Conservative management versus tonsillectomy in adults with recurrent acute tonsillitis in the UK (NATTINA): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Tonsillectomy is regularly performed in adults with acute tonsillitis, but with scarce evidence. A reduction in tonsillectomies has coincided with an increase in acute adult hospitalisation for tonsillitis complications. We aimed to assess the clinical effectiveness and cost-effectiveness of conservative management versus tonsillectomy in patients with recurrent acute tonsillitis. METHODS: This pragmatic multicentre, open-label, randomised controlled trial was conducted in 27 hospitals in the UK. Participants were adults aged 16 years or older who were newly referred to secondary care otolaryngology clinics with recurrent acute tonsillitis. Patients were randomly assigned (1:1) to receive tonsillectomy or conservative management using random permuted blocks of variable length. Stratification by recruiting centre and baseline symptom severity was assessed using the Tonsil Outcome Inventory-14 score (categories defined as mild 0-35, moderate 36-48, or severe 49-70). Participants in the tonsillectomy group received elective surgery to dissect the palatine tonsils within 8 weeks after random assignment and those in the conservative management group received standard non-surgical care during 24 months. The primary outcome was the number of sore throat days collected during 24 months after random assignment, reported once per week with a text message. The primary analysis was done in the intention-to-treat (ITT) population. This study is registered with the ISRCTN registry, 55284102. FINDINGS: Between May 11, 2015, and April 30, 2018, 4165 participants with recurrent acute tonsillitis were assessed for eligibility and 3712 were excluded. 453 eligible participants were randomly assigned (233 in the immediate tonsillectomy group vs 220 in the conservative management group). 429 (95%) patients were included in the primary ITT analysis (224 vs 205). The median age of participants was 23 years (IQR 19-30), with 355 (78%) females and 97 (21%) males. Most participants were White (407 [90%]). Participants in the immediate tonsillectomy group had fewer days of sore throat during 24 months than those in the conservative management group (median 23 days [IQR 11-46] vs 30 days [14-65]). After adjustment for site and baseline severity, the incident rate ratio of total sore throat days in the immediate tonsillectomy group (n=224) compared with the conservative management group (n=205) was 0·53 (95% CI 0·43 to 0·65; <0·0001). 191 adverse events in 90 (39%) of 231 participants were deemed related to tonsillectomy. The most common adverse event was bleeding (54 events in 44 [19%] participants). No deaths occurred during the study. INTERPRETATION: Compared with conservative management, immediate tonsillectomy is clinically effective and cost-effective in adults with recurrent acute tonsillitis. FUNDING: National Institute for Health Research.

Ecological divergence of wild birds drives avian influenza spillover and global spread.

The diversity of influenza A viruses (IAV) is primarily hosted by two highly divergent avian orders: Anseriformes (ducks, swans and geese) and Charadriiformes (gulls, terns and shorebirds). Studies of IAV have historically focused on Anseriformes, specifically dabbling ducks, overlooking the diversity of hosts in nature, including gull and goose species that have successfully adapted to human habitats. This study sought to address this imbalance by characterizing spillover dynamics and global transmission patterns of IAV over 10 years at greater taxonomic resolution than previously considered. Furthermore, the circulation of viral subtypes in birds that are either host-adapted (low pathogenic H13, H16) or host-generalist (highly pathogenic avian influenza-HPAI H5) provided a unique opportunity to test and extend models of viral evolution. Using Bayesian phylodynamic modelling we uncovered a complex transmission network that relied on ecologically divergent bird hosts. The generalist subtype, HPAI H5 was driven largely by wild geese and swans that acted as a source for wild ducks, gulls, land birds, and domestic geese. Gulls were responsible for moving HPAI H5 more rapidly than any other host, a finding that may reflect their long-distance, pelagic movements and their immuno-naïve status against this subtype. Wild ducks, long viewed as primary hosts for spillover, occupied an optimal space for viral transmission, contributing to geographic expansion and rapid dispersal of HPAI H5. Evidence of inter-hemispheric dispersal via both the Pacific and Atlantic Rims was detected, supporting surveillance at high latitudes along continental margins to achieve early detection. Both neutral (geographic expansion) and non-neutral (antigenic selection) evolutionary processes were found to shape subtype evolution which manifested as unique geographic hotspots for each subtype at the global scale. This study reveals how a diversity of avian hosts contribute to viral spread and spillover with the potential to improve surveillance in an era of rapid global change.

