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Risk of a subsequent diagnosis of inflammatory bowel disease in subjects with ophthalmic disorders associated with inflammatory bowel disease: a retrospective cohort analysis of UK primary care data.
No full textOBJECTIVES
Ophthalmic conditions including anterior uveitis (AU), episcleritis and scleritis may occur in association with the inflammatory bowel diseases (IBD) as ophthalmic extraintestinal manifestations. The aim of this study was to assess the risk of a later IBD diagnosis in those presenting with IBD associated ocular inflammation (IAOI).
DESIGN
Retrospective cohort study.
SETTING
Primary care UK database.
PARTICIPANTS
38 805 subjects with an IAOI were identified (median age 51 (38-65), 57% women) and matched to 153 018 subjects without IAOI.
MEASURES
The risk of a subsequent diagnosis of IBD in subjects with IAOIs compared with age/sex matched subjects without IAOI. HRs were adjusted for age, sex, body mass index, deprivation, comorbidity, smoking, baseline axial arthropathy, diarrhoea, loperamide prescription, anaemia, lower gastrointestinal bleeding and abdominal pain.Logistic regression was used to produce a prediction model for a diagnosis of IBD within 3 years of an AU diagnosis.
RESULTS
213 (0.6%) subsequent IBD diagnoses (102 ulcerative colitis (UC) and 111 Crohn's disease (CD)) were recorded in those with IAOIs and 329 (0.2%) (215 UC and 114 CD) in those without. Median time to IBD diagnosis was 882 (IQR 365-2043) days in those with IAOI and 1403 (IQR 623-2516) in those without. The adjusted HR for a subsequent diagnosis of IBD was 2.25 (95% CI 1.89 to 2.68), p<0.001; for UC 1.65 (95% CI 1.30 to 2.09), p<0.001; and for CD 3.37 (95% CI 2.59 to 4.40), p<0.001 in subjects with IAOI compared with those without.Within 3 years of an AU diagnosis, 84 (0.5%) subjects had a recorded diagnosis of IBD. The prediction model performed well with a C-statistic of 0.75 (95% CI 0.69 to 0.80).
CONCLUSIONS
Subjects with IAOI have a twofold increased risk of a subsequent IBD diagnosis. Healthcare professionals should be alert for potential signs and symptoms of IBD in those presenting with ophthalmic conditions associated with IBD
Eosinophilic Asthma Secondary to Adjuvant Anti-PD-1 Immune Checkpoint Inhibitor Treatment in a Melanoma Patient.
No full textBackground
Adjuvant immune checkpoint inhibitors are a new standard of care in melanoma. However, the immune related toxicity associated with these agents can be serious, and the long-term implications are yet to be defined especially in the adjuvant setting. We report, to our knowledge, the first case of anti-PD-1-induced eosinophilic asthma in a melanoma patient treated with adjuvant pembrolizumab. A 72-year-old man commenced pembrolizumab in the adjuvant setting after resection of a stage IIIB cutaneous melanoma. The patient experienced episodes of breathlessness 4 weeks after cycle 1. These episodes were nocturnal and caused acute respiratory distress and cough, occasionally waking him up. The episodes progressed, and he was admitted after cycle 2 with a productive cough, wheeze, and breathlessness. Observations showed saturations on air of 94% and a respiratory rate of 19/min. The only laboratory abnormality was a raised eosinophil count of 1.1 × 10. Spirometry showed a FEV1 of 2.57 (91% predicted), FVC of 4.04 (108% predicted), and ratio of 64%. Peak expiratory flow rate was 94% predicted, and corrected gas transfer was 6.29 (78% predicted) with KCO 1.18 (93% predicted). FeNO was raised at 129 indicating inflammation of his airways, and peak flow was 422 l/min. CT of the chest did not show pneumonitis or other lung pathology. A diagnosis of acute eosinophilic asthma was made. Treatment with steroids and beclometasone dipropionate and formoterol inhaler produced rapid resolution of symptoms and normalisation of the eosinophil count. Pembrolizumab was safely recommenced once steroids had discontinued and symptoms had resolved.
