2017

Two decades of coeliac disease in a district general hospital in England: What has changed? (2017)

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Type of publication:
Conference abstract

Author(s):
*Singh R.; *Ayub N.

Citation:
Archives of Disease in Childhood; May 2017; vol. 102, Suppl. 1

Abstract:
Aim To determine the changes in clinical presentation of Coeliac Disease in children aged less than 16 years over a period of 20 years (January 1996 to December 2015) at a DGH in England Methods A retrospective case study of the clinical presentation of biopsy-proven Coeliac disease in children, at a DGH over a period of 20 years divided into four equal periods (1996-2000, 2001-2005, 2006-2010 and 2011-2015). Relevant information was extracted and input into an Excel database by a single researcher for further analysis. Results Coeliac Disease was diagnosed in 114 children over the study period. Twelve children were excluded from final analysis. These comprised of 05 children with insufficient information and 07 children with Insulin-Dependent Diabetes Mellitus( IDDM) diagnosed with Coeliac Disease as a result of their annual screening investigations. Twenty (20) new cases of Coeliac disease were identified during each of the study periods 1996-2000 and 2001-2005. This increased to 31 cases during the study periods of 2006-2010 and 2011-2015. Although 85% of cases were diagnosed under the age of 12 years, there was a trend towards diagnosis at an older age and increasing female representation. Anaemia (53%) and diarrhoea (49%) were the commonest and most consistent symptoms. Constipation (10%) occurred in a significant minority. However, recurrent abdominal pain (46%) was not only a major symptom after the age of 3 years but increasingly likely from 2006 onwards with 71% affected in 2011-2015. Abdominal distension (24%) remained relatively unchanged while faltering growth (27%) and small stature (8%) showed a decreasing trend. Vomiting (17%) was more likely in children under the age of 4 years. Conclusion Although Coeliac Disease is being diagnosed more frequently, there is a trend towards diagnosis at an older age with increasing female representation. Iron deficiency anaemia and diarrhoea have remained unchanged as the commonest symptoms but recurrent abdominal pain is a significant symptom, especially in the older child. Constipation is found in a significant minority but both faltering growth and small stature show a decreasing trend.

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Gefitinib and EGFR gene copy number aberrations in esophageal cancer (2017)

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Type of publication:
Conference abstract

Author(s):
Petty R.D.; Dahle-Smith A.; Stevenson D.A.J.; Osborne A.; Massie D.; Clark C.; Miedzybrodzka Z.; Murray G.I.; Dutton S.J.; Roberts C.; Chong I.Y.; Mansoor W.; Thompson J.; Harrison M.; *Chatterjee A.; Falk S.J.; Elyan S.; Garcia-Alonso A.; Fyfe D.W.; Wadsley J.; Chau I; Ferry D.R.; Miedzybrodzka Z.

Citation:
Journal of Clinical Oncology; Jul 2017; vol. 35 (no. 20); p. 2279-2287

Abstract:
Purpose The Cancer Esophagus Gefitinib trial demonstrated improved progression-free survival with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib relative to placebo in patients with advanced esophageal cancer who had disease progression after chemotherapy. Rapid and durable responses were observed in a minority of patients. We hypothesized that genetic aberration of the EGFR pathway would identify patients benefitting from gefitinib. Methods A prespecified, blinded molecular analysis of Cancer Esophagus Gefitinib trial tumors was conducted to compare efficacy of gefitinib with that of placebo according to EGFR copy number gain (CNG) and EGFR, KRAS, BRAF, and PIK3CA mutation status. EGFR CNG was determined by fluorescent in situ hybridization (FISH) using prespecified criteria and EGFR FISH-positive status was defined as high polysomy or amplification. Results Biomarker data were available for 340 patients. In EGFR FISH-positive tumors (20.2%), overall survival was improved with gefitinib compared with placebo (hazard ratio [HR] for death, 0.59; 95% CI, 0.35 to 1.00; P = .05). In EGFR FISH-negative tumors, there was no difference in overall survival with gefitinib compared with placebo (HR for death, 0.90; 95% CI, 0.69 to 1.18; P = .46). Patients with EGFR amplification (7.2%) gained greatest benefit from gefitinib (HR for death, 0.21; 95% CI, 0.07 to 0.64; P = .006). There was no difference in overall survival for gefitinib versus placebo for patients with EGFR, KRAS, BRAF, and PIK3CA mutations, or for any mutation versus none. Conclusion EGFR CNG assessed by FISH appears to identify a subgroup of patients with esophageal cancer who may benefit from gefitinib as a secondline treatment. Results of this study suggest that anti- EGFR therapies should be investigated in prospective clinical trials in different settings in EGFR FISH-positive and, in particular, EGFR-amplified esophageal cancer.

