Imperial College London

Paul Ziprin

Faculty of MedicineDepartment of Surgery & Cancer

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3312 7635p.ziprin

 
 
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Assistant

 

Ms Caroline Hurley +44 (0)20 3312 2124

 
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Location

 

Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Publication Type
Year
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167 results found

Herrera C, Harman S, Aldon Y, Rogers P, Armanasco N, Ziprin P, Stieh D, Nuttall J, Shattock RJet al., 2021, The entry inhibitor DS003 (BMS-599793): a BMS-806 analogue, provides superior activity as a pre-exposure prophylaxis candidate., AIDS, Vol: 35, Pages: 1907-1917

OBJECTIVE: Small molecule inhibitors able to bind to gp120 and prevent CD4+-induced HIV-1 envelope conformational change provide an important class of inhibitors. Currently, only Fostemsavir is approved for HAART, which makes this class of inhibitors attractive candidates for prevention. We assessed the activity of DS003 (BMS-599793), an analogue of BMS-378806, in different mucosal tissues and elucidated its mechanism of action. DESIGN: Preclinical analysis was performed with human mucosal tissue models as surrogates of in-vivo activity. METHODS: Antiviral efficacy of DS003 was assessed in mucosal tissue explants (ecto-cervical, penile and colorectal) and in trans-infection models (co-cultures of dendritic or mucosal migratory cells with CD4+ T cells) with several dosing times (2, 24 h and sustained) and in combination with a fusion inhibitor. Binding of DS003 to gp120 was assessed by flow cytometry and bio-layer interferometry and further probed in competitive studies using soluble CD4+ (sCD4+) and an anti-CD4+ induced antibody, 17b. RESULTS: In all models, the inhibitory activity of DS003 was increased with longer periods of exposure and by combination with a fusion inhibitor. Pre-exposure to sCD4+ impeded DS003 binding to viral envelope. In contrast, DS003 did not impact subsequent binding of sCD4+. Furthermore, sCD4+-induced epitope exposure as assessed by 17b binding was significantly reduced in the presence of DS003. CONCLUSION: DS003 inhibits HIV-1 infection by binding to or near the CD4+ binding site of gp120, preventing CD4+-induced conformational change essential for viral fusion. These data highlight the potential of DS003 for development as a pre-exposure prophylaxis candidate.

Journal article

Hernon J, Saxton J, Jones M, Howard G, Swart AM, Clark A, Stirling S, Turner D, Murdoch J, Nortje J, Bach S, Fearnhead N, Din F, Stephens A, Lund J, Tou S, Kelly S, Ziprin P, Dennis R, Smart N, Roxburgh C, Simpson A, Mishra A, Knight K, Dresser Ket al., 2021, SupPoRtive Exercise Programmes for Accelerating REcovery after major ABdominal Cancer surgery trial (PREPARE-ABC): Pilot phase of a multicentre randomised controlled trial, COLORECTAL DISEASE, ISSN: 1462-8910

Journal article

Moussa O, Ardissino M, Eichhorn C, Reddy RK, Khan O, Ziprin P, Darzi A, Collins P, Purkayastha Set al., 2021, Atrial fibrillation and obesity: long-term incidence and outcomes after bariatric surgery, European Journal of Preventive Cardiology, Vol: 28, Pages: e22-e24, ISSN: 2047-4873

Journal article

D'Souza N, Monahan K, Benton SC, Wilde L, Abulafi Met al., 2021, Finding the needle in the haystack: the diagnostic accuracy of the faecal immunochemical test for colorectal cancer in younger symptomatic patients, COLORECTAL DISEASE, ISSN: 1462-8910

Journal article

Gómara MJ, Pons R, Herrera C, Ziprin P, Haro Iet al., 2021, Peptide Amphiphilic-Based Supramolecular Structures with Anti-HIV-1 Activity., Bioconjug Chem

In a previous work, we defined a novel HIV-1 fusion inhibitor peptide (E1P47) with a broad spectrum of activity against viruses from different clades, subtypes, and tropisms. With the aim to enhance its efficacy, in the present work we address the design and synthesis of several peptide amphiphiles (PAs) based on the E1P47 peptide sequence to target the lipid rafts of the cell membrane where the cell-cell fusion process takes place. We report the synthesis of novel PAs having a hydrophobic moiety covalently attached to the peptide sequence through a hydrophilic spacer of polyethylene glycol. Characterization of self-assembly in condensed phase and aqueous solution as well as their interaction with model membranes was analyzed by several biophysical methods. Our results demonstrated that the length of the spacer of polyethylene glycol, the position of the peptide conjugation as well as the type of the hydrophobic residue determine the antiviral activity of the construct. Peptide amphiphiles with one alkyl tail either in C-terminus (C-PAmonoalkyl) or in N-terminus (N-PAmonoalkyl) showed the highest anti-HIV-1 activities in the cellular model of TZM-bl cells or in a preclinical model of the human mucosal tissue explants.

