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Objective: Estrogen is a well-established risk factor for various cancers. It causes endometrial proliferation, which is assessed routinely as endometrial thickness (ET) using transvaginal ultrasound (TVS). Only one previous study, restricted to endometrial and breast cancer, has considered ET and the risk of non-endometrial cancer. The aim of this study was to explore the association between baseline and serial ET measurements and nine non-endometrial hormone-sensitive cancers, in postmenopausal women, using contemporary statistical methodology that attempts to minimize the biases typical of endogenous serial data.Methods: This was a cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). In the ultrasound arm of UKCTOCS, 50639 postmenopausal women, aged 50-74, underwent annual TVS examination, of whom 38 105 had a valid ET measurement, no prior hysterectomy and complete covariate data, and were included in this study. All women were followed up through linkage to national cancer registries. The effect of ET on the risk of six estrogen-dependent cancers (breast, ovarian, colorectal, bladder, lung and pancreatic) was assessed using joint models for longitudinal biomarker and time-to-event data, and Cox models were used to assess the association between baseline ET measurement and these six cancers in addition to liver cancer, gastric cancer and non-Hodgkin's lymphoma (NHL). All models were adjusted for current hormone-replacement therapy (HRT) use, body mass index, age at last menstrual period, parity and oral contraceptive pill use.Results: The 38 105 included women had a combined total of 267 567 (median, 8; interquartile range, 5-9) valid ET measurements. During a combined total of 407 838 (median, 10.9) years of follow-up, 1398 breast, 351 endometrial, 381 lung, 495 colorectal, 222 ovarian, 94 pancreatic, 79 bladder, 62 gastric, 38 liver cancers and 52 NHLs were registered. Using joint models, a doubling of ET increased significantly the risk of breast (hazard ratio (HR), 1.21; 95% CI, 1.09-1.36; P = 0.001), ovarian (HR, 1.39; 95% CI, 1.06-1.82; P = 0.018) and lung (HR, 1.25; 95% CI, 1.02-1.54; P = 0.036) cancers. There were no statistically significant associations between ET and the remaining six cancers.Conclusion: Postmenopausal women with high/increasing ET on TVS are at increased risk of breast, ovarian and lung cancer. It is important that clinicians are aware of these risks, as TVS is a common investigation. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Randomised controlled trials are challenging to deliver. There is a constant need to review and refine recruitment and implementation strategies if they are to be completed on time and within budget. We present the strategies adopted in the United Kingdom Collaborative Trial of Ovarian Cancer Screening, one of the largest individually randomised controlled trials in the world. The trial recruited over 202,000 women (2001–5) and delivered over 670,000 annual screens (2001–11) and over 3 million women-years of follow-up (2001–20). Key to the successful completion were the involvement of senior investigators in the day-to-day running of the trial, proactive trial management and willingness to innovate and use technology. Our underlying ethos was that trial participants should always be at the centre of all our processes. We ensured that they were able to contact either the site or the coordinating centre teams for clarifications about their results, for follow-up and for rescheduling of appointments. To facilitate this, we shared personal identifiers (with consent) with both teams and had dedicated reception staff at both site and coordinating centre. Key aspects were a comprehensive online trial management system which included an electronic data capture system (resulting in an almost paperless trial), biobanking, monitoring and project management modules. The automation of algorithms (to ascertain eligibility and classify results and ensuing actions) and processes (scheduling of appointments, printing of letters, etc.) ensured the protocol was closely followed and timelines were met. Significant engagement with participants ensured retention and low rates of complaints. Our solutions to the design, conduct and analyses issues we faced are highly relevant, given the renewed focus on trials for early detection of cancer. Future work There is a pressing need to increase the evidence base to support decision making about all aspects of trial methodology. Trial registration ISRCTN-22488978; ClinicalTrials.gov-NCT00058032. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 16/46/01. The long-term follow-up UKCTOCS (2015 20) was supported by National Institute for Health and Care Research (NIHR HTA grant 16/46/01), Cancer Research UK, and The Eve Appeal. UKCTOCS (2001–14) was funded by the MRC (G9901012 and G0801228), Cancer Research UK (C1479/A2884), and the UK Department of Health, with additional support from The Eve Appeal. Researchers at UCL were supported by the NIHR UCL Hospitals Biomedical Research Centre and by the MRC Clinical Trials Unit at UCL core funding (MC_UU_00004/09, MC_UU_00004/08, MC_UU_00004/07). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the UK Department of Health and Social Care. Plain language summary Randomised controlled trials help us decide whether new health-care approaches are better than those in current use. To successfully complete these on time and within budget, there is a constant need to review and revise the procedures used for delivering various aspects such as invitation, enrolment, follow-up of participants, delivery of the new test, data collection, and analysis. We report on the processes used in the United Kingdom Collaborative Trial of Ovarian Cancer Screening, one of the largest such trials. The United Kingdom Collaborative Trial of Ovarian Cancer Screening enrolled over 202,000 women (2001–5), delivered over 670,000 yearly screens (2001–11) and followed all participants until 2020. Key to our successful completion were the involvement of senior investigators in day-to-day running of the trial, a pre-emptive approach to issues, a willingness to innovate, and the use of technology. Our underlying ethos was that trial participants should always be at the centre of all our processes. We ensured that they were able to always contact either their local or the central team for clarifications and rescheduling of appointments. To facilitate this, we shared participant contact details (with consent) with both teams. We built a comprehensive electronic system to manage all aspects of the trial. This included online forms that the teams completed in real time (resulting in an almost paperless trial) and systems to check and manage trial processes and track blood samples. We automated key steps such as checking whether participants were eligible, assigning correct action based on results of screening tests, scheduling appointments and printing letters. As a result, all participants were treated as set out in the trial plan. Our engagement with participants ensured that they continued participating and we had a low rate of complaints. We faced issues with regard to our initial trial design and the way we planned to analyse the data. We feel that our solutions are highly relevant, especially as there is a renewed focus on trials for early detection of cancer.

