Gareth Griffiths

University of Bonn | Uni Bonn · Institute for Computer Sciences

Unlocking the power of personalised medicine in oncology hinges on the integration of clinical trial data with translational data (i.e. biospecimen-derived molecular information). This combined analysis allows researchers to tailor treatments to a patient’s unique biological makeup. However, current practices within UK Clinical Trials Units present...

Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or the peritoneum. Treatment options are limited, and the prognosis is dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, the determinants of responsiveness remain elusive. Here, we report the outcomes of...

Background Cervical cancer is the fourth most common cancer in women, with an estimated 342,000 deaths worldwide in 2020. Current standard of care in the UK for locally advanced cervical cancer is concurrent chemoradiotherapy with weekly cisplatin, yet 5-year overall survival rates are only 65% with a distant relapse rate of 50%. Inhibitors of Apop...

Importance There is significant concern regarding increasing long-term antidepressant treatment for depression beyond an evidence-based duration. Objective To determine whether adding internet and telephone support to a family practitioner review to consider discontinuing long-term antidepressant treatment is safe and more effective than a practit...

Background: The anti-IgE monoclonal, omalizumab, is widely used for severe asthma. This study aimed to identify biomarkers that predict clinical improvement during one year of omalizumab treatment. Methods: 1-year, open-label, Study of Mechanisms of action of Omalizumab in Severe Asthma (SoMOSA) involving 216 severe (GINA step 4/5) uncontrolled...

Immune checkpoint inhibitors (ICI) are established as first-line treatment for inoperable esophageal adenocarcinomas (EAC), in combination with chemotherapy (CTX). Unfortunately, response to immunochemotherapy is highly variable, despite most EAC cases featuring a high mutation burden. EAC response to ICI is assessed using radiological criteria suc...

Background Guidelines on the management of depression recommend that practitioners use patient-reported outcome measures for the follow-up monitoring of symptoms, but there is a lack of evidence of benefit in terms of patient outcomes. Objective To test using the Patient Health Questionnaire-9 questionnaire as a patient-reported outcome measure fo...

Background Outcome monitoring of depression treatment is recommended but there is a lack of evidence on patient benefit in primary care. Aim To test monitoring depression using the Patient Health Questionnaire (PHQ-9) with patient feedback. Design and setting An open cluster-randomised controlled trial was undertaken in 141 group practices. Meth...

Background Two online behavioural interventions (one website for parents/carers of children with eczema; and one for young people with eczema) have been shown in randomised controlled trials to facilitate a sustained improvement in eczema severity. Aim To describe intervention use and examine potential mediators of intervention outcomes and contex...

Objective To estimate the cost-effectiveness of online behavioral interventions (EczemaCareOnline.org.uk) designed to support eczema self-care management for parents/carers and young people from an NHS perspective. Methods Two within-trial economic evaluations, using regression-based approaches, adjusting for baseline and pre-specified confounder...

Background Many cancer survivors following primary treatment have prolonged poor quality of life. Aim To determine the effectiveness of a bespoke digital intervention to support cancer survivors. Design and setting This was a pragmatic parallel open randomised trial in UK general practices (ISRCTN:96374224). Method People having finished primary...

Objective This study aims to estimate the cost-effectiveness of oral spironolactone plus routine topical treatment compared with routine topical treatment alone for persistent acne in adult women from a British NHS perspective over 24 weeks. Design Economic evaluation undertaken alongside a pragmatic, parallel, double-blind, randomised trial. Set...

Simple Summary The early detection of pancreatic cancer is critical as it is usually too late for potentially curative surgical resection when obvious symptoms such as jaundice have developed. The pancreas has two main functions in the body, namely, an endocrine role, where it produces insulin to control blood glucose levels; and an exocrine role,...

Background Malignant mesothelioma is a rapidly lethal cancer that has been increasing at an epidemic rate over the last three decades. Targeted therapies for mesothelioma have been lacking. A previous study called MiST1 (NCT03654833), evaluated the efficacy of Poly (ADP-ribose) polymerase (PARP) inhibition in mesothelioma. This study met its primar...

By 2050, aviation-related carbon emissions are expected to quadruple to over 3000 million tonnes of carbon dioxide, so finding sustainable alternative solutions to minimise pollution is a key scientific challenge. Aviation gasoline and kerosene are currently used to power most jet engines. While battery-powered planes and planes that could utilise...

Background: Although many acute exacerbations of COPD (AECOPD) are triggered by non-bacterial causes, they are often treated with antibiotics. Preliminary research suggests that the Chinese herbal medicine “Shufeng Jiedu” (SFJD), may improve recovery and therefore reduce antibiotic use in patients with AECOPD. Aims: To assess the feasibility of con...