Journal article

D'Souza N, Delisle TG, Chen M, Benton SC, Abulafi Met al., 2021, Faecal immunochemical testing in symptomatic patients to prioritize investigation: diagnostic accuracy from NICE FIT Study, BRITISH JOURNAL OF SURGERY, Vol: 108, Pages: 804-810, ISSN: 0007-1323

Journal article

Arhi C, Askari A, Nachiappan S, Bottle A, Arebi N, Athanasiou T, Ziprin P, Aylin P, Faiz Oet al., 2021, Stage at Diagnosis and Survival of Colorectal Cancer With or Without Underlying Inflammatory Bowel Disease: A Population-based Study, JOURNAL OF CROHNS & COLITIS, Vol: 15, Pages: 375-382, ISSN: 1873-9946

Journal article

Bach SP, Gilbert A, Brock K, Korsgen S, Geh I, Hill J, Gill T, Hainsworth P, Tutton MG, Khan J, Robinson J, Steward M, Cunningham C, Levy B, Beveridge A, Handley K, Kaur M, Marchevsky N, Magill L, Russell A, Quirke P, West NP, Sebag-Montefiore D, TREC collaboratorset al., 2021, Radical surgery versus organ preservation via short-course radiotherapy followed by transanal endoscopic microsurgery for early-stage rectal cancer (TREC): a randomised, open-label feasibility study., The Lancet Gastroenterology and Hepatology, Vol: 6, Pages: 92-105, ISSN: 2468-1253

BACKGROUND: Radical surgery via total mesorectal excision might not be the optimal first-line treatment for early-stage rectal cancer. An organ-preserving strategy with selective total mesorectal excision could reduce the adverse effects of treatment without substantially compromising oncological outcomes. We investigated the feasibility of recruiting patients to a randomised trial comparing an organ-preserving strategy with total mesorectal excision. METHODS: TREC was a randomised, open-label feasibility study done at 21 tertiary referral centres in the UK. Eligible participants were aged 18 years or older with rectal adenocarcinoma, staged T2 or lower, with a maximum diameter of 30 mm or less; patients with lymph node involvement or metastases were excluded. Patients were randomly allocated (1:1) by use of a computer-based randomisation service to undergo organ preservation with short-course radiotherapy followed by transanal endoscopic microsurgery after 8-10 weeks, or total mesorectal excision. Where the transanal endoscopic microsurgery specimen showed histopathological features associated with an increased risk of local recurrence, patients were considered for planned early conversion to total mesorectal excision. A non-randomised prospective registry captured patients for whom randomisation was considered inappropriate, because of a strong clinical indication for one treatment group. The primary endpoint was cumulative randomisation at 12, 18, and 24 months. Secondary outcomes evaluated safety, efficacy, and health-related quality of life assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and CR29 in the intention-to-treat population. This trial is registered with the ISRCTN Registry, ISRCTN14422743. FINDINGS: Between Feb 22, 2012, and Dec 19, 2014, 55 patients were randomly assigned at 15 sites; 27 to organ preservation and 28 to radical surgery. Cumulatively, 18 patients had been randomly assigned at 12 months, 31 a

Journal article

D'Souza N, Georgiou-Delisle T, Chen M, Benton S, Abulafi M, The NICE FIT Steering Groupet al., 2020, Faecal immunochemical test is superior to symptoms in predicting pathology in patients with suspected colorectal cancer symptoms referred on a 2WW pathway; a diagnostic accuracy study, Gut, Vol: 70, Pages: 1130-1138, ISSN: 0017-5749

Objective To assess whether a faecal immunochemical test (FIT) could be used to select patients with suspected colorectal cancer (CRC) symptoms for urgent investigation.Design Multicentre, double-blinded diagnostic accuracy study in 50 National Health Service (NHS) hospitals across England between October 2017 and December 2019. Patients referred to secondary care with suspected CRC symptoms meeting NHS England criteria for urgent 2 weeks wait referral and triaged to investigation with colonoscopy were invited to perform a quantitative FIT. The sensitivity of FIT for CRC, and effect of relevant variables on its diagnostic accuracy was assessed.Results 9822 patients were included in the final analysis. The prevalence of CRC at colonoscopy was 3.3%. The FIT positivity decreased from 37.2% to 19.0% and 7.6%, respectively, at cut-offs of 2, 10 and 150 µg haemoglobin/g faeces (µg/g). The positive predictive values of FIT for CRC at these cut-offs were 8.7% (95% CI, 7.8% to 9.7%), 16.1% (95% CI 14.4% to 17.8%) and 31.1% (95% CI 27.8% to 34.6%), respectively, and the negative predictive values were 99.8% (95% CI 99.7% to 99.9%), 99.6% (95% CI 99.5% to 99.7%) and 98.9% (95% CI 98.7% to 99.1%), respectively. The sensitivity of FIT for CRC decreased at the same cut-offs from 97.0% (95% CI 94.5% to 98.5%) to 90.9% (95% CI 87.2% to 93.8%) and 70.8% (95% CI 65.6% to 75.7%), respectively, while the specificity increased from 64.9% (95% CI 63.9% to 65.8%) to 83.5% (95% CI 82.8% to 84.3%) and 94.6% (95% CI 94.1% to 95.0%), respectively. The area under the receiver operating characteristic curve was 0.93 (95% CI 0.92 to 0.95).Conclusion FIT sensitivity is maximised to 97.0% at the lowest cut-off (2 µg/g); a negative FIT result at this cut-off can effectively rule out CRC and a positive FIT result is better than symptoms to select patients for urgent investigations.Trial registration number ISRCTN49676259.