Background Ovarian and tubal cancers are lethal gynaecological cancers, with over 50% of the patients diagnosed at advanced stage. Trial design Randomised controlled trial involving 27 primary care trusts adjacent to 13 trial centres based at NHS Trusts in England, Wales and Northern Ireland. Methods Participants Postmenopausal average-risk women, aged 50–74, with intact ovaries and no previous ovarian or current non-ovarian cancer. Interventions One of two annual screening strategies: (1) multimodal screening (MMS) using a longitudinal CA125 algorithm with repeat CA125 testing and transvaginal scan (TVS) as second line test (2) ultrasound screening (USS) using TVS alone with repeat scan to confirm any abnormality. The control (C) group had no screening. Follow-up was through linkage to national registries, postal follow-up questionnaires and direct communication with trial centres and participants. Objective To assess comprehensively risks and benefits of ovarian cancer screening in the general population. Outcome Primary outcome was death due to ovarian or tubal cancer as assigned by an independent outcomes review committee. Secondary outcomes included incidence and stage at diagnosis of ovarian and tubal cancer, compliance, performance characteristics, harms and cost-effectiveness of the two screening strategies and a bioresource for future research. Randomisation The trial management system confirmed eligibility and randomly allocated participants using computer-generated random numbers to MMS, USS and C groups in a 1:1:2 ratio. Blinding Investigators and participants were unblinded and outcomes review committee was masked to randomisation group. Analyses Primary analyses were by intention to screen, comparing separately MMS and USS with C using the Versatile test. Results Recruitment 1,243,282 women were invited and 205,090 attended for recruitment between April 2001 and September 2005. Randomised 202,638 women: 50,640 MMS, 50,639 USS and 101,359 C group. Numbers analysed for primary outcome 202,562 (>99.9%): 50,625 (>99.9%) MMS, 50,623 (>99.9%) USS, and 101,314 (>99.9%) C group. Outcome Women in MMS and USS groups underwent 345,570 and 327,775 annual screens between randomisation and 31 December 2011. At median follow-up of 16.3 (IQR 15.1–17.3) years, 2055 women developed ovarian or tubal cancer: 522 (1.0% of 50,625) MMS, 517 (1.0% of 50,623) USS, and 1016 (1.0% of 101314) in C group. Compared to the C group, in the MMS group, the incidence of Stage I/II disease was 39.2% (95% CI 16.1 to 66.9) higher and stage III/IV 10.2% (95% CI –21.3 to 2.4) lower. There was no difference in stage in the USS group. 1206 women died of the disease: 296 (0.6%) MMS, 291 (0.6%) USS, and 619 (0.6%) C group. There was no significant reduction in ovarian and tubal cancer deaths in either MMS (p = 0.580) or USS (p = 0.360) groups compared to the C group. Overall compliance with annual screening episode was 80.8% (345,570/420,047) in the MMS and 78.0% (327,775/420,047) in the USS group. For ovarian and tubal cancers diagnosed within one year of the last test in a screening episode, in the MMS group, the sensitivity, specificity and positive predictive values were 83.8% (95% CI 78.7 to 88.1), 99.8% (95% CI 99.8 to 99.9), and 28.8% (95% CI 25.5 to 32.2) and in the USS group, 72.2% (95% CI 65.9 to 78.0), 99.5% (95% CI 99.5 to 99.5), and 9.1% (95% CI 7.8 to 10.5) respectively. The final within-trial cost-effectiveness analysis was not undertaken as there was no mortality reduction. A bioresource (UKCTOCS Longitudinal Women’s Cohort) of longitudinal outcome data and over 0.5 million serum samples including serial annual samples in women in the MMS group was established and to date has been used in many new studies, mainly focused on early detection of cancer. Harms Both screening tests (venepuncture and TVS) were associated with minor complications with low (8.6/100,000 screens MMS; 18.6/100,000 screens USS) complication rates. Screening itself did not cause anxiety unless more intense repeat testing was required following abnormal screens. In the MMS group, for each screen-detected ovarian or tubal cancer, an additional 2.3 (489 false positives; 212 cancers) women in the MMS group had unnecessary false-positive (benign adnexal pathology or normal adnexa) surgery. Overall, 14 (489/345,572 annual screens) underwent unnecessary surgery per 10,000 screens. In the USS group, for each screen-detected ovarian or tubal cancer, an additional 10 (1630 false positives; 164 cancers) underwent unnecessary false-positive surgery. Overall, 50 (1630/327,775 annual screens) women underwent unnecessary surgery per 10,000 screens. Conclusions Population screening for ovarian and tubal cancer for average-risk women using these strategies should not be undertaken. Decreased incidence of Stage III/IV cancers during multimodal screening did not translate to mortality reduction. Researchers should be cautious about using early stage as a surrogate outcome in screening trials. Meanwhile the bioresource provides a unique opportunity to evaluate early cancer detection tests. Funding Long-term follow-up