To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Otitis media (OM) is a common reason for children to be prescribed antibiotics and undergo surgery but a thorough understanding of disease mechanisms is lacking. We evaluate the evidence of a dysregulated immune response in the pathogenesis of OM.
A comprehensive systematic review of the literature using search terms [otitis media OR glue ear OR AOM OR OME] OR [middle ear AND (infection OR inflammation)] which were run through Medline and Embase via Ovid, including both human and animal studies. In total, 82 955 studies underwent automated filtering followed by manual screening. One hundred studies were included in the review.
Most studies were based on in vitro or animal work. Abnormalities in pathogen detection pathways, such as Toll-like receptors, have confirmed roles in OM. The aetiology of OM, its chronic subgroups (chronic OM, persistent OM with effusion) and recurrent acute OM is complex; however, inflammatory signalling mechanisms are frequently implicated. Host epithelium likely plays a crucial role, but the characterisation of human middle ear tissue lags behind that of other anatomical subsites.
Translational research for OM presently falls far behind its clinical importance. This has likely hindered the development of new diagnostic and treatment modalities. Further work is urgently required; particularly to disentangle the respective immune pathologies in the clinically observed phenotypes and thereby work towards more personalised treatments.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
Fungal otitis externa is prevalent in tropical and sub-tropical climates; however, over the past two decades, there has been a reported increase in the prevalence of otomycosis in paediatric patients from more temperate climates. This study aimed to review the children diagnosed with otomycosis at the University Hospital Limerick with reference to frequency, causative organism, predisposing factors and management.
A retrospective review was conducted of paediatric patients from 2001 to 2015. Patients with positive fungal ear swabs and a diagnosis of otomycosis were identified.
Ninety-three patients were positive for candida (mean age, 5.8 years), 10 patients were positive for aspergillus (mean age, 9.1 years) and 1 patient had mixed fungal infection containing both fungi. There was a positive correlation between a diagnosis of otomycosis and prior treatment with topical fluoroquinolones (r = 0.8; p < 0.01).
The incidence of otomycosis has been increasing since 2001, which correlates with an increase in the use of topical fluoroquinolones. Previous studies identify aspergillus as the commonest causative fungi; however, this study found that candida was the commonest isolated fungi in the paediatric population.
Mastoiditis is the most common intra-temporal complication of acute otitis media. Despite potentially lethal sequelae, optimal management remains poorly defined.
A retrospective case review was conducted of children diagnosed with mastoiditis at a tertiary referral centre, in North East England, between 2010 and 2017.
Fifty-one cases were identified, 49 without cholesteatoma. Median patient age was 42 months (2 months to 18 years) and median hospital stay was 4 days (range, 0–27 days). There was no incidence trend over time. Imaging was conducted in 15 out of 49 cases. Surgery was performed in 29 out of 49 cases, most commonly mastoidectomy with (9 out of 29) or without (9 out of 29) grommets. Complications included sigmoid sinus thrombosis (3 out of 49) and extradural abscess (2 out of 51), amongst others; no fatalities occurred.
A detailed contemporary description of paediatric mastoiditis presentation and management is presented. The findings broadly mirror those published by other UK centres, but suggest a higher rate of identified disease complications and surgical interventions.
Mastoiditis is an otological emergency, and cross-sectional imaging has a role in the diagnosis of complications and surgical planning. Advances in imaging technology are becoming increasingly sophisticated and, by the same token, the ability to accurately interpret findings is essential.
This paper reviews common and rare complications of mastoiditis using case-led examples. A radiologist-derived systematic checklist is proposed, to assist the ENT surgeon with interpreting cross-sectional imaging in emergency mastoiditis cases when the opinion of a head and neck radiologist may be difficult to obtain.
A 16-point checklist (the ‘mastoid 16’) was used on a case-led basis to review the radiological features of both common and rare complications of mastoiditis; this is complemented with imaging examples.