Journal article

Crakes KR, Herrera C, Morgan JL, Olstad K, Hessell AJ, Ziprin P, LiWang PJ, Dandekar Set al., 2020, Efficacy of silk fibroin biomaterial vehicle for in vivo mucosal delivery of Griffithsin and protection against HIV and SHIV infection ex vivo, Journal of the International AIDS Society, Vol: 23, ISSN: 1758-2652

INTRODUCTION: The majority of new HIV infections occur through mucosal transmission. The availability of readily applicable and accessible platforms for anti-retroviral (ARV) delivery is critical for the prevention of HIV acquisition through sexual transmission in both women and men. There is a compelling need for developing new topical delivery systems that have advantages over the pills, gels and rings, which currently fail to guarantee protection against mucosal viral transmission in vulnerable populations due to lack of user compliance. The silk fibroin (SF) platform offers another option that may be better suited to individual circumstances and preferences to increase efficacy through user compliance. The objective of this study was to test safety and efficacy of SF for anti-HIV drug delivery to mucosal sites and for viral prevention. METHODS: We formulated a potent HIV inhibitor Griffithsin (Grft) in a mucoadhesive silk fibroin (SF) drug delivery platform and tested the application in a non-human primate model in vivo and a pre-clinical human cervical and colorectal tissue explant model. Both vaginal and rectal compartments were assessed in rhesus macaques (Mucaca mulatta) that received SF (n = 4), no SF (n = 7) and SF-Grft (n = 11). In this study, we evaluated the composition of local microbiota, inflammatory cytokine production, histopathological changes in the vaginal and rectal compartments and mucosal protection after ex vivo SHIV challenge. RESULTS: Effective Grft release and retention in mucosal tissues from the SF-Grft platform resulted in protection against HIV in human cervical and colorectal tissue as well as against SHIV challenge in both rhesus macaque vaginal and rectal tissues. Mucoadhesion of SF-Grft inserts did not cause any inflammatory responses or changes in local microbiota. CONCLUSIONS: We demonstrated that in vivo delivery of SF-Grft in rhesus macaques fully protects against SHIV challenge ex vivo after two

Journal article

Gomara MJ, Perez Y, Gomez-Gutierrez P, Herrera C, Ziprin P, Martinez JP, Meyerhans A, Perez JJ, Haro Iet al., 2020, Importance of structure-based studies for the design of a novel HIV-1 inhibitor peptide, Scientific Reports, Vol: 10, Pages: 1-14, ISSN: 2045-2322

Based on the structure of an HIV-1 entry inhibitor peptide two stapled- and a retro-enantio peptides have been designed to provide novel prevention interventions against HIV transmission. The three peptides show greater inhibitory potencies in cellular and mucosal tissue pre-clinical models than the parent sequence and the retro-enantio shows a strengthened proteolytic stability. Since HIV-1 fusion inhibitor peptides need to be embedded in the membrane to properly interact with their viral target, the structural features were determined by NMR spectroscopy in micelles and solved by using restrained molecular dynamics calculations. Both parent and retro-enantio peptides demonstrate a topology compatible with a shared helix–turn–helix conformation and assemble similarly in the membrane maintaining the active conformation needed for its interaction with the viral target site. This study represents a straightforward approach to design new targeted peptides as HIV-1 fusion inhibitors and lead us to define a retro-enantio peptide as a good candidate for pre-exposure prophylaxis against HIV-1.

Journal article

Arhi CS, Burns EM, Bottle A, Bouras G, Aylin P, Ziprin P, Darzi Aet al., 2020, Delays in referral from primary care worsen survival for patients with colorectal cancer: a retrospective cohort study, British Journal of General Practice, Vol: 70, Pages: E463-E471, ISSN: 0960-1643

Background Delays in referral for patients with colorectal cancer may occur if the presenting symptom is falsely attributed to a benign condition.Aim To investigate whether delays in referral from primary care are associated with a later stage of cancer at diagnosis and worse prognosis.Design and setting A national retrospective cohort study in England including adult patients with colorectal cancer identified from the cancer registry with linkage to Clinical Practice Research Datalink, who had been referred following presentation to their GP with a ‘red flag’ or ‘non-specific’ symptom.Method The hazard ratios (HR) of death were calculated for delays in referral of between 2 weeks and 3 months, and >3 months, compared with referrals within 2 weeks.Results A total of 4527 (63.5%) patients with colon cancer and 2603 (36.5%) patients with rectal cancer were included in the study. The percentage of patients presenting with red-flag symptoms who experienced a delay of >3 months before referral was 16.9% of those with colon cancer and 13.5% of those with rectal cancer, compared with 35.7% of patients with colon cancer and 42.9% of patients with rectal cancer who presented with non-specific symptoms. Patients referred after 3 months with red-flag symptoms demonstrated a significantly worse prognosis than patients who were referred within 2 weeks (colon cancer: HR 1.53; 95% confidence interval [CI] = 1.29 to 1.81; rectal cancer: HR 1.30; 95% CI = 1.06 to 1.60). This association was not seen for patients presenting with non-specific symptoms. Delays in referral were associated with a significantly higher proportion of late-stage cancers.Conclusion The first presentation to the GP provides a referral opportunity to identify the underlying cancer, which, if missed, is associated with a later stage in diagnosis and worse survival.

