2017

Border-line coeliac serology in children - Outcome and correlation with histology (2017)

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Type of publication:
Conference abstract

Author(s):
*Fox H.; Cheng J.H.; *Singh R.; *Ayub N.

Citation:
Journal of Pediatric Gastroenterology and Nutrition; Apr 2017; vol. 64 ; Supplement 1, p. 18

Abstract:
Objectives and study: Coeliac disease is an immune-mediated condition that affects the lining of the intestine when exposed to gluten. The British Society of Paediatric Gastroenterology, Hepatology and Nutrition guideline on Coeliac Disease (2013) recommends that patients with Tissue Transglutaminase antibodies (TTG) less than 10 times normal should undergo duodenal biopsy to confirm a diagnosis of Coeliac Disease. However, there is a paucity of data on how often this correlates with a final diagnosis of Coeliac disease. This study is to measure the sensitivity of borderline Tissue Transglutaminase Antibody (TTG) levels (greater than normal but less than 10 times of normal values) in diagnosing Coeliac disease. Methods: The Study Population was children aged 1-16 years with TTG levels less than 10 times of normal seen at The Shrewsbury & Telford Hospitals NHS Trust. The study period was from January 2010 to September 2016. Patients were identified from the biochemistry database. Relevant data including the clinical symptoms, TTG levels, IgA levels, HLA status and histology results were collected using the hospital data base. The histology results were classified according to the Modified Marsh Criteria. Results: A total of 52 patients had TTG levels between 2 – 19.9 U/ml which is less than ten times of the normal range used by our biochemistry laboratory. The median age of presentation was 10 years while the median TTG value was 4.2U/ml. 10 patients with Type 1 Diabetes Mellitus were detected to have border-line positive coeliac serology on routine testing. Thirty-nine patients underwent endoscopy with duodenal biopsies. Ten patients had neither endoscopy nor HLA testing performed because of various reasons including parental choice, symptom resolution prior to endoscopy while still on a normal diet, or repeat TTG levels within the normal range. 29 children (56%) out of the cohort of 52 had histological changes consistent with coeliac disease and were diagnosed as such. Seven of these (24%) had Grade 1 Marsh criteria, 3 children (10%) had Grade 2 Marsh criteria and 19 (66%) had Grade 3 Marsh criteria. There was no significant difference in symptomatology between the children who were diagnosed with coeliac disease and those with normal biopsies, apart from recurrent abdominal pain which was commoner in coeliac disease. Conclusion: 56% of children with borderline TTG levels were diagnosed with coeliac disease based on biopsy changes. Symptomatology was of poor discriminatory value apart from recurrent abdominal pain which was commoner in coeliac disease. Children with border-line positive coeliac serology should have duodenal biopsies to confirm a diagnosis of coeliac disease.

Link to more details or full-text: http://pdfs.journals.lww.com/jpgn/2017/04001/50th_ESPGHAN_Annual_Meeting_.1.pdf

Addition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial (2017)

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Type of publication:
Randomised controlled trial

Author(s):
Earl, Helena M; Hiller, Louise; Howard, Helen C; Dunn, Janet A; Young, Jennie; Bowden, Sarah J; McDermaid, Michelle; Waterhouse, Anna K; Wilson, Gregory; *Agrawal, Rajiv; O'Reilly, Susan; Bowman, Angela; Ritchie, Diana M; Goodman, Andrew; Hickish, Tamas; McAdam, Karen; Cameron, David; Dodwell, David; Rea, Daniel W; Caldas, Carlos; Provenzano, Elena; Abraham, Jean E; Canney, Peter; Crown, John P; Kennedy, M John; Coleman, Robert; Leonard, Robert C; Carmichael, James A; Wardley, Andrew M; Poole, Christopher J; tAnGo trial collaborators

