Poor correlation between airway fluoroscopy and rigid bronchoscopic evaluation in paediatric tracheomalacia.

INTRODUCTION: Tracheomalacia is a common congenital condition causing stridor in young children. However, the evaluation of these children remains poorly standardised across institutions. METHODS: We conducted a retrospective review of all children undergoing an elective laryngotracheobronchoscopy at a single tertiary paediatric institution between March 2010 and December 2018. Emergency bronchoscopies and children with tracheostomies were excluded. 1163 children undergoing an elective bronchoscopy were included in this study, and 545 children also had an airway fluoroscopy. RESULTS: The median age at bronchoscopy was 17 months, and the majority of children were male. Tracheomalacia was diagnosed in 21.6% of children at bronchoscopy, of these 48.5% had tracheomalacia diagnosed on a previous airway fluoroscopy. Overall, airway fluoroscopy had a low sensitivity (62.3%) and a low specificity (67.5%) for diagnosis of tracheomalacia when compared with bronchoscopy. Increasing severity of tracheomalacia on airway screen significantly predicted a diagnosis of tracheomalacia on bronchoscopy. CONCLUSIONS: Airway fluoroscopy has a low sensitivity and specificity in diagnosis of tracheomalacia and should be used judiciously rather than as a screening tool for children with stridor. However, this imaging technique may be beneficial in investigating children with severe symptoms who have had other conditions such as laryngomalacia excluded.

Cholinesterase inhibitor to prevent falls in Parkinson's disease (CHIEF-PD) trial: a phase 3 randomised, double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson's disease.

BACKGROUND: Falls are a common complication of Parkinson's disease. There is a need for new therapeutic options to target this debilitating aspect of the disease. Cholinergic deficit has been shown to contribute to both gait and cognitive dysfunction seen in the condition. Potential benefits of using cholinesterase inhibitors were shown during a single centre phase 2 trial. The aim of this trial is to evaluate the effectiveness of a cholinesterase inhibitor on fall rate in people with idiopathic Parkinson's disease. METHODS: This is a multi-centre, double-blind, randomised placebo-controlled trial in 600 people with idiopathic Parkinson's disease (Hoehn and Yahr stages 1 to 4) with a history of a fall in the past year. Participants will be randomised to two groups, receiving either transdermal rivastigmine or identical placebo for 12 months. The primary outcome is the fall rate over 12 months follow-up. Secondary outcome measures, collected at baseline and 12 months either face-to-face or via remote video/telephone assessments, include gait and balance measures, neuropsychiatric indices, Parkinson's motor and non-motor symptoms, quality of life and cost-effectiveness. DISCUSSION: This trial will establish whether cholinesterase inhibitor therapy is effective in preventing falls in Parkinson's disease. If cost-effective, it will alter current management guidelines by offering a new therapeutic option in this high-risk population. TRIAL REGISTRATION: REC reference: 19/SW/0043. EudraCT: 2018-003219-23. ISCRTN: 41639809 (registered 16/04/2019). ClinicalTrials.gov Identifier: NCT04226248 PROTOCOL AT TIME OF PUBLICATION: Version 7.0, 20th January 2021.

MicroRNA expression is associated with human papillomavirus status and prognosis in mucosal head and neck squamous cell carcinomas.

OBJECTIVES: The major cause of mucosal squamous cell carcinomas of the head and neck (HNSCCs) has been attributed to human papillomavirus (HPV) infection. Here we investigate if microRNA expression in HNSCC can be used as a prognostic tool with or without HPV status. MATERIALS AND METHODS: We performed a discovery miRNA microarray (miRBase v.21) profiling of 52 tonsillar SCCs with TaqMan real-time PCR validation of 228 HNSCCs. Patients had a histologically confirmed primary SCC of the oropharynx, oral cavity, hypopharynx or larynx. Logistic regression models were used to estimate the magnitude of the effect of association with clinical factors and miRNAs associated with HPV status. For recurrence and survival analysis, we used unadjusted and multivariable adjusted Cox proportional hazard regression models. RESULTS: Seventeen miRNAs were significantly associated with better prognosis in the discovery phase and were validated in the extended dataset. The best fitting model (AUC = 0.92) for HPV status included age, smoking, and miRNAs: miR-15b, miR-20b, miR-29a, miR-29c, miR-142, miR-146a and miR-205. Using Cox regression model for recurrence, miR-29a was associated with 49% increased risk of recurrence while miR-30e and miR-342 were associated with decreased risk of recurrence with HRs 0.92 (95% CI 0.85-0.99) and 0.84 (95% CI 0.73-0.98), respectively. Our best fitting model for survival included age, gender, alcohol consumption, N stage, recurrence, HPV status, together with miRNAs-20b, 29a, and 342. CONCLUSION: miRNAs show potential to serve as usual biomarkers to predict the clinical course of patients with mucosal HNSCC.