Journal article

Abdulaal A, Arhi C, Ziprin P, 2020, Effect of Health Care Provider Delays on Short-Term Outcomes in Patients With Colorectal Cancer: Multicenter Population-Based Observational Study, INTERACTIVE JOURNAL OF MEDICAL RESEARCH, Vol: 9, ISSN: 1929-073X

Journal article

Pathiraja AA, Weerakkody RA, von Roon AC, Ziprin P, Bayford Ret al., 2020, The clinical application of electrical impedance technology in the detection of malignant neoplasms: a systematic review, JOURNAL OF TRANSLATIONAL MEDICINE, Vol: 18

Journal article

Moussa O, Ardissino M, Heaton T, Tang A, Khan O, Ziprin P, Darzi A, Collins P, Purkayastha Set al., 2020, Effect of bariatric surgery on long-term cardiovascular outcomes: a nationwide nested cohort study, European Heart Journal, Vol: 41, Pages: 2660-2667, ISSN: 0195-668X

AIMS: This study aims to evaluate the long-term effect of bariatric surgery on cardiovascular outcomes of patients with obesity. METHODS AND RESULTS: A nested cohort study was carried out within the Clinical Practice Research Datalink. The study cohort included the 3701 patients on the database who had undergone bariatric surgery and 3701 age, gender, and body mass index-matched controls. The primary endpoint was the composite of fatal or non-fatal myocardial infarction and fatal or non-fatal ischaemic stroke. Secondary endpoints included fatal or non-fatal myocardial infarction alone, fatal or non-fatal ischaemic stroke alone, incident heart failure, and mortality. The median follow-up achieved was 11.2 years. Patients who had undergone bariatric surgery had a significantly lower occurrence of major adverse cardiovascular events [hazard ratio (HR) 0.410, 95% confidence interval (CI) 0.274-0.615; P < 0.001]. This was mainly driven by a reduction in myocardial infarction (HR 0.412, 95% CI 0.280-0.606; P < 0.001) and not in acute ischaemic stroke (HR 0.536, 95% CI 0.164-1.748; P = 0.301). A reduction was also observed in new diagnoses of heart failure (HR 0.403, 95% CI 0.181-0.897; P = 0.026) and mortality (HR 0.254, 95% CI 0.183-0.353; P < 0.001). CONCLUSION: The results of this large, nationwide cohort study support the association of bariatric surgery with lower long-term risk of major cardiovascular events and incident heart failure in patients with obesity.

Journal article

Moussa O, Ardissino M, Tang A, Lazzari L, Millar O, Ziprin P, Darzi A, Khan O, Collins P, Purkayastha Set al., 2019, Long-term impact of bariatric surgery on venous thromboembolic risk: a matched cohort study., Annals of Surgery, Pages: 1-8, ISSN: 0003-4932

OBJECTIVE: The aim of this study is to evaluate the effect of bariatric surgery on long-term risk of VTEs in a large cohort of patients with obesity. BACKGROUND: Obesity is a well-established risk factor for VTEs, such as pulmonary embolism and deep vein thrombosis. The rising prevalence of obesity and its associated co-morbidities, including VTE, represent a growing public health issue. METHODS: A nested, retrospective matched cohort study was designed and conducted on prospectively collected national electronic healthcare records data from the Clinical Practice Research Datalink. Eight thousand, one hundred twelve patients were included in the study: the 4056 patients on the database who had undergone bariatric surgery, and equal numbers of age, sex, and body mass index matched controls. The primary endpoint was the occurrence of VTEs; secondary endpoints were the occurrence of deep vein thrombosis alone, pulmonary embolism alone. RESULTS: Patients were followed up for a median of 10.7 years. The bariatric surgery cohort had a significantly lower occurrence of the primary outcome [hazard ratio (HR) 0.601; 95% confidence interval (CI) 0.430-0.841, P = 0.003]; mainly driven by a reduction in deep vein thrombosis (HR 0.523; 95% CI 0.349-0.783, P = 0·002) and not in pulmonary embolism (HR 0.882; 95% CI 0.511-1.521, P = 0.651). CONCLUSIONS: The results of this nation-wide study set out to characterize the impact of bariatric surgery on long-term risk of thromboembolic events outline a significant reduction in thromboembolic events, driven by a reduction in deep vein thrombosis.

Journal article

Arhi CS, Ziprin P, Bottle A, Burns EM, Aylin P, Darzi Aet al., 2019, Colorectal cancer patients under the age of 50 experience delays in primary care leading to emergency diagnoses: a population-based study, Colorectal Disease, Vol: 21, Pages: 1270-1278, ISSN: 1462-8910

AIM: The incidence of colorectal cancer in the under 50s is increasing. In this national population-based study we aim to show that missed opportunities for diagnosis in primary care are leading to referral delays and emergency diagnoses in young patients. METHOD: We compared the interval before diagnosis, presenting symptom(s) and the odds ratio (OR) of an emergency diagnosis for those under the age of 50 with older patients sourced from the cancer registry with linkage to a national database of primary-care records. RESULTS: The study included 7315 patients, of whom 508 (6.9%) were aged under 50 years, 1168 (16.0%) were aged 50-59, 2294 (31.4%) were aged 60-69 and 3345 (45.7%) were aged 70-79 years. Young patients were more likely to present with abdominal pain and via an emergency, and had the lowest percentage of early stage cancer. They experienced a longer interval between referral and diagnosis (12.5 days) than those aged 60-69, reflecting the higher proportion of referrals via the nonurgent pathway (33.3%). The OR of an emergency diagnosis did not differ with age if a red-flag symptom was noted at presentation, but increased significantly for young patients if the symptom was nonspecific. CONCLUSION: Young patients present to primary care with symptoms outside the national referral guidelines, increasing the likelihood of an emergency diagnosis.

