2018

Biomarkers and Pharmacogenomics in Kidney Transplantation (2018)

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Type of publication:
Journal article

Author(s):
Crowley, L E; *Mekki, M; *Chand, S

Citation:
Molecular Diagnosis and Therapy; Oct 2018; vol. 22 (no. 5); p. 537-550

Abstract:
This review is focused on present and future biomarkers, along with pharmacogenomics used in clinical practice for kidney transplantation. It aims to highlight biomarkers that could potentially be used to improve kidney transplant early and long-term graft survival, but also potentially patient co-morbidity. Future directions for improving outcomes are discussed, which include immune tolerance and personalising immunosuppression regimens.

Over 70s breast cancer management: A single institute experience (2018)

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Type of publication:
Conference abstract

Author(s):
Dube M.; Talaat A.; *Rastall S.; *Przyczyna A.; *Usman T.

Citation:
European Journal of Surgical Oncology; Jun 2018; vol. 44 (no. 6); p. 898

Abstract:
Introduction: With increasing life expectancy, awareness and improved referral system more women over the age of 70 (70+) are diagnosed with breast cancer. NICE guidelines recommended standard treatment of breast cancer irrespective of age and decision rather based on co-morbidities and frailty. To review our compliance with NICE guidelines we audited management of breast cancer of 70+ women over a period of five years. Methods: Retrospective case note analysis of 833 70+ women with breast cancer diagnosed from April 2010 to March 2015. Breast MDT recommendations, reason for choice of treatment, co-morbidities and performance status recorded. Results: Out of 2729 breast cancer diagnosis 30% (833) were 70+. The median age was 78. Surgery was the treatment of choice in all five years and is represented by 60% in year one, four and five; 55% in year two; 45% in year three. Primary endocrine treatment was the next treatment of choice among 28% in year one, 23% in year two, 30% in year three, 20% in year four, and 25% in year five. Offer and acceptance adjuvant treatments have increased in year wise analysis. Conclusions: We have noticed a shift towards surgery from primary endocrine therapy in year wise analysis. There has been an increase of number of 70+ patients diagnosed with breast cancer. Inclusion of performance status had improved offer of adjuvant treatment in the last year of the study. More individualised and evidence based management recommended to offer appropriate treatment in this age group.

Revision surgery following extended latissimus dorsi flap and implant based breast reconstruction: a district general hospital experience (2018)

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Type of publication:
Conference abstract

Author(s):
Dube M.; *Sheikh H.; *Rastall S.

Citation:
European Journal of Surgical Oncology; Jun 2018; vol. 44 (no. 6); p. 902-903

Abstract:
Introduction: Extended latissimus dorsi (ELD) flap breast reconstruction has been a very well-established reconstruction modality after mastec-tomy. Although recently number of ELD flap operation has decreased due to popularity of implant based reconstruction we found rate of revisional surgery were less with ELD reconstruction. Rates of revisional surgery have been quoted between 30%-75% in the literature. After 5 years we evaluate our rates of revision surgery. Methods: Analysis of a prospectively maintained breast reconstruction database. Types of initial surgery, complications and rate of revision sur-gery after radiotherapy specifically noted. Results: Total Reconstructions: 127 Immediate Reconstructions: 90 (78 ELD flap, 12 Implant only with acellular dermal matrix (ADM) Total patients who had further surgery 5 Fat grafting after ELD Flap 3 Fat grafting after implant only 1 Changeofimplant 1 *Patients with ELD reconstruction also had post-operative radiotherapy and 1 had small skin breakdown of the breast after primary surgery. Delayed Reconstructions: 37 Fat grafting after ELDflap Reconstruction 1 Symmetrisation surgery: 9 Total Patients requiring contralateral symmetry surgery 9 Augmentation mastopexy after immediate ELD 2 Mastopexy after delayed ELD 1 Reduction mastopexy after immediate ELD 4 Reduction mastopexy after delayed ELD 2 Time from primary surgery to symmetrisation or corrective surgery was between 8 months to 3 years. Conclusions: About 1.5% of patients required corrective surgery to the reconstructed or contralateral breast. High level of patient satisfaction found with ELD flap breast reconstruction than implant as only small number of patient required corrective surgery even after postoperative radiotherapy.