UKCTOCS (2015–2020) – National Institute for Health and Care Research (NIHR HTA grant 16/46/01), Cancer Research UK, and The Eve Appeal. UKCTOCS (2001–2014) – Medical Research Council (MRC) (G9901012/G0801228), Cancer Research UK (C1479/A2884), and the UK Department of Health, with additional support from The Eve Appeal. Researchers at UCL were supported by the NIHR UCL Hospitals Biomedical Research Centre and by MRC Clinical Trials Unit at UCL core funding (MR_UU_12023). Plain language summary What was the question? Most women with ovarian cancer are diagnosed after the disease has spread widely (advanced stage – III and IV) and more than half die within 5 years. We wanted to find out if testing women without symptoms could pick up ovarian cancer at an earlier stage before it has spread beyond the ovaries and tubes and reduce deaths. We also wanted to assess the risks and benefits of such screening. What did we do? We invited over 1.2 million women living near 13 centres in England, Wales and Northern Ireland. Of them, 202,638 joined the trial. All women were between 50 and 74 and were no longer having periods. They had never been diagnosed with ovarian cancer or were not having treatment for any other cancer. They did not have many relatives with ovarian or breast cancer. The volunteers were placed into one of three groups at random: The blood test group contained 50,640 women who had yearly CA125 blood tests. If these showed a moderate or high chance of ovarian cancer, they had repeat CA125 tests and a scan. The scan group contained 50,639 women who had yearly internal scans of their ovaries and tubes which were repeated if they showed an abnormality. The no-screening group contained 101,359 women. Those in the blood and scan groups had screening every year until December 2011. We sent all women health questionnaires and also, with their permission, received information about them from the national cancer and death registries till mid-2020. What did we find? Women in the screened groups had an average of eight years of screening. We followed them for approximately 16 years after they had joined the trial. During this period, 2055 women were diagnosed with ovarian and tubal cancer. It was about 1 in 100 women (1%) in all three groups: 522 of 50,625 in the blood group 517 of 50,623 in the scan group 1016 of 101,314 in the no-screening group More women were diagnosed with early-stage cancer and fewer were diagnosed with advanced cancer in the blood group compared to the no-screening group. There was no difference in the number diagnosed with early or advanced disease between the scan and no-screening group. Despite this difference, the number of women in each group who died from ovarian and tubal cancer was similar in all three groups: 296 of 50,625 (0.6%) in the blood group, 291 of 50,623 (0.6%) in the scan group and 619 of 101,314 (0.6%) in the no-screening group. Other results showed: Overall, 81% women in the blood group and 78% in the scan group attended all of their annual screening appointments. In the blood group, screening detected 84% of ovarian and tubal cancers diagnosed within one year of the test and correctly classified as normal 99.8% of women who did not have ovarian and tubal cancer. In the scan group, screening detected 72% of ovarian and tubal cancers diagnosed within one year of the last test and correctly classified 99.5% of those who did not have ovarian and tubal cancer. Both screening tests were associated with minor complications. While screening did not increase anxiety, there was slightly increased worry in women who were asked to return for more intense repeat testing. Both screening methods picked up changes that were in fact not ovarian cancer. This meant that women had unnecessary surgery together with the worry and risk of complications that go with it. ◦In the blood group 14 women had unnecessary surgery for every 10,000 women screened annually. This means that for each woman found to have ovarian cancer, an additional 2 women had unnecessary surgery. ◦In the scan group 50 women had unnecessary surgery for every 10,000 women screened annually. This means that for each woman found to have ovarian cancer, an additional 10 women had unnecessary surgery. A biobank with all the donated data and over 0.5 million serum samples, including yearly samples from women in the blood group, was built and continues to be used in many new studies, mainly focused on early detection of cancer. What does this mean? Screening using the CA125 blood test or transvaginal ultrasound scan to test for ovarian cancer did not save lives. Additionally, it was associated with some harm. Therefore, an ovarian cancer screening programme for most women cannot be currently recommended. The trial also showed for the first time that ovarian cancer can be detected earlier through screening. However, for screening to save lives, the test needs to pick up many more women earlier in the course of the disease so that available treatments are effective. The biobank provides an opportunity for scientists to see if newer tests for cancer can detect the disease earlier.