Acute mastoiditis has a range of serious complications that may be amenable to treatment, once diagnosed using appropriate imaging. The proposed checklist provides a systematic approach to identifying complications of mastoiditis.
The objective of this study was to systematically assess the literature regarding postnatal healthcare utilization and barriers/facilitators of healthcare in neonatal abstinence syndrome (NAS) children.
A systematic search was performed in PubMed, Cochrane Database of Systematic Reviews, PsychINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science to identify peer-reviewed research. Eligible studies were peer-reviewed articles reporting on broad aspects of primary and specialty healthcare utilization and access in NAS children. Three investigators independently reviewed all articles and extracted data. Study bias was assessed using the Newcastle–Ottawa Assessment Scale and the National Institute of Health Study Quality Assessment Tool.
This review identified 14 articles that met criteria. NAS children have poorer outpatient appointment adherence and have a higher rate of being lost to follow-up. These children have overall poorer health indicated by a significantly higher risk of ER visits, hospital readmission, and early childhood mortality compared with non-NAS infants. Intensive multidisciplinary support provided through outpatient weaning programs facilitates healthcare utilization and could serve as a model that could be applied to other healthcare fields to improve the health among this population.
This review investigated the difficulties in accessing outpatient care as well as the utilization of such care for NAS infants. NAS infants tend to have decreased access to and utilization of outpatient healthcare following hospital birth discharge. Outpatient weaning programs have proven to be effective; however, these programs require intensive resources and care coordination that has yet to be implemented into other healthcare areas for NAS children.
Introduction: Although oral rehydration therapy is recommended for children with acute gastroenteritis (AGE) with none to some dehydration, intravenous (IV) rehydration is still commonly administered to these children in high-income countries. IV rehydration is associated with pain, anxiety, and emergency department (ED) revisits in children with AGE. A better understanding of the factors associated with IV rehydration is needed to inform knowledge translation strategies. Methods: This was a planned secondary analysis of the Pediatric Emergency Research Canada (PERC) and Pediatric Emergency Care Applied Research Network (PECARN) randomized, controlled trials of oral probiotics in children with AGE-associated diarrhea. Eligible children were aged 3-48 months and reported > 3 watery stools in a 24-hour period. The primary outcome was administration of IV rehydration at the index ED visit. We used mixed-effects logistic regression model to explore univariable and multivariable relationships between IV rehydration and a priori risk factors. Results: From the parent study sample of 1848 participants, 1846 had data available for analysis: mean (SD) age of 19.1 ± 11.4 months, 45.4% females. 70.2% (1292/1840) vomited within 24 hours of the index ED visit and 34.1% (629/1846) received ondansetron in the ED. 13.0% (240/1846) were administered IV rehydration at the index ED visit, and 3.6% (67/1842) were hospitalized. Multivariable predictors of IV rehydration were Clinical Dehydration Scale (CDS) score [compared to none: mild to moderate (OR: 8.1, CI: 5.5-11.8); severe (OR: 45.9, 95% CI: 20.1-104.7), P < 0.001], ondansetron in the ED (OR: 1.8, CI: 1.2-2.6, P = 0.003), previous healthcare visit for the same illness [compared to no prior visit: prior visit with no IV (OR: 1.9, 95% CI: 1.3-2.9); prior visit with IV (OR: 10.5, 95% CI: 3.2-34.8), P < 0.001], and country [compared to Canada: US (OR: 4.1, CI: 2.3-7.4, P < 0.001]. Significantly more participants returned to the ED with symptoms of AGE within 3 days if IV fluids were administered at the index visit [30/224 (13.4%) versus 88/1453 (6.1%), P < 0.001]. Conclusion: Higher CDS scores, antiemetic use, previous healthcare visits and country were independent predictors of IV rehydration which was also associated with increased ED revisits. Knowledge translation focused on optimizing the use of antiemetics (i.e. for those with dehydration) and reducing the geographic variation in IV rehydration use may improve the ED experience and reduce ED-revisits.