A phase 2b, randomized, double-blind, placebo-controlled trial of presatovir (GS-5806), a novel oral rsv fusion inhibitor, for the treatment of respiratory syncytial virus (RSV) in hospitalized adults (2018)

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Type of publication:
Conference abstract

Author(s):
Hanfelt-Goade D.; Maimon N.; Nimer A.; Riviere F.; Catherinot E.; Ison M.; Jeong S.; Walsh E.; Falsey A.R.; Gafter-Gvili A.; Nama S.; Napora P.; Chowers M.; Bergeron A.; Zeltser D.; *Moudgil H.; Limaye A.P.; Couturaud F.; Nseir W.; McKevitt M.; Porter D.; Jordan R.; Guo Y.; German P.; Watkins T.R.; Gossage D.L.; Chien J.W.

Citation:
American Journal of Respiratory and Critical Care Medicine; May 2018; vol. 197

Abstract:
RATIONALE: Presatovir has been shown to significantly reduce nasal viral load and signs and symptoms of RSV infection in a healthy human challenge study. We evaluated the safety and efficacy of presatovir in hospitalized adults infected with RSV. METHODS: RSV infected subjects with <= 5 days of symptoms were randomized (1:1) to oral presatovir 200 mg or placebo once on Day 1, in addition to standard of care. Subjects were stratified by 4 categories: no chronic airways or lung disease, chronic obstructive pulmonary disease (COPD), asthma or other chronic airways or lung disease. The primary endpoint was the time weighted average change (TWAC) in nasal RSV viral load from baseline through Day 5. Secondary endpoints included mean TWAC in patient reported outcomes (Flu-PROTM), duration of hospital stay following study drug administration and rate of unplanned medical encounters related to a respiratory illness after initial hospital discharge through Day 28. RESULTS: From May 2014 to May 2017, 189 subjects from 78 centers were enrolled. Mean (SD) duration of symptoms prior to first dose of study drug was 3 (1.2) and 3 (1.1) days for the presatovir and placebo groups respectively. Despite maintaining mean plasma levels above 4-fold paEC95 for 5 days, presatovir treatment did not reduce the TWAC in viral load or the mean number of hospitalization free days (Table). The placebo group had a greater TWAC in Flu-PROTM score and a lower rate of unplanned medical encounters after initial hospital discharge than the presatovir group. The percentage of subjects with Treatment- Emergent Adverse Events (TEAE) and >= Grade 3 TEAEs (presatovir vs. placebo) were similar in both groups [65.2% vs. 67.0%] and [6.5% vs. 8.5%] respectively. The percentage of subjects with serious adverse events was also similar [8.7% vs 13.8%]. Two COPD subjects in the presatovir group died due to worsening COPD, one on day 5 during the study period and the other on day 36 after the study period. CONCLUSIONS: Presatovir did not significantly reduce viral load or improve clinical outcomes in hospitalized adults with RSV. (Table Presented) .

Prospective validation of the rapid clinical risk prediction score in patients with pleural infection: The pleural infection longitudinal outcome study (PILOT) (2018)

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Type of publication:
Conference abstract

Author(s):
Corcoran J.P.; Dobson M.; Shaw R.; Hedley E.L.; Sabia A.; Robinson B.; Rahman N.M.; Psallidas I.; Hallifax R.J.; Gerry S.; Collins G.S.; Piccolo F.; Read C.; Koegelenberg C.F.; Saba T.; Saba J.; Daneshvar C.; Ward N.; Fairbairn I.; *Heinink R.; West A.; Stanton A.E.; Holme J.; Kastelik J.A.; Steer H.; Downer N.J.; Haris M.; Baker E.H.; Everett C.F.; Pepperell J.; Bewick T.; Yarmus L.B.; Maldonado F.; Khan B.; Hart-Thomas A.; Hands G.; Warwick G.; Munavvar M.; Guhan A.; Shahidi M.; Pogson Z.E.; Dowson L.; Bhatnagar R.; Davies H.E.; Yu L.; Maskell N.A.; Miller R.F.

