A challenge to the evidence behind noise guidelines for UK hospitals.

BACKGROUND: Teams assessing hospital noise against international guidelines regularly find that noise exceeds perceived safe levels in clinical settings. The care of sick people may be inherently noisy but recent efforts to tackle the problem propose a wider scope to identify sources and qualities of noise as well as more precision with noise recording. AIMS: We sought to challenge the scientific evidence cited in the four major documents pertaining to hospital noise in the UK to clarify if evidence of harm from noise included in guidelines is available, contemporary and of high quality. METHODS: Our team of hearing-health clinicians, acoustic scientists and acoustic engineers have conducted a narrative scoping review focused on critically appraising four of the most cited guidelines against which noise is measured in healthcare settings in the UK. RESULTS: There is a lack of high-quality evidence for commonly accepted consequences of noise cited in current guidelines. CONCLUSIONS: The current evidence base for noise guidelines in a healthcare setting is largely based on subjective heterogeneous and inconclusive research. Whilst reduced noise is not disputed as potentially beneficial for patient care, further hypothesis-driven research and interventions assessing the benefits or outcomes of any such intervention should be sought to produce high-quality evidence of relevance on the clinical coalface.

Has the survival of patients with glioblastoma changed over the years?

BACKGROUND: Over the last decade, the approach to the management of brain tumours and the understanding of glioblastoma tumour biology has advanced and a number of therapeutic interventions have evolved, some of which have shown statistically significant effects on overall survival (OS) and progression-free survival in glioblastoma. The aim of this study is to compare survival in glioblastoma patients over a 10-year period (1999-2000 and 2009-2010). METHODS: A retrospective cohort study was performed. Identification of all histologically confirmed glioblastoma in a single centre in years 1999, 2000, 2009 and 2010, and production of survival analysis comparing 1999-2000 and 2009-2010 were achieved. RESULTS: A total of 317 patients were included in the analysis (133 in year 1999-2000, and 184 in year 2009-2010). Cox regression analysis showed that the survival was significantly longer in patients in years 2009-2010 than those in 1999-2000 at P<0.001 with HR=0.56, confidence interval (CI) (0.45-0.71). The 1- and 3-year survival rates were 20.7% and 4.4%, respectively, for patients in 1999-2000, improving to 40.0% and 10.3%, respectively, for patients in 2009-2010. The comparisons between the two groups in survival at 1, 2 and 3 years are all statistically significant at P<0.001, respectively. The median OS was 0.36 and 0.74 in 1999-2000 and 2009-2010 groups, respectively. CONCLUSIONS: Over this period, OS from glioblastoma has increased significantly in our unit. We believe this is due to the institution of evidence-based surgical and oncological strategies practised in a multidisciplinary setting.

Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis.

Atrioventricular and semilunar valve abnormalities are common birth defects, but how cardiac valvulogenesis is directed remains largely unknown. During studies of genetic interaction between Egfr, encoding the epidermal growth factor receptor, and Ptpn11, encoding the protein-tyrosine-phosphatase Shp2, we discovered that Egfr is required for semilunar, but not atrioventricular, valve development. Although unnoticed in earlier studies, mice homozygous for the hypomorphic Egfr allele waved-2 (Egfrwa2/wa2) exhibit semilunar valve enlargement resulting from over-abundant mesenchymal cells. Egfr-/- mice (CD1 background) have similar defects. The penetrance and severity of the defects in Egfrwa2/wa2 mice are enhanced by heterozygosity for a targeted mutation of exon 2 of Ptpn11 (ref. 3). Compound (Egfrwa2/wa2:Ptpn11+/-) mutant mice also show premature lethality. Electrocardiography, echocardiography and haemodynamic analyses showed that affected mice develop aortic stenosis and regurgitation. Our results identify the Egfr and Shp2 as components of a growth-factor signalling pathway required specifically for semilunar valvulogenesis, support the hypothesis that Shp2 is required for Egfr signalling in vivo, and provide an animal model for aortic valve disease.

The effect on the T-14 paediatric throat disorders outcome score of delaying adenotonsillectomy surgery due to COVID-19.

