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Fractional Exhaled Nitric Oxide Nonsuppression Identifies Corticosteroid-Resistant Type 2 Signaling in Severe Asthma.
No full textLansoprazole for persistent throat symptoms in secondary care: the TOPPITS RCT.
No full textBACKGROUND
Persistent throat symptoms are commonly attributed to 'laryngopharyngeal reflux'. Despite a limited evidence base, these symptoms are increasingly being treated in primary care with proton pump inhibitors.
OBJECTIVE
To assess the value of proton pump inhibitor therapy in patients with persistent throat symptoms.
DESIGN
This was a double-blind, placebo-controlled, randomised Phase III trial.
SETTING
This was a multicentre UK trial in eight UK ear, nose and throat departments.
PARTICIPANTS
A total of 346 participants aged ≥ 18 years with persistent throat symptoms and a Reflux Symptom Index score of ≥ 10, exclusive of the dyspepsia item, were recruited.
INTERVENTION
Random allocation (1 : 1 ratio) to either 30 mg of lansoprazole twice daily or matched placebo for 16 weeks.
MAIN OUTCOME MEASURE
Symptomatic response (i.e. total Reflux Symptom Index score after 16 weeks of therapy).
RESULTS
A total of 1427 patients were screened and 346 were randomised. The mean age was 52 years (standard deviation 13.7 years, range 20-84 years); 150 (43%) participants were male and 196 (57%) were female; 184 (53%) participants had a mild Reflux Symptom Index minus the heartburn/dyspepsia item and 162 (47%) had a severe Reflux Symptom Index minus the heartburn/dyspepsia item. A total of 172 patients were randomised to lansoprazole and 174 were randomised to placebo.
MAIN OUTCOMES
A total of 267 participants completed the primary end-point visit (lansoprazole, = 127; placebo, = 140), of whom 220 did so between 14 and 20 weeks post randomisation ('compliant' group); 102 received lansoprazole and 118 received placebo. The mean Reflux Symptom Index scores at baseline were similar [lansoprazole 22.0 (standard deviation 8.0), placebo 21.7 (standard deviation 7.1), overall 21.9 (standard deviation 7.5)]. The mean Reflux Symptom Index scores at 16 weeks reduced from baseline in both groups [overall 17.4 (standard deviation 9.9), lansoprazole 17.4 (standard deviation 9.9), placebo 15.6 (standard deviation 9.8)]. Lansoprazole participants had estimated Reflux Symptom Index scores at 16 weeks that were 1.9 points higher (worse) than those of placebo participants (95% confidence interval -0.3 to 4.2; = 0.096), adjusted for site and baseline severity.
SECONDARY OUTCOMES
Ninety-five (43%) participants achieved a Reflux Symptom Index score in the normal range (< 12) at 16 weeks: 42 (41%) in the lansoprazole group and 53 (45%) in the placebo group. A total of 226 participants completed the end-of-trial follow-up visit (lansoprazole, = 109; placebo, = 117), of whom 181 were 'compliant'. The mean Reflux Symptom Index scores at 12 months reduced from baseline in both groups [lansoprazole 16.0 (standard deviation 10.8), placebo 13.6 (standard deviation 9.6), overall 14.7 (standard deviation 10.2)]. A total of 87 (48%) participants achieved a Reflux Symptom Index score in the normal range at 12 months: 33 (40%) in the lansoprazole group and 54 (55%) in the placebo group. Likewise, the Comprehensive Reflux Symptom Score and Laryngopharyngeal Reflux - Health Related Quality of Life total scores and subscales all showed very similar changes in the lansoprazole and placebo cohorts at both 16 weeks and 12 months.
LIMITATIONS
Drop-out rate and compliance are issues in pragmatic clinical trials. The Trial Of Proton Pump Inhibitors in Throat Symptoms (TOPPITS) aimed to detect clinically relevant difference with 90% power. The 346 randomised participants reduced to 283 at the primary end point; 267 completed the primary outcome measure, 220 within the protocol time scale. Despite this, the powers to detect the clinically relevant difference in Reflux Symptom Index score at 16 weeks were 82% (compliant comparison) and 89% (pragmatic comparison). The lack of difference between lansoprazole and placebo is generalisable across NHS clinics.