Hard tissue formation in pulpotomized primary teeth in dogs with nanomaterials MCM-48 and MCM-48/hydroxyapatite: an in vivo animal study.

BACKGROUND: This animal study sought to evaluate two novel nanomaterials for pulpotomy of primary teeth and assess the short-term pulpal response and hard tissue formation in dogs. The results were compared with mineral trioxide aggregate (MTA). METHODS: This in vivo animal study on dogs evaluated 48 primary premolar teeth of 4 mongrel female dogs the age of 6-8 weeks, randomly divided into four groups (n = 12). The teeth underwent complete pulpotomy under general anesthesia. The pulp tissue was capped with MCM-48, MCM-48/Hydroxyapatite (HA), MTA (positive control), and gutta-percha (negative control), and the teeth were restored with intermediate restorative material (IRM) paste and amalgam. After 4-6 weeks, the teeth were extracted and histologically analyzed to assess the pulpal response to the pulpotomy agent. RESULTS: The data were analyzed using the Kruskal‒Wallis, Fisher's exact, Spearman's, and Mann‒Whitney tests. The four groups were not significantly different regarding the severity of inflammation (P = 0.53), extent of inflammation (P = 0.72), necrosis (P = 0.361), severity of edema (P = 0.52), extent of edema (P = 0.06), or connective tissue formation (P = 0.064). A significant correlation was noted between the severity and extent of inflammation (r = 0.954, P < 0.001). The four groups were significantly different regarding the frequency of bone formation (P = 0.012), extent of connective tissue formation (P = 0.047), severity of congestion (P = 0.02), and extent of congestion (P = 0.01). No bone formation was noted in the gutta-percha group. The type of newly formed bone was not significantly different among the three experimental groups (P = 0.320). CONCLUSION: MCM-48 and MCM-48/HA are bioactive nanomaterials that may serve as alternatives for pulpotomy of primary teeth due to their ability to induce hard tissue formation. The MCM-48 and MCM-48/HA mesoporous silica nanomaterials have the potential to induce osteogenesis and tertiary (reparative) dentin formation.

Age and season predict influenza A virus dynamics in urban gulls: consequences for natural hosts in unnatural landscapes.

Gulls are ubiquitous in urban areas due to a growing reliance on anthropogenic feeding sites, which has led to changes in their abundance, distribution, and migration ecology, with implications for disease transmission. Gulls offer a valuable model for testing hypotheses regarding the dynamics of influenza A virus (IAV) - for which gulls are a natural reservoir in urban areas. We sampled sympatric populations of Ring-billed (Larus delawarensis), Herring (L. argentatus), and Great Black-backed Gulls (L. marinus) along the densely populated Atlantic rim of North America to understand how IAV transmission is influenced by drivers such as annual cycle, host species, age, habitat type, and their interplay. We found that horizontal transmission, rather than vertical transmission, played an outsized role in the amplification of IAV due to the convergence of gulls from different breeding grounds and age classes. We detected overlapping effects of age and season in our prevalence model, identifying juveniles during autumn as the primary drivers of the seasonal epidemic in gulls. Gulls accumulated immunity over their lifespan, however short-term fluctuations in seroprevalence were observed, suggesting that migration may impose limits on the immune system to maintain circulating antibodies. We found that gulls in coastal urban habitats had higher viral prevalence than gulls captured inland, correlating with higher richness of waterbird species along the coast, a mechanism supported by our movement data. The peak in viral prevalence in newly fledged gulls that are capable of long-distance movement has important implications for the spread of pathogens to novel hosts during the migratory season as well as for human health as gulls increasingly utilize urban habitats.

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study.

OBJECTIVE: To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. PATIENTS AND METHODS: This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. RESULTS: Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3-34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1-30.2), UTUC (n = 128) 1.14% (95% CI 0.77-1.52), renal cancer (n = 107) 1.05% (95% CI 0.80-1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32-2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03-1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90-4.15; P < 0.001), male sex 1.30 (95% CI 1.14-1.50; P < 0.001), and smoking 2.70 (95% CI 2.30-3.18; P < 0.001). CONCLUSIONS: A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer.

