Quality Assurance and its impact on ovarian visualisation rates in the multicentre United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

OBJECTIVE: To describe the quality assurance (QA) processes and their impact on visualisation of postmenopausal ovaries in the ultrasound arm of a multicentre ovarian cancer screening trial. METHODS: In UKCTOCS, 50,640 women aged 50-74 at recruitment were randomised to the ultrasound arm and underwent annual transvaginal scans. QA processes were developed during the course of the trial and included regular monitoring of Visualisation Rate (VR) of right ovary. Non-subjective factors previously identified as impacting on VR of right ovary were included in a generalised estimating equation(GEE) model for binary outcomes to enable comparison of observed versus adjusted VR between individual sonographers who had undertaken >1000scans on trial /centres. Analysis of annual VR of sonographers / centres was undertaken. RESULTS: Between June 2001 and December 2010, across 13 centres, 48230 (of 50639) women attended for 270035 annual transvaginal scans. One or both ovaries were seen in 84.5% (228145/270035) of scans. The observed VR of the right ovary was 72.7% (196426/270035). For the 78 sonographers included in the model, the median difference between observed and adjusted VR was 2% (range 0-8%) and median change in rank was 3 (range 0-18). For the 13 centres, the median difference between observed versus adjusted VR was 0% (range 0-2%) with no change in ranking. The median adjusted VR for sonographers was 73% (IQR 65-82%) and for centres was 74.7% (IQR 67.1-79.0%). Despite increasing age of the cohort, there was a steady decrease in the number of sonographers with VR80% (14.3% in 2002 to 40.8 % in 2010). Median centre VR increased from 65.5% (range 55.7-81.0%) in 2001 to 80.3% (range74.5%-90.9%) in 2010. CONCLUSIONS: A robust QA programme can improve visualisation of postmenopausal ovaries and is an essential component of ultrasound-based ovarian cancer screening trials. While VR should be adjusted for non-subjective factors that impact on ovarian visualisation, subjective factors are likely to be the largest contributors to VR differences

Pseudomonas aeruginosa Induced Airway Epithelial Injury Drives Fibroblast Activation:A Mechanism in Chronic Lung Allograft Dysfunction

Bacterial infections after lung transplantation cause airway epithelial injury and are associated with an increased risk of developing bronchiolitis obliterans syndrome. The damaged epithelium is a source of alarmins that activate the innate immune system, yet their ability to activate fibroblasts in the development of bronchiolitis obliterans syndrome has not been evaluated. Two epithelial alarmins were measured longitudinally in bronchoalveolar lavages from lung transplant recipients who developed bronchiolitis obliterans syndrome and were compared to stable controls. In addition, conditioned media from human airway epithelial cells infected with Pseudomonas aeruginosa was applied to lung fibroblasts and inflammatory responses were determined. Interleukin‐1 alpha (IL‐1α) was increased in bronchoalveolar lavage of lung transplant recipients growing P. aeruginosa (11.5 [5.4–21.8] vs. 2.8 [0.9–9.4] pg/mL, p < 0.01) and was significantly elevated within 3 months of developing bronchiolitis obliterans syndrome (8.3 [1.4–25.1] vs. 3.6 [0.6–17.1] pg/mL, p < 0.01), whereas high mobility group protein B1 remained unchanged. IL‐1α positively correlated with elevated bronchoalveolar lavage IL‐8 levels (r(2) = 0.6095, p < 0.0001) and neutrophil percentage (r(2) = 0.25, p = 0.01). Conditioned media from P. aeruginosa infected epithelial cells induced a potent pro‐inflammatory phenotype in fibroblasts via an IL‐1α/IL‐1R‐dependent signaling pathway. In conclusion, we propose that IL‐1α may be a novel therapeutic target to limit Pseudomonas associated allograft injury after lung transplantation

Quality assurance and its impact on ovarian visualization rates in the multicenter United Kingdom collaborative trial of ovarian cancer screening (UKCTOCS)