Citation:
American Journal of Respiratory and Critical Care Medicine; May 2018; vol. 197

Abstract:
RATIONALE Pleural infection is increasingly common and associated with significant morbidity and mortality, with no current robust means of predicting which patients will suffer poor clinical outcomes. A validated risk score at baseline would allow high-risk patients to be identified early, and directed towards more invasive management strategies aimed at improving prognosis. METHODS The Pleural Infection Longitudinal Outcome Study (PILOT) was a prospective observational cohort study, recruiting adult patients with pleural infection from 29 centres in four countries, with patients undergoing protocolised management based on widely accepted national guidelines adapted for local practice. The study was powered to validate a previously described clinical risk prediction score (RAPID), derived and retrospectively validated using data from two large multicentre randomised trials in pleural infection (MIST1 and MIST2). The primary outcome was mortality associated with pleural infection at 3 months; secondary outcomes included mortality at 12 months, length of hospital stay, need for thoracic surgical intervention, failure of initial medical management (according to predefined criteria), and lung function impairment at 3 months. Study follow-up was for 12 months. The study was funded by the UK Medical Research Council, and registered with ClinicalTrials.gov (ISRCTN 50236700). RESULTS 551 participants were recruited between October 2013 and October 2016, and data were available in 542 (98.4%) patients. 383/542 (70.7%) were male; mean age was 58 years (SD 20). Overall mortality was 10% at 3 months (54/542) and 19% (101/542) at 12 months. Mortality increased according to RAPID score overall (Figure 1a) and 3 month mortality was closely associated with RAPID category; low-risk (RAPID score 0-2) 4/216 (1.9%, 95% CI 0.5 to 3.6), medium risk (RAPID score 3-4) 22/233 (9.4%, 95% CI 5.7 to 13.2), and high-risk (RAPID score 5- 7) 28/93 (30.1%, 95% CI 20.8 to 39.4) (Figure 1b). C-indexes (AUROC) for the prediction score at 3 months and 12 months were 0.79 (95% CI 0.73 to 0.85) and 0.77 (95% CI 0.72 to 0.82) respectively. CONCLUSIONS RAPID is a robust prediction score for mortality in adult patients with pleural infection, and should now be used to guide clinical care. Further studies are now required to assess if targeting more interventional treatment strategies in higher risk groups can reduce mortality.

Correlating chest CT radiological reporting of tree-in-bud with clinical diagnosis (2018)

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Type of publication:
Conference abstract

Author(s):
*Muthusami R.; *Makan A.; *Ahmad N.; *Srinivasan K.S.; *Moudgil H.

Citation:
American Journal of Respiratory and Critical Care Medicine; May 2018; vol. 197

Abstract:
RATIONALE Although initially describing Endobronchial Tuberculosis, the Tree-in-Bud (TIB) pattern is increasingly recognised in a wider number of conditions. Objective here was to establish how frequently this was reported and the spectrum of subsequent diagnosis. METHODS Reports relating to all Chest CT scans undertaken at our District General Hospital during 2015 were identified and those with reference to TIB further explored from electronic medical records. RESULTS 27 patients had the TIB (2.7% of total CTs) pattern reported. Average age was 72 years with 59% female. The right lung was affected (78%) more than the left (52%) along with one of the lower lobes (55%). The most common lobe affected was the RLL (41%) followed by the RML (37%) and then RUL & LLL (both 33%). 21 (78%) were seen by a Respiratory Physician. For the group as a whole, two had died from advanced cancer (1 lung cancer) and one with advanced dementia. An Infectious Aetiology was proposed in 16 (59%) with half confirmed with a positive microbiological result. 2 patients had Non-Tuberculous Mycobacteria, alongside Chronic Cavitatory Pulmonary Aspergillosis (1), ABPA (Allergic BronchoPulmonary Aspergillosis) in 3 (11%), Emphysema (3), Asbestos Disease (2) and one each had Pulmonary Sarcoid and BOOP (Bronchiolitis Obliterans Organizing Pneumonia). CONCLUSION The Tree-in-Bud pattern occurs as a result of a number of processes, although often they co-exist in the same condition and though we identified some mycobacterial disease, cases identified had a wider spectrum including other infectious, allergic, and vasculitic pathways alongside malignancy. The radiological distribution of disease within the lungs further proposes a role for silent aspiration into the airways. (Figure Presented) .