INTRODUCTION: Adenotonsillectomy is commonly performed for recurrent tonsillitis and obstructive sleep apnoea. These conditions may improve with age. The COVID-19 pandemic led to all UK elective surgery being suspended. This study aimed to determine whether delaying surgery had any effect on a patient's symptoms using the validated T-14 paediatric throat disorders outcome test. METHODS: Patients completed a T-14 questionnaire when the child was listed for surgery; this was repeated on the revised surgery date and a paired t test was used to compare the responses. RESULTS: Questionnaires were completed by 29 patients a mean of 6.4 months apart. There was a significant improvement in scores (p<0.02) for five domains: eating habits, visits to a doctor/A&E, antibiotics for less than 2 weeks, chronic infections and school missed due to sore throats. CONCLUSIONS: This study demonstrates that following delays resulting from the COVID-19 pandemic, paediatric patients experienced an improvement in some aspects of their quality of life while awaiting tonsillectomy and/or adenoidectomy. This was most apparent in quality-of-life measures relating to recurrent tonsillitis, namely visits to a doctor/A&E, antibiotics for less than 2 weeks, chronic infections and school missed due to sore throats. Patients may experience an improvement in some of their individual symptoms, in particular their infective symptoms, during an observation period.

Prevalence of streptococci and increased polymicrobial diversity associated with cystic fibrosis patient stability.

Diverse microbial communities chronically colonize the lungs of cystic fibrosis patients. Pyrosequencing of amplicons for hypervariable regions in the 16S rRNA gene generated taxonomic profiles of bacterial communities for sputum genomic DNA samples from 22 patients during a state of clinical stability (outpatients) and 13 patients during acute exacerbation (inpatients). We employed quantitative PCR (qPCR) to confirm the detection of Pseudomonas aeruginosa and Streptococcus by the pyrosequencing data and human oral microbe identification microarray (HOMIM) analysis to determine the species of the streptococci identified by pyrosequencing. We show that outpatient sputum samples have significantly higher bacterial diversity than inpatients, but maintenance treatment with tobramycin did not impact overall diversity. Contrary to the current dogma in the field that Pseudomonas aeruginosa is the dominant organism in the majority of cystic fibrosis patients, Pseudomonas constituted the predominant genera in only half the patient samples analyzed and reported here. The increased fractional representation of Streptococcus in the outpatient cohort relative to the inpatient cohort was the strongest predictor of clinically stable lung disease. The most prevalent streptococci included species typically associated with the oral cavity (Streptococcus salivarius and Streptococcus parasanguis) and the Streptococcus milleri group species. These species of Streptococcus may play an important role in increasing the diversity of the cystic fibrosis lung environment and promoting patient stability.

Temozolomide in the management of dopamine agonist-resistant prolactinomas.

BACKGROUND: The majority of prolactinomas respond to dopamine agonist therapy, but a proportion are resistant, requiring other treatments including surgery and/or radiotherapy. Temozolomide is an oral chemotherapy agent, which has been used as a salvage therapy to treat aggressive pituitary adenomas and carcinomas, including prolactinomas, unresponsive to all conventional treatment. CASE SERIES: We report three patients where temozolomide was used in the treatment of refractory prolactinomas. Case 1 describes a patient with a highly invasive prolactinoma, resistant to all conventional therapy, which responded dramatically to temozolomide used as a salvage treatment. In case 2, temozolomide was used after incomplete surgical resection to relieve chiasmal compression and avoid chiasm exposure to radiotherapy. In case 3, temozolomide enabled radiotherapy to be deferred in a 16-year old with a resistant prolactinoma. In all three cases, the tumours were negative by immunostaining for methylguanine methyltransferase (MGMT). LITERATURE REVIEW AND DISCUSSION: A review of the published literature reveals 51 reported cases of temozolomide treatment for pituitary tumours, including 20 prolactinomas. Fifteen of the 20 prolactinomas showed a good response to temozolomide. Our analysis demonstrates a strong association between MGMT-negative staining and a good response to temozolomide (OR 9.35, P = 0.0030). Current clinical practice is to use temozolomide as a salvage therapy after all conventional modalities of treatment have failed. We suggest that, in selected cases, consideration should be given to using temozolomide earlier in the treatment algorithm.

Who operates on the children?

An unexpectedly high burden of elective paediatric surgery is being performed by the Ear, Nose and Throat (ENT) surgeons in Moshi, Tanzania.We believe this brief survey demonstrates the capacity for elective paediatric surgery in the sub-Saharan setting, comparable to the elective operative numbers of an equivalent tertiary centre in Liverpool, UK.

PR39, a peptide regulator of angiogenesis.

Although tissue injury and inflammation are considered essential for the induction of angiogenesis, the molecular controls of this cascade are mostly unknown. Here we show that a macrophage-derived peptide, PR39, inhibited the ubiquitin-proteasome-dependent degradation of hypoxia-inducible factor-1alpha protein, resulting in accelerated formation of vascular structures in vitro and increased myocardial vasculature in mice. For the latter, coronary flow studies demonstrated that PR39-induced angiogenesis resulted in the production of functional blood vessels. These findings show that PR39 and related compounds can be used as potent inductors of angiogenesis, and that selective inhibition of hypoxia-inducible factor-1alpha degradation may underlie the mechanism of inflammation-induced angiogenesis.