Conclusions
Specialist respiratory input was needed for optimal patient management and is ongoing. Although a safe rechallenge with pembrolizumab was possible, treatment in the adjuvant setting is curative in intent and long-term safety follow-up is required to assess for delayed toxicity and long-term health implications. This is likely to require large regional/national/international databases to detect, monitor, and educate the wider medical community as these patients are followed up in primary care following initial specialist follow-up
Functional in-vitro evaluation of the non-specific effects of BCG vaccination in a randomised controlled clinical study.
No full textBacille Calmette-Guérin (BCG), the only currently licenced tuberculosis vaccine, may exert beneficial non-specific effects (NSE) in reducing infant mortality. We conducted a randomised controlled clinical study in healthy UK adults to evaluate potential NSE using functional in-vitro growth inhibition assays (GIAs) as a surrogate of protection from four bacteria implicated in infant mortality. Volunteers were randomised to receive BCG intradermally (n = 27) or to be unvaccinated (n = 8) and were followed up for 84 days; laboratory staff were blinded until completion of the final visit. Using GIAs based on peripheral blood mononuclear cells, we observed a significant reduction in the growth of the Gram-negative bacteria Escherichia coli and Klebsiella pneumonia following BCG vaccination, but no effect for the Gram-positive bacteria Staphylococcus aureus and Streptococcus agalactiae. There was a modest association between S. aureus nasal carriage and growth of S. aureus in the GIA. Our findings support a causal link between BCG vaccination and improved ability to control growth of heterologous bacteria. Unbiased assays such as GIAs are potentially useful tools for the assessment of non-specific as well as specific effects of TB vaccines. This study was funded by the Bill and Melinda Gates Foundation and registered with ClinicalTrials.gov (NCT02380508, 05/03/2015; completed)
Treatment of unresectable locally advanced pancreatic cancer with percutaneous irreversible electroporation (IRE) following initial systemic chemotherapy (LAP-PIE) trial: study protocol for a feasibility randomised controlled trial.
No full textBACKGROUND
Approximately 30% of patients with pancreas cancer have unresectable locally advanced disease, which is currently treated with systemic chemotherapy. A new treatment option of irreversible electroporation (IRE) has been investigated for these patients since 2005. Cohort studies suggest that IRE confers a survival advantage, but with associated, procedure-related complications. Selection bias may account for improved survival and there have been no prospective randomised trials evaluating the harms and benefits of therapy. The aim of this trial is to evaluate the feasibility of a randomised comparison of IRE therapy with chemotherapy versus chemotherapy alone in patients with locally advanced pancreatic cancer (LAPC).
METHODS AND ANALYSIS
Eligible patients with LAPC who have undergone first-line 5-FluoroUracil, Leucovorin, Irinotecan and Oxaliplatin chemotherapy will be randomised to receive either a single session of IRE followed by (if indicated) further chemotherapy or to chemotherapy alone (standard of care). Fifty patients from up to seven specialist pancreas centres in the UK will be recruited over a period of 15 months. Trial follow-up will be 12 months. The primary outcome measure is ability to recruit. Secondary objectives include practicality and technical success of treatment, acceptability of treatment to patients and clinicians and safety of treatment. A qualitative study has been incorporated to evaluate the patient and clinician perspective of the locally advanced pancreatic cancer with percutaneous irreversible electroporation trial. It is likely that the data obtained will guide the structure, the primary outcome measure, the power and the duration of a subsequent multicentre randomised controlled trial aimed at establishing the clinical efficiency of pancreas IRE therapy. Indicative procedure-related costings will be collected in this feasibility trial, which will inform the cost evaluation in the subsequent study on efficiency.
ETHICS AND DISSEMINATION
The protocol has received approval by London-Brent Research Ethics Committee reference number 21/LO/0077.Results will be analysed following completion of trial recruitment and follow-up. Results will be presented to international conferences with an interest in oncology, hepatopancreaticobiliary surgery and interventional radiology and be published in a peer-reviewed journal.
TRIAL REGISTRATION NUMBER
ISRCTN14986389
Thoracic imaging tests for the diagnosis of COVID-19.
No full textBACKGROUND
Our March 2021 edition of this review showed thoracic imaging computed tomography (CT) to be sensitive and moderately specific in diagnosing COVID-19 pneumonia. This new edition is an update of the review.