Journal article

Collins P, Moussa O, Ardissino M, Heaton O, Tang A, Khan O, Ziprin P, Darzi A, Purkayastha Set al., 2019, Effect of bariatric surgery on long-term cardiovascular outcomes A nation-wide nested cohort study, European Heart Journal, Vol: 40, ISSN: 0195-668X

BackgroundObesity is a cardinal risk factor for the development of atherosclerotic cardiovascular disease. Bariatric surgery is an effective method of achieving weight reduction and improving control of cardiovascular risk factors in patients with obesity. However, the effect of bariatric surgery on long-term cardiovascular outcomes has yet to be defined.PurposeThe aim of this study is to evaluate the effect of bariatric surgery on long-term risk of major adverse cardiovascular events in a large population of patients with obesity.MethodsA nested cohort study was carried out; including the 3,701 patients of the Clinical Practice Research Datalink database who had undergone bariatric surgery, and 3,701 age, gender and BMI matched controls. The primary endpoint was the composite of fatal or non-fatal myocardial infarction; and fatal or non-fatal acute ischaemic stroke. Secondary endpoints included all-cause mortality, new diagnosis of heart failure, fatal or non-fatal myocardial infarction, and fatal or non-fatal acute ischaemic stroke. Data was analysed using a Cox proportional hazards model to account for multiple covariates.ResultsPatients were followed up for a median of 11.2 years; 20.3% of the population were female, the median age was 36 years and median BMI was 40.4 kg/m2. Patients who had undergone bariatric surgery had a significantly lower occurrence of the primary composite outcome (HR 0.450; 95% CI 0.312–0.671, p<0.001, NNT=62); this was driven by a reduction in myocardial infarction (HR 0.444; 95% CI 0.302–0.654, p<0.001, NNT=64) and not in acute ischaemic stroke (HR 0.528; 95% CI 0.159–1.751, p=0.296). A significant reduction was observed in rates all-cause mortality (HR 0.254; 95% CI 0.183–0.353; p<0.001, NNT=27) and of new diagnosis of heart failure (HR 0.519; 95% CI 0.311–0.864, p=0.012, NNT=153).ConclusionThe results of this large, nation-wide nested cohort study support the role of bariatric surgery in reducin

Journal article

Arhi CS, Markar S, Burns EM, Bouras G, Bottle A, Hanna G, Aylin P, Ziprin P, Darzi Aet al., 2019, Delays in referral from primary care are associated with a worse survival in patients with esophagogastric cancer, Diseases of the Esophagus, Vol: 32, Pages: 1-11, ISSN: 1120-8694

NICE referral guidelines for suspected cancer were introduced to improve prognosis by reducing referral delays. However, over 20% of patients with esophagogastric cancer experience three or more consultations before referral. In this retrospective cohort study, we hypothesize that such a delay is associated with a worse survival compared with patients referred earlier. By utilizing Clinical Practice Research Datalink, a national primary care linked database, the first presentation, referral date, a number of consultations before referral and stage for esophagogastric cancer patients were determined. The risk of a referral after one or two consultations compared with three or more consultations was calculated for age and the presence of symptom fulfilling the NICE criteria. The risk of death according to the number of consultations before referral was determined, while accounting for stage and surgical management. 1307 patients were included. Patients referred after one (HR 0.80 95% CI 0.68-0.93 p = 0.005) or two consultations (HR 0.81 95% CI 0.67-0.98 p = 0.034) demonstrated significantly improved prognosis compared with those referred later. The risk of death was also lower for patients who underwent a resection, were younger or had an earlier stage at diagnosis. Those presenting with a symptom fulfilling the NICE criteria (OR 0.27 95% CI 0.21-0.35 p < 0.0001) were more likely to be referred earlier. This is the first study to demonstrate an association between a delay in referral and worse prognosis in esophagogastric patients. These findings should prompt further research to reduce primary care delays.

Journal article

Moussa OM, Erridge S, Chidambaram S, Ziprin P, Darzi A, Purkayastha Set al., 2019, Mortality of the severely obese: a population study, Annals of Surgery, Vol: 269, Pages: 1087-1091, ISSN: 0003-4932

OBJECTIVE: This study aimed to analyze the Clinical Practice Research Datalink to identify the prognostic factors of all-cause mortality in the severely obese. BACKGROUND: Patients who are severely obese [body mass index (BMI) ≥35 kg/m] are at increased risk of all-cause mortality as a result of metabolic sequelae including hyperlipidemia, hypertension, and diabetes. Bariatric surgery has been shown to reduce the severity of the metabolic complications of obesity. METHOD: A case-controlled analysis was carried out of patients with a BMI of 35 kg/m or more from the Clinical Practice Research Datalink, a UK database of primary care clinics. Clinicopathological characteristics at baseline diagnosis were extracted. Cases of all-cause mortality were identified as a clinical endpoint. A Cox proportional hazard model was used to calculate hazard ratios (HRs) for different patient factors. A P value less than 0.050 was defined as significant. RESULTS: A total of 187,061 records were identified for analysis. Median follow-up time was 98.0 months (range: 3.0-1095.0). A total of 8655(4.6%) were identified as having died during the study period. The median time from baseline obesity diagnosis until death was 137.0 months (range: 3.0-628.7). Multivariate analysis found bariatric surgery to be associated with reduced risk of all-cause mortality (HR: 0.487; P < 0.001). The following were associated with increased risk of death: male sex (HR: 1.805; P < 0.001), BMI of 60 or greater (HR: 2.541; P < 0.001), hypertension (HR: 2.108; P < 0.001), diabetes (HR: 2.766; P < 0.001), and hyperlipidemia (HR: 1.641; P < 0.001). CONCLUSIONS: Factors such as high BMI, diabetes, hyperlipidemia, and hypertension at first diagnosis of severe obesity were each independently associated with an increased risk of death. Bariatric surgery was shown to be associated with reduced risk of all-cause mortality. Improving access to bariatric surgery and public health campaigns can improve