Assessment of chronic obstructive airways disease in heart failure : An analysis of current practice (2018)

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Type of publication:
Conference abstract

Author(s):
*Muthusami R.; *Mahmoud M.; *Crawford E.; *Makan A.; *Ahmad N.; *Srinivasan K.S.; *Moudgil H.; *Candassamy N.

Citation:
American Journal of Respiratory and Critical Care Medicine; May 2018; vol. 197

Abstract:
RATIONALE Heart Failure (HF) and Chronic Obstructive Pulmonary Disease (COPD) are global epidemics incurring significant morbidity and mortality with overlapping symptoms & risk factors. Whereas with other coexisting co-morbidities such as with Diabetes Mellitus and Ischaemic Heart Disease, much work has been done to concurrently improve outcomes from both pathologies, whether anything is uniformly undertaken in practice to firstly recognize and secondly improve outcomes from HF and COPD is less understood. The objective here was to establish our current pattern of assessment to identify potential areas of improvement that would enable us to better manage the modern multi-morbid patient. METHODS Electronic medical records of all patients admitted to our District General Hospital (serving fairly static population 250,000) over a 6 month period to end December 2016 and referred internally to our Heart Failure Specialist Team were assessed. Data for all admitted cases were cross-referenced to Electrocardiography (ECHO) and Pulmonary Function Lab Databases. RESULTS 116 patients (63% male) with mean (SD, range) age 74.9 (11.7, 32-100) years had been admitted and of these 37% had died over the subsequent 12 months follow up period. Of the total, 113 (97%) had prior transthoracic cardiac ECHO (updated within a two year window); Mean estimated Left Ventricular Ejection Fraction (LVEF) was 41%. Comparatively, only 31 (27%) patients had undergone Spirometry testing at our centre over the preceding 10 year period and of these approximately half (51%) had shown obstructive spirometry. Collectively, 44 (38%) were known to have any Obstructive Airways Disease with 32 (28%) being COPD but a slightly higher figure at 50 (43%) were on inhaler treatment. . Sub-analysing, the 59 (51%) specifically with Ischaemic Heart Disease as opposed to other causes for Heart Failure (Valvular Heart Disease, Cardiomyopathy etc.) had a higher 12 month mortality rate (49%) as well as higher prevalence of known COPD (32%), higher proportion of patients with obstructive spirometry (65%) and patients on inhaler therapy (45%). Only 2 of the 7 patients on Amiodarone had Spirometry. CONCLUSION The basic provision of spirometry to Heart Failure patients, and in particular those with Ischaemic Heart Disease, needs to be improved with our findings probably consistent with others providing the same models of diagnosis driven care. Our findings are in a population with established Heart Failure and potentially in their final years of life but there may be improved quality of life and care planning, if assessing those presenting earlier.

Iron deficiency in heart failure: A retrospective review of current practice and patient outcomes in a district general hospital (2018)

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Type of publication:
Conference abstract

Author(s):
*Chatrath N.; *Kundu S.; *Makan J.