Workplace-based assessments (WBAs) are trainee-led formative assessments that measure the highest level of competence of the ability to do a task. So far WBAs are the only available assessment tools to measure performance integrated into practice. Over the years, WBAs have become an integral part of dental foundation and specialty training. The numerous WBAs available can be broadly categorised into three types. The first type involves observation of clinical encounters, for example mini-clinical evaluation exercises; direct observation of procedural skills; and dental evaluation of performance and procedure-based assessments. The second type involves discussion of clinical cases, such as case-based discussions. Finally, the third type includes the mini-peer assessment tool, team assessment of behaviour, 360° assessments and multi-source feedback, and all involve receiving feedback from a combination of colleagues, staff and patients. This article describes the WBAs currently used in postgraduate dental training and explores their strengths, weaknesses, perceived value by trainees and trainers and how these tools can be used in a reliable and valid way. [ABSTRACT FROM AUTHOR]

Peptides from VH regions of antibodies to DNA drive immune responses in systemic lupus erythematosus (SLE). We studied peptide-induced cytokine release by peripheral blood mononuclear cells (PBMC) of patients, the influence of peptide concentration, disease characteristics and HLA-D haplotypes. Cells secreting cytokines (IFNγ, IL-2, IL-4 and IL-10) were measured by ELISPOT in PBMC from 31 patients with SLE and 20 matched healthy controls in response to seven peptides (A – G) from the CDR1/FR2 to CDR2/FR3 VH regions of human anti-DNA MAbs. Disease activity was assessed by SELENA-SLEDAI. HLA-DR and -DQ alleles were determined by molecular typing techniques. PBMC from significantly higher proportions of SLE patients than controls responded to VH peptides by generating IFNγ and IL-10. Type of cytokines released in response to at least one peptide (D) depended on antigen concentration. Cytokine release was not associated with clinical features of SLE except for disease duration. A shift occurred from IFNγ, IL-4 and IL-10 production in early disease to IL-4 and IL-10 in late disease (suggesting increasing TH2-like responses over time). Three peptides (B, D, G) were more stimulatory in the SLE patients than controls. Although none of the peptides was restricted by any particular MHC class II allele, among responders there was increased prevalence of HLA- DQB1*0201 and/or DRB1*0301, alleles known to predispose to SLE. Thus, responses to some VH peptides are more frequent in SLE and vary with disease duration. Increased responses in individuals with HLA class II genotypes that predispose to SLE suggest that peptide presentation by those molecules permits brisker peripheral blood cell responses to autoantibody peptides, thus increasing risk for disease. [ABSTRACT FROM AUTHOR]

The frequency and clinical associations of anti-RNA antibodies measured by ELISA were assessed in 138 patients with systemic lupus erythematosus (SLE). Of the sera from these patients 9.4% had anti-RNA antibodies but no distinguishing features, clinical, serological or immunogenetic, between those with or without these antibodies could be identified. However, investigations of patients with other autoimmune rheumatic diseases did not reveal any anti-RNA positivity, which indicates a marked disease specificity for anti-RNA antibodies in SLE. The initial anti-RNA antibody screen used a soluble yeast extract as lest antigen. The positive sera were further tested against a range of RNAs from 10 different types of rat tissue. In essence few differences were observed, suggesting that the anti-RNA response is directed against common, highly conserved epitopes. [ABSTRACT FROM AUTHOR]

In a group of patients with chronic liver diseases (CLD), including both chronic active hepatitis of 'immunological type and alcoholic cirrhosis, simultaneous measurements were made of serum immunoglobulin levels, in vitro synthesis of immunoglobulin by peripheral blood mononuclear cells, and in vitro short lived suppressor cell activity. In both forms of CLD, decreased short lived suppressor cell activity was found. There was a strong linear correlation between the amount of IgG released into supernatant of 7 day in vitro cultures and the serum IgG levels amongst patients with CLD. There was also a strong inverse correlation in the patient group between in vitro synthesis of IgG and IgA and the suppressor cell activity measured in the same cell population, suggesting that the short lived suppressor cell test may reflect activity of cells modulating immunoglobulin both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

We describe a human monoclonal antibody designated WRI 176 β and a common idiotype that it carries. This antibody was derived from the spleen of a patient with SLE. WRI 176 is an IgM kappa monoclonal reacting with ssDNA, dsDNA, poly(dT) and it is likely that mAb WRI 176 β is a representative of the so-called natural autoantibodies. The common Id designated WRI 176 Id β is located on the heavy chain of the mAb WRI 176 β molecule and appears to be located outside the binding site. Sequence analysis of the WRI 176 β heavy chain showed it to be highly homologous (97.3%) with a germline gene 56PI derived from a human fetus. In a retrospective analysis, although 44% of SLE patients had raised levels of the WRI 176 β no correlation was found with the activity of the disease. The idiotype was also expressed frequently in a range of autoimmune rheumatic and infectious diseases and in some healthy first-degree relatives of SLE patients. [ABSTRACT FROM PUBLISHER]