Results of a prospective surgical audit of bilateral paediatric cochlear implantation in the UK.

BACKGROUND: Following the approval of bilateral paediatric cochlear implantation in 2009, the prospective multi-centre UK National Paediatric Cochlear Implant Audit was established to collect a large dataset of paediatric implantations. The aim of the surgical part of the audit, reported here, was to collect data on surgical practice, outcomes and complications. METHODS: Data from 14 surgical centres was collected prospectively, including simultaneous and sequential bilateral as well as unilateral implantations. Data collected included age at implantation, aetiology of deafness, implant type, duration of surgery, the use of electrophysiological testing, and the use of pre- and post-operative imaging. Details of major and immediate minor complications were also recorded. RESULTS: 1397 CI procedures in 961 CI recipients were included; 436 bilateral simultaneous, 394 bilateral sequential, 131 unilateral. The overall major complication rate was 1.6% (0.9% excluding device failure) and was similar following bilateral CI compared to sequential and unilateral CI. CONCLUSION: This prospective multi-centre audit provides evidence that bilateral paediatric CI is a safe procedure in the UK, thus endorsing its role as a major therapeutic intervention in childhood deafness.

The safety of peri-articular local anaesthetic injection for patients undergoing total knee replacement with autologous blood transfusion: a randomised trial.

Intra-operative, peri-articular injection of local anaesthesia is an increasingly popular way of controlling pain following total knee replacement. At the same time, the problems associated with allogenic blood transfusion have led to interest in alternative methods for managing blood loss after total knee replacement, including the use of auto-transfusion of fluid from the patient's surgical drain. It is safe to combine peri-articular infiltration with auto-transfusion from the drain. We performed a randomised clinical trial to compare the concentration of local anaesthetic in the blood and in the fluid collected in the knee drain in patients having either a peri-articular injection or a femoral nerve block. Clinically relevant concentrations of local anaesthetic were found in the fluid from the drains of patients having peri-articular injections (4.92 µg/ml (sd 3.151)). However, none of the patients having femoral nerve blockade had detectable levels. None of the patients in either group had clinically relevant concentrations of local anaesthetic in their blood after re-transfusion. The evidence from this study suggests that it is safe to use peri-articular injection in combination with auto-transfusion of blood from peri-articular drains during knee replacement surgery.

Auto-stratification in drying colloidal dispersions: a diffusive model.

The mechanism by which the particles in a drying film come into close packing during solvent evaporation has an important role to play in the final film morphology. During drying the particles can develop non-uniform concentrations across the vertical height of the film, depending on their diffusion rate. By applying the principles of classical diffusion mechanics to a hard sphere system, a theory for this novel method of stratification during drying of a two component film has been derived. The model is dependent on the particle Peclet numbers and when one is above unity and the other below, maximum stratification is observed.

Autostratification in drying colloidal dispersions: experimental investigations.

In films cast from a colloidal dispersion comprising two particle sizes, we experimentally examine the distribution of particles normal to the substrate. The particle concentrations at various positions in the film are determined through atomic force microscopy and NMR profiling. The results are compared to a previously derived diffusional model. Evidence for diffusional driven stratification is found, but the importance of other flows is also highlighted. The conditions that enhance particle stratification are found to be a colloidally stable dispersion, low initial volume fractions, a low concentration of the stratifying particle, and for the Peclet numbers of the two components to straddle unity.

World without borders: integrating clinical perspectives into the coronial jurisdiction in Victoria, Australia.