Background Bladder and urinary tract cancers account for approximately 21,000 new diagnoses and 5,000 deaths annually in the UK. Approximately 90% are transitional cell carcinomas where advanced disease is treated with platinum based chemotherapy and PD-1/PD-L1 directed immunotherapy. Urinary tract squamous cell carcinoma (UTSCC) accounts for about...

Background The optimum curative approach to adenocarcinoma of the oesophagus and oesophagogastric junction is unknown. We aimed to compare trimodality therapy (preoperative radiotherapy with carboplatin plus paclitaxel [CROSS regimen]) with optimum contemporaneous perioperative chemotherapy regimens (epirubicin plus cisplatin or oxaliplatin plus fl...

Background The optimum curative approach to adenocarcinoma of the oesophagus and oesophagogastric junction is unknown. We aimed to compare trimodality therapy (preoperative radiotherapy with carboplatin plus paclitaxel [CROSS regimen]) with optimum contemporaneous perioperative chemotherapy regimens (epirubicin plus cisplatin or oxaliplatin plus fl...

Background The optimum curative approach to adenocarcinoma of the oesophagus and oesophagogastric junction is unknown. We aimed to compare trimodality therapy (preoperative radiotherapy with carboplatin plus paclitaxel [CROSS regimen]) with optimum contemporaneous perioperative chemotherapy regimens (epirubicin plus cisplatin or oxaliplatin plus fl...

Background Increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020–001736-95). Methods ACCORD-2 was an open-label, phase 2a study in...

Background Androgen deprivation therapy (ADT) is prescribed to almost half of all men diagnosed with prostate cancer. Although ADT is effective treatment, with virtually all men with advanced disease showing initial clinical response, it is associated with troublesome side effects including hot flushes and night sweats (HFNS). HFNS can be both freq...

Background: The utility of early metabolic response assessment to guide selection of the systemic component of definitive chemoradiotherapy (dCRT) for oesophageal cancer is uncertain. Methods: In this multi-centre, randomised, open-label, phase II substudy of the radiotherapy dose-escalation SCOPE2 trial we evaluated the role of 18F-Fluorodeoxyg...

Acne is common and results in significant burden and patients with acne frequently receive prolonged oral antibiotics leading to antimicrobial resistance. Oral spironolactone is prescribed for acne, although there is a paucity of evidence on its effectiveness. The aim of this pragmatic parallel, double-blind, superiority trial was to assess the eff...

REMoDL-A is a stratified open-label, multicentre, randomised phase II study. Eligible patients have untreated histologically confirmed DLBCL (Diffuse Large B-cell Lymphoma) requiring full course R-CHOP.

TPS8600 Background: Malignant mesothelioma is a universally lethal cancer that has been increasing over the last three decades. No treatment has been licenced for patients with relapsed mesothelioma after receipt of licenced systemic anti-cancer therapy in the UK. A previous single-arm phase IIa trial (MiST1) evaluated the efficacy of Poly (ADP-rib...

8506 Background: Leveraging adaptive immunity to control mesothelioma is now a standard approach, however the factors that underpin clinical response are poorly understood. Here we report the final analysis of the CONFIRM trial (NCT03063450), a double-blind phase III randomized study of the PD-1 inhibitor nivolumab (N) versus placebo (P) in patient...

Objective To assess the effectiveness of oral spironolactone for acne vulgaris in adult women. Design Pragmatic, multicentre, phase 3, double blind, randomised controlled trial. Setting Primary and secondary healthcare, and advertising in the community and on social media in England and Wales. Participants Women (≥18 years) with facial acne for...

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO...

Introduction: There is paucity of evidence and consensus on various aspects of management of penile cancer (PeCa), which is intuitive considering the rarity of this disease. We present here the details of an online survey conducted by the Global Society of Rare Genito-urinary Tumors (GSRGT) with the aim of capturing the variations in PeCa care acr...

Background: Neuroinflammation is ubiquitous in acute stroke and worsens outcome. However, the precise timing of the inflammatory response is unknown, hindering the design of acute anti-inflammatory therapeutic interventions. We sought to identify the onset of the neuroinflammatory cascade using a mobile stroke unit. Methods: The study is a proof...

398 Background: Phase III studies have shown a survival benefit for the addition of immune checkpoint inhibitors to conventional chemotherapy for patients with gastroesophageal cancer (GEC). Large scale studies of chemoimmunotherapy prior to and after surgery are under way. We sought to characterise the effects of the PDL1 inhibitor durvalumab (D)...

295 Background: The optimum combination curative approach to locally advanced adenocarcinoma of the esophagus and esophago-gastric junction (AEG) remains controversial, specifically whether multimodal therapy or perioperative chemotherapy is superior. Neo-AEGIS was designed as the first randomized clinical trial (RCT) to directly compare the multim...