VIPoma: A rare cause of life threatening diarrhoea (2017)

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Type of publication:
Conference abstract

Author(s):
*Bevis M.

Citation:
Anaesthesia; Jul 2017; vol. 72 ; p. 30

Abstract:
VIPomas are rare neuroendocrine tumours that secrete excessive vasoactive intestinal peptide causing refractory diarrhoea, hypokalaemia and metabolic acidosis. This case describes the difficulties in diagnosing a rare cause of diarrhoea on the ITU. A 76-year-old male, with a background of type 2 diabetes, presented to hospital with a 3-day history of confusion, muscle weakness, lethargy and profuse diarrhoea. The patient had been having diarrhoea for two months but colonoscopy was unremarkable. On examination the patient was dehydrated and had a heart rate of 110 min-1, otherwise no abnormality was found. Blood tests showed metabolic acidosis (pH 7.17, base excess -15.4 mmol.L-1, bicarbonate 12.9 mmol.L-1) and severe hypokalaemia (K+ 1.3 mmol.L-1). He was admitted to ITU for aggressive fluid resuscitation and electrolyte correction. The patient had large volumes of watery diarrhoea (8 l every 24 h) which was unresponsive to loperamide and codeine. Stool cultures were negative. CT of the abdomen revealed a solitary focal liver lesion and a possible focal abnormality in the pancreatic tail. A gut hormone profile was sent for analysis. Although the diagnosis was unclear, the patient was started on octreotide which slowed the diarrhoea after a few days. Histology of the liver lesion confirmed neuroendocrine tumour, and both vasoactive intestinal peptide and pancreatic polypeptide were raised in the blood, therefore a diagnosis of pancreatic VIPoma was made. Discussion VIPomas are very rare, affecting less than 1 in 1,000,000 patients each year in the UK [1]. The cause of most VIPomas is unknown; however multiple endocrine neoplasia type 1 is a risk factor [1]. VIPomas are slow growing and are often malignant. Patients often develop symptoms slowly and may have diarrhoea for years before a diagnosis is made. The diarrhoea is large-volume, has a dilute tea appearance, and is not affected by fasting. Tests for VIPoma include serum vasoactive intestinal peptide (however this needs to be processed at a specialist centre), CT, MRI and octreoscan [1, 2]. Initial treatment focuses on fluid and electrolyte replacement as untreated severe electrolyte imbalance can lead to arrhythmias, cardiovascular collapse and death. Somatostatin analogues, such as octreotide, help control the symptoms of diarrhoea; however, the main treatment is surgical [2]. In conclusion, although VIPomas are rare they should be suspected in patients that present with profuse chronic diarrhoea with no obvious cause.

Abiraterone for prostate cancer not previously treated with hormone therapy (2017)

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Type of publication:
Randomised controlled trial