Increased incidence of idiopathic paediatric facial palsy during the coronavirus disease 2019 pandemic.

BACKGROUND: Bell's palsy is a lower motor neurone facial weakness of unknown aetiology, although reactivation of a virus within the facial nerve has been proposed. METHODS: A prospective study was conducted of Bell's palsy cases presenting to our paediatric ENT unit over a 19-week period, from February to June 2020. Patients were invited for severe acute respiratory syndrome coronavirus-2 antibody testing. A text-message questionnaire was sent to other ENT centres to determine their observational experience. RESULTS: During the study period, 17 children presented with Bell's palsy, compared with only 3 children in the same time period in the previous year (p < 0.0001). Five patients underwent severe acute respiratory syndrome coronavirus-2 antibody testing, the results of which were all negative. Four out of 15 centres questioned perceived an increased incidence in paediatric Bell's palsy. CONCLUSION: Clinicians are encouraged to be vigilant to the increase in paediatric Bell's palsy seen during the coronavirus disease 2019 pandemic, which may represent a post-viral sequela of coronavirus disease 2019.

Recurrent acute otitis media: a survey of current management in England.

OBJECTIVE: Recurrent acute otitis media is common in children. The preferred treatment measures for recurrent acute otitis media have a mixed evidence base. This study sought to assess baseline practice across ENT departments in England. METHODS: A national telephone survey of healthcare staff was conducted. Every ENT centre in England was contacted. A telephone script was used to ask about antibiotic and grommet use and duration in recurrent acute otitis media cases. RESULTS: Ninety-six centres (74 per cent) provided complete information. Recurrent acute otitis media treatment across England by ENT departments varied. The antibiotic first- and second-line prophylaxis offered varies, with trimethoprim used in 33 centres and 29 centres not offering any antibiotics. The timing or choice about when to use grommets also varies, but 87 centres (91 per cent) offer grommet surgery at one stage. CONCLUSION: The treatments received by children in England for recurrent acute otitis media vary by centre; collaborative research in this area is advised.

Coblation versus cold dissection in paediatric tonsillectomy: a systematic review and meta-analysis.

BACKGROUND: Cold dissection is the most commonly used tonsillectomy technique, with low post-operative haemorrhage rates. Coblation is an alternative technique that may cause less pain, but could have higher post-operative haemorrhage rates. OBJECTIVE: This study evaluated the peri-operative outcomes in paediatric tonsillectomy patients by comparing coblation and cold dissection techniques. METHODS: A systematic review was conducted of all comparative studies of paediatric coblation and cold dissection tonsillectomy, up to December 2018. Any studies with adults were excluded. Outcomes such as pain, operative time, and intra-operative, primary and secondary haemorrhages were recorded. RESULTS: Seven studies contributed to the summative outcome. Coblation tonsillectomy appeared to result in less pain, less intra-operative blood loss (p < 0.01) and a shorter operative time (p < 0.01). There was no significant difference between the two groups for post-operative haemorrhage (p > 0.05). CONCLUSION: The coblation tonsillectomy technique may offer better peri-operative outcomes when compared to cold dissection, and should therefore be offered in paediatric cases, before cold dissection tonsillectomy.

Altered iron metabolism in cystic fibrosis macrophages: the impact of CFTR modulators and implications for Pseudomonas aeruginosa survival.

Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in chronic bacterial lung infections and tissue damage. CF macrophages exhibit reduced bacterial killing and increased inflammatory signaling. Iron is elevated in the CF lung and is a critical nutrient for bacteria, including the common CF pathogen Pseudomonas aeruginosa (Pa). While macrophages are a key regulatory component of extracellular iron, iron metabolism has yet to be characterized in human CF macrophages. Secreted and total protein levels were analyzed in non-CF and F508del/F508del CF monocyte derived macrophages (MDMs) with and without clinically approved CFTR modulators ivacaftor/lumacaftor. CF macrophage transferrin receptor 1 (TfR1) was reduced with ivacaftor/lumacaftor treatment. When activated with LPS, CF macrophage expressed reduced ferroportin (Fpn). After the addition of exogenous iron, total iron was elevated in conditioned media from CF MDMs and reduced in conditioned media from ivacaftor/lumacaftor treated CF MDMs. Pa biofilm formation and viability were elevated in conditioned media from CF MDMs and biofilm formation was reduced in the presence of conditioned media from ivacaftor/lumacaftor treated CF MDMs. Defects in iron metabolism observed in this study may inform host-pathogen interactions between CF macrophages and Pa.