OBJECTIVES
Our objectives were to evaluate the diagnostic accuracy of thoracic imaging in people with suspected COVID-19; assess the rate of positive imaging in people who had an initial reverse transcriptase polymerase chain reaction (RT-PCR) negative result and a positive RT-PCR result on follow-up; and evaluate the accuracy of thoracic imaging for screening COVID-19 in asymptomatic individuals. The secondary objective was to assess threshold effects of index test positivity on accuracy.
SEARCH METHODS
We searched the COVID-19 Living Evidence Database from the University of Bern, the Cochrane COVID-19 Study Register, The Stephen B. Thacker CDC Library, and repositories of COVID-19 publications through to 17 February 2021. We did not apply any language restrictions.
SELECTION CRITERIA
We included diagnostic accuracy studies of all designs, except for case-control, that recruited participants of any age group suspected to have COVID-19. Studies had to assess chest CT, chest X-ray, or ultrasound of the lungs for the diagnosis of COVID-19, use a reference standard that included RT-PCR, and report estimates of test accuracy or provide data from which we could compute estimates. We excluded studies that used imaging as part of the reference standard and studies that excluded participants with normal index test results.
DATA COLLECTION AND ANALYSIS
The review authors independently and in duplicate screened articles, extracted data and assessed risk of bias and applicability concerns using QUADAS-2. We presented sensitivity and specificity per study on paired forest plots, and summarized pooled estimates in tables. We used a bivariate meta-analysis model where appropriate.
MAIN RESULTS
We included 98 studies in this review. Of these, 94 were included for evaluating the diagnostic accuracy of thoracic imaging in the evaluation of people with suspected COVID-19. Eight studies were included for assessing the rate of positive imaging in individuals with initial RT-PCR negative results and positive RT-PCR results on follow-up, and 10 studies were included for evaluating the accuracy of thoracic imaging for imagining asymptomatic individuals. For all 98 included studies, risk of bias was high or unclear in 52 (53%) studies with respect to participant selection, in 64 (65%) studies with respect to reference standard, in 46 (47%) studies with respect to index test, and in 48 (49%) studies with respect to flow and timing. Concerns about the applicability of the evidence to: participants were high or unclear in eight (8%) studies; index test were high or unclear in seven (7%) studies; and reference standard were high or unclear in seven (7%) studies. Imaging in people with suspected COVID-19 We included 94 studies. Eighty-seven studies evaluated one imaging modality, and seven studies evaluated two imaging modalities. All studies used RT-PCR alone or in combination with other criteria (for example, clinical signs and symptoms, positive contacts) as the reference standard for the diagnosis of COVID-19. For chest CT (69 studies, 28285 participants, 14,342 (51%) cases), sensitivities ranged from 45% to 100%, and specificities from 10% to 99%. The pooled sensitivity of chest CT was 86.9% (95% confidence interval (CI) 83.6 to 89.6), and pooled specificity was 78.3% (95% CI 73.7 to 82.3). Definition for index test positivity was a source of heterogeneity for sensitivity, but not specificity. Reference standard was not a source of heterogeneity. For chest X-ray (17 studies, 8529 participants, 5303 (62%) cases), the sensitivity ranged from 44% to 94% and specificity from 24 to 93%. The pooled sensitivity of chest X-ray was 73.1% (95% CI 64. to -80.5), and pooled specificity was 73.3% (95% CI 61.9 to 82.2). Definition for index test positivity was not found to be a source of heterogeneity. Definition for index test positivity and reference standard were not found to be sources of heterogeneity. For ultrasound of the lungs (15 studies, 2410 participants, 1158 (48%) cases), the sensitivity ranged from 73% to 94% and the specificity ranged from 21% to 98%. The pooled sensitivity of ultrasound was 88.9% (95% CI 84.9 to 92.0), and the pooled specificity was 72.2% (95% CI 58.8 to 82.5). Definition for index test positivity and reference standard were not found to be sources of heterogeneity. Indirect comparisons of modalities evaluated across all 94 studies indicated that chest CT and ultrasound gave higher sensitivity estimates than X-ray (P = 0.0003 and P = 0.001, respectively). Chest CT and ultrasound gave similar sensitivities (P=0.42). All modalities had similar specificities (CT versus X-ray P = 0.36; CT versus ultrasound P = 0.32; X-ray versus ultrasound P = 0.89). Imaging in PCR-negative people who subsequently became positive For rate of positive imaging in individuals with initial RT-PCR negative results, we included 8 studies (7 CT, 1 ultrasound) with a total of 198 participants suspected of having COVID-19, all of whom had a final diagnosis of COVID-19. Most studies (7/8) evaluated CT. Of 177 participants with initially negative RT-PCR who had positive RT-PCR results on follow-up testing, 75.8% (95% CI 45.3 to 92.2) had positive CT findings. Imaging in asymptomatic PCR-positive people For imaging asymptomatic individuals, we included 10 studies (7 CT, 1 X-ray, 2 ultrasound) with a total of 3548 asymptomatic participants, of whom 364 (10%) had a final diagnosis of COVID-19. For chest CT (7 studies, 3134 participants, 315 (10%) cases), the pooled sensitivity was 55.7% (95% CI 35.4 to 74.3) and the pooled specificity was 91.1% (95% CI 82.6 to 95.7).