In this study the concentration of the different subclasses of IgG in sera from patients with a range of autoimmune rheumatic diseases (ARD) was detected by radial immunodiffusion. In the second part the IgG subclasses of autoantibodies that recognize single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), Ro, La, Sm and RNP in patients with ARD were measured by enzyme-linked immunosorbent assay.We studied 15 patients with lupus, 20 patients each with primary and secondary Sjögren's syndrome (SS) and 10 each with rheumatoid arthritis (RA), scleroderma and myositis. Twenty healthy controls were also measured.The serum concentration of IgG2 in ARD patients was generally reduced. In contrast, the concentrations of IgG1, IgG3 and IgG4 subclasses were normal or raised. A high degree of correspondence in the IgG1, IgG2 and IgG3 responses to dsDNA and ssDNA in SLE was found. Notable differences in the IgG1 anti-Ro and ssDNA responses compared to the other subclasses were seen in 1° and 2° SS. In addition, an unexpected high level of IgG4 antibodies to ssDNA in 1° SS (65%) and IgG4 antibodies to Sm/RNP in RA was observed. [ABSTRACT FROM PUBLISHER]

The antigen-binding specificity of human hybridoma-derived monoclonal autoantibodies (mAb) was analysed with mAbs derived from the spleens of two patients with active systemic lupus erythematosus (SLE). From one patient 72 mAbs (RSP clones) and from the other 173 mAbs (RT clones) were obtained. The binding specificity of these mAbs was analysed by solid- and fluid-phase ELISA against the autoantigens ssDNA, dsDNA, cardiolipin, SmRNP, histones, Sm-D and SS-B (La) synthetic peptides, and foreign antigens including bacterial polysaccharides. In addition, antinuclear antibody activity and anti-dsDNA binding were con firmed by fluorescence staining methods. Reflecting the patient's serological profile, none of the antibodies from the RSP clones reacted with ssDNA or dsDNA but 12 reacted with car diolipin. In addition, three mAbs reacted with H4, five with U 1 RNP, two with Sm-D peptides and 12 with SS-B peptides. In contrast, from the RT fusion, nine mAbs reacted with ssDNA, HI and SS-B peptides, seven with cardiolipin, four with dsDNA, two with Sm-D peptides and one each with H2A, H3 and H4. In many cases one mAb showed reactivity with more than one antigen: for example, mAb RT 72 binds to ssDNA, dsDNA, cardiolipin, H1, H4 and an Sm-D peptide; RT 6 binds to H1, SmRNP and ubiquitinated histone H2A. However, none of the antibodies showed 'across the board' polyreactivity; indeed, the selectivity of the reactions was notable and marked variation in antibody affinity was recorded. Eight of the mAbs bound to Salmonella typhimurium and two to the Klebsiella polysaccharide K-30. This report con firms the diversity in the antigen-binding pattern and polyreactivity of autoantibodies derived from SLE patients and supports the notion that antibodies to autoantigens can also bind to foreign antigens. It also suggests that the antigen-binding profiles of human hybridoma- derived antibodies reflect the range of antibodies present in the serum of individual patients. [ABSTRACT FROM PUBLISHER]

Abstract Background Participants in trials evaluating preventive interventions such as screening are on average healthier than the general population. To decrease this 'healthy volunteer effect' (HVE) women were randomly invited from population registers to participate in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and not allowed to self refer. This report assesses the extent of the HVE still prevalent in UKCTOCS and considers how certain shortfalls in mortality and incidence can be related to differences in socioeconomic status. Methods Between 2001 and 2005, 202 638 postmenopausal women joined the trial out of 1 243 312 women randomly invited from local health authority registers. The cohort was flagged for deaths and cancer registrations and mean follow up at censoring was 5.55 years for mortality, and 2.58 years for cancer incidence. Overall and cause-specific Standardised Mortality Ratios (SMRs) and Standardised Incidence Ratios (SIRs) were calculated based on national mortality (2005) and cancer incidence (2006) statistics. The Index of Multiple Deprivation (IMD 2007) was used to assess the link between socioeconomic status and mortality/cancer incidence, and differences between the invited and recruited populations. Results The SMR for all trial participants was 37%. By subgroup, the SMRs were higher for: younger age groups, extremes of BMI distribution and with each increasing year in trial. There was a clear trend between lower socioeconomic status and increased mortality but less pronounced with incidence. While the invited population had higher mean IMD scores (more deprived) than the national average, those who joined the trial were less deprived. Conclusions Recruitment to screening trials through invitation from population registers does not prevent a pronounced HVE on mortality. The impact on cancer incidence is much smaller. Similar shortfalls can be expected in other screening RCTs and it maybe prudent to use the various mortality and incidence rates presented as guides for calculating event rates and power in RCTs involving women. Trial Registration This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN22488978. Medical Research Council (grant no. G990102), Cancer Research UK (grant no. C1479/A2884) and Department of Health