Journal article

Moussa OM, Ardissino M, Kulatilake P, Faraj A, Muttoni E, Darzi A, Ziprin P, Scholtz S, Purkayastha Set al., 2019, Effect of body mass index on depression in a UK cohort of 363 037 obese patients: A longitudinal analysis of transition, Clinical Obesity, Vol: 9, ISSN: 1758-8103

With obesity levels increasing, it is important to consider the mental health risks associated with this condition to optimize patient care. Links between depression and obesity have been explored, but few studies focus on the risk profiles of patients across stratified body mass index (BMI) classes above 30 kg/m2 . This study aims to determine the impact of BMI on depression risk in patients with obesity and to investigate trends of depression in a large cohort of British patients with BMI > 30 kg/m2 . A nationwide primary care database, the Clinical Practice Research Datalink (CPRD), was analysed for diagnoses of obesity (BMI > 30 kg/m2 ). Obese patients were then sub-classified into seven BMI categories. Primary health care-based records of patients entered in the CPRD were analysed. A total of 363 037 patients had a BMI ≥ 30 kg/m2 ; of these patients 97 392 (26.8%) also had a diagnosis of depression. Absolute event rates over time and hazard risk of depression were analysed by BMI category. On Cox regression analysis of time to development of depression, the cumulative hazard increased significantly and linearly across BMI groups (P < 0.001). Compared to those with BMI 30 to 35 kg/m2 , patients with BMI 35 to 40 kg/m2 had a 20% higher risk of depression (hazard ratio [HR] 1.206, confidence interval [CI] 1.170-1.424), and those with BMI > 60 kg/m2 had a 98% higher risk (HR 1.988, CI 1.513-2.612). This study identified the prevalence and time course of depression in a cohort of obese patients in the United Kingdom. Findings suggest the risk of depression is directly proportional to BMI above 30 kg/m2 . Therefore, clinicians should note higher BMI levels confer increased risk of depression.

Journal article

Markar SR, Chin S-T, Romano A, Wiggins T, Antonowicz S, Paraskeva P, Ziprin P, Darzi A, Hanna GBet al., 2019, Breath Volatile Organic Compound Profiling of Colorectal Cancer Using Selected Ion Flow-Tube Mass Spectrometry., Annals of Surgery, Vol: 269, Pages: 903-910, ISSN: 0003-4932

OBJECTIVE: BACKGROUND:: Breath VOCs have the potential to noninvasively diagnose cancer. METHODS: Exhaled breath samples were collected using 2-L double-layered Nalophan bags, and were analyzed using selected-ion-flow-tube mass-spectrometry. Gold-standard test for comparison was endoscopy for luminal inspection and computed tomography (CT) to confirm cancer recurrence. Three studies were conducted: RESULTS:: CONCLUSION:: This study suggests the association of a single breath biomarker with the primary presence and recurrence of CRCa. Further multicenter validation studies are required to validate these findings.

Journal article

Arhi CS, Burns EM, Bouras G, Aylin P, Ziprin P, Darzi Aet al., 2019, Complications after discharge and delays in adjuvant chemotherapy following colonic resection: a cohort study of linked primary and secondary care data, Colorectal Disease, Vol: 21, Pages: 307-314, ISSN: 1462-8910

AIM: By understanding the reasons for delays in adjuvant chemotherapy (AC) after colonic resection, there is the potential to improve patient outcome. The aim of this study is to determine the extent and impact of complications after hospital discharge on delays to AC. METHOD: The study cohort included patients from Hospital Episode Statistics (HES) who had a colorectal cancer resection; linkage to primary care data was provided by the Clinical Practice Research Datalink (CPRD). Complications during the index hospital stay (from HES) and after discharge (from CPRD) were compared. The risk of late AC treatment (8 weeks or later) following a complication, stoma at the index procedure or emergency admission was described after accounting for age and Charlson score. A Cox hazards model determined the association of these factors with overall survival (OS). RESULTS: A total of 1266 patients underwent AC following colon cancer resection, of whom 598 (47.2%) received treatment within 8 weeks. Patients receiving late AC had a significantly higher proportion of re-operations (7.0% vs 3.3% P < 0.005) and wound infections (5.5% vs 3.7% P = 0.042), with 96% of the latter only being noted in CPRD. In multivariate analysis, the risk of AC delay significantly increased following a complication (OR 1.53, 95% CI 1.16-2.03, P = 0.003) or a stoma at the index operation. AC delay was associated with worse OS [hazard ratio (HR) 1.44, 95% CI 1.16-1.79, P = 0.001], as was an emergency admission (HR 1.59, 95% CI 1.21-1.98, P < 0.0005). However, the presence of a complication did not independently reduce OS (HR 1.15, 95%CI 0.89-1.48, P = 0.295). CONCLUSION: The true extent and impact of complications following colonic resection is underestimated when only secondary care data are used.