CONCLUSIONS
Participants on lansoprazole did not report significantly better outcomes than participants on placebo on any of the three patient-reported outcome tools (Reflux Symptom Index, Comprehensive Reflux Symptom Score and Laryngopharyngeal Reflux - Health Related Quality of Life). This multicentre, pragmatic, powered, definitive Phase III trial found no evidence of benefit for patients by treating persistent throat symptoms with lansoprazole.
TRIAL REGISTRATION
Current Controlled Trials ISRCTN38578686 and EudraCT number 2013-004249-17.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 25, No. 3. See the NIHR Journals Library website for further project information
Comparing an Imaging-guided Pathway with the Standard Pathway for Staging Muscle-invasive Bladder Cancer: Preliminary Data from the BladderPath Study.
No full textTransurethral resection of bladder tumour (TURBT) is central to the diagnosis of muscle-invasive bladder cancer (MIBC). With the oncological safety of TURBT unknown, staging inaccuracies commonplace, and correct treatment of MIBC potentially delayed, multiparametric magnetic resonance imaging (mpMRI) may offer rapid, accurate, and noninvasive diagnosis of MIBC. BladderPath is a randomised trial comparing risk-stratified (5-point Likert scale) image-directed care with TURBT for patients with newly diagnosed BC. To date, we have screened 279 patients and randomised 113. Here we report on the first 100 participants to complete staging: 48 in pathway 1 (TURBT) and 52 in pathway 2 (mpMRI for possible MIBC, Likert 3-5). Fifty of 52 participants designated Likert 1-2 (probable NMIBC) from both pathways were confirmed as having NMIBC (96%). Ten of 11 cases diagnosed as NMIBC by mpMRI have been pathologically confirmed as NMIBC, and 10/15 cases diagnosed as MIBC by mpMRI have been treated as MIBC (5 participants underwent TURBT). The specificity of mpMRI for identification of MIBC remains a limitation. These initial experiences indicate that it is feasible to direct possible MIBC patients to mpMRI for staging instead of TURBT. Furthermore, a 5-point Likert scale accurately identifies patients with low risk of MIBC (Likert 1-2), and flexible cystoscopy biopsies appear sufficient for diagnosing BC. PATIENT SUMMARY: We are conducting a clinical trial to assess whether some bladder tumour surgery can be replaced by magnetic resonance imaging scans to determine the stage of the cancer in patients whose tumours appear to be invasive. Our early data suggest that this approach is feasible. The data also show that using a visual score ('Likert scale') can help to identify bladder tumours that are very unlikely to be invasive, and that taking a biopsy in the outpatient clinic when first inspecting the bladder via a camera (diagnostic flexible cystoscopy) is useful for confirming bladder cancer
ENT UK coronavirus disease 2019 adult tonsillitis and quinsy guidelines: translating guidance into practice.
No full textOBJECTIVES
This study examined the uptake of ENT UK coronavirus disease 2019 adult tonsillitis and quinsy guidelines at our tertiary centre, and assessed perceived barriers to uptake.
METHODS
A retrospective case series of tonsillitis and quinsy patients was analysed in two arms: before and after the introduction of new ENT UK management guidelines. A survey assessed perceptions and practice differences between ENT and emergency department doctors.
RESULTS
Each study arm examined 82 patients. Following the introduction of new ENT UK guidelines, ENT clinicians demonstrated significant changes in practice, unlike their emergency department counterparts. Survey results from emergency department doctors highlighted a lack of appreciation of guideline change and identified barriers to guideline uptake.
CONCLUSION
The introduction of new management guidelines for tonsillitis and quinsy patients during the pandemic resulted in disparate uptake within ENT and emergency department departments at the tertiary centre. Clearer dissemination to all affected clinicians is paramount for future rapidly introduced changes to practice, to ensure clinician safety
Completion of annual diabetes care processes and mortality: A cohort study using the National Diabetes Audit for England and Wales.
No full textAIM
To conduct an analysis to assess whether the completion of recommended diabetes care processes (glycated haemoglobin [HbA1c], creatinine, cholesterol, blood pressure, body mass index [BMI], smoking habit, urinary albumin, retinal and foot examinations) at least annually is associated with mortality.