Pan-Scotland tonsillectomy outcomes: A national cross-sectional study.

OBJECTIVES: The aim of this study was to assess the current post-tonsillectomy haemorrhage and return to theatre rates in Scotland. DESIGN: National cross-sectional study. PARTICIPANTS AND SETTING: Tonsillectomy outcomes data were collated for all NHS patients undergoing tonsillectomy in Scotland between 1998-2002 and 2013-2017. MAIN OUTCOME MEASURES: Using Information Services Division (ISD) Scotland retrospective data, 30-day re-admission and 30-day return to theatre rates allowed an assessment of post-tonsillectomy haemorrhage rates. Data were validated through comparison with an audit conducted in NHS Greater Glasgow & Clyde between 2015 and 2016. RESULTS: Tonsillectomy was performed in 27 819 patients between 1998 and 2002, and 23 184 patients between 2013 and 2017. 30-day re-admission rates increased considerably between the 1998-2002 and 2013-2017 cohorts, from 4.7% to 12.1% in paediatric patients, and 9.8%-19.9% in adult patients. Similarly, 30-day "return to theatre rates" increased between the two cohorts, from 1.2% to 1.7% in paediatric patients, and 3.6%-4.9% in adult patients. Re-admission and return to theatre rates were similar across Health Boards for both adult and paediatric tonsillectomies in each cohort. CONCLUSIONS: Current 30-day re-admission and return to theatre rates are significantly higher than the majority of reported series to date. The rising rate of tonsillectomy haemorrhage between cohorts is likely to be multifactorial, possibly reflecting an underestimation of previous rates and the changing profile of the tonsillectomy patient. A detailed audit of current practice is needed to investigate these tonsillectomy outcomes, which are similar across all Health Boards in Scotland. Of most significance are the implications for accurate patient consent and non-elective ENT service provision.

Patterns of urgent hoarseness referrals to ENT-When should we be suspicious of cancer?

BACKGROUND: Current UK referral criteria stipulate that hoarseness should be persistent to merit 2 week wait (2WW) or urgent suspicion of cancer (USOC) referral. This study delineates patterns of hoarseness presentation with a view to assisting referral pathways, and whereby reassurance could be provided. METHODS: A pre-existing database of patients referred with hoarseness under the urgent suspicion of cancer (USOC) category was analysed. Univariate and multivariate analyses were performed on a variety of demographic and comorbid features to produce odds ratios (OR) of features either related or not related to laryngeal cancer. RESULTS: Of 698 consecutive hoarseness referrals were studied. In these referrals there were 506(73%) with persistent hoarseness and 192(27%) with intermittent hoarseness. The most significant patient variables related to laryngeal cancer were persistent hoarseness (OR 4.97), recreational drug use (OR 4.94), male gender (OR 4.01) and weight loss (OR 3.75). Significant patient variables present not related to laryngeal cancer diagnosis were intermittent hoarseness (OR 0.2), the presence of cough (OR 0.2), globus sensation (OR 0.25) and recent viral infection (OR 0.29). CONCLUSION: The strongest association with cancer is seen in patients that are persistently hoarse. Patients with fluctuating hoarseness do not need an "urgent suspicion of cancer" referral. Additional demographic referral information could help to streamline the referral of these patients, and reassure others.

Head and neck cancer risk calculator (HaNC-RC)-V.2. Adjustments and addition of symptoms and social history factors.