We sought to define the prevalence of echocardiographic abnormalities in long-term survivors of paediatric hematopoietic stem cell transplantation and determine the utility of screening in asymptomatic patients. We analysed echocardiograms performed on survivors who underwent hematopoietic stem cell transplantation from 1982 to 2006. A total of 389 patients were alive in 2017, with 114 having an echocardiogram obtained ⩾5 years post-infusion. A total of 95 patients had echocardiogram performed for routine surveillance. The mean time post-hematopoietic stem cell transplantation was 13 years. Of 95 patients, 77 (82.1%) had ejection fraction measured, and 10/77 (13.0%) had ejection fraction z-scores ⩽−2.0, which is abnormally low. Those patients with abnormal ejection fraction were significantly more likely to have been exposed to anthracyclines or total body irradiation. Among individuals who received neither anthracyclines nor total body irradiation, only 1/31 (3.2%) was found to have an abnormal ejection fraction of 51.4%, z-score −2.73. In the cohort of 77 patients, the negative predictive value of having a normal ejection fraction given no exposure to total body irradiation or anthracyclines was 96.7% at 95% confidence interval (83.3–99.8%). Systolic dysfunction is relatively common in long-term survivors of paediatric hematopoietic stem cell transplantation who have received anthracyclines or total body irradiation. Survivors who are asymptomatic and did not receive radiation or anthracyclines likely do not require surveillance echocardiograms, unless otherwise indicated.
Filamentary structures can form within the beam of protons accelerated during the interaction of an intense laser pulse with an ultrathin foil target. Such behaviour is shown to be dependent upon the formation time of quasi-static magnetic field structures throughout the target volume and the extent of the rear surface proton expansion over the same period. This is observed via both numerical and experimental investigations. By controlling the intensity profile of the laser drive, via the use of two temporally separated pulses, both the initial rear surface proton expansion and magnetic field formation time can be varied, resulting in modification to the degree of filamentary structure present within the laser-driven proton beam.
Introduction: Emergency Department Overcrowding (EDOC) is a multifactorial issue that leads to Access Block for patients needing emergency care. Identified as a national problem, patients presenting to a Canadian Emergency Department (ED) at a time of overcrowding have higher rates of admission to hospital and increased seven-day mortality. Using the well accepted input-throughput-output model to study EDOC, current research has focused on throughput as a measure of patient flow, reported as ED length of stay (LOS). In fact, ED LOS and ED beds occupied by inpatients are two “extremely important indicators of EDOC identified by a 2005 survey of Canadian ED directors. One proposed solution to improve ED throughput is to utilize a physician at triage (PAT) to rapidly assess newly arriving patients. In 2017, a pilot PAT program was trialed at Kelowna General Hospital (KGH), a tertiary care hospital, as part of a PDSA cycle. The aim was to mitigate EDOC by improving ED throughput by the end of 2018, to meet the national targets for ED LOS suggested in the 2013 CAEP position statement. Methods: During the fiscal periods 1-6 (April 1 to September 7, 2017) a PAT shift occurred daily from 1000-2200, over four long weekends. ED LOS, time to inpatient bed, time to physician initial assessment (PIA), number of British Columbia Ambulance Service (BCAS) offload delays, and number of patients who left without being seen (LWBS) were extracted from an administrative database. Results were retrospectively analyzed and compared to data from 1000-2200 of non-PAT trial days during the trial periods. Results: Median ED LOS decreased from 3.8 to 3.4 hours for high-acuity patients (CTAS 1-3), from 2.1 to 1.8 hours for low-acuity patients (CTAS 4-5), and from 9.3 to 8.0 hours for all admitted patients. During PAT trial weekends, there was a decrease in the average time to PIA by 65% (from 73 to 26 minutes for CTAS 2-5), average number of daily BCAS offload delays by 39% (from 2.3 to 1.4 delays per day), and number of patients who LWBS from 2.4% to 1.7%. Conclusion: The implementation of PAT was associated with improvements in all five measures of ED throughput, providing a potential solution for EDOC at KGH. ED LOS was reduced compared to non-PAT control days, successfully meeting the suggested national targets. PAT could improve efficiency, resulting in the ability to see more patients in the ED, and increase the quality and safety of ED practice. Next, we hope to prospectively evaluate PAT, continuing to analyze these process measures, perform a cost-benefit analysis, and formally assess ED staff and patient perceptions of the program.