MATERIALS AND METHODS
A cohort from the National Diabetes Audit of England and Wales comprising 179 105 people with type 1 and 1 397 790 people with type 2 diabetes, aged 17 to 99 years on January 1, 2009, diagnosed before January 1, 2009 and alive on April 1, 2013 was followed to December 31, 2019. Cox proportional hazards models adjusting for demographic characteristics, smoking, HbA1c, blood pressure, serum cholesterol, BMI, duration of diagnosis, estimated glomerular filtration rate, prior myocardial infarction, stroke, heart failure, respiratory disease and cancer, were used to investigate whether care processes recorded January 1, 2009 to March 31, 2010 were associated with subsequent mortality.
RESULTS
Over a mean follow-up of 7.5 and 7.0 years there were 26 915 and 388 093 deaths in people with type 1 and type 2 diabetes, respectively. Completion of five or fewer, compared to eight, care processes (retinal screening not included as data were not reliable) had a mortality hazard ratio (HR) of 1.37 (95% confidence interval [CI] 1.28-1.46) in people with type 1 and 1.32 (95% CI 1.30-1.35) in people with type 2 diabetes. The HR was higher for respiratory disease deaths and lower in South Asian ethnic groups.
CONCLUSIONS
People with diabetes who have fewer routine care processes have higher mortality. Further research is required into whether different approaches to care might improve outcomes for this high-risk group
The epidemiology of epidermolysis bullosa in England and Wales: data from the national epidermolysis bullosa database.
No full textBACKGROUND
The National Health Service (NHS) epidermolysis bullosa (EB) service, established in 2002, offers comprehensive, free care to all patients in England and Wales.
OBJECTIVES
To quantify prevalence, incidence and mortality of EB in England and Wales.
METHODS
Demographic data for patients in England and Wales were collected on a secure electronic database, prospectively from January 2002 to April 2021 and retrospectively for cases prior to 2002. Vital status was verified using central NHS data.
RESULTS
By March 2021, 2594 individuals were registered, of whom 2361 were living, which yielded a prevalence of 34·8 per million of the population for all EB types [EB simplex (EBS) 17 per million, dystrophic EB (DEB) 10·7 per million, junctional EB (JEB) 1 per million and Kindler EB 0·3 per million]. We recorded 1200 babies with EB born since 2002. The average incidence per million live births for EBS, DEB, JEB and Kindler EB was 32·5, 26·1, 8·9 and 0·9, respectively (total incidence for all types of EB was 67·8 per million). Birth rates fell progressively over the 19-year period for JEB-severe (JEB-S) (r = -0·56) and recessive DEB-severe (r = -0·44) and also for milder types of EB. We observed longer survival in JEB-S over the 19-year period (r = 0·18) with a median survival of 12·7 months over the past 5 years.
CONCLUSIONS
In this study, we provide the first accurate epidemiological data for EB in England and Wales. We believe the observed reduction in birth incidence of severe types of EB reflects an uptake of genetic counselling advice, whereas the reduction in milder types may be due to delayed presentation. A potential small trend towards longer survival of babies with JEB-S may reflect improved multidisciplinary care
Use of Social Media as a Platform for Education and Support for People With Diabetes During a Global Pandemic.
No full textBACKGROUND
Patient education is a fundamental aspect of self-management of diabetes. The aim of this study was to understand whether a social media platform is a viable method to deliver education to people with diabetes and understand if people would engage and interact with it.
METHODS
Education sessions were provided via 3 platforms in a variety of formats. "Tweetorials" and quizzes were delivered on the diabetes101 Twitter account, a virtual conference via Zoom and video presentations uploaded to YouTube. Audience engagement during and after the sessions were analyzed using social media metrics including impressions and engagement rate using Twitter analytics, Tweepsmap, and YouTube Studio.
RESULTS
A total of 22 "tweetorial" sessions and 5 quizzes with a total of 151 polls (both in tweetorial and quiz sessions) receiving a total of 21,269 votes took place. Overall, the 1-h tweetorial sessions gained 1,821,088 impressions with an engagement rate of 6.3%. The sessions received a total of 2,341 retweets, 2,467 replies and 10,060 likes. The quiz days included 113 polls receiving 16,069 votes. The conference covered 8 topics and was attended live by over 100 people on the day. The video presentations on YouTube have received a total of 2,916 views with a watch time of 281 h and 8,847 impressions.