OBJECTIVES: Head and neck cancer (HNC) diagnosis through the 2-week wait, urgent suspicion of cancer (USOC) pathway has failed to increase early cancer detection rates in the UK. A head and neck cancer risk calculator (HaNC-RC) has previously been designed to aid referral of high-risk patients to USOC clinics (predictive power: 77%). Our aim was to refine the HaNC-RC to increase its prediction potential. DESIGN: Following sample size calculation, prospective data collection and statistical analysis of referral criteria and outcomes. SETTING: Large tertiary care cancer centre in Scotland. PARTICIPANTS: 3531 new patients seen in routine, urgent and USOC head and neck (HaN) clinics. MAIN OUTCOME MEASURES: Data collected were as follows: demographics, social history, presenting symptoms and signs and HNC diagnosis. Univariate and multivariate regression analysis were performed to identify significant predictors of HNC. Internal validation was performed using 1000 sample bootstrapping to estimate model diagnostics included the area under the receiver operator curve (AUC), sensitivity and specificity. RESULTS: The updated version of the risk calculator (HaNC-RC v.2) includes age, gender, unintentional weight loss, smoking, alcohol, positive and negative symptoms and signs of HNC. It has achieved an AUC of 88.6% with two recommended triage referral cut-offs to USOC (cut-off: 7.1%; sensitivity: 85%, specificity: 78.3%) or urgent clinics (cut-off: 2.2%; sensitivity: 97.1%; specificity of 52.9%). This could redistribute cancer detection through USOC clinics from the current 60.9%-85.2%, without affecting total numbers seen in each clinical setting. CONCLUSIONS: The use of the HaNC-RC v.2 has a significant potential in both identifying patients at high risk of HNC early thought USOC clinics but also improving health service delivery practices by reducing the number of inappropriately urgent referrals.

Patient-reported outcomes and urodynamic findings in men with persistent lower urinary tract symptoms following robot-assisted radical prostatectomy.

AIMS: To evaluate the patient-reported outcome measures (PROMs) and urodynamic findings in men seeking intervention for lower urinary tract symptoms (LUTS) after robotic-assisted radical prostatectomy (RARP) in a regional referral center for continence surgery. METHODS: Consecutive men with post-RARP LUTS, who were referred for specialist evaluation and urodynamics between December 2012 and October 2017, were evaluated. Men were invited to complete the International Consultation on Incontinence Questionnaire on Male Lower Urinary Tract Symptoms Long Form (ICIQ-MLUTS) pre-operatively and at 6, 12 and 18 months post-RARP. RESULTS: In total 64/860 (7.4%) men post-RARP were referred for specialist evaluation. There was a significant increase in total ICIQ-MLUTS and bother scores at 6, 12 and 18 months compared with the baseline in these men (P < 0.001 and P < 0.05, respectively). Urodynamics identified 41/64 (64%) had urodynamic stress incontinence (USI) only, 2/64 (3%) had detrusor overactivity (DO) only and 11/64 (17%) had a combination of USI and DO. Of those referred to a continence specialist 29/64 (45%) underwent a continence procedure. CONCLUSIONS: Patients with bothersome LUTS post-RARP have higher baseline ICIQ-MLUTs scores and significant worsening of total scores at all time points compared with the baseline. Routine use of PROMs may identify patients at risk of bothersome symptoms after RARP and prompt earlier referral for further management of their LUTS. Urodynamic evaluation revealed that the most common finding was pure stress incontinence but the range of urodynamic diagnoses highlights the need to perform urodynamics before making treatment decisions for men with LUTS post-RARP.

Synthesis of belite cement from nano-silica extracted from two rice husk ashes.

Nano-silicas extracted from a pure rice husk ash calcined in the laboratory (RHA) and ash from an impure industrial rice husk waste (BRHA), were used to form belite cement by firing with two different calcium sources (calcium carbonate and calcium nitrate). The nano-silica extracted from RHA was highly reactive due to its high pore volume and low activation energy of dehydration. The formation of belite cement from both nano-silicas was studied by firing with two different calcium sources, Ca(NO3)2 and CaCO3 at 800-1100 °C. Both nano-silicas formed the principal phase in belite cement (larnite or ß-C2S) at temperatures as low as 800 °C, especially with calcium nitrate as the calcium source. Thus, highly impure BRHA is shown to be very suitable as a starting material for the low-temperature production of belite cement, especially in conjunction with calcium nitrate as the calcium source.

Defining competency in flexible cystoscopy: a novel approach using cumulative Sum analysis.