Author(s):
James, Nicholas D. Ph.D.; de Bono, Johann S. Ph.D.; Spears, Melissa R. M.Sc.; Clarke, Noel W. Ch.M.; Mason, Malcolm D. F.R.C.R.; Dearnaley, David P. F.R.C.R.; Ritchie, Alastair W.S. M.D.; Amos, Claire L. Ph.D.; Gilson, Clare M.R.C.P.; Jones, Rob J. M.B., Ch.B.; Matheson, David Ph.D.; Millman, Robin; Attard, Gerhardt M.D.; Chowdhury, Simon Ph.D.; Cross, William R. F.R.C.S.; Gillessen, Silke M.D.; Parker, Christopher C. M.D.; Russell, Martin J. F.R.C.R.; Berthold, Dominik R. M.D.; Brawley, Chris M.Sc.; Adab, Fawzi F.R.C.R.; Aung, San M.R.C.P.; Birtle, Alison J. F.R.C.R.; Bowen, Jo F.R.C.R.; Brock, Susannah F.R.C.R.; Chakraborti, Prabir F.R.C.R.; Ferguson, Catherine F.R.C.R.; Gale, Joanna B.M.; Gray, Emma F.R.C.R.; Hingorani, Mohan Ph.D.; Hoskin, Peter J. F.R.C.R.; Lester, Jason F. F.R.C.R.; Malik, Zafar I. F.R.C.R.; McKinna, Fiona F.R.C.R.; McPhail, Neil F.R.C.R.; Money-Kyrle, Julian F.R.C.R.; O'Sullivan, Joe Ph.D.; Parikh, Omi F.R.C.R.; Protheroe, Andrew F.R.C.P.; Robinson, Angus F.R.C.R.; *Srihari, Narayanan N. F.R.C.R.; Thomas, Carys M.R.C.P.; Wagstaff, John Ch.B.; Wylie, James F.R.C.R.; Zarkar, Anjali F.R.C.R.; Parmar, Mahesh K.B. D.Phil.; Sydes, Matthew R. M.Sc.; the STAMPEDE Investigators

Citation:
New England Journal of Medicine; Jul 2017; vol. 377 (no. 4); p. 338-351

Abstract:
BACKGROUND: Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer. We assessed the effect of this combination in men starting long-term androgen-deprivation therapy (ADT), using a multigroup, multistage trial design. METHODS: We randomly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate (1000 mg daily) and prednisolone (5 mg daily) (combination therapy). Local radiotherapy was mandated for patients with node-negative, nonmetastatic disease and encouraged for those with positive nodes. For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease, treatment continued until radiologic, clinical, or prostatespecific
antigen (PSA) progression; otherwise, treatment was to continue for 2 years or until any type of progression, whichever came first. The primary outcome measure was overall survival. The intermediate primary outcome was failure-free survival (treatment failure was defined as radiologic, clinical, or PSA progression or death from prostate cancer). RESULTS: A total of 1917 patients underwent randomization from November 2011 through January 2014. The median age was 67 years, and the median PSA level was 53 ng per milliliter. A total of 52% of the patients had metastatic disease, 20% had node-positive or node-indeterminate nonmetastatic disease, and 28% had node-negative, nonmetastatic disease; 95% had newly diagnosed disease. The median follow-up was 40 months. There were 184 deaths in the combination group as compared with 262 in the ADT-alone group (hazard ratio, 0.63; 95% confidence interval [CI], 0.52 to 0.76; P<0.001); the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease. There were 248 treatment-failure events in the combination group as compared with 535 in the ADT-alone group (hazard ratio, 0.29; 95% CI, 0.25 to 0.34; P<0.001); the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease. Grade 3 to 5 adverse events occurred in 47% of the patients in the combination group (with nine grade 5 events) and in 33% of the patients in the ADT-alone group (with three grade 5 events). CONCLUSIONS: Among men with locally advanced or metastatic prostate cancer, ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure-free survival than ADT alone. (Funded by Cancer Research U.K. and others; STAMPEDE ClinicalTrials.gov number, NCT00268476, and Current Controlled Trials number, ISRCTN78818544.)

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Medical student's perceptions of forensic pathology (2017)

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Type of publication:
Conference abstract

Author(s):
*Iles K.L.

Citation:
Journal of Pathology; Mar 2017; vol. 241, Supplement 1, Page S6

Abstract:
Forensic pathology is an important sub-specialty of pathology which requires a variety skills that are relevant and transferable to many other areas of medicine. Despite this, it does not feature in the undergraduate curriculum of most medical schools meaning that knowledge specific to forensic medicine such as wound terminology may not be taught. A lack of formal teaching and an ever increasing dramatised presence of the  specialty in the media may lead to a misrepresentation of the role of forensic pathologists. As a result this study  aimed to examine final year medical student's perceptions of the role of the forensic pathologists and their confidence in knowledge of important aspects of forensic medicine. An online survey was developed to assess these areas which was distributed to final year medical students at a UK institution via email. From the  respondents, the overall perception of the job role was correct, however there appeared to be some misconceptions regarding the role of a forensic scientist, or crime scene investigator in comparison to a forensic  pathologist. The study also highlighted that students did not feel confident in differentiating between wound  types using the correct terminology. This is important as injuries are common presentations in many clinical areas, and incorrect terminology may have mediocolegal implications. This study has highlighted the need for clarification of the job role of the forensic pathologist. There is a greater need for forensic pathology in the undergraduate curriculum, which should focus on description and terminology of wounds and injuries.