A professional world without borders would allow for more appropriate collaboration between the Coroner's office and the healthcare sector in their endeavours to improve patient safety. In Victoria (Australia), the Clinical Liaison Service draws on the distinct experiences and expertise of medical, nursing and research personnel to evaluate clinical evidence for the investigation of healthcare deaths reported to the State Coroner's Office. This approach allows for greater intersectoral collaboration between the Coroner's office and healthcare sector than a traditional English-style coronial system that relies on the expertise of coroners, forensic pathologists and police officers to investigate unexpected deaths. Encouraging collaboration between these two sectors may have averted or at least mitigated the atrocities caused by Harold Shipman or the events at Bristol's Royal Infirmary. This paper describes the work processes employed by the Clinical Liaison Service (CLS) to investigate healthcare deaths in a coronial setting. To describe how this work has fostered the advancement of patient care.

Experience with practice guidelines for medico-legal death investigations: the case of falls-related deaths in hospital.

Western philosophical and political thought has focussed on the significance of individual relativism. The legal system's approach to the investigation and regulation of medical practice is generally ad hoc and based on case law. In contrast, medical knowledge and understanding is progressively shifting towards a system of taxonomies and norms. Clinical guidelines and evidence-based medical practice are now commonplace in clinical practice. Due to the polarity of professional frameworks underpinning medicine and law, there has been an on-going struggle for the successful use of medical law that benefits both the quality of medical practice as well as its practitioners. This paper discusses the principles in developing and implementing a standard investigation tool for the coronial sector using the Falls Investigation Standard as an example, which has been in use for 12 months in the state of Victoria, Australia. It is hoped that using a standardised tool can balance the often conflicting tensions between medical and legal sectors by enabling an in-depth review of each issue while also strengthening the health system's capacity for self-regulation.

Perceived prevalence of peanut allergy in Great Britain and its association with other atopic conditions and with peanut allergy in other household members.

BACKGROUND: Despite increasing awareness of peanut allergy, little is known of its prevalence. We report on a two-stage interview survey conducted in Great Britain. METHODS: A total of 16434 adults (aged 15+ years) reported their own allergies and atopies and named cohabitants with peanut allergy (stage 1). Follow-up interviews were conducted with identified sufferers from peanut allergy (stage 2). RESULTS: At stage 1, peanut allergy was reported in 58 respondents and 205 other household members. When we accounted for cases where peanut allergy was unconfirmed or newly reported at stage 2, the prevalence, based on 124 confirmed sufferers, was estimated as 0.48% (95% confidence interval 0.40%-0.55%). The prevalence in children (0.61%, 0.41%-0.82%) was slightly higher than in adults; age-of-onset was strikingly earlier. Prevalence was strongly associated with other atopies, particularly tree-nut allergy. Cases tended significantly to cluster in households. Half of cases had never consulted a doctor. Exactly 7.4% reported being hospitalized after a reaction. CONCLUSIONS: Peanut allergy is reported by 1 in 200 of the population and is commoner in those reporting other atopies. The fact of similar rates in children and adults argues against a recent marked rise in prevalence. The frequency and potential lethality of this disorder emphasize the need for sufferers to demographic factors, other food allergies, atopic conditions, and allergy in family/household members. Our study comprised a screening survey and detailed interviews with sufferers identified. The frequency and potential lethality of this disorder emphasize the need for sufferers to receive correct medical advice on management [corrected].

Effects of alpha-erabutoxin, alpha-bungarotoxin, alpha-cobratoxin and fasciculin on the nicotine-evoked release of dopamine in the rat striatum in vivo.

Snake neurotoxins (NTX) have proven to be valuable tools for the characterisation of muscular nicotinic acetylcholine receptor structure and function. It is very likely that they could also be utilised to identify subtypes of neuronal nicotinic receptors controlling specific functions within the central nervous system. In this study we examined the effects of long alpha NTX (alpha-bungarotoxin, alpha-Bgt, and alpha-cobratoxin, alpha-Cbt) and short alpha NTX (alpha-erabutoxin a, alpha-Ebt) as well as the anticholinesterase toxin fasciculin-2 (FAS), on the nicotine-evoked release of dopamine (DA) in the striatum, using the in vivo push-pull technique. The short toxins alpha-Ebt and FAS blocked the extracellular increase of DA evoked by nicotine at 4.2 microM concentrations and alpha-Ebt was more potent, as reflected by the blockade at the lower dose of 0.42 microM. In contrast, the long toxins showed a different profile of action. Alpha-Cbt did not show any blockade of the nicotine-evoked release of DA at the doses studied while alpha-Bgt did block it only at the higher dose (4.2 microM) These results indicate that short neurotoxins show a stronger interaction with striatal nicotinic receptors subtypes controlling DA release when compared to the long ones. This interaction of short neurotoxin polypeptides and presynaptic receptors may permit the further elucidation of the particular nicotinic receptor populations responsible for the modulation of striatal DA release.