BACKGROUND: Flexible cystoscopy (FC) is one of the most frequently performed urological intervention. Cumulative sum analysis (CUSUM) allows objective assessment of a proceduralist's performance to ensure acceptable outcomes. This study investigated the application of CUSUM to assess a trainee's learning curve and maintenance of competence in performing FC. METHODS: A single urology trainee, with no previous experience of FC, performed FCs between August 2013 and February 2014. For assessment FC was divided into 5 steps. Each step was assigned a CUSUM completion score. The primary outcome measure was successful performance of a complete FC. Prospective data were collected and analysed using CUSUM. RESULTS: In total, 419 FCs were performed. Acceptable performance of FC was achieved by the 122(nd) procedure. Complete assessment of the ureteric orifices and trigone was the most difficult step of FC to achieve consistently. Competence for complete FC was achieved following 289 procedures. CONCLUSION: CUSUM analysis objectively assesses acquisition of competence in flexible cystoscopy. Recommended indicative numbers may underestimate the number of FCs trainees require to achieve, and maintain, competency. Validation of CUSUM method in a larger cohort of trainees should be considered.

Cytological accuracy and radiological staging in patients with thyroid cancer in Glasgow.

To assess the accuracy of initial combined cytological accuracy and radiological staging of patients suspected of having thyroid malignancy with their final histopathology. Retrospective case series in a tertiary referral centre for head and neck malignancy. All patients with malignant thyroid cytology and cytology suspicious for malignancy, between the dates of June 2010 and July 2014, were included. The pre-operative staging was compared against the final histological staging. Demographics and outcomes for each patient were recorded. Sixty-five patients were recorded in this group. 20 (30.7 %) were male. The mean age at presentation was 51 years (SD 16.8 years). 39 (60 %) patients were aged over 45 years. Fine needle aspiration cytology (FNAC) was performed in all patients and was Thy 4 in 40 (62 %) and Thy 5 in 25 (38 %). Following surgery or subsequent biopsy, FNAC was found to be accurate in 38/40 (Thy 4) and 25/25 (Thy 5) cases in diagnosing malignancy, with Thy 4 yielding 95 % malignancy and Thy 5 % 100 %. Fifty-eight patients underwent a surgical procedure for thyroid cancer. Two further patients had a diagnostic hemi-thyroidectomy for later proven benign disease. Five patients due to medical co morbidities, inoperable disease or refusal of surgery were managed non-surgically. In the surgical group 16 patients underwent a diagnostic hemi-thyroidectomy and 11 of these required a completion thyroidectomy. Forty-six patients underwent total thyroidectomy. Forty-six patients underwent a neck dissection: 27 prophylactic central compartment neck dissections and 19 planned therapeutic neck dissections were performed. Radiological staging correctly predicted final pathological TNM staging in 25 (43 %) patients. 27 (47 %) patients had radiological staging which under staged their final histological staging and 6 (10 %) patients had scans that over staged their cancer. Of those that were under staged, 15 (56 %) had their nodal disease under staged (following prophylactic central neck dissection). Radiological staging comprised ultrasound (n = 58) and CT scanning (n = 45/58 pre-operatively). Pre-operative staging in thyroid cancer should include cytology, ultrasound and CT scanning. Unless low-risk papillary thyroid cancer is suspected pre-operatively, patients with Thy 4 cytology can be given the offer of a total thyroidectomy as surgical management.

Managing lower urinary tract symptoms in men.

Male lower urinary tract symptoms (LUTS) are common and increase in prevalence with age. Up to 90% of men aged 50 to 80 may suffer from troublesome LUTS. Men may attend expressing direct concern about micturition, describing one or more LUTS and the related impact on their quality of life. Frequently men may present for other medical or urological reasons such as concern regarding their risk of having prostate cancer or erectile dysfunction but on taking a history bothersome LUTS are identified. Men may present late in the community with urinary retention: the inability to pass urine. A thorough urological history is essential to inform management. It is important to determine whether men have storage or voiding LUTS or both. All patients must have a systematic comprehensive examination including genitalia and a digital rectal examination. Investigations performed in primary care should be guided by the history and examination findings, taking into account the impact of the LUTS on the individual's quality of life. Current NICE guidelines recommend the following to be performed at initial assessment: frequency volume chart (FVC); urine dipstick to detect blood, glucose, protein, leucocytes and nitrites; and prostate specific antigen. Men should be referred for urological review if they have: bothersome LUTS which have not responded to conservative management or medical therapy; LUTS in association with recurrent or persistent UTIs; urinary retention; renal impairment suspected to be secondary to lower urinary tract dysfunction; or suspected urological malignancy. All patients not meeting criteria for immediate referral to urology can be managed initially in primary care. Based on history, examination and investigation findings an individualised management plan should be formulated. Basic lifestyle advice should be given regarding reduction or avoidance of caffeinated products and alcohol. The FVC should guide advice regarding fluid intake management and all medications should be reviewed.

