Rhian Gabe

Hull York Medical School

Introduction Lung cancer screening (LCS) saves lives by detecting cancers early, but continued adherence to screening is necessary for participants to realise maximum clinical benefit. Pooled adherence in US LCS programmes was only 55%.¹ The logistics of screening provision differ significantly between geographical areas, so it is important for ind...

Background Low-dose CT screening reduces lung cancer-specific mortality in people at higher risk. Factors that contribute to lung cancer risk are also associated with comorbid disease; frailty and comorbidity are, therefore, important considerations for lung cancer screening (LCS). Here, we describe the prevalence of frailty and comorbidity in LCS...

Introduction Lung cancer screening (LCS) with low-dose CT reduces mortality, but the presence of frailty and comorbidities in eligible subjects might limit the overall life years gained by LCS due to competing causes of death. Here, we compare frailty, comorbidity, and 3-year survival between populations identified by different LCS eligibility crit...

Introduction Lung cancer is the most common cause of cancer death globally. In 2022 the UK National Screening Committee recommended the implementation of a national targeted lung cancer screening programme, aiming to improve early diagnosis and survival rates. Research studies and services internationally consistently observe socioeconomic and smok...

Background Up to 50% of those attending for low-dose computed tomography screening for lung cancer continue to smoke and co-delivery of smoking cessation services alongside screening may maximise clinical benefit. Here we present data from an opt-out co-located smoking cessation service delivered alongside the Yorkshire Lung Screening Trial (YLST)....

Objectives To assess the cost-effectiveness of cytisine over and above brief behavioural support (BS) for smoking cessation among patients who are newly diagnosed with pulmonary tuberculosis (TB) in low-income and middle-income countries. Design An incremental cost-utility analysis was undertaken alongside a 12-month, double-blind, two-arm, indivi...

Background Multiparametric MRI localizes cancer in the prostate, allowing for MRI guided biopsy (MRI-GB) 43 alongside transrectal ultrasound-guided systematic biopsy (TRUS-GB). Three MRI-GB approaches exist; visual estimation (COG-TB); fusion software-assisted (FUS-TB) and MRI ‘in-bore’ biopsy (IB-TB). It is unknown whether any of these are superio...

Background Despite treatment, patients with tuberculosis (TB) who smoke have poorer outcomes compared with non-smokers. It is unknown, however, if quitting smoking during the 6 months of TB treatment improves TB outcomes. Methods The TB & Tobacco Trial was a double-blind, placebo-controlled randomised trial of cytisine for smoking cessation in 247...

Post kala azar dermal leishmaniasis (PKDL) is a chronic, stigmatising skin condition occurring frequently after apparent clinical cure from visceral leishmaniasis. Given an urgent need for new treatments, we conducted a Phase IIa safety and immunogenicity trial of ChAd63-KH vaccine in Sudanese patients with persistent PKDL. LEISH2a (NCT02894008) wa...

374 Background: Survival after orchiectomy in stage I seminoma is almost 100%. CT surveillance is an international standard of care, and avoids adjuvant therapy. In this young population, who are unlikely to die from testicular cancer, minimizing irradiation is vital. The Trial of Imaging and Surveillance in Seminoma Testis (TRISST, NCT00589537), a...

Post kala azar dermal leishmaniasis (PKDL) is a chronic, stigmatising skin condition occurring frequently after apparent clinical cure from visceral leishmaniasis. Given an urgent need for new treatments, we conducted a Phase IIa safety and immunogenicity trial of ChAd63-KH vaccine in Sudanese patients with persistent PKDL. LEISH2a ( NCT02894008 )...

Summary Background Smoking cessation is important in patients with tuberculosis because it can reduce the high rates of treatment failure and mortality. We aimed to assess the effectiveness and safety of cystine as a smoking cessation aid in patients with tuberculosis in Bangladesh and Pakistan. Methods We did a randomised, double-blind, placebo-c...

Aims: Morphine is shown to relieve chronic breathlessness in chronic obstructive pulmonary disease. There are no definitive data in people with heart failure. We aimed to determine the effectiveness and cost-effectiveness of 12 weeks morphine therapy for the relief of chronic breathlessness in people with chronic heart failure compared with placeb...

Background Venous leg ulcers (VLUs) are the most common cause of leg ulceration, affecting 1 in 100 adults. VLUs may take many months to heal (25% fail to heal). Estimated prevalence is between 1% and 3% of the elderly population. Compression is the mainstay of treatment and few additional therapies exist to improve healing. Two previous trials hav...