Background: Neuroinflammation is ubiquitous in acute stroke and worsens outcome. However, the precise timing of the inflammatory response is unknown, hindering the design of acute anti-inflammatory therapeutic interventions. We used a mobile stroke unit (MSU) to identify the onset of the neuroinflammatory cascade within minutes of symptom onset. Me...

Background Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a major reason for consultations in primary care, hospital admissions, deterioration in function, and mortality. Despite the majority of exacerbations not being caused by bacteria, as many as 70% of patients who present in UK primary care with AECOPD are prescribed...

Objective To determine the effectiveness of two online behavioural interventions, one for parents and carers and one for young people, to support eczema self-management. Design Two independent, pragmatic, parallel group, unmasked, randomised controlled trials. Setting 98 general practices in England. Participants Parents and carers of children (...

Background There is a lack of well-conducted randomised controlled trials evaluating the effectiveness of theory-based online interventions for eczema. To address these deficiencies, we previously developed and demonstrated the effectiveness of two online behavioural interventions: Eczema Care Online for parents/carers of children with eczema, and...

Molnupiravir is an antiviral, currently approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA) for treating at-risk COVID-19 patients, that induces lethal error catastrophe in SARS-CoV-2. How this drug-induced mechanism of action might impact the emergence of resistance mutations is unclear. To investigate this, we used sampl...

p>Background: the antiviral drug molnupiravir was licensed for treating at-risk patients with COVID-19 on the basis of data from unvaccinated adults. We aimed to evaluate the safety and virological efficacy of molnupiravir in vaccinated and unvaccinated individuals with COVID-19. Methods: this randomised, placebo-controlled, double-blind, phase 2...

Background Palliative radiotherapy is widely used in stage IV NSCLC. A number of radiotherapy dose fractionation studies have confirmed its ability to control symptoms and indicated improvements in local control and survival when higher radiation doses were used in good performance status patients. Recent advances in radiotherapy planning and deli...

The development of a new treatment in cancer generally involves its assessment in Phase I, II and III prospective clinical trials. This article gives an overview of these phases of clinical trials, through which almost every new treatment must pass on the journey from its discovery in the laboratory to its routine use in clinical practice. The aim...

Background The antiviral drug molnupiravir was licensed for treating at-risk patients with COVID-19 on the basis of data from unvaccinated adults. We aimed to evaluate the safety and virological efficacy of molnupiravir in vaccinated and unvaccinated individuals with COVID-19. Methods This randomised, placebo-controlled, double-blind, phase 2 tria...

Background Impaired double strand DNA repair by homologous repair deficiency (HRD) leads to sensitivity to poly ADP ribose polymerase (PARP) inhibition. Poly-ADP ribose polymerase (PARP) inhibitors target HRD to induce synthetic lethality and are used routinely in the treatment of BRCA1 mutated ovarian cancer in the platinum-sensitive maintenance s...

One of the most promising approaches for converting waste plastics into oil is fast pyrolysis. This study reviews the current state of the art and recent progress made on the thermal conversion of plastic to oil technologies, and their uses as alternatives to fossil fuels. The fuel properties of waste plastic pyrolysis oil (WPPO) are close to the d...

As the SARS-CoV-2 pandemic has proceeded, ventilation has been increasingly recognised as an important tool in infection control. Many hospitals in Ireland and the UK do not have mechanical ventilation and depend on natural ventilation. The effectiveness of natural ventilation varies with atmospheric conditions and building design. In a challenge t...

Introduction Multidomain interventions to address modifiable risk factors for dementia are promising, but require more cost-effective, scalable delivery. This study investigated the feasibility of the “Active Brains” digital behavior change intervention and its trial procedures. Materials and methods Active Brains aims to reduce cognitive decline...

Background For patients with oesophagogastric adenocarcinoma, surgery is the only curative option and despite the use of multimodality therapy, which combines it with chemotherapy and/or radiotherapy, more than 50% of patients will relapse and die. Many UK patients present with advanced disease which is already inoperable or metastatic at diagnosis...

Background: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are a major reason for consultations in primary care, hospital admissions, deterioration in function, and mortality. 70% of patients presenting with AECOPD in UK primary care are currently in receipt of antibiotics which is part of the standard care. However, the major...

Background Molnupiravir was licensed for treating high-risk patients with COVID-19 based on data from unvaccinated adults. AGILE CST-2 ( NCT04746183 ) Phase II reports safety and virological efficacy of molnupiravir in vaccinated and unvaccinated individuals. Methods Adult out-patients with PCR-confirmed SARS-CoV-2 infection within five days of sy...

Molnupiravir is an antiviral approved for treating COVID-19, which is thought to drive lethal error catastrophe. How this drug-induced mechanism of action impacts the emergence of resistance mutations is unclear. AGILE Candidate Specific Trial (CST)-2 is a phase IIa trial randomising 180 adult outpatients with SARS-COV-2 infection within five days...

