2017

Thrombolysis for pulmonary embolism in palliative care: a case report (2017)

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Type of publication:Conference abstract

Author(s):Macfarlane M.; Gilhooley L.; *Griffiths T.; Frost S.; Willis D.

Citation:BMJ Supportive and Palliative Care. Conference: APM ASP Conference. Belfast United Kingdom. 7(Supplement 1) (pp A31-A32), 2017. Date of Publication: March 2017.

Abstract:Background Thrombolysis for pulmonary embolism (PE) in a patient with advanced cancer has never been reported in the literature. Whilst not an absolute contraindication, most clinicians would be wary of thrombolysing a patient with a limited life expectancy. A case is presented of a patient with advanced mesothelioma who received thrombolysis treatment with a resultant significant improvement in pleuritic chest pain and dyspnoea. History The patient was a 69 year old man who was diagnosed with epithelioid mesothelioma and received radiotherapy to his right chest followed by palliative chemotherapy. Subsequent CT scanning showed disease progression and the patient declined further chemotherapy. Thrombolysis The patient was admitted to hospital with sudden- onset shortness of breath and right sided chest discomfort which was felt to be due to disease progression. Three days later the patient developed new, severe left sided pleuritic chest pain and acute breathlessness. The patient was thrombolysed with alteplase (50 mg IV over 1 hour) on clinical suspicion of a PE. The pleuritic chest pain resolved completely and the acute severe dyspnoea improved significantly within two hours of treatment and a CTPA later confirmed acute-onchronic pulmonary thromboembolism as well as progressive mesothelioma. The patient was transferred to the hospice four days later for ongoing management and end-of-life care. Effect of Thrombolysis on Symptom Control On admission to the hospice, the patient continued to complain of mild to moderate dyspnoea but had no pain. He was commenced on regular immediate-release morphine (10 mg QDS) for breathlessness but only required one breakthrough dose of analgesia before his condition deteriorated. The patient died comfortably nine days after thrombolysis treatment. Conclusion Thrombolysis was very effective in controlling pleuritic chest pain and acute severe dyspnoea in this patient with PE and advanced cancer with a limited life expectancy.

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Identifying demographics and co-morbidities among hospitalised adults infected with acute respiratory syncytial virus (RSV) (2017)

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Type of publication:
Conference abstract

Author(s):
*Huntley C.; *Ahmad N.; *Makan A.; *Srinivasan K.; *Moudgil H.

Citation:
European Respiratory Journal; Sep 2017; vol. 50

Abstract:
Background/Objectives: The importance of RSV infection among adults admitted to secondary care is not well defined. Objectives were to identify patient demographics and co-morbidities and relate findings to length of hospital stay (LOS). Method(s): A retrospective review of adults admitted to one NHS trust with confirmed RSV (PCR respiratory swabs), identified during 3 months until 31st January 2017, coinciding with the UK winter. Result(s): Peak incidence was the 3rd week of December 2016 whilst later with Influenza (n=145) and earlier with paediatric admissions with RSV (n=3) throughout the study. Mean (SD, range) age of admitted adult patients (n=50) was 68.9 (19.5, 23-96) years with 27 (54%) female and LOS 8.8 (9.6, 0-41) days. 3 (6%) had concurrent RSV/Influenza A infection. 46 (92%) were admitted from home mainly via A&E (60%), General Practitioner (28%), and ambulatory care (8%). 73.5% had at least four co-morbidities, predominantly cardiorespiratory (50%) with a longer LOS (10.7 days), but also diabetes (20%), dementia (10%), malignancy (20%), and immunosuppression (10%). LOS correlated (Spearman rho) positively with both age (r =0.481, p<0.001) and number of co-morbidities (r< =0.486, p<0.0001). LOS was shorter where RSV was a primary as opposed to concurrent diagnosis (6.13, 0-21 vs 13.8, 1-41) days. Conclusion(s): RSV was detected at greater numbers during different times of the three month period among hospital admissions compared with paediatric RSV and influenza admissions, suggesting a staggered temporal relationship. Increasing age and the number of co-morbidities, predominantly cardio-respiratory, correlated positively with longer LOS.