The negative impact of wearing personal protective equipment on communication during coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 personal protective equipment has been reported to affect communication in healthcare settings. This study sought to identify those challenges experimentally. METHOD: Bamford-Kowal-Bench speech discrimination in noise performance of healthcare workers was tested under simulated background noise conditions from a variety of hospital environments. Candidates were assessed for ability to interpret speech with and without personal protective equipment, with both normal speech and raised voice. RESULTS: There was a significant difference in speech discrimination scores between normal and personal protective equipment wearing subjects in operating theatre simulated background noise levels (70 dB). CONCLUSION: Wearing personal protective equipment can impact communication in healthcare environments. Efforts should be made to remind staff about this burden and to seek alternative communication paradigms, particularly in operating theatre environments.

A multi-centre analysis of a decade of endoscopic pharyngeal pouch surgery in Cheshire and Merseyside.

BACKGROUND: There are sparse data on the outcomes of endoscopic stapling of pharyngeal pouches. The Mersey ENT Trainee Collaborative compared regional practice against published benchmarks. METHODS: A 10-year retrospective analysis of endoscopic pharyngeal pouch surgery was conducted and practice was assessed against eight standards. Comparisons were made between results from the tertiary centre and other sites. RESULTS: A total of 225 procedures were performed (range of 1.2-9.2 cases per centre per year). All centres achieved 90 per cent resumption of oral intake within 2 days. All centres achieved less than 2-day hospital stays. Primary success (84 per cent (i.e. abandonment of endoscopic stapling in 16 per cent)), symptom resolution (83 per cent) and recurrence rates (13 per cent) failed to meet the standard across the non-tertiary centres. CONCLUSION: Endoscopic pharyngeal pouch stapling is a procedure with a low mortality and brief in-patient stay. There was significant variance in outcomes across the region. This raises the question of whether this service should become centralised and the preserve of either tertiary centres or sub-specialist practitioners.

Effects of feeding a dietary antioxidant in diets with oxidized fat on lactation performance and antioxidant status of the cow.

The objective of the study was to evaluate the effect of feeding the dietary antioxidant Agrado Plus (AOX; Novus International, St. Louis, MO) in diets that contained 2% fresh fat (FF) or oxidized fat (OF) on milk production and composition and antioxidant status of cows during mid to late lactation. Forty-four mid to late lactating primiparous cows housed in a tie-stall barn were fed a diet that contained 2% FF for 15 d as adaptation period and then randomly allocated to 1 of the 4 dietary treatments (FF, FF+AOX, OF, OF +AOX) for 6 wk. Feeding AOX increased dry matter intake, 3.5% fat-corrected milk, and milk fat yield, and decreased milk protein content but not yield. Feeding OF increased milk fat yield, but decreased dry matter intake and body weight gain. Milk fat composition changed with treatments: AOX increased cis 18:1 and decreased trans-11 18:1, whereas OF decreased trans-9 and trans-11 18:1 and cis-9, trans-11 18:2 in milk. Plasma antioxidant enzymes and status were affected by treatments. Feeding OF increased superoxidase dismutase activity but decreased plasma antioxidant status, whereas AOX supplementation increased glutathione peroxidase activity across fat types and increased the antioxidant status and superoxidase dismutase activity when feeding OF diets. It can be concluded that feeding AOX improved lactation performance and the antioxidant status of the cow across fat types, and feeding OF increased milk fat yield but decreased dry matter intake, body weight gain, and antioxidant status. The negative effects of feeding OF were partially alleviated by AOX.

Stretch-induced VEGF expression in the heart.

Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen involved in vascular development and angiogenesis. Recently we have observed increased VEGF expression in the normal myocardium after myocardial infarction in a rat heart. This study was designed to explore the mechanism responsible for this increase in VEGF expression. Induction of myocardial stretch in an isolated perfused Langendorff preparation by inflation of an intraventricular balloon to an end-diastolic load of 35 mmHg for 30 min resulted in a nearly sixfold increase in VEGF message level not only in the chamber subjected to stretch (left ventricle) but also in the unstretched right ventricle, thus raising the possibility of a soluble factor mediating stretch- induced induction of VEGF expression. This was further confirmed by demonstrating that coronary venous effluent collected from the stretched heart and used to perfuse isolated hearts in which no balloon was present was able to induce VEGF expression in these normal hearts. Inhibition of TGF-beta activity using a neutralizing antibody, but not antagonists/inhibitors of endothelin and angiotensin II, eliminated stretch-induced increase in VEGF expression. Staurosporine, a protein kinase C inhibitor, also blocked stretch-induced increase of VEGF expression. Measurement of TGF-beta concentration in the perfusate demonstrated increased amounts of the cytokine after myocardial stretch, and addition of TGF-beta protein to the perfusion buffer resulted in increased VEGF expression in control hearts. These results suggest that stretch-induced increase of VEGF expression in the heart is mediated at least in part by TGF-beta.