Adult-onset laryngomalacia: case reports and review of management.

Laryngomalacia is a dynamic airway condition characterised by inward collapse of flaccid supraglottic structures during inspiration. Although the most common cause of stridor in the paediatric population, adult-onset laryngomalacia remains a rare entity and its management, challenging. Two cases of adult-onset laryngomalacia are reported. A review of the English literature is performed and additional publications identified by hand-searching relevant papers; 13 case reports/series comprising 28 cases of adult-onset laryngomalacia were identified, divided into two main groups: idiopathic (6/28) and acquired (22/28). The aetiology of the acquired form includes neurological, traumatic and iatrogenic. Reported therapeutic measures used are laser supraglottoplasty, epiglottopexy, partial epiglottidectomy, defunctioning tracheostomy and intubation whilst correcting the underlying cause. The majority of patients only required one therapeutic procedure (follow-up of 2-24 months). A strong index of suspicion is required to diagnose adult-onset laryngomalacia aided by in-office laryngoscopy. The rarity of this condition prevents management-based randomised controlled trials.

GPs could play key role in prostate cancer survivorship programmes.

The number of men living with prostate cancer in the UK is predicted to rise from 255,000 to 416,000 in 2020 and 620,000 by 2030. More than 80% of men diagnosed with prostate cancer can expect to survive for at least five years. Up to 87% of men with prostate cancer may have unmet supportive care needs. Patients regularly cite psychological and sexual issues as the most significant. Poor functional outcomes after treatment such as incontinence and erectile dysfunction have a major impact on quality of life. The traditional model of hospital follow-up fails to deliver optimum patient-centred cancer care. Holistic aspects of care such as psychological needs and factors which may facilitate full rehabilitation of patients back into society may be missed. The key elements of a survivorship programme are: education, intervention, surveillance and co-ordination of care. Interventions which may improve immediate care include: structured holistic needs assessment and care planning, treatment summaries and cancer care reviews, patient education and support events and advice about, and access to, physical activity schemes. Urologists and GPs need to collaborate to establish shared care pathways for prostate cancer patients. Elements of these innovative pathways will include clear follow-up protocols for prostate cancer survivors discharged into the community and rapid access arrangements for patients about whom GPs are concerned.

Multi-parametric magnetic resonance imaging of the prostate in Victoria, Australia; unintended consequences of changing Medicare Benefits Schedule access.

ObjectiveTo assess whether prostate biopsy rates have altered with the July 2018 change in Australian Medicare Benefits Schedule (MBS) rebates supporting multiparametric magnetic resonance imaging (mpMRI) for diagnosing prostate cancer.MethodsBiopsy data (both trans-rectal and trans-perineal) were obtained from the Victorian Agency for Health Information from July 2016 to June 2022. The data were stratified by financial year, age group and hospital type (public vs private). Comparison was made between rates pre and post the mpMRI MBS code change.ResultsThere was an 11.9% increase in the number of biopsies performed per year compared to the pre-MBS change period. There is a significant decreasing trend (P<0.001-4) in number of biopsies in the 40-49, 50-59 and 60-69-year-old age groups with a significant increasing trend (P<0.001) in the 70-79 and 80-89-year-old age groups. There was a 32.9% reduction in the mean number of biopsies performed per year in public hospitals, compared with an 18.3% increase in private.ConclusionContrary to expectations, and proposed funding, there has been an increase in the number of prostate biopsies since MRI became more easily available. This change will put increased pressure on the health budget and the large increase in biopsies in elderly patients was not anticipated when the changes were proposed. A review of the criteria is suggested.

Accurate and efficient integration for molecular dynamics simulations at constant temperature and pressure.