Design and implementation of a custom next generation sequencing panel for selected vitamin D associated genes (2017)

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Type of publication:
Journal article

Author(s):
Benson K.A.; Maxwell A.P.; Smyth L.J.; Kilner J.; McKnight A.J.; *Chand S. ; Borrows R.

Citation:
BMC Research Notes; Jul 2017; vol. 10 (no. 1); p. 348

Abstract:
 BACKGROUND: Biologically active vitamin D has an important regulatory role within the genome. It binds the vitamin D receptor (VDR) in order to control the expression of a wide range of genes as well as interacting with the epigenome to modify chromatin and methylation status. Vitamin D deficiency is associated with several human diseases including end-stage renal disease.METHODS: This article describes the design and testing of a custom, targeted next generation sequencing (NGS) panel for selected vitamin D associated genes. Sequencing runs were used to determine the effectiveness of the panel for variant calling, to compare efficiency and data across different sequencers, and to perform representative, proof of principle association analyses. These analyses were underpowered for significance testing. Amplicons were designed in two pools (163 and 166 fragments respectively) and used to sequence two cohorts of renal transplant recipients on the Ion Personal Genome Machine (PGM)TM and Ion S5TM XL desktop sequencers.RESULTS: Coverage was provided for 43.8 kilobases across seven vitamin D associated genes (CYP24A1, CUBN, VDR, GC, NADSYN1, CYP27B1, CYP2R1) as well as 38 prioritised SNPs. Sequencing runs provided sufficient sequencing quality, data output and validated the effective library preparation and panel design.CONCLUSIONS: This novel, custom-designed, validated panel provides a fast, cost effective, and specific approach for the analysis of vitamin D associated genes in a wide range of patient cohorts. This article does not report results from a controlled health-care intervention.

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Approaches to alcohol screening in secondary care: a review and meta-analysis (2017)

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Type of publication:
Conference abstract

Author(s):
*Walsh S.; Haroon S.; Nirantharakumar K.; Bhala N.

Citation:
The Lancet; Nov 2017; vol. 390

Abstract:
Background Alcohol misuse is common among patients accessing secondary care and an important cause of premature disability and death. The objective of this review was to summarise approaches to alcohol screening in secondary care, including the diagnostic accuracy, uptake, yield, and implementation challenges. Methods Search terms for alcohol, screening, and secondary care were combined in Medline, EMBASE, and other bibliographic databases for English language studies published from Jan 1, 2000, to Sept 4, 2015. We included studies and reviews of any design that evaluated alcohol screening with questionnaires or biochemical tests among adolescents and adults in secondary care. The primary outcomes were the diagnostic accuracy, uptake, and yield of alcohol screening. A random-effects proportion meta-analysis summarised screening uptake and yield, stratified by clinical setting. Findings 97 articles met the inclusion criteria and were included, with data from 1 213 761 screened patients. The Alcohol Use Disorders Identification Test (AUDIT) and AUDITConsumption (AUDIT-C) were the most widely validated screening tests and demonstrated high diagnostic accuracy and uptake. Overall, uptake for alcohol screening in secondary care was 79% (95% CI 74-84; n=45 studies, 477 533 of 604 471 screened patients) and the highest uptake was in outpatient clinics at 91% (82-96; n=8, 208 245 of 228 841). Overall, the proportion of patients screening positive for alcohol misuse was 28% (23-32, n=44; 135 741 of 484 788) with the highest yield in outpatient clinics of 31% (22-41; n=7, 72 270 of 233 128). However, there was significant heterogeneity in estimates of both uptake and yield of alcohol screening (I2>90%). Interpretation Alcohol screening in secondary care is likely to have a high uptake and yield, particularly in outpatient clinics. AUDIT and AUDIT-C are the most widely validated screening tools for alcohol misuse in secondary care and have high diagnostic accuracy and uptake. The review included a large number of studies, and a range of clinical settings and patient groups, strengthening the generalisability of the findings. However, a systematic assessment of risk of bias was not conducted and study selection was performed by one reviewer. Further research is needed to evaluate the cost-effectiveness of alcohol screening in secondary care.