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Clinical risk factors predicting genital fungal infections with sodium–glucose cotransporter 2 inhibitor treatment: The ABCD nationwide dapagliflozin audit (2017)

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Type of publication:
Journal article

Author(s):
Ken Yan Thong, Mahender Yadagiri, Dennis Joseph Barnes, *David Stuart Morris, Tahseen Ahmad Chowdhury, Ling Ling Chuah, Anthony Michael Robinson, Stephen Charles Bain, Karen Ann Adamson, Robert Elford John Ryder, ABCD Nationwide Dapagliflozin Audit contributors

Citation:
Primary Care Diabetes 2017 [published online 29th June 2017]

Abstract:
Introduction

Treatment of type 2 diabetes with sodium–glucose cotransporter 2 (SGLT2) inhibitors may result in genital fungal infections. We investigated possible risk factors for developing such infections among patients treated with the SGLT2 inhibitor dapagliflozin.

Methods

The Association of British Clinical Diabetologists (ABCD) collected data on patients treated with dapagliflozin in routine clinical practice from 59 diabetes centres. We assessed possible associations of patient’s age, diabetes duration, body mass index, glycated haemoglobin, renal function, patient sex, ethnicity and prior genital fungal infection, urinary tract infection, urinary incontinence or nocturia, with the occurrence of ≥1 genital fungal infection within 26 weeks of treatment.

Results

1049 out of 1116 patients (476 women, 573 men) were analysed. Baseline characteristics were, mean ± SD, age 56.7 ± 10.2 years, BMI 35.5 ± 6.9 kg/m2 and HbA1c 9.4 ± 1.5%. Only patient sex (13.2% women vs 3.3% men) and prior history of genital fungal infection (21.6% vs 7.3%) were found to be associated with occurrence of genital fungal infections after dapagliflozin treatment, adjusted OR 4.22 [95%CI 2.48,7.19], P < 0.001 and adjusted OR 2.41 [95% CI 1.04,5.57], P = 0.039, respectively.

Conclusion

Women and patients with previous genital fungal infections had higher risks of developing genital fungal infections with dapagliflozin treatment.

Lack of risk factors predicting the development of genital mycotic infections among patients treated with dapagliflozin: the ABCD Nationwide Dapagliflozin Audit (2017)

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Type of publication:
Poster presentation

Author(s):
Thong KY, Yadagiri M, Tong P, Barnes D, *Morris D et al.

Citation:
American Diabetes Association annual meeting June 2017, San Diego.

Abstract:

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Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): a multicentre, phase 3, open-label, randomised, controlled trial (2017)

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Type of publication:
Randomised controlled trial

Author(s):
David Cameron, James P Morden, Peter Canney, Galina Velikova, Robert Coleman, John Bartlett, *Rajiv Agrawal, Jane Banerji, Gianfilippo Bertelli, David Bloomfield, A Murray Brunt, Helena Earl, Paul Ellis, Claire Gaunt, Alexa Gillman, Nicholas Hearfield, Robert Laing, Nicholas Murray, Niki Couper, Robert C Stein, Mark Verrill, Andrew Wardley, Peter Barrett-Lee, Judith M Bliss, on behalf of the TACT2 Investigators

Citation:
Lancet Oncology; Jul 2017; vol. 18 (no. 7); p. 929-945

Abstract:
Adjuvant chemotherapy for early breast cancer has improved outcomes but causes toxicity. The UK TACT2 trial used a 2 × 2 factorial design to test two hypotheses: whether use of accelerated epirubicin would improve time to tumour recurrence (TTR); and whether use of oral capecitabine instead of cyclophosphamide would be non-inferior in terms of patients’ outcomes and would improve toxicity, quality of life, or both.

Link to full-text [Open access]

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