Citation:
The Lancet. Oncology, Volume 18, No. 6, p755–769, June 2017

Abstract:
BACKGROUND The tAnGo trial was designed to investigate the potential role of gemcitabine when added to anthracycline and taxane-containing adjuvant chemotherapy for early breast cancer. When this study was developed, gemcitabine had shown significant activity in metastatic breast cancer, and there was evidence of a favourable interaction with paclitaxel. METHOD StAnGo was an international, open-label, randomised, phase 3 superiority trial that enrolled women aged 18 years or older with newly diagnosed, early-stage breast cancer who had a definite indication for chemotherapy, any nodal status, any hormone receptor status, Eastern Cooperative Oncology Group performance status of 0-1, and adequate bone marrow, hepatic, and renal function. Women were recruited from 127 clinical centres and hospitals in the UK and Ireland, and randomly assigned (1:1) to one of two treatment regimens: epirubicin, cyclophosphamide, and paclitaxel (four cycles of 90 mg/m2 intravenously administered epirubicin and 600 mg/m2 intravenously administered cyclophosphamide on day 1 every 3 weeks, followed by four cycles of 175 mg/m2 paclitaxel as a 3 h infusion on day 1 every 3 weeks) or epirubicin, cyclophosphamide, and paclitaxel plus gemcitabine (the same chemotherapy regimen as
the other group, with the addition of 1250 mg/m2 gemcitabine to the paclitaxel cycles, administered intravenously as a 0·5 h infusion on days 1 and 8 every 3 weeks). Patients were randomly assigned by a central computerised deterministic minimisation procedure, with stratification by country, age, radiotherapy intent, nodal status, and oestrogen receptor and HER-2 status. The primary endpoint was disease-free survival and the trial aimed to detect 5% differences in 5-year disease-free survival between the treatment groups. Recruitment completed in 2004 and this is the final, intention-to-treat analysis. This trial is registered with EudraCT (2004-002927-41), ISRCTN (51146252), and ClinicalTrials.gov (NCT00039546).FINDINGS Between Aug 22, 2001, and Nov 26, 2004, 3152 patients were enrolled and randomly assigned to epirubicin, cyclophosphamide, paclitaxel, and gemcitabine (gemcitabine group; n=1576) or to epirubicin, cyclophosphamide, and paclitaxel (control group; n=1576). 11 patients (six in the gemcitabine group and five in the control group) were ineligible because of pre-existing metastases and were therefore excluded from the analysis. At this protocol-specified final analysis (median follow-up 10 years [IQR 10-10]), 1087 disease-free survival events and 914 deaths had occurred. Disease-free survival did not differ significantly between the treatment groups at 10 years (65% [63-68] in the gemcitabine group vs 65% [62-67] in the control group), and median disease-free survival was not reached (adjusted hazard ratio 0·97 [95% CI 0·86-1·10], p=0·64). Toxicity, dose intensity, and a detailed safety substudy showed both regimens to be safe, deliverable, and tolerable. Grade 3 and 4 toxicities were reported at expected levels in both groups. The most common were neutropenia (527 [34%] of 1565 patients in the gemcitabine group vs 412 [26%] of 1567 in the control group), myalgia and arthralgia (207 [13%] vs 186 [12%]), fatigue (207 [13%] vs 152 [10%]), infection (202 [13%] vs 141 [9%]), vomiting (143 [9%] vs 108 [7%]), and nausea (132 [8%] vs 102 [7%]).INTERPRETATION The addition of gemcitabine to anthracycline and taxanebased adjuvant chemotherapy at this dose and schedule confers no therapeutic advantage in terms of disease free survival in early breast cancer, although it can cause increased toxicity. Therefore, gemcitabine has not been added to standard adjuvant chemotherapy in breast cancer for any subgroup.FUNDING Cancer Research UK core funding for Clinical Trials Unit at the University of Birmingham, Eli Lilly, Bristol-Myers Squibb, and Pfizer.

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Gefitinib and EGFR Gene Copy Number Aberrations in Esophageal Cancer (2017)

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Type of publication:
Journal article

Author(s):
Petty, Russell D; Dahle-Smith, Asa; Stevenson, David A J; Osborne, Aileen; Massie, Doreen; Clark, Caroline; Murray, Graeme I; Dutton, Susan J; Roberts, Corran; Chong, Irene Y; Mansoor, Wasat; Thompson, Joyce; Harrison, Mark; *Chatterjee, Anirban; Falk, Stephen J; Elyan, Sean; Garcia-Alonso, Angel; Fyfe, David Walter; Wadsley, Jonathan; Chau, Ian; Ferry, David R; Miedzybrodzka, Zosia

Citation:
Journal of Clinical Oncology : official journal of the American Society of Clinical Oncology; July 10;35(20):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.