In molecular dynamics simulations, control over temperature and pressure is typically achieved by augmenting the original system with additional dynamical variables to create a thermostat and a barostat, respectively. These variables generally evolve on timescales much longer than those of particle motion, but typical integrator implementations update the additional variables along with the particle positions and momenta at each time step. We present a framework that replaces the traditional integration procedure with separate barostat, thermostat, and Newtonian particle motion updates, allowing thermostat and barostat updates to be applied infrequently. Such infrequent updates provide a particularly substantial performance advantage for simulations parallelized across many computer processors, because thermostat and barostat updates typically require communication among all processors. Infrequent updates can also improve accuracy by alleviating certain sources of error associated with limited-precision arithmetic. In addition, separating the barostat, thermostat, and particle motion update steps reduces certain truncation errors, bringing the time-average pressure closer to its target value. Finally, this framework, which we have implemented on both general-purpose and special-purpose hardware, reduces software complexity and improves software modularity.

Tonsillectomy compared with conservative management in patients over 16 years with recurrent sore throat: the NATTINA RCT and economic evaluation.

Background: The place of tonsillectomy in the management of sore throat in adults remains uncertain. Objectives: To establish the clinical effectiveness and cost-effectiveness of tonsillectomy, compared with conservative management, for tonsillitis in adults, and to evaluate the impact of alternative sore throat patient pathways. Design: This was a multicentre, randomised controlled trial comparing tonsillectomy with conservative management. The trial included a qualitative process evaluation and an economic evaluation. Setting: The study took place at 27 NHS secondary care hospitals in Great Britain. Participants: A total of 453 eligible participants with recurrent sore throats were recruited to the main trial. Interventions: Patients were randomised on a 1 : 1 basis between tonsil dissection and conservative management (i.e. deferred surgery) using a variable block-stratified design, stratified by (1) centre and (2) severity. Main outcome measures: The primary outcome measure was the total number of sore throat days over 24 months following randomisation. The secondary outcome measures were the number of sore throat episodes and five characteristics from Sore Throat Alert Return, describing severity of the sore throat, use of medications, time away from usual activities and the Short Form questionnaire-12 items. Additional secondary outcomes were the Tonsil Outcome Inventory-14 total and subscales and Short Form questionnaire-12 items 6 monthly. Evaluation of the impact of alternative sore throat patient pathways by observation and statistical modelling of outcomes against baseline severity, as assessed by Tonsil Outcome Inventory-14 score at recruitment. The incremental cost per sore throat day avoided, the incremental cost per quality-adjusted life-year gained based on responses to the Short Form questionnaire-12 items and the incremental net benefit based on costs and responses to a contingent valuation exercise. A qualitative process evaluation examined acceptability of trial processes and ramdomised arms. Results: There was a median of 27 (interquartile range 12-52) sore throats over the 24-month follow-up. A smaller number of sore throats was reported in the tonsillectomy arm [median 23 (interquartile range 11-46)] than in the conservative management arm [median 30 (interquartile range 14-65)]. On an intention-to-treat basis, there were fewer sore throats in the tonsillectomy arm (incident rate ratio 0.53, 95% confidence interval 0.43 to 0.65). Sensitivity analyses confirmed this, as did the secondary outcomes. There were 52 episodes of post-operative haemorrhage reported in 231 participants undergoing tonsillectomy (22.5%). There were 47 re-admissions following tonsillectomy (20.3%), 35 relating to haemorrhage. On average, tonsillectomy was more costly and more effective in terms of both sore throat days avoided and quality-adjusted life-years gained. Tonsillectomy had a 100% probability of being considered cost-effective if the threshold for an additional quality-adjusted life year was £20,000. Tonsillectomy had a 69% probability of having a higher net benefit than conservative management. Trial processes were deemed to be acceptable. Patients who received surgery were unanimous in reporting to be happy to have received it. Limitations: The decliners who provided data tended to have higher Tonsillectomy Outcome Inventory-14 scores than those willing to be randomised implying that patients with a higher burden of tonsillitis symptoms may have declined entry into the trial. Conclusions: The tonsillectomy arm had fewer sore throat days over 24 months than the conservative management arm, and had a high probability of being considered cost-effective over the ranges considered. Further work should focus on when tonsillectomy should be offered. National Trial of Tonsillectomy IN Adults has assessed the effectiveness of tonsillectomy when offered for the current UK threshold of disease burden. Further research is required to define the minimum disease burden at which tonsillectomy becomes clinically effective and cost-effective. Trial registration: This trial is registered as ISRCTN55284102. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/146/06) and is published in full in Health Technology Assessment; Vol. 27, No. 31. See the NIHR Funding and Awards website for further award information.