Journal article

Ardissino M, Moussa O, Tang A, Muttoni E, Ziprin P, Purkayastha Set al., 2019, Idiopathic intracranial hypertension in the British population with obesity, Acta Neurochirurgica: the European journal of neurosurgery, Vol: 161, Pages: 239-246, ISSN: 0001-6268

PurposeIdiopathic intracranial hypertension (IIH) is a syndrome that is characterized by persistently high intracranial pressure and associated with high rates of morbidity and visual loss. Its exact etiology and clinical picture is poorly understood, but it is known to be associated with obesity. The aim of this study was to investigate the prevalence and clinical manifestations of IIH using a large nationwide database of British subjects.Materials and methodsThe anonymized healthcare records of patients with a BMI of ≥ 30 kg/m2 were extracted from the Clinical Practice Research Datalink (CPRD), and analyzed.ResultsThe patients with IIH were older and more likely to have peripheral vascular disease, ischemic heart disease, and anemia; to have had a previous myocardial infarction; and have used non-steroidal anti-inflammatory drugs (NSAIDs) and steroids. Multivariate analysis with adjustment for confounders showed that anemia (p = 0.033) and the use of NSAIDs (p = 0.011) were the only factors independently associated with IIH. Increases in BMI beyond the threshold of obesity did not independently increase risk of IIH.ConclusionsIIH is a multifactorial disease; the risk of which is increased in patients with a background of anemia, and those who use NSAIDs. Across BMI categories beyond the threshold for obesity (BMI ≥ 30 kg/m2), there is no continuation of the previously described “dose-response” relationship between BMI and IIH.Ethical approvalScientific approval for the study was granted from the Regulatory Agency’s Independent Scientific Advisory Committee and ethical approval by the Health Research Authority IRAS Project ID: 203143. ISAC approval registration number 16_140R2.

Journal article

Griffiths EA, Hodson J, Vohra RS, Marriott P, Katbeh T, Zino S, Nassar AHM, Vohra RS, Kirkham AJ, Pasquali S, Marriott P, Johnstone M, Spreadborough P, Alderson D, Griffiths EA, Fenwick S, Elmasry M, Nunes QM, Kennedy D, Khan RB, Khan MAS, Magee CJ, Jones SM, Mason D, Parappally CP, Mathur P, Saunders M, Jamel S, Haque SU, Zafar S, Shiwani MH, Samuel N, Dar F, Jackson A, Lovett B, Dindyal S, Winter H, Fletcher T, Rahman S, Wheatley K, Nieto T, Ayaani S, Youssef H, Nijjar RS, Watkin H, Naumann D, Emesih S, Sarmah PB, Lee K, Joji N, Lambert J, Heath J, Teasdale RL, Weerasinghe C, Needham PJ, Welbourn H, Forster L, Finch D, Blazeby JM, Robb W, McNair AGK, Hrycaiczuk A, Charalabopoulos A, Kadirkamanathan S, Tang C-B, Jayanthi NVG, Noor N, Dobbins B, Cockbain AJ, Nilsen-Nunn A, de Siqueira J, Pellen M, Cowley JB, Ho W-M, Miu V, White TJ, Hodgkins KA, Kinghorn A, Tutton MG, Al-Abed YA, Menzies D, Ahmad A, Reed J, Khan S, Monk D, Vitone LJ, Murtaza G, Joel A, Brennan S, Shier D, Zhang C, Yoganathan T, Robinson SJ, McCallum IJD, Jones MJ, Elsayed M, Tuck L, Wayman J, Carney K, Aroori S, Hosie KB, Kimble A, Bunting DM, Hosie KB, Fawole AS, Basheer M, Dave RV, Sarveswaran J, Jones E, Kendal C, Tilston MP, Gough M, Wallace T, Singh S, Downing J, Mockford KA, Issa E, Shah N, Chauhan N, Wilson TR, Forouzanfar A, Wild JRL, Nofal E, Bunnell C, Madbak K, Rao STV, Devoto L, Siddiqi N, Khawaja Z, Hewes JC, Gould L, Chambers A, Rodriguez DU, Sen G, Robinson S, Carney K, Bartlett F, Rae DM, Stevenson TEJ, Sarvananthan K, Dwerryhouse SJ, Higgs SM, Old OJ, Hardy TJ, Shah R, Hornby ST, Keogh K, Frank L, Al-Akash M, Upchurch EA, Frame RJ, Hughes M, Jelley C, Weaver S, Roy S, Sillo TO, Galanopoulos G, Cuming T, Cunha P, Tayeh S, Kaptanis S, Heshaishi M, Eisawi A, Abayomi M, Ngu WS, Fleming K, Bajwa DS, Chitre V, Aryal K, Ferris P, Silva M, Lammy S, Mohamed S, Khawaja A, Hussain A, Ghazanfar MA, Bellini MI, Ebdewi H, Elshaer M, Gravante G, Drake B, Ogedegbe A, Mukherjee D, Arhi C, Giwa L, Iqet al., 2019, Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy, 20th Annual Scientific Meeting of the Association-of-Upper-Gastrointestinal-Surgeons-of-Great-Britain-and-Ireland (AUGIS), Publisher: SPRINGER, Pages: 110-121, ISSN: 0930-2794