Feasibility of performing MRI prostate before prostate biopsy in a district general hospital in the UK (2017)

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Type of publication:
Conference abstract

Author(s):
*Phan Y.; *Loh A.; *Anandakumar A.; *Umranikar S.; *Lynn N.

Citation:
Journal of Endourology; Sep 2017; vol. 31, S2

Abstract:
Introduction & Objective: Men with abnormal digital rectal examination or raised PSA usually undergo
transrectal ultrasound (TRUS) prostate biopsies. NICE guidelines do not recommend routine MRI prostate before prostate biopsy unless they have a previous negative prostate biopsy. However, all men with positive prostate biopsies will have MRI prostates. The recent publication of PROMIS (Prostate MR Imaging Study) trial suggests that MRI prostate can reduce unnecessary biopsies by a quarter and can improve detection of clinically significant cancer. In light of this, we would like to determine if performing MRI prostate before biopsy is likely to increase workload in our radiology department in a district general hospital in the UK. Materials and Methods: Patients who underwent TRUS prostate biopsy between 3 Dec 2015 to 28 April 2016 were identified. Their data were analysed retrospectively. 1 year follow-up was chosen to see how many patients would have had MRIs. Results: 173 patients were listed for prostate biopsies but only 158 patients had biopsies with an average age of 69.8 years old (range: 49-88 years old) and an average PSA of 48.1ug/l (range: 0.5-3283.1ug/l). 57 patients had a negative prostate biopsy during this period. 30/57 patients did not have a MRI at all; 12/57 patients had a MRI after biopsy; 1/57 patient had a MRI as an acute setting after biopsy to look for abscesses; and 14/57 patients had a MRI before biopsy. Conclusions: In our study, 30/158 (19.0%) did not have any MRI prostate in 1 year after their first prostate biopsy. However, it is possible that this group of patients will have a MRI prostate in the second year or later. If we were to perform a MRI prostate before TRUS prostate biopsy for all patients, it would increase 19.0% workload for our radiology department.

Current trends in cytoreductive nephrectomy in the era of targeted molecular therapy (2017)

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Type of publication:
Conference abstract

Author(s):
*Phan Y.; *Segaran S.; *Bell J.; *Nakada S.Y.; *Rane A.

Citation:
Journal of Endourology; Sep 2017; vol. 31, S2

Abstract:
Introduction & Objective: Several factors are considered when determining if a patient is a candidate for
cytoreductive nephrectomy (CN). Our aim was to study geographic trends and factors associated with the decision to consider CN. Materials and Methods: An investigator designed survey was created to assess the rate of CN being performed around the world and the factors considered when determining patient eligibility. This was distributed to attendees at the World Congress of Endourology 2016 in Cape Town in order to capture an international cohort of urologists. The survey included questions about physician demographics, the timing of CN, what patient factors were considered prior performing CN, and if they followed any guidelines when deciding on CN. Results: 158 urologists responded to our survey (Asia = 46, Europe = 35, Africa = 34, North America = 29, South America = 13 and Australia = 1). 78 (49.4%) urologists indicated that they follow guidelines for recommending CN. 107 (67.7%) of respondents stated they perform CN. 64 urologists perform CN prior to systemic therapy while 20 urologists perform CN after systemic treatment, and 22 urologists perform CN before or after systemic treatment. Performance status was the most considered factor while calcium level was the least considered factor when determining eligibility for CN. Conclusions: This cohort of urologists most commonly consider performance status, age and extent of metastatic disease when determining candidacy for CN; while the grade of the tumour and the calcium level were the least considered. We eagerly await the results of CARMENA and SURTIME trials.