To report a novel management strategy for mixed hearing loss in advanced otosclerosis.
A 50-year-old male was referred to St Thomas’ Hearing Implant Centre with otosclerosis; he was no longer able to wear conventional hearing aids because of recurrent otitis externa. The patient underwent short process incus vibroplasty (using the Med-El Vibrant Soundbridge device), followed at a suitable interval (six weeks) by stapes surgery. The main outcome measures were: pure tone audiometry, functional gain and monosyllabic word recognition scores.
Post-operative pure tone audiometry showed a reduction of the mean air–bone gap from 55 dB HL to 20 dB HL. The residual mixed hearing loss was rehabilitated with the Vibrant Soundbridge, with an average device gain of 32 dB. The monosyllabic word recognition scores in quiet at 65 dB improved from 37 to 100 per cent when using the Vibrant Soundbridge at six months after switch-on of the device.
Stapedotomy in conjunction with incus short process vibroplasty (i.e. inner-ear vibroplasty) is a safe and promising procedure for managing advanced otosclerosis with mixed hearing loss in selected patients.
A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.
This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.
The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.
The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
Eslicarbazepine is a novel anti-epileptic agent indicated for the treatment of partial-onset seizures. We present the case of an 18 year old female that presented to the Emergency Department four hours after a reported intentional ingestion of an estimated 5600 mg of eslicarbazepine. Although initially hemodynamically stable and neurologically normal, shortly after arrival she developed confusion, rigidity and clonus, followed by recurrent seizures, hypoxemia and cardiac arrest which responded to cardiopulmonary resuscitation and wide complex tachycardia requiring defibrillation. Treatment for refractory seizures included benzodiazepines and eventual intubation and sedation with propofol. Cardiac toxicity responded to sodium bicarbonate. In addition, empiric hemodialysis was performed. In this case report, we discuss the successful management of the first reported overdose of eslicarbazepine using supportive care and hemodialysis.
Background: The diagnosis of a sports-related concussion is often dependent on the athlete self-reporting their symptoms. It has been suggested that improving youth athlete knowledge and attitudes toward concussion may increase self-reporting behaviour. The objective of this study was to determine if a novel Concussion-U educational program improves knowledge of and attitudes about concussion among a cohort of elite male Bantam and Midget AAA hockey players. Methods: Fifty-seven male Bantam and Midget AAA-level hockey players (mean age=14.52±1.13 years) were recruited from the local community. Each participant completed a modified version of the Rosenbaum Concussion Knowledge and Attitudes Survey–Student Version immediately before and after a Concussion-U educational presentation. Follow-up sessions were arranged 4 to 6 months after the presentation, and assessed retention of knowledge and attitude changes. Results: Forty-three players completed all three surveys. Concussion knowledge and attitude scores significantly (p<0.01) increased from pre- to post-presentation by 12.79 and 8.41%, respectively. At long-term follow-up, knowledge levels remained significantly (p<0.01) higher than baseline by 8.49%. Mean attitude scores were also increased at follow-up; however, this increase was not statistically significant. Conclusions: A Concussion-U educational program led to an immediate improvement in concussion knowledge and attitudes among elite male Bantam and Midget AAA hockey players. Increased knowledge was maintained at long-term follow-up, but improved attitude was not. Future studies should investigate whether similar educational programs influence symptom reporting and concussion incidence. In addition, they should focus on how to maintain improved concussion attitudes.