CONCLUSION
Despite the limitations of social media, it can be harnessed to provide relevant reliable information and education about diabetes allowing people the time and space to learn at their own pace
Impact of Platelet Count on Perioperative Bleeding in Patients With Cirrhosis Undergoing Surgical Treatments of Liver Cancer.
No full textIn patients with cirrhosis with severe thrombocytopenia (platelet count [PC] 100 × 10 /L), intermediate (51-100 × 10 /L), and low (≤50 × 10 /L). PC was also analyzed as a continuous covariate on multivariable analysis. The primary endpoint was major perioperative bleeding. The overall event rate of major perioperative bleeding was 8.9% and was not found to differ significantly between the high, intermediate, and low platelet groups (8.1% vs. 10.2% vs. 10.8%, P = 0.48). On multivariable analysis, greater age, aspartate aminotransferase, lower hemoglobin, and treatment with LR (vs. RFA) were found to be significant independent predictors of major perioperative bleeding, with associations with disease etiology and year of surgery also observed. After adjusting for these factors, the association between PC and major perioperative bleeding remained nonsignificant. Conclusion: Major perioperative bleeding was not significantly associated with PC in patients with cirrhosis undergoing surgical treatment of HCC, even when their PC was <50 × 10 /L. With the limit of a retrospective analysis, our data do not support the recommendation of increasing PC in patients with severe thrombocytopenia in order to decrease their perioperative bleeding risk
Circulating tumour DNA (ctDNA) in metastatic melanoma, a systematic review and meta-analysis.
No full textINTRODUCTION
Circulating tumour DNA (ctDNA) is an emerging biomarker in melanoma. We performed a systematic review and meta-analysis to explore its clinical utility as a prognostic, pharmacodynamic (PD) and predictive biomarker.
METHODS
A systematic search was conducted from Jan 2015 to April 2021, of the electronic databases PubMed, Cochrane Library and Ovid MEDLINE to identify studies. Studies were restricted to those published in English within the last 5 years, evaluating ctDNA in humans in ≥10 patients. Survival data were extracted for meta-analysis using pooled treatment effect (TE), i.e. log hazard ratios (HRs) and corresponding standard error of TE for progression-free survival or overall survival differences in patients who were ctDNA positive or negative. PRISMA statement guidelines were followed.
RESULTS
A meta-analysis of 19 studies grouped according to methodology of ctDNA detection, revealed a combined estimate for HR of progression-free survival (13 studies using droplet digital Polymerase Chain Reaction (ddPCR) methodology (N = 1002) of 2.10 (95% CI: 1.71-2.59) revealing a poorer prognosis when ctDNA was detected. This result was confirmed in the smaller analysis of (non-ddPCR, N = 347) five studies: HR = 2.45 (95% CI: 1.29-4.63). Similar findings were found in the overall survival analysis of nine studies (ddPCR methodology, N = 841) where the combined HR was 2.78 (95% CI: 2.21-3.49) and of the five studies (non-ddPCR methodology, N = 326) where the combined HR was 2.58 (95% CI: 1.74-3.84). Serial ctDNA levels on treatment showed a pharmacodynamic role reflecting response or resistance earlier than radiological assessment.
CONCLUSIONS
Circulating tumour DNA is a predictive, prognostic and PD biomarker in melanoma. Technical standardisation of assays is required before clinical adoption
Exploring Associations Between Self-Compassion, Self-Criticism, Mental Health, and Quality of Life in Adults with Cystic Fibrosis: Informing Future Interventions.
No full textSelf-compassion is increasingly recognised as an important and beneficial factor in quality of life and mental health-related research, but research within the adult cystic fibrosis (CF) population is scarce. In a cross-sectional study, 114 (56 female, 58 male) adults with CF completed and returned a series of validated questionnaires that assessed CF-related quality of life, negative emotional states (depression, anxiety and stress), self-compassion, and self-criticism. Quality of life and self-compassion were positively correlated, and each in turn were inversely correlated with negative emotional states and self-criticism. Negative emotional states correlated positively to self-criticism. Self-compassion and/or self-criticism moderated ten relationships between various sub-domains of quality of life and negative emotions. Psychological interventions that increase self-compassion may be beneficial for enhancing mental health and quality of life for adults with CF