Managing problems with medications for type 2 diabetes (2017)

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Type of publication:
Journal article

Author(s):
*Morris, David

Citation:
Practice Nursing; Apr 2017; vol. 28 (no. 4); p. 148-152

Abstract:
The most recent National Institue for Health and Care Excellence (NICE) and European Association for the Study of Diabetes guidelines on management of type 2 diabetes (NICE, 2015; Inzucchi et al, 2015) emphasise the need to individualise glycemic targets and treatments, and highlight that working in partnership with the person concerned should be central to decision making. In addition to assessing the likely efficacy of a treatment, consideration should be given to tolerability and safety. The possibility of medication problems and side- effects needs to be anticipated and if a medication is chosen then a means for identifying and dealing with these should be considered in advance. Most adverse drug reactions are predictable and dose- dependent, the exception being allergic reactions. This article will consider problems arising with medications used for type 2 diabetes, excluding insulin.

Overview of diabetes... This reflective account is based on NS852 Mayo P (2016) An overview of diabetes (2017)

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Type of publication:
Journal article

Author(s):
*Ponomarenko-Jones, Rosalind

Citation:
Nursing Standard; May 2017; vol. 31 (no. 36); p. 64-65

Abstract:
The article presents a reflective account of how a continuing professional development (CPD) article improved Rosalind Ponomarenko-Jones's knowledge of the pathophysiology, symptoms and diagnosis of diabetes. Topics discussed include the nature of the CPD activity, lesson learned from the CPD activity and how she changed or improved her practice.

Does CIN2 Have the Same Aggressive Potential As CIN3? A Secondary Analysis of High-Grade Cytology Recurrence in Women Treated with Cold-Coagulation Cervical Treatment (2017)

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Type of publication:
Journal article

Author(s):
*Papoutsis D.; *Underwood M .; *Parry-Smith W.; *Panikkar J.

Citation:
Geburtshilfe und Frauenheilkunde; Mar 2017; vol. 77 (no. 3); p. 284-289

Abstract:
Introduction To determine whether women with CIN2 versus CIN3 on pretreatment cervical punch biopsy have less high-grade cytology recurrence following cold-coagulation cervical treatment. Materials and Methods This was a retrospective study of women having had cold coagulation between 2001-2011 in our colposcopy unit. Women with previous cervical treatment were excluded. Results We identified 402 women with 260 (64.7?%) cases of CIN2 and 142 (35.3?%) cases of CIN3 on pretreatment cervical punch biopsy. In the total sample, the mean age of women was 27.5 years (SD = 4.9), 75.1?% were nulliparous and 36.6?% were smokers. Referral cytology and pretreatment colposcopic appearance were high-grade in 62.7?% and 57.1?%. The mean follow-up period was 2.8 years (SD = 2.1). Women with CIN2 on pretreatment cervical biopsy when compared to those with CIN3 had less frequently high-grade referral cytology and high-grade pretreatment colposcopic appearances, and had less pretreatment cervical biopsies taken. During the follow-up period, women with CIN2 on pretreatment cervical biopsy had less high-grade cytology recurrence when compared to those women with CIN3 (1.9 vs. 5.6?%, p = 0.046). Multiple stepwise Cox regression analysis showed that women with CIN3 on pretreatment cervical biopsy had 3.21 times greater hazard for high-grade cytology recurrence (HR = 3.21, 95?% CI: 1.05-9.89; p = 0.041) in comparison with CIN2 cases. Conclusion We found that women with CIN2 on pretreatment cervical punch biopsy had less high-grade cytology recurrence following cold-coagulation treatment in comparison to those with CIN3. This finding lends support to the theory that CIN2 even though a high-grade abnormality might not have the same aggressive potential as CIN3.