Citation:
Heart; Jun 2018; vol. 104, Supp 6

Abstract:
Iron deficiency (ID) affects up to 50% of patients with heart failure (HF) with higher rates in decompensated, hospitalised patients.1 ID is associated with poor functional capacity and recurrent hospital admissions. The 2016 European Society of Cardiology (ESC) guidelines for management of HF advocate measurement of ferritin and Transferrin Saturations (TSAT) in all HF patients. ID is defined by serum ferritin <100 mg/L or 100-299 mg/ L and TSAT <20%0.2 Intravenous Iron therapy is recommended for any patient meeting these parameters. This retrospective study looked at the diagnosis and management of ID in HF patients in a district general hospital. All 111 (n=111) inpatients with a diagnosis of HF with reduced ejection fraction (HFrEF), admitted between April-October 2016 were included. The mean age of the population was 75 (30100), 37% female and 63% male. 64% (n=71) were anaemic (Male n=46, Female n=25) as defined by our laboratory haemoglobin reference ranges for gender. Only 51% (n=57) of all patients had Ferritin checked during admission or within 3 months of discharge with an average Ferritin of 161 mg/L (11-1432). 30.6% (n=34) of all patients had absolute iron deficiency (Ferritin <100 mg/L) and 14.4% (n=11) had ferritin in the range 100300 mg/L, in which further TSAT testing to confirm functional iron deficiency is recommended but is not performed locally unless specifically requested by the clinician. Only 4.5% (n=5) of all patients had further investigations looking into causes of ID, including gastro-intestinal work-up. 47.8% (n=53) died in the 1 year follow-up period with 9% (n=10) not surviving past the initial admission. Of the 101 patients surviving the initial admission, there was a total of 135 hospital admissions within the follow-up period, 58% (n=78) of which were directly related to HF. 11.7% of all patients (n=13) were prescribed oral iron therapy on discharge and only 2 out of all patients had intravenous iron therapy during admission or within 6 months of discharge. This study highlights the high readmission and mortality rates of hospitalised HF patients and that ID is an underdiagnosed comorbidity in this population. A new protocol has been proposed which involves mandatory testing of ferritin, and TSAT if required, at the time of diagnosis and during regular follow-up. Local research is underway to further evaluate the benefits of iron replacement in HF and the effects of the proposed protocol on this population.

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Individual and monitoring centre influences upon anticoagulation control of AF patients on warfarin: a longitudinal multicentre UK-based study (2018)

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Type of publication:
Journal article

Author(s):
Abohelaika, Salah; Wynne, Hilary; Avery, Peter; Robinson, Brian; Jones, Lisa; Tait, Campbell; Dickinson, Bradley; Salisbury, Julie; Nightingale, Joanna; *Green, Louise; Kamali, Farhad

Citation:
European Journal of Haematology 2018 October, 101:486–495.

Abstract:
OBJECTIVES Time within therapeutic INR range (TTR) predicts benefits/risk of warfarin therapy. Identification of individual- and centre-related factors that influence TTR, and addressing them to improve anticoagulation control, are important. This study examined the impact of individual and centre-related factors uponlong-term anticoagulation control in atrial fibrillation patients in seven UK-based monitoring services. METHODS Data between 2000 and 2014 on 25,270 patients (equating to 203,220 patient years) [18,120 (71.7%) in general practice, 2,348 (9.3%) in hospital-based clinics and 4,802 (19.0%) in domiciliary service] were analysed. RESULTS TTR increased with increasing age, peaking around 77% at 70-75 years, and then declined, was lower in females than males, and in dependent home-monitored patients than those attending clinic (P<0.0001). TTR, number of dose changes and INR monitoring events, and the probability of TTR≤ 65%, differed across the centres (P<0.0001). CONCLUSIONS Although all the participating centres ostensively followed a standard dosing algorithm, our results indicate that variations in practice do occur between different monitoring sites. We suggest feedback on TTR for individual monitoring sites gauged against the average values reported by others would empower the individual centres to improve quality outcomes of anticoagulation therapy by identifying and adjusting contributory factors within their management system.

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