The ethical dilemma of health education.

There are many different and evolving definitions of health. Different concepts of health held by the patient, his or her family and the nurse can lead to ethical dilemmas for the nursing profession. Health education or health promotion may not always be used in the patient's best interest, affecting the patient's right to autonomy and self-determination.

Acetylcholinesterase inhibitors block acetylcholine-evoked release of dopamine in rat striatum, in vivo.

In the rat striatum, acetylcholine (ACh) increases dopamine (DA) release. The role of increased cholinergic activity provoked by acetylcholinesterase inhibitors (AChEi) on DA release is currently under revision after recent papers have shown a blockade of nicotinic transmission by AChEi in vitro. To study the effects of AChEi in vivo, Fasciculin2 (FAS), a peptidergic AChEi, and physostigmine (PHY), a classical carbamate AChEi, were applied through push-pull or microdialysis cannulae respectively, to the striatum of rats, alone or with ACh. Extracellular concentrations of DA were assessed by HPLC with electrochemical detection. Alone, the AChEi studied did not provoke changes in basal extracellular levels of DA, in the different doses studied. ACh (100 microM, 1 and 5 mM) applied through the push-pull cannulae in basal conditions provoked a dose-dependent increase of extracellular DA. This effect was not observed with ACh in concentrations of 100 microM and 1 mM if FAS (0.4 and 4.2 microM) was applied first. Higher concentrations of ACh (5 mM) evoked a partial response after FAS 0.42 microM, an effect still blocked by FAS at 4.2 microM. PHY 50 microM applied through microdialysis completely blocked the increase in DA release provoked by ACh 10, 20 mM, while at ACh 30 mM, PHY 50 microM only partially blocked the evoked increase. A partial blockade was also observed with PHY 20 microM, on the three different concentrations of ACh. On the other hand PHY 10 microM did not block any of the ACh doses perfused. These results showed that AChEi like FAS and PHY interfere with the ACh-evoked DA release in the striatum.

ICP-MS: a new look at trace elements in Alzheimer's disease.

It has been known for over 100 years that trace elements play an essential role in metabolism. Some 24 elements are now acknowledged as being essential to life. Many conditions have been examined in recent years from a trace element viewpoint. Alzheimer's disease and the part played by aluminium has received much attention, particularly since Crapper's work in the early 1970's. Extremely low levels of elements of interest and inappropriate methods of analysis are problems common to elemental tissue studies. Many early studies are now known to have reported falsely high levels of elements in tissues for just these reasons. Much research in recent years has been directed to looking at a range of trace elements thought to play a part in neurological disorders, particularly Alzheimer's disease. Inductively Coupled Plasma Source Mass Spectrometry (ICP-MS) is an ultra-sensitive, multi-element technique which can determine up to 90% of the elements in the periodic table, many at the sub ng.g-1 level. Developed and adopted commercially within the last 10 years, ICP-MS has to date been applied mainly to geological and environmental studies. Its suitability for use in biological investigations is now being exploited to examine the levels of 20 elements in brain tissue, cerebrospinal fluid, serum and aqueous humour from Alzheimer victims and matched control subjects.

Pediatric cardiac resuscitation team: a 6 year study.

A cardiopulmonary resuscitation team based in the pediatric intensive care unit responded to 239 cardiac arrests over a 6 year period. Patients with respiratory problems and infectious diseases requiring isolation composed the largest groups in whom unexpected arrests occurred. There was a 78 per cent rate of initial response to therapy and a 47 per cent survival rate. This is almost twice the survival rate of the best previously reported study and five times the average.