Comparing quality of life outcomes between Laparoscopic Sleeve Gastrectomy and Laparoscopic RouxY Gastric Bypass using the RAND36 questionnaire (2017)

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Type of publication:
Journal article

Author(s):
*Macano C.A.W.; *Brookes A.; *Lafaurie G.; *Riera M.; Nyasavajjala S.M.

Citation:
International Journal of Surgery; Jun 2017; vol. 42 ; p. 138-142

Abstract:
Background Obesity surgery is an effective treatment to improve the health of patients. There is a lack of data regarding weight loss surgery outcomes and effects on Quality of Life (QoL). This study aims to compare changes in QoL following either Laparoscopic Sleeve Gastrectomy (LSG) or Laparoscopic Roux-en-Y Gastric Bypass (LRYGB). Methods SF36 questionnaires were mailed to all LSG and LRYGB patients who underwent surgery in 2013. Demographic data was obtained from hospital records. Statistical analysis was undertaken using Stats direct. Results 158 patients were sent postal questionnaires. 60 were returned (38%). 41 were women, 16 LSG, 44 LRYGB, mean age 52 years, mean BMI pre-surgery 41.0. Both procedures yielded similar weight loss over 2 year follow up (p = 0.01), and similar improvements in obesity related co-morbidities. These procedures yielded significant improvements in all QoL scales and domains other than the emotional role limitations scale following sleeve gastrectomy. Conclusion Bariatric surgery has been shown to improve a patient's QoL. More research is needed to explain the reasons why there was a difference between Sleeve and Bypass procedures in emotional changes to patients.

Congenital talipes equinovarus and congenital vertical talus secondary to sacral agenesis (2017)

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Type of publication:
Journal article

Author(s):
Bray J.J.H.; Brown R.; *Crosswell S.

Citation:
BMJ Case Reports; 2017

Abstract:
Sacral agenesis is a rare congenital defect which is associated with foot deformities such as congenital talipes equinovarus (CTEV) and less commonly congenital vertical talus (CVT). We report a 3-year-old Caucasian girl who was born with right CTEV and left CVT secondary to sacral agenesis. Her right foot was managed with a Ponseti casting method at 2 weeks, followed by an Achilles tenotomy at 4 months. The left foot was initially managed with a nocturnal dorsi-flexion splint. Both feet remained resistant and received open foot surgery at 10 months producing plantigrade feet with neutral hindfeet. At 19 months, she failed to achieve developmental milestones and examinations revealed abnormal lower limb reflexes. A full body MRI was performed which identified the sacral agenesis. We advocate early MRI of the spine to screen for spinal defects when presented with resistant foot deformities, especially when bilateral.

Link to more details or full-text: http://casereports.bmj.com/content/2017/bcr-2017-219786.abstract [NHS OpenAthens account required]

Can trainees design and deliver a national audit of epistaxis management? A pilot of a secure web-based audit tool and research trainee collaboratives (2017)

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Type of publication:
Journal article

Author(s):
Mehta N.; Williams R.J.; Smith M.E.; Hall A.; Hardman J.C.; Cheung L.; Ellis M.P.; *Fussey J.M.; Lakhani R.; Hopkins C.; McLaren O.; Nankivell P.C.; Sharma N.; Yeung W.; Carrie S.

Citation:
Journal of Laryngology and Otology; Jun 2017; vol. 131 (no. 6); p. 518-522

Abstract:
Objective: To investigate the feasibility of a national audit of epistaxis management led and delivered by a multiregion trainee collaborative using a web-based interface to capture patient data. Methods: Six trainee collaboratives across England nominated one site each and worked together to carry out this pilot. An encrypted data capture tool was adapted and installed within the infrastructure of a university secure server. Site-lead feedback was assessed through questionnaires. Results: Sixty-three patients with epistaxis were admitted over a two-week period. Site leads reported an average of 5 minutes to complete questionnaires and described the tool as easy to use. Data quality was high, with little missing data. Site-lead feedback showed high satisfaction ratings for the project (mean, 4.83 out of 5). Conclusion: This pilot showed that trainee collaboratives can work together to deliver an audit using an encrypted data capture tool cost-effectively, whilst maintaining the highest levels of data quality.