The use of antioxidant compounds with differing modes of action has clearly demonstrated involvement of oxidative processes in the activation of T lymphocytes.-In this paper, we show that a novel antioxidant (lazaroid U75412E, a free radical scavenger) suppressed mitogen-induced T cell proliferation in vitro. Similar results were obtained with diphenylene iodonium (DPI), a known inhibitor of NADPH oxidase. The lazaroid was further shown to inhibit IL 2 production but to be less potent in suppressing IL 2 receptor expression. Thus, scavenger-type antioxidants act on T cells primarily by blocking a signal necessary for the induction of IL 2 synthesis such as the activation of NFκB. Furthermore, the potent inhibition of lymphocyte responses caused by the specific enzyme inhibitor DPI provides direct proof of the source of the oxidants involved in these processes. [ABSTRACT FROM AUTHOR]

Introduction: Intimate physical examination is an integral part of our urological practice. There is a paucity of literature regarding the use of chaperones among urologists. As per GMC guidelines: The offer, and use, of a chaperone, including their full name and designation, should be clearly documented in patients' notes. Objective: Given the importance of this ethical topic for both patient safety as well as in providing support for the urologist, we decided to assess our performance as per the GMC guidelines for good medical practice. Methods: We completed an audit loop to evaluate the performance of 12 members in our urology team as regards compliance with GMC guidance for the documentation of chaperone use in urology clinic. Based on our scoring system, we objectively assessed both overall team performance as well as individual scores for documenting chaperone use. • For each urologist, We checked records for 10 patients who attended urology clinic AND had a physical examination as evidenced in the notes and/or clinic letter •N= 120 patient records checked • Each urologist was given a score; NO mention of a chaperone= 0 point A chaperone JUST mentioned= 1 point The chaperone specified (name/signature)= 2 points Results: Initial audit revealed overall chaperone documentation in clinical notes was 75.25% which may be acceptable while in the clinic letters, it was only 14.6%. At individual level, results were quiet variable reflecting the actual difference in practice between individuals in real life. Following the discussion of the 1st audit results in the urology clinical governance meeting, posters were made to raise awareness of the audit outcome as well as direct discussions with the urology team members to encourage them to improve their score. Six months later, re-audit showed significant improvement was achieved for individual as well as overall documentation to 85% of clinical notes and more than 50% of clinic letters. Conclusions: Documenting chaperone presence during patient examination in urology clinics, is mandatory given the intimate nature of urological examination. We present the first report using a scoring system for objective assessment of a pertinent topic such as the use of chaperone and its documentation. This managed to achieve a significant improvement in our practice in accordance with GMC guidance for Good Medical Practice. Disclosure: No. [ABSTRACT FROM AUTHOR]

Introduction: A common surgical technique for gallbladder disorders is laparoscopic cholecystectomy (LC), which has the benefits of less postoperative discomfort and quicker recovery. The purpose of this retrospective research was to assess postoperative outcomes and complications in patients having laparoscopic correction., Methods: In total, 200 patients who had LC at the tertiary care center between 2017 and 2022 were the subjects of a retrospective investigation. We gathered and examined data on preoperative conditions, surgical specifics, postoperative results, and demographics., Results: Notable findings from the study were as follows: (1) The average age of the patients was 47.5 years (±12.3), and there were strong correlations ( P < 0.001) between age and problems. (2) Significant correlations were found between many covariates and postoperative outcomes, such as a 10% readmission rate and a mean hospital stay of 3.6 days (±1.2) ( P < 0.05). (3) Different relationships were seen between the complications ( P values ranging from 0.021 to <0.001), including wound infections (6%) and bile duct injuries (2.5%)., Conclusion: To enhance patient care, a thorough assessment and focused treatments are required. This study sheds light on the frequency of postoperative problems and outcomes in patients receiving LC., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Introduction: Although PCOS affects reproductive health, its consequences on the outcome of pregnancies are still up for discussion. Comparing the pregnancy outcomes of women with PCOS to a control group was the goal of this retrospective research., Methods: Analysis of data from tertiary care centers between 2017 and 2022 was done in retrospective. While the controls ( n = 300) matched for age, BMI, and parity, the PCOS group ( n = 300) satisfied Rotterdam criteria. Maternal-fetal health, birth outcomes, and gestational problems were evaluated., Results: Compared to controls, women with PCOS had a greater incidence of preeclampsia (12.3% vs. 8.1%, P = 0.023) and gestational diabetes (18.7% vs. 9.8%, P < 0.001). On the other hand, there were no