Background Men with suspected prostate cancer usually undergo transrectal ultrasound (TRUS)-guided prostate biopsy. TRUS-guided biopsy can cause side effects and has relatively poor diagnostic accuracy. Multiparametric magnetic resonance imaging (mpMRI) used as a triage test might allow men to avoid unnecessary TRUS-guided biopsy and improve diagno...

Background Depression in older adults is common and is associated with poor quality of life, increased morbidity and early mortality, and increased health and social care use. Collaborative care, a low-intensity intervention for depression that is shown to be effective in working-age adults, has not yet been evaluated in older people with depressio...

Background and aims Tuberculosis (TB) patients who quit smoking have much better disease outcomes than those who continue to smoke. Behavioural support combined with pharmacotherapy is the most effective strategy in helping people to quit, in general populations. However, there is no evidence for the effectiveness of this strategy in TB patients wh...

Background Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated i...

DE gene list for low dose subjects. (XLSX)

Gene set enrichment analysis using modules described by Li et al. (XLSX)

HLA typing of study subjects. (PDF)

DE gene list for high dose subjects. (XLS)

IPA predicted upstream regulators in high and low dose subjects. (XLSX)

Kinetics of IFNγ response to vaccination. A-C. IFNγ response determined by ELISPOT before and at the indicated times following vaccination of low dose (A and C, left panel) and high dose (B and C, right panel) subjects to individual peptide pools spanning the KH antigen (A, B). The summed response is also shown (C). Data are shown as box and whispe...

(DOCX)

Blood leucocyte composition pre- and post-vaccination. A and B. High resolution blood composition was inferred by deconvolution of whole blood RNA-Seq data using CIBERSORT. Data are shown for each low dose (A) and high dose (B) subject pre- and post-vaccination. C. Differential blood counts obtained by routine clinical hematology for all subjects p...

Pathway analysis of DE genes. A. Top 16 enriched IPA canonical pathways. Bars (left axis) indicate percentage of genes per pathway up-regulated (red) or down-regulated (green). Line graph (right axis) indicates log10 probability (P value) vs. randomly selected gene group of same size. Numbers above bars indicate the number of genes included each pa...

Cytokine production by KH-specific CD8+ T cells. IFNγ (black bars), TNF (grey bars) and IL-2 (white bars) were measured by ICS in CD8+ T cells at day 28 post-vaccination for ELISPOT non-responder subjects 18, 19 and 28. Data represent mean frequency of antigen-specific T cells producing each cytokine in response to peptide pools spanning the KH ant...

Background Efforts to reduce the burden of illness and personal suffering associated with depression in older adults have focused on those with more severe depressive syndromes. Less attention has been paid to those with mild disorders/subthreshold depression, but these patients also suffer significant impairments in their quality of life and leve...

Key Points Question Is collaborative care an effective method to reduce depressive symptoms in older people with mild depression? Findings In the CASPER randomized trial of 705 participants aged 65 years or older with subthreshold depression, those randomized to a collaborative care intervention had lower depression scores as measured by the Pati...

IMPORTANCE There is little evidence to guide management of depressive symptoms in older people. OBJECTIVE To evaluate whether a collaborative care intervention can reduce depressive symptoms and prevent more severe depression in older people. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial conducted from May 24, 2011, to November 14, 20...

VEINES-QOL/Sym is a disease-specific quality of life instrument for use in venous diseases of the leg. Its relative scoring system precludes comparisons between studies. There were very few venous leg ulcer patients in the validation samples. We report a validation study for venous leg ulcers and develop a scoring system which enables comparison be...

Background: Venous leg ulcers (VLUs) are the commonest cause of leg ulceration, affecting 1 in 100 adults. There is a significant health burden associated with VLUs - it is estimated that the cost of treatment for 1 ulcer is up to £1300 per year in the NHS. The mainstay of treatment is with graduated compression bandaging; however, treatment is of...

Background: Venous leg ulcers (VLUs) are the commonest cause of leg ulceration, affecting 1 in 100 adults. There is a significant health burden associated with VLUs – it is estimated that the cost of treatment for 1 ulcer is up to £1300 per year in the NHS. The mainstay of treatment is with graduated compression bandaging; however, treatment is oft...

