high, although significantly greater with standard consultations. The mode and order of delivery of the consultations did not influence the outcomes. CONCLUSION: Teleaudiology hearing aid follow-up consultations can deliver significant improvements, and do not differ from standard consultations. Blended services also deliver significant improvements. Satisfaction can be negatively impacted by technical or human-related issues.

Elucidation of Diverse Solid-State Packing in a Family of Electron-Deficient Expanded Helicenes via Microcrystal Electron Diffraction (MicroED)*.

Solid-state packing plays a defining role in the properties of a molecular organic material, but it is difficult to elucidate in the absence of single crystals that are suitable for X-ray diffraction. Herein, we demonstrate the coupling of divergent synthesis with microcrystal electron diffraction (MicroED) for rapid assessment of solid-state packing motifs, using a class of chiral nanocarbons-expanded helicenes-as a proof of concept. Two highly selective oxidative dearomatizations of a readily accessible helicene provided a divergent route to four electron-deficient analogues containing quinone or quinoxaline units. Crystallization efforts consistently yielded microcrystals that were unsuitable for single-crystal X-ray diffraction, but ideal for MicroED. This technique facilitated the elucidation of solid-state structures of all five compounds with <1.1 Šresolution. The otherwise-inaccessible data revealed a range of notable packing behaviors, including four different space groups, homochirality in a crystal for a helicene with an extremely low enantiomerization barrier, and nanometer scale cavities.