notable variations in low birth weight ( P = 0.589) or preterm delivery ( P = 0.321)., Conclusion: In summary, the correlation between PCOS and increased risks of gestational diabetes and preeclampsia emphasizes the necessity of customized therapies. The intricacy of PCOS's influence on birth outcomes is shown by the inconclusive results regarding preterm delivery and low birth weight, which call for more research to enhance mother and newborn health in this group., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Background: "Proximal humerus fractures [PHFs]" are common orthopedic injuries, often requiring surgical intervention for optimal outcomes. However, the choice of surgical approach remains controversial, with varying outcomes reported in the literature., Methods: A retrospective research was overseen among subjects who had surgery for PHFs. Three surgical approaches were compared: "Open Reduction Internal Fixation (ORIF)", "Hemiarthroplasty [HA]", and "Reverse Shoulder Arthroplasty [RSA]". Demographic data, fracture characteristics, surgical details, and postoperative outcomes were analyzed., Results: ORIF confirmed smaller operative time and shorter complication levels compared to HA and RSA. Complications included surgical site infection, implant-related issues, and reoperation. Age, fracture type, and surgeon experience influenced the choice of surgical approach., Conclusion: This research provides valuable insights into the outcomes of different surgical approaches for PHFs. ORIF may offer advantages in select cases, but individualized treatment decisions are necessary. Further research is warranted to refine treatment algorithms and optimize patient outcomes., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Background: There has been a significant increase in the utilization of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in recent years. Cardiothoracic surgery teams have historically led VA-ECMO care teams, with little data available on alternative care models., Methods: We performed a retrospective review of a cardiovascular medicine inclusive VA-ECMO service, analyzing patients treated with peripheral VA-ECMO at a large quaternary care center from 2018 to 2022. The primary outcome was death while on VA-ECMO or within 24 hours of decannulation. Univariate and multivariate analyses were used to identify predictors of the primary outcome., Results: Two hundred forty-four patients were included in the analysis (median age 61 years; 28.7% female), of whom 91.8% were cannulated by interventional cardiologists, and 84.4% were managed by a cardiology service comprised of interventional cardiologists, cardiac intensivists or advanced heart failure cardiologists. Indications for VA-ECMO included acute myocardial infarction (34.8%), decompensated heart failure (30.3%), and refractory cardiac arrest (10.2%). VA-ECMO was utilized during cardiopulmonary resuscitation in 26.6% of cases, 48% of which were peri-procedural arrest. Of the patients, 46% survived to decannulation, the majority of whom were decannulated percutaneously in the cardiac catheterization laboratory. There was no difference in survival following cannulation by a cardiac surgeon vs interventional cardiologist (50% vs 45%; P = .90). Complications included arterial injury (3.7%), compartment syndrome (4.1%), cannulation site infection (1.2%), stroke (14.8%), acute kidney injury (52.5%), access site bleeding (16%) and need for blood transfusion (83.2%). Elevated baseline lactate (odds ratio [OR], 1.13 per unit increase) and sequential organ failure assessment score (OR, 1.27 per unit increase) were independently associated with the primary outcome. Conversely, an elevated baseline survival after VA ECMO score (OR, 0.92 per unit increase) and 8-hour serum lactate clearance (OR, 0.98 per % increase) were independently associated with survival., Conclusions: The use of a cardiovascular medicine inclusive ECMO service is feasible and may be practical in select centers as indications for VA-ECMO expand., (© 2024 The Author(s).)

Introduction: Intravascular ultrasound (IVUS) provides intra-procedural guidance in optimizing percutaneous coronary interventions (PCI) and has been shown to improve clinical outcomes in stent implantation. However, current data on the benefit of IVUS during PCI in ST-elevation myocardial infarction (STEMI) patients is mixed. We performed meta-analysis pooling available data assessing IVUS-guided versus angiography-guided PCI in STEMI patients., Methods: We conducted a systematic search on PubMed and Embase for studies comparing IVUS versus angiography-guided PCI in STEMI. Mantel-Haenszel random effects model was used to calculate risk ratios (RRs) with 95% confidence intervals (CIs) for outcomes of major adverse cardiovascular events (MACEs), death, myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST) and in-hospital mortality., Results: A total of 8 studies including 336,649 individuals presenting with STEMI were included for the meta-analysis. Follow-up ranged from 11 to 60 months. We found significant association between IVUS-guided PCI with lower risk for MACE (RR 0.82, 95% CI 0.76-0.90) compared with angiography-guided PCI. We also found significant association between IVUS-guided PCI with lower risk for death, MI, TVR, and in-hospital mortality but not ST., Conclusion: In our meta-analysis, IVUS-guided compared with angiography-guided PCI was associated with improved long-term and short-term clinical outcomes in STEMI patients., (© 2024 S. Karger AG, Basel.)