Purpose: Up to 50% of patients diagnosed with stage I non-seminomatous germ cell tumors (NSGCT) harbor occult metastases. Patients are managed by surveillance with chemotherapy at relapse or adjuvant treatment up-front. Late toxicities from chemotherapy are increasingly recognised. Based on a potential biological role in germ cells/tumors and pilo...

To validate the Whooley questions as a screening tool for depression amongst a population of older adults in UK primary care. To assess the diagnostic performance of the Whooley questions as a screening tool for depression amongst older adults in UK primary care. A cross-sectional validation study was conducted with 766 patients aged ≥75 from UK pr...

Despite widespread popularity, text messaging has rarely been used for data collection in clinical research. This paper reports on the development, feasibility, acceptability, validity, and discriminant utility of a single item depression rating scale, delivered weekly via an automated SMS system, as part of a large randomised controlled trial. 755...

There is policy interest in the screening and treatment of mental health problems in young people who offend, but the value of such screening is not yet known. Objectives To assess the diagnostic test accuracy of screening measures for mental health problems in young people who offend; to evaluate the clinical effectiveness and cost-effectiveness...

Background Patient safety training often provides learners with a health professional's perspective rather than the patient's. Personal narratives of health-related harm allow patients to share their stories with health professionals to influence clinical behaviour by rousing emotions and improving attitudes to safety. Aim This study measured the i...

New evidence on the clinical effectiveness of acupuncture plus usual care (acupuncture) and counselling plus usual care (counselling) for patients with depression suggests the need to investigate the health-related quality of life and costs of these treatments to understand whether they should be considered a good use of limited health resources. T...

Background: Compression is an effective and recommended treatment for venous leg ulcers. Although the four-layer bandage (4LB) is regarded as the gold standard compression system, it is recognised that the amount of compression delivered might be compromised by poor application technique. Also the bulky nature of the bandages might reduce ankle or...

Background Integrin αvβ6 promotes migration, invasion, and survival of cancer cells; however, the relevance and role of αvβ6 has yet to be elucidated in breast cancer. Methods Protein expression of integrin subunit beta6 (β6) was measured in breast cancers by immunohistochemistry (n > 2000) and ITGB6 mRNA expression measured in the Molecular Taxon...

Background Standard chemotherapy for poor-prognosis metastatic nonseminoma has remained bleomycin, etoposide, and cisplatin (BEP) for many years; more effective regimens are required. Objective To explore whether response rates with a new intensive chemotherapy regimen, CBOP/BEP (carboplatin, bleomycin, vincristine, cisplatin/BEP), versus those in...

We evaluated the prognostic and predictive value of a range of molecular changes in the setting of a randomised trial comparing standard PCV (procarbazine, CCNU (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea) and vincristine) chemotherapy with the standard temozolomide (TMZ) 5-day (200 mg/m2/day) schedule and a 21-day (100 mg/m2/day) schedule in che...

Introduction and AimsTo examine the relationship between three outcome measures used by a specialist addiction service (UK): the Leeds Dependence Questionnaire (LDQ), the Social Satisfaction Questionnaire (SSQ) and the 10-item Clinical Outcomes in Routine Evaluation (CORE-10).Design and MethodA clinical sample of 715 service user records was extrac...

s: Thirty-Sixth Annual CTRC-AACR San Antonio Breast Cancer Symposium - Dec 10-14, 2013; San Antonio, TX The integrin avβ6 promotes migration, invasion and survival of cancer cells, but the biological relevance has yet to be ascertained in breast cancer. Our immunhistochemical analysis of over 2000 breast cancers has revealed that high expression o...

Venous thromboembolism (VTE) risk assessment for adults admitted to hospital is commonplace, but the utility of assessment tools in patients admitted to hospices or palliative care units and prediction of symptomatic VTE is unknown. To investigate the relationship between risk of VTE and development of symptoms. Retrospective consecutive admission,...

Drawbacks exist with the standard treatment (four-layer compression bandages) for venous leg ulcers. We have therefore compared the clinical effectiveness and cost-effectiveness of two-layer compression hosiery with the four-layer bandage for the treatment of such ulcers. We undertook this pragmatic, open, randomised controlled trial with two paral...

Background: Integrin αvβ6 promotes migration, invasion and survival of cancer cells, however, the relevance and role of αvβ6 has yet to be elucidated in breast cancer. Methods: Protein expression of integrin subunit beta6 (β6) was measured in over 2000 breast cancers by immunohistochemistry and ITGB6 mRNA expression measured in the METABRIC dataset...