Evidence of a different dose response in turkeys when fed 2-hydroxy-4(methylthio) butanoic acid versus DL-methionine.

In broilers, 2-hydroxy-4(methylthio) butanoic acid (HMTBA) can elicit a different dose response relative to dl-Met (DLM) such that birds could have lower gain responses at deficient TSAA concentrations but greater gain responses at maximum response concentrations. Two experiments tested if the 2 Met sources have a different dose response in 1-d-old turkeys using a 2 x 4 factorial plus a control design with 8 replicates of 12 toms per treatment. 2-Hydroxy-4(methylthio) butanoic acid and DLM were supplemented at equimolar concentrations of 0.05, 0.10, 0.15, and 0.20% or 0.04, 0.08, 0.16, and 0.32% for experiments 1 and 2, respectively, in commercial-type TSAA-deficient (0.99 to 1.02%) diets for 21 d. No differences in any performance parameter tested were found between HMTBA and DLM in either trial by ANOVA. Linear (LIN), quadratic (QUAD), and exponential regressions were fitted to the gain response of birds fed HMTBA or DLM. Equations with better goodness of fit as determined by Schwarz's Bayesian information criteria index were used for further calculations of predicted differences between HMTBA and DLM. In both trials, the shape of the dose response differed according to the Met source used, and best-fit equations were obtained when using Met intake over control rather than dietary Met concentration as the dependent variable. In experiment 1, the best-fit equations were an inverse QUAD for HMTBA and a LIN for DLM, and in experiment 2 with higher Met concentrations, the best-fit equations were a QUAD for DLM and a LIN for HMTBA. Feeding HMTBA at deficient TSAA resulted in lower (P <0.05) gains in experiment 1 but greater gains at maximum response concentrations (P <0.05) in both experiments. Plasma-free Met increased at 3 times the rate for DLM than HMTBA (P <0.01) with increasing Met concentration, which may play a role in the evolution of different dose responses at the extremes of the Met dose response. These results demonstrate that Met sources elicit a differential dose response in turkeys such that feeding HMTBA at deficient TSAA concentrations can be lower than DLM and can reach a higher maximum performance than with DLM.

Evidence for 2-hydroxy-4(methylthio) butanoic acid and DL-methionine having different dose responses in growing broilers.

The objective of this study was to compare the gain-response curve to dietary levels of 2-hydroxy-4(methylthio) butanoic acid (HMTBA) and DL-Met (DLM) across 4 floor pen trials in which different diets were used. Six replicates of 38 or 41 birds per pen (trials 1 to 2 and 3 to 4, respectively) were used in a 2 x 3 factorial arrangement. A control with 12 replicates was also included. The 2 Met sources were fed at 3 equimolar levels equally spaced, with the highest level added at requirements from 1 to 48, 49, 43, or 49 d for trials 1, 2, 3, and 4, respectively. Commercial-type TSAA-deficient control diets contained sorghum, wheat, corn, or corn plus meat and bone meal for trials 1, 2, 3, and 4, respectively. Performance improved at all times for most parameters after supplementing with HMTBA or DLM (P < 0.05). No differences were found in the birds fed HMTBA or DLM at any age and trial (P > 0.05), except for trial 1, in which 17-d-old birds performed better when fed HMTBA than DLM (P < 0.05). In each trial, linear, quadratic, and exponential regressions were conducted upon the gain response of birds fed HMTBA and DLM separately. Equations with better goodness of fit were used to compare the estimated gain responses to feeding HMTBA vs. DLM. In 3 trials, the shape of the gain-response curve differed when feeding HMTBA vs. DLM. In trials 3 and 4, feeding HMTBA at commercial levels resulted in greater gain responses than DLM (P < 0.05), whereas, in trials 2 and 4, at very deficient levels, DLM-fed birds outperformed those fed HMTBA (P < 0.05). When the 4 trials were combined, the dose-response curve with the best goodness of fit was linear for HMTBA and quadratic for DLM. It can be concluded that the 2 Met sources have a different dose-response form, HMTBA could outperform DLM at commercial levels, and DLM could outperform HMTBA at deficient levels.