Objective: UKCTOCS provides an opportunity to explore symptoms in preclinical invasive epithelial ovarian cancer (iEOC). We report on symptoms in women with pre-clinical (screen-detected) cancers (PC) compared to clinically diagnosed (CD) cancers., Methods: In UKCTOCS, 202638 postmenopausal women, aged 50-74 were randomly allocated (April 17, 2001-September 29, 2005) 2:1:1 to no screening or annual screening till Dec 31,2011, using a multimodal or ultrasound strategy. Follow-up was through national registries. An outcomes committee adjudicated on OC diagnosis, histotype, stage. Eligible women were those diagnosed with iEOC at primary censorship (Dec 31, 2014). Symptom details were extracted from trial clinical-assessment forms and medical records. Descriptive statistics were used to compare symptoms in PC versus CD women with early (I/II) and advanced (III/IV/unable to stage) stage high-grade-serous (HGSC) cancer. ISRCTN-22488978; ClinicalTrials.gov-NCT00058032., Results: 1133 (286PC; 847CD) women developed iEOC. Median age (years) at diagnosis was earlier in PC compared to CD (66.8PC, 68.7CD, p = 0.0001) group. In the PC group, 48% (112/234; 90%, 660/730CD) reported symptoms when questioned. Half PC (50%, 13/26PC; 36%, 29/80CD; p = 0.213) women with symptomatic HGSC had >1symptom, with abdominal symptoms most common, both in early (62%, 16/26, PC; 53% 42/80, CD; p = 0.421) and advanced (57%, 49/86, PC; 74%, 431/580, CD; p = 0.001) stages. In symptomatic early-stage HGSC, compared to CD, PC women reported more gastrointestinal (change in bowel habits and dyspepsia) (35%, 9/26PC; 9%, 7/80CD; p = 0.001) and systemic (mostly lethargy/tiredness) (27%, 7/26PC; 9%, 7/80CD; p = 0.017) symptoms., Conclusions: Our findings, add to the growing evidence, that we should reconsider what constitutes alert symptoms for early tubo-ovarian cancer. We need a more nuanced complex of key symptoms which is then evaluated and refined in a prospective trial., Competing Interests: Declaration of Competing Interest UM had stock ownership awarded by University College London (UCL) between until October 2021 in Abcodia, which holds the licence for ROCA. She and MP have received grants and AGM, MB, JK and AR have been funded by grants from the Medical Research Council (MRC), Cancer Research UK, National Institute for Health Research (NIHR) and The Eve Appeal. UM has also received grants from UK Innovate and National Health and Medical Research Council (NHMRC), Australia and salary support from UCL Hospital Biomedical Research Centre. UM, AGM and SA report funded research collaborations with industry - iLOF (intelligent Lab on Fiber), RNA Guardian, Micronoma, MercyBio Analytics and academics -Cambridge University, QIMR Berghofer Medical Research Institute Imperial College London, University of Innsbruck and Dana Farber USA. UM holds patent number EP10178345.4 for Breast Cancer Diagnostics. AGM is a member of ACED Gynaecological Cancer Working Group and is ACED Co-Director Research Domain Trials. MP was an Associate Member of the EME funding committee while the project was active. SJS reports that Massachusetts General Hospital (MGH) has co-licensed software for ROCA to Abcodia, now owned by GenInCode, with MGH licence revenue to MGH and research laboratories per MGH institutional policies. SJS receives grant support from National Cancer Institute (USA) and National Institute for Health Research (NIHR) (UK). He is paid for service on the clinical advisory board for Guardant Health. He serves on the Scientific Advisory Board for LUNGevity. He has stock options from SISCAPA Assay Technologies for participation on its Scientific Advisory Board. IJJ reports grants from Eve Appeal Charity, MRC, Cancer Research UK, and NIHR during the conduct of the study. He co-invented the ROCA in 1995. Massachusetts General Hospital and Queen Mary University of London granted a licence for the ROCA to Abcodia in 2014. IJJ is non-executive director, shareholder, and consultant to Abcodia and has rights to royalties from sales of the ROCA. He founded (1985), was a trustee of (2012–14), and is now an Emeritus trustee (2015–present) of The Eve Appeal, one of the funding agencies for UKCTOCS. LF reports MRC funding for the psychosocial arm of the UKCTOCS study 2001–13, paid to University of Sussex. NS received honoraria from Astra-Zeneca-MPC and GlaxoSmithKline for participation in advisory boards. AMcG was a member of NIHR HTA and EME Editoral Board (2012 to 2022). RM reports funding from The Eve Appeal, Rosetrees Trust, Barts Charity, Yorkshire Cancer Research, Ovacure, British Gynaecological Cancer Society (BGCS), GlaxoSmithKline (GSK), and Honoraria from Astrazeneca and EGL. All other authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)