AUTHORS' CONCLUSIONS
Chest CT and ultrasound of the lungs are sensitive and moderately specific in diagnosing COVID-19. Chest X-ray is moderately sensitive and moderately specific in diagnosing COVID-19. Thus, chest CT and ultrasound may have more utility for ruling out COVID-19 than for differentiating SARS-CoV-2 infection from other causes of respiratory illness. The uncertainty resulting from high or unclear risk of bias and the heterogeneity of included studies limit our ability to confidently draw conclusions based on our results
Evaluating the performance characteristics of five lateral flow assays for the detection of the SARS-CoV-2 nucleocapsid antigen.
No full textIn response to the COVID-19 pandemic, lateral flow assays (LFAs) for the detection of SARS-CoV-2 antigen have been proposed as a complementary option to the more costly and time consuming reverse-transcriptase polymerase chain reaction (RT-PCR). We assessed five commercially available SARS-CoV-2 antigen detecting LFAs (ASSUT EUROPE (Rome, Italy), Besthree (Taizhou, China), Encode (Zhuhai, China), Fortress (Antrim UK), and Hughes Medical (Buckinghamshire, UK), using samples collected from hospitalised individuals with COVID-19 and compared these results against established RT-PCR assays with the aim of estimating test performance characteristics. We performed a diagnostic accuracy study of the five LFAs on 110 inpatients with confirmed COVID-19 and 75 COVID-19 negative control participants. Assay evaluation was performed using a modified version of each manufacturer's protocol allowing for parallel testing of a single sample on multiple assays. Additional variables were studied including infection acquisition, oxygenation requirements at time of swabbing, and patient outcomes. The 110 patients were 48% (53) female, with mean age 67 years (range 26-100 years), and 77% (85) cases were community onset SARS-CoV-2. Across the five assays, sensitivity ranged from 64 (95% CI 53-73) to 76% (95% CI 65-85); Fortress performed best with sensitivity of 76% (95% CI 65-85). Specificity was high across all assays with 4/5 LFAs achieving 100%. LFA sensitivity was not dependant on RT-PCR cycle thresholds. SARS-CoV-2 antigen detecting LFAs may complement RT-PCR testing to facilitate early diagnosis and provide community testing strategies for identification of patients with COVID-19, however we find suboptimal test performance characteristics across a range of commercially available manufacturers, below WHO and MHRA pre-set sensitivity performance thresholds. With such variation in sensitivity between LFAs and PCR testing and between assay brands, we advise caution in the deployment of LFAs outside of environments with clinical oversight
Risk of incident obstructive sleep apnoea in patients with type 1 diabetes: a population-based retrospective cohort study.
No full textAIMS/HYPOTHESIS
People with type 2 diabetes are at increased risk of developing obstructive sleep apnoea. However, it is not known whether people with type 1 diabetes are also at an increased risk of obstructive sleep apnoea. This study aimed to examine whether people with type 1 diabetes are at increased risk of incident obstructive sleep apnoea compared with a matched cohort without type 1 diabetes.
METHODS
We used a UK primary care database, The Health Improvement Network (THIN), to perform a retrospective cohort study between January 1995 and January 2018 comparing sleep apnoea incidence between patients with type 1 diabetes (exposed) and without type 1 diabetes (unexposed) (matched for age, sex, BMI and general practice). The outcome was incidence of obstructive sleep apnoea. Baseline covariates and characteristics were assessed at the start of the study based on the most recent value recorded prior to the index date. The Cox proportional hazards regression model was used to estimate unadjusted and adjusted hazard ratios, based on a complete-case analysis.