Depression is a significant cause of morbidity. Many patients have communicated an interest in non-pharmacological therapies to their general practitioners. Systematic reviews of acupuncture and counselling for depression in primary care have identified limited evidence. The aim of this study was to evaluate acupuncture versus usual care and counse...

319 Background: Stage I NSGCT harbor occult metastatic disease in up to 50% of patients and undergo surveillance with chemotherapy at relapse or adjuvant treatment with excellent survival but concern around subsequent toxicity. Better prediction of relapse would minimize exposure to unnecessary treatments. Previous data suggested CXCL12 aided asses...

TO THE EDITOR: In their editorial 1 accompanying our article, 2 Bosl and Patil make a number of incorrect assertions which require a response. The majority of these issues relate directly to the design and interpretation of the TE19/30982 trial, while their current preferred managementoptionissurveillance.Whileweagreedinourpaperthat surveillance is...

Initial results of a randomized trial comparing carboplatin with radiotherapy (RT) as adjuvant treatment for stage I seminoma found carboplatin had a noninferior relapse-free rate (RFR) and had reduced contralateral germ cell tumors (GCTs) in the short-term. Updated results with a median follow-up of 6.5 years are now reported. Random assignment wa...

From July 1, 1989, through March 31, 2001, 2466 patients with stage I seminoma were evaluated in three randomized noninferiority trials: the TE10, TE18, and TE19 trials. We analyzed mature results of these studies. The TE10 trial randomly assigned 478 patients to para-aortic and ipsilateral iliac lymph node (dogleg field) or para-aortic only radiat...

Temozolomide (TMZ) is an alkylating agent licensed for treatment of high-grade glioma (HGG). No prospective comparison with nitrosourea-based chemotherapy exists. We report, to our knowledge, the first randomized trial of procarbazine, lomustine, and vincristine (PCV) versus TMZ in chemotherapy-naive patients with recurrent HGG. Four hundred forty-...

Background Evidence supports a reduction in mortality from breast cancer with mammographic screening in the general population of women aged 40—49 years, but the effect of family history is not clear. We aimed to establish whether screening affects the disease stage and projected mortality of women younger than 50 years who have a clinically signif...

Interaction between the chemokine CXCL12 (SDF1) and the G-protein coupled receptor CXCR4 is responsible for the maintenance of adult stem cell niches and is known to play an important role in utero in the migration of primordial germ cells. We demonstrate expression of CXCL12 by Sertoli cells and confirm CXCR4 expression by the germ cell population...

In case-control evaluations of cancer screening, subjects who have died from the cancer in question (cases) are compared with those who have not (controls) with respect to screening histories. This method is subject to a rather subtle bias, among others, whereby the cases have greater opportunity to have been screened than the controls. In this pap...

The Icelandic breast cancer screening program, initiated November 1987 in Reykjavik and covering the whole country from December 1989, comprises biennial invitation to mammography for women aged 40-69 years old. To estimate the impact of mammography service screening in Iceland on deaths from breast cancer. Cases were deaths from breast cancer from...

With the conclusive evidence from randomized controlled trials of the efficacy of mammographic screening in reducing mortality from breast cancer, the emphasis for the public health community has shifted to evaluation of service screening programs. Here, we briefly review the major approaches available for mortality-based evaluation of breast cance...

Background: Sometimes in descriptive epidemiology or in the evaluation of a health intervention policy change, proportions exposed to a risk factor or to an intervention are used as explanatory variables in log-linear regressions for disease incidence or mortality. Aim: To demonstrate how estimates from such models can be substantially inaccurat...

It has been recommended that women aged 40-49 years with a significant family history of breast cancer should be offered annual mammography screening (http://www.nice.org.uk). An observational study known as FH01 (http: //www. screening services.org/btw/fh01/index.asp) is evaluating this policy in a cohort of 6000 women at moderately increased risk...

There are some issues in screening for cancer, especially breast cancer, which are worthy of further study. We reviewed some approaches to the following issues in breast cancer screening: absolute benefit, overdiagnosis, separation of effects of screening from effects of others on deaths from breast cancer over time and determination of which tumou...

This phase I dose-ranging study of 2 weeks of twice-daily dextrin sulphate (DS), a sulphated polymer with in vitro activity against HIV, was designed in 2 parts. Part A was a randomized, placebo-controlled, double-blind, 3-arm trial (DS4%, DS1%, placebo) in HIV-negative women. In part B, HIV-positive women received DS4% and HIV-negative women were...