OBJECTIVE: To describe the quality assurance (QA) processes and their impact on visualization of postmenopausal ovaries in the ultrasound arm of a multicenter screening trial for ovarian cancer. METHODS: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 50 639 women aged 50–74 years were randomized to the ultrasound arm and underwent annual transvaginal ultrasound (TVS) examinations. QA processes were developed during the course of the trial and included regular monitoring of the visualization rate (VR) of the right ovary. Non‐subjective factors identified previously as impacting on VR of the right ovary were included in a generalized estimating equation model for binary outcomes to enable comparison of observed vs adjusted VR between individual sonographers who had undertaken > 1000 scans during the trial and comparison between centers. Observed and adjusted VRs of sonographers and centers were ranked according to the highest VR. Analysis of annual VRs of sonographers and those of the included centers was undertaken. RESULTS: Between June 2001 and December 2010, 48 230 of 50 639 women attended one of 13 centers for a total of 270 035 annual TVS scans. One or both ovaries were seen in 228 145 (84.5%) TVS scans. The right ovary was seen on 196 426 (72.7%) of the scans. For the 78 sonographers included in the model, the median difference between observed and adjusted VR was −0.7% (range, −7.9 to 5.9%) and the median change in VR rank after adjustment was 3 (range, 0–18). For the 13 centers, the median difference between observed and adjusted VR was −0.5% (range, −2.2 to 1%), with no change in ranking after adjustment. The median adjusted VR was 73% (interquartile range (IQR), 65–82%) for sonographers and 74.7% (IQR, 67.1–79.0%) for centers. Despite the increasing age of the women being scanned, there was a steady decrease in the number of sonographers with VR < 60% (21.4% in 2002 vs 2.0% in 2010) and an increase in sonographers with VR > 80% (14.3% in 2002 vs 40.8% in 2010). The median VR of the centers increased from 65.5% (range, 55.7–81.0%) in 2001 to 80.3% (range, 74.5–90.9%) in 2010. CONCLUSIONS: A robust QA program can improve visualization of postmenopausal ovaries and is an essential component of ultrasound‐based ovarian cancer screening trials. While VR should be adjusted for non‐subjective factors that impact on ovarian visualization, subjective factors are likely to be the largest contributors to differences in VR. © 2015 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd. on behalf of the International Society of Ultrasound in Obstetrics and Gynecology

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease

Factors affecting visualization of postmenopausal ovaries: Descriptive study from the multicenter United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

Objective: Transvaginal sonography (TVS) is core to any ovarian cancer screening strategy. General-population screening involves older postmenopausal women in whom ovarian visualization is difficult because of decreasing ovarian size and lack of follicular activity. We report on factors affecting the visualization of postmenopausal ovaries in the multicenter United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Methods: The UKCTOCS is a randomized controlled trial of 202 638 postmenopausal women with 50 639 women in the ultrasound scan arm. TVS is the primary screening modality in the ultrasound scan arm. Age, education, ethnicity, body mass index (BMI), previous pelvic surgery, lifestyle and reproductive factors, and a personal/family history of cancer were assessed for their effects on ovarian visualization at the initial TVS. Results: Between 11 June 2001 and 18 August 2007, 43 867 women underwent TVS. The median age and BMI of the women were 60.6 (interquartile range (IQR), 9.9) years and 25.7 (IQR, 5.8), respectively. The right ovary was visualized in 29 297 (66.8%) and the left ovary was visualized in 28 726 (65.5%). Visualization of ovaries decreased with previous hysterectomy (odds ratio (OR) = 0.534; 95% CI, 0.504–0.567), previous tubal ligation (OR = 0.895; 95% CI, 0.852–0.940), increasing age (OR = 0.953; 95% CI, 0.950–0.956), unilateral oophorectomy (OR = 0.224; 95% CI, 0.186–0.269) and being overweight (OR = 0.918; 95% CI, 0.876–0.962) or obese (OR = 0.715; 95% CI, 0.677–0.755). Increased visualization was observed with a history of infertility (OR = 1.134; 95% CI, 1.005–1.279) and increasing age (in years) at menopause (OR = 1.005; 95% CI, 1.001–1.009). Conclusions: Several factors affect the visualization of postmenopausal ovaries. Their impact needs to be taken into consideration when developing quality assurance for ovarian ultrasound scanning or comparing study results as their prevalence may differ between populations