Tonsillectomy is an operation to take out the pair of tonsil glands at the back of the throat. It is an option for adults who suffer from repeated, severe sore throats. Adults who have a tonsillectomy say that they get fewer sore throats afterwards, but it is not clear whether or not they would have got better over time without the operation. There is pressure on doctors to limit the number of tonsillectomies carried out. At the same time, emergency hospital admissions for adults with severe throat infections have been increasing. NAtional Trial of Tonsillectomy IN Adults aimed to find out whether tonsillectomy is an effective and worthwhile treatment for repeated severe sore throats or whether patients would be better off treated without an operation. A total of 453 patients from 27 hospitals in Great Britain took part in the study. Patients were assigned at random to receive either tonsillectomy or conservative management (treatment as needed from their general practitioner). We measured how many sore throats patients had in the next 2 years by sending them text messages every week. We asked about the impact of their sore throats on their quality of life and time off work, and looked at the costs of treatment. We also interviewed 47 patients, general practitioners and hospital staff about their experiences of tonsillectomy and NAtional Trial of Tonsillectomy IN Adults. The typical patient in the tonsillectomy arm had 23 days of sore throat compared with 30 days of sore throat in the conservative management arm. Tonsillectomy resulted in higher quality of life. We looked to see whether or not it was only those with the most severe sore throats who benefited from tonsillectomy, but we found that patients with more or less severe sore throats at the start all did better with tonsillectomy. Patients who had a tonsillectomy were happy to have undertaken this. Our findings suggest a clear benefit of tonsillectomy using modest additional NHS resources for adults with repeated severe sore throats.

Developing a Diagnostic Multivariable Prediction Model for Urinary Tract Cancer in Patients Referred with Haematuria: Results from the IDENTIFY Collaborative Study.

BACKGROUND: Patient factors associated with urinary tract cancer can be used to risk stratify patients referred with haematuria, prioritising those with a higher risk of cancer for prompt investigation. OBJECTIVE: To develop a prediction model for urinary tract cancer in patients referred with haematuria. DESIGN, SETTING, AND PARTICIPANTS: A prospective observational study was conducted in 10 282 patients from 110 hospitals across 26 countries, aged ≥16 yr and referred to secondary care with haematuria. Patients with a known or previous urological malignancy were excluded. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcomes were the presence or absence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC], and renal cancer). Mixed-effect multivariable logistic regression was performed with site and country as random effects and clinically important patient-level candidate predictors, chosen a priori, as fixed effects. Predictors were selected primarily using clinical reasoning, in addition to backward stepwise selection. Calibration and discrimination were calculated, and bootstrap validation was performed to calculate optimism. RESULTS AND LIMITATIONS: The unadjusted prevalence was 17.2% (n = 1763) for bladder cancer, 1.20% (n = 123) for UTUC, and 1.00% (n = 103) for renal cancer. The final model included predictors of increased risk (visible haematuria, age, smoking history, male sex, and family history) and reduced risk (previous haematuria investigations, urinary tract infection, dysuria/suprapubic pain, anticoagulation, catheter use, and previous pelvic radiotherapy). The area under the receiver operating characteristic curve of the final model was 0.86 (95% confidence interval 0.85-0.87). The model is limited to patients without previous urological malignancy. CONCLUSIONS: This cancer prediction model is the first to consider established and novel urinary tract cancer diagnostic markers. It can be used in secondary care for risk stratifying patients and aid the clinician's decision-making process in prioritising patients for investigation. PATIENT SUMMARY: We have developed a tool that uses a person's characteristics to determine the risk of cancer if that person develops blood in the urine (haematuria). This can be used to help prioritise patients for further investigation.