Conference paper

Griffiths EA, Hodson J, Vohra RS, Marriott P, Katbeh T, Zino S, Nassar AHM, Vohra RS, Kirkham AJ, Pasquali S, Marriott P, Johnstone M, Spreadborough P, Alderson D, Griffiths EA, Fenwick S, Elmasry M, Nunes QM, Kennedy D, Khan RB, Khan MAS, Magee CJ, Jones SM, Mason D, Parappally CP, Mathur P, Saunders M, Jamel S, Ul Haque S, Zafar S, Shiwani MH, Samuel N, Dar F, Jackson A, Lovett B, Dindyal S, Winter H, Fletcher T, Rahman S, Wheatley K, Nieto T, Ayaani S, Youssef H, Nijjar RS, Watkin H, Naumann D, Emesih S, Sarmah PB, Lee K, Joji N, Lambert J, Heath J, Teasdale RL, Weerasinghe C, Needham PJ, Welbourn H, Forster L, Finch D, Blazeby JM, Robb W, McNair AGK, Hrycaiczuk A, Charalabopoulos A, Kadirkamanathan S, Tang C-B, Jayanthi NVG, Noor N, Dobbins B, Cockbain AJ, Nilsen-Nunn A, de Siqueira J, Pellen M, Cowley JB, Ho W-M, Miu V, White TJ, Hodgkins KA, Kinghorn A, Tutton MG, Al-Abed YA, Menzies D, Ahmad A, Reed J, Khan S, Monk D, Vitone LJ, Murtaza G, Joel A, Brennan S, Shier D, Zhang C, Yoganathan T, Robinson SJ, McCallum IJD, Jones MJ, Elsayed M, Tuck L, Wayman J, Carney K, Aroori S, Hosie KB, Kimble A, Bunting DM, Hosie KB, Fawole AS, Basheer M, Dave RV, Sarveswaran J, Jones E, Kendal C, Tilston MP, Gough M, Wallace T, Singh S, Mockford JDKA, Issa E, Shah N, Chauhan N, Wilson TR, Forouzanfar A, Wild JRL, Nofal E, Bunnell C, Madbak K, Rao STV, Devoto L, Siddiqi N, Khawaja Z, Hewes JC, Gould L, Chambers A, Rodriguez DU, Sen G, Robinson S, Carney K, Bartlett F, Rae DM, Stevenson TEJ, Sarvananthan K, Dwerryhouse SJ, Higgs SM, Old OJ, Hardy TJ, Hornby RSST, Keogh K, Frank L, Al-Akash M, Upchurch EA, Frame RJ, Hughes M, Jelley C, Weaver S, Roy S, Sillo TO, Galanopoulos G, Cuming T, Cunha P, Tayeh S, Kaptanis S, Heshaishi M, Eisawi A, Abayomi M, Ngu WS, Fleming K, Bajwa DS, Chitre V, Aryal K, Ferris P, Silva M, Mohamed SLS, Khawaja A, Hussain A, Ghazanfar MA, Bellini MI, Ebdewi H, Elshaer M, Gravante G, Drake B, Ogedegbe A, Mukherjee D, Arhi C, Iqbal LGN, Watson NF, Aggarwalet al., 2019, Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy (vol 33, pg 110, 2019), SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 33, Pages: 122-125, ISSN: 0930-2794

Journal article

Arhi CS, Bottle A, Burns EM, Clarke JM, Aylin P, Ziprin P, Darzi Aet al., 2018, Comparison of cancer diagnosis recording between the Clinical Practice Research Datalink, Cancer Registry and Hospital Episodes Statistics, Cancer Epidemiology, Vol: 57, Pages: 148-157, ISSN: 0361-090X

IntroductionThe Clinical Practice Research Datalink (CPRD) is a large electronic dataset of primary care medical records. For the purpose of epidemiological studies, it is necessary to ensure accuracy and completeness of cancer diagnoses in CPRD.MethodCases included had a colorectal, oesophagogastric (OG), breast, prostate or lung cancer diagnosis recorded in a least one of CPRD, Cancer Registry (CR) or Hospital Episodes Statistics(HES) between 2000 and 2013. Agreement in diagnosis between the datasets, difference in dates, survival at one and five-years, and whether patient characteristics differed according to the dataset or the timing of diagnosis were investigated.Results116,769 patients were included. For each cancer, approximately 10% of cases identified from CPRD or HES were not confirmed in the CR. 25.5% colorectal, 26.0% OG, 8.9% breast, 32.0% lung and 18.6% prostate cases identified from the CR were missing in CPRD. The diagnosis date was recorded later in CPRD compared with CR for each cancer, ranging from 81.1% for prostate to 59.6% for colorectal, especially if the diagnosis was an emergency. Compared with the CR and HES, the adjusted risk of a missing diagnosis in CPRD was significantly higher if the patient was older, had more co-morbidities or was diagnosed as an emergency. Survival at one and five-years was highest for CPRD.ConclusionPatient demographics and the route of diagnosis impact the accuracy of cancer diagnosis in CPRD. Although CPRD provides invaluable primary care data, patients should ideally be identified from the CR to reduce bias.

Journal article

Arhi C, Ziprin P, Bottle A, Burns E, Aylin P, Darzi Aet al., 2018, Young colorectal cancer patients experience referral delays in primary care leading to emergency diagnoses, National-Cancer-Research-Institute (NCRI) Cancer Conference, Publisher: NATURE PUBLISHING GROUP, Pages: 4-4, ISSN: 0007-0920

Conference paper

Arhi C, Burns E, Bottle A, Bouras G, Aylin P, Ziprin P, Darzi Aet al., 2018, Delays in primary care are associated with a late stage and worse prognosis for colorectal cancer patients: A population based study, National-Cancer-Research-Institute (NCRI) Cancer Conference, Publisher: NATURE PUBLISHING GROUP, Pages: 4-4, ISSN: 0007-0920

Conference paper

Arhi C, Moussa O, Aylin P, Darzi A, Purkayastha S, Ziprin Pet al., 2018, SYMPTOM AT PRESENATION FOR OBESITY PATIENTS WITH COLORECTAL CANCER, 23rd World Congress of the International-Federation-for-the-Surgery-of-Obesity-and-Metabolic-Disorders (IFSO), Publisher: SPRINGER, Pages: 329-329, ISSN: 0960-8923

Conference paper

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