RESULTS
In total, 34,147 exposed and 129,500 matched unexposed patients were included. The median follow-up time was 5.43 years ((IQR 2.19-10.11), and the mean BMI was 25.82 kg/m (SD 4.33). The adjusted HR for incident obstructive sleep apnoea in patients with type 1 diabetes vs those without type 1 diabetes was 1.53 (95% CI 1.25, 1.86; p<0.001). Predictors of incident obstructive sleep apnoea in patients with type 1 diabetes were older age, male sex, obesity, being prescribed antihypertensive or lipid-lowering drugs, atrial fibrillation and depression.
CONCLUSIONS/INTERPRETATION
Individuals with type 1 diabetes are at increased risk of obstructive sleep apnoea compared with people without diabetes. Clinicians should suspect obstructive sleep apnoea in patients with type 1 diabetes if they are old, have obesity, are male, have atrial fibrillation or depression, or if they are taking lipid-lowering or antihypertensive drugs
Diagnostic test accuracy network meta-analysis methods: A scoping review and empirical assessment.
No full textOBJECTIVE
To a) identify methodological and application papers reporting a model developed specifically for diagnostic test accuracy network meta-analysis (DTA-NMA) or a hierarchical meta-regression method for comparing at least three index tests; b) review and summarize the characteristics of the methods and the application papers; and c) compare DTA-NMA and hierarchical meta-regression methods empirically.
STUDY DESIGN AND SETTINGS
We performed a scoping review and searched major databases until 3 March 2021. We assessed the characteristics of the identified methods, conducted a descriptive analysis of characteristics of the application articles, and applied the DTA-NMA and meta-regression methods to the available data.
RESULTS
We included 49 articles, of which 9 were methodological (describing 11 DTA-NMA methods) and 40 were application papers (data available for 32 DTA-NMAs). Our results showed a steep increase in recent years in DTA-NMA publications. DTA-NMA models may lead to different results. Although sensitivity estimates were comparable between meta-regression and DTA-NMA models, specificity estimates were higher in meta-regression.
CONCLUSIONS
The choice of a DTA-NMA model will depend on the available data, including the use of different thresholds for test positivity, different study designs, and software familiarity. Selection between the methods may impact on the NMA results, especially for specificity
Exploring the lived experience of women with rosacea: visible difference and psychological impact.
No full textTrajectories of muscle quantity, quality and function measurements in hospitalized older adults.
No full textAIM
Acute sarcopenia is defined by the development of incident sarcopenia (low muscle quantity/quality and function) within 6 months of a stressor event. However, outcome measures for clinical trials have not been validated. This study aimed to characterize changes in muscle quantity, quality, strength, and physical function during and after hospitalization.
METHODS
Patients aged ≥70 years admitted for elective colorectal surgery, emergency abdominal surgery or acute infections were recruited from a single university hospital. Assessments were carried out at baseline, and within 7 ± 2 days and 13 ± 1 weeks postoperatively or post-admission.
RESULTS
A total of 79 participants (mean age 79 years, 39% female) were included. Physical function defined by the Patient-Reported Outcome Measures Information System T-score declined from baseline (42.3, 95% CI 40.2-44.3) to 7 days (36.6, 95% CI 34.5-38.8; P = 0.001), with improvement after 13 weeks (40.5, 95% CI 37.9-43.0). Changes in muscle quantity, quality and function measurements were overall heterogeneous, with few significant changes at the study population level. Change in rectus femoris echogenicity over 13 weeks correlated with changes in handgrip strength (r = 0.53; P < 0.001) and gait speed (r = 0.59; P = 0.003) over the same period.
CONCLUSIONS
Patient-Reported Outcome Measures Information System T-score provides a sensitive measure of change in physical function in hospitalized older patients. However, changes in muscle quantity, quality and function measurements were heterogeneous, and not significant at the study population level. Further research should assess for factors that might be predictive of changes within individuals to enable stratified interventions. Geriatr Gerontol Int 2022; ••: ••-••