Mesothelioma is a rare, lethal cancer caused by asbestos. Despite recent advances molecularly stratified therapy is lacking, in part due to the challenge of targeting the preponderance of tumor suppressors. Recent efforts to select therapy from our group have focused on poly(ADP-ribose) polymerase (PARP) and cyclin-dependent kinase 4/6 (CDK4/6) how...

Patient-derived cell (PDC) models are a tool that bridge the gap between conventional cancer lines that do not faithfully replicate clinical responses and costly and time-consuming patient derived xenograft (PDX) models. Imagen Therapeutics is establishing the world’s largest biobank of PDC models for both patient diagnostic (PredictRx) and biophar...

Background Currently, there is no US Food and Drug Administration approved therapy for patients with pleural mesothelioma who have relapsed following platinum-doublet based chemotherapy. Vinorelbine has demonstrated useful clinical activity in mesothelioma, however its efficacy has not been formally evaluated in a randomised setting. BRCA1 expressi...

TPS4619 Background: Immunotherapy improves outcomes in the advanced (Bellmunt 2019; Powles 2020) as well as in the adjuvant setting post cystectomy (Bajorin 2021) for muscle invasive bladder cancer (MIBC) patients. Trimodality treatment (TMT) consisting of transurethral resection of bladder tumor (TURBT) followed by chemoradiotherapy (CRT) may be c...

The PI3K/AKT/PTEN pathway is frequently deregulated in metastatic castration-resistant prostate cancer (mCRPC). ProCAID was a phase 2 trial assessing addition of the AKT1/2/3 inhibitor capivasertib to docetaxel for patients with mCRPC. We previously reported that capivasertib did not extend a composite progression-free survival primary endpoint but...

Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and withou...

Sustainable energy derived from waste resources helps to mitigate the greenhouse gas emissions generated from fossil fuels. In this study, a solid heterogeneous catalyst was synthesized by using eggshell and copper oxide [CaCu(OCH3)2]. Using this catalyst, biodiesel fuels were produced from waste sardine fish oil using either methanol, ethanol, or...

ß-d-N4-hydroxycytidine (NHC), the parent nucleoside of molnupiravir, a COVID-19 antiviral, was quantified at SARS-CoV-2 transmission sites in 12 patients enrolled in AGILE Candidate-Specific Trial-2. Saliva, nasal, and tear NHC concentrations were 3%, 21%, and 22% that of plasma. Saliva and nasal NHC were significantly correlated with plasma (P < ....

108 Background: The AKT pathway is frequently deregulated in mCRPC. ProCAID tested addition of capivasertib, a potent selective inhibitor of all three AKT isoforms (AKT1/2/3) to docetaxel chemotherapy vs. placebo plus docetaxel for mCRPC. The primary analysis showed no difference between treatment arms for the primary endpoint of composite progress...

The aim of surgical training across the 10 surgical specialties is to produce competent day 1 consultants. Progression through training in the UK is assessed by the Annual Review of Competency Progression (ARCP). Objective This study aimed to examine variation in ARCP outcomes within surgical training and identify differences in outcomes between s...

The valorization of macroalgae digestate as a secondary resource for high value chemicals and nutrients will promote the sustainability and circularity of anaerobic digestion based biorefinery. In this study, three digestates from A. nodosum C.linum and L. digitata were separated into liquid and solid fractions to investigate the production of high...

i>Excavations at Chester. Roman land division and a probable villa in the hinterland of Deva reports on excavations carried out by Northern Archaeological Associates (NAA) at Saighton Camp – a former British Army training camp – located to the south of the Roman legionary fortress of Chester (Deva Victrix) which revealed important and extensive Rom...

Background: Molnupiravir, an orally administered prodrug of the broadly active, direct-acting antiviral, ribonucleoside analogue β-d-N4-hydroxycytidine (NHC) is a promising COVID-19 drug candidate. We characterised the pharmacokinetics of NHC in saliva, nasal secretions and tears of patients enrolled in the phase I AGILE trial (NCT04746183) to unde...

Female breast cancer (BC) became the most commonly diagnosed cancer globally in 2020. One of the hallmarks of BC is both intratumor and intertumor heterogeneity. Efforts have been made to categorize this heterogeneity based on the presence or absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2...

Background: CD27 antibody stimulation of T cells has been shown to activate and promote myeloid cell infiltration leading to enhanced antibody-dependent cellular phagocytosis (ADCP) by anti-CD20 in lymphoma preclinical models (Turaj et al Cancer Cell 2017). In this phase IIa study (RiVa NCT03307746), the safety and efficacy of rituximab (ritux) and...