Risk of epithelial ovarian cancer in asymptomatic women with ultrasound-detected ovarian masses: A prospective cohort study within the UK collaborative trial of ovarian cancer screening (UKCTOCS)

Objective. To estimate the risk of primary epithelial ovarian cancer (EOC) and slow growing borderline or Type I and aggressive Type II EOC in postmenopausal women with adnexal abnormalities on ultrasound. Methods. This was a prospective cohort study in the ultrasound group of the UK Collaborative Trial of Ovarian Cancer Screening of postmenopausal women with ultrasound-detected abnormal adnexal (unilocular, multilocular, unilocular solid and multilocular solid, solid) morphology on their first scan. Women were followed up through the national cancer registries and by postal questionnaires. Absolute risks of EOC and borderline, Type I and Type II EOC within 3 years of initial scan were calculated. Results. Of 48 053 women who underwent ultrasound examination and had complete scan data, 4367 (9.1% (95% CI, 8.8–9.3%)) had abnormal adnexal morphology. Median follow-up was 7.09 (25th–75th centiles, 6.03–7.92) years. Forty-seven (32 borderline or Type I, 15 Type II) were diagnosed with EOC. The overall absolute risk of EOC associated with abnormal adnexal morphology was 1.08% (95% CI, 0.79–1.43%); for borderline and Type I it was 0.73% (95% CI, 0.5–1.03%); and for Type II it was 0.34% (95% CI, 0.33–0.79%). In the subgroup (n = 741) with solid elements (unilocular solid, multilocular solid and solid) overall absolute risk was 4.45% (95% CI, 3.08–6.20%), for borderline and Type I it was 3.1% (95% CI, 1.9–4.6%) and for Type II it was 1.3% (95% CI, 0.6–2.4%). 11 982 women had both ovaries visualized and normal annual scans throughout the 3-year follow-up period. In this group, no borderline or Type I and eight Type II cancers were diagnosed. Conclusion. Asymptomatic postmenopausal women with ultrasound-detected adnexal abnormalities with solid elements have a 1 in 22 risk for EOC. Despite the higher prevalence of Type II EOC, the risk of borderline or Type I cancer in women with ultrasound abnormalities seems to be higher than does the risk of Type II cancer. This has important immediate implications for patients with incidental adnexal findings as well as for any future ultrasound-based screening

Pulmonary tuberculosis diagnostic delays in Chad: a multicenter, hospital-based survey in Ndjamena and Moundou

<p>Abstract</p> <p>Background</p> <p>Tuberculosis remains one of the leading causes of morbidity and mortality in low-resource countries. One contagious patient can infect 10 to 20 contacts in these settings. Delays in diagnosing TB therefore contribute to the spread of the disease and sustain the epidemic.</p> <p>Objectives</p> <p>The aim of this study was to assess delays in diagnosing tuberculosis and the factors associated with these delays in the public hospitals in Moundou and Ndjamena, Chad.</p> <p>Methods</p> <p>A structured questionnaire was administered to 286 new tuberculosis patients to evaluate patient delay (time from the onset of symptoms to the first formal or informal care), health-care system delay (time from the first health care to tuberculosis treatment) and total delay (sum of the patient and system delays). Logistic regression was used to identify risk factors associated with long diagnostic delays (defined as greater than the median).</p> <p>Results and discussion</p> <p>The median [interquartile range] patient delay, system delay and total delay were 15 [7–30], 36 [19–65] and 57.5 [33–95] days, respectively. Low economic status (aOR [adjusted odds ratio] =2.38 [1.08-5.25]), not being referred to a health service (aOR = 1.75 [1.02- 3.02]) and a secondary level education (aOR = 0.33 [0.12-0.92]) were associated with a long patient delay. Risk factors for a long system delay were a low level of education (aOR = 4.71 [1.34-16.51]) and the belief that traditional medicine and informal care can cure TB (aOR = 5.46 [2.37-12.60]).</p> <p>Conclusion</p> <p>Targeted strengthening of the health-care system, including improving patient access, addressing deficiencies in health-related human resources, and improving laboratory networks and linkages as well as community mobilization will make for better outcomes in tuberculosis diagnosis.</p

Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19. Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24). Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research