A pilot experience in using a digital app to follow-up prostate cancer patients in Shropshire, UK (2017)

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Type of publication:
Conference abstract

Author(s):
*Phan Y.; *Loh A.; *Anandakumar A.; *Umranikar S.; *Elves A.

Citation:
Journal of Endourology; Sep 2017; vol. 31, S2

Abstract:
Introduction & Objective: It is not uncommon for patients with cancer to experience physical, mental and social distress, forming a significant burden that has a negative impact on their quality of life. We have piloted a digital app called VitruCare in our hospital in order to address these issues in patients with prostate cancer. More importantly, the app also serves as a communication tool between the hospital medical team and the patients. Materials and Methods: Patients with prostate cancer were invited to use VitruCare in our pilot study. 53 users were followed prospectively. Data on various domains such as "My Goals", "My Lifestyle", "My Priorities", "My Diaries", and "How Do I Feel Today" were analysed retrospectively. Results: The users of this application have a median age of 72.5 years old. 14% have nodal or bone metastasis, and median time since treatment is 48 months. 60% have completed the lifestyle questionnaire and "How Do I Feel Today" trackers. 20% of the users who completed the lifestyle questionnaire reported anxiety. 42% have used the diary function and 47% have used the secured messaging function. Usage of the lifestyle questionnaire, "How Do I Feel Today" trackers, secured messaging and diary functions does not appear to be age related. Patients who have been treated and further away from treatment in time are more likely to be used the app. Conclusions: The level of engagement in this pilot study reflects the willingness of patients to utilize this innovative app that has the potential to monitor the well-being of patients with prostate cancer out with the constraints of a fixed clinic appointment.

Real world efficacy of 12 weeks sofosbuvir, daclastivir with ribavirin among cirrhotic pre and post-transplant genotype 3 (2017)

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Type of publication:
Conference abstract

Author(s):
Schmidt-Martin D.; Bufton S.; Haydon G.H.; Mutimer D.; Elsharkawy A.M.; Roberts M.; *Rye K.; Singhal S.; Eldred S.; Perry I.; Corbett C.; Unitt E.; Wood V.; Dillon H.

Citation:
Journal of Hepatology; 2017; vol. 66 (no. 1)

Abstract:
Background and Aims: Current EASL guidelines recommend combined Sofosbuvir and Daclatasvir with Ribavirin (SOF + DCV + RBV) for 24 weeks in compensated/decompensated cirrhosis for genotype 3 patients. We investigated response to 12weeks treatment in a large cohort of pre and post-transplant predominantly compensated cirrhotic genotype 3 patients. Methods: All patients who received a single dose and treated in 8 treatment centres within our hospital network included. SVR12 rates for all patients who started treatment are reported on an intention to treat (ITT) basis and we include a modified intention to treat (mITT) analysis excluding non virological failures. Results: 156 patients ((M:F) 109:47) mean age 51.5 were commenced on treatment. The overall SVR12 rate was 88.5% (138/156) (ITT) and 95.8% (138/144) (mITT). 2 patients stopped treatment without side effects. Five patients did not attend for confirmation of SVR12, three patients died on treatment (2 due to cardiac arrest, 1 due to sepsis) and a further patient died following completion of treatment prior to SVR12 (hepatocellular carcinoma). mITT SVR12 for patients with compensated and decompensated cirrhosis (Child Pugh B/C) were 96.7% (116/120) and 82% (23/28)respectively. 96.4% (80/83) of patients with previous exposure to interferon and ribavirin achieved SVR12. All patients with HIV co infection achieved SVR (n = 8). 89% of liver transplant patients achieved SVR. 18%(5/28) of the decompensated cohort (Child Pugh B/C) had died within 2 years of commencing treatment. Conclusions: SOF + DCV + RBV for 12 weeks achieved real world SVR12 rates comparable with 24 weeks treatment in cirrhotic genotype 3 patients or 12 weeks sofosbuvir/velpastasvir. This is the largest reported cohort of posttransplant genotype 3 patients with advanced fibrosis. Our data suggests 12 weeks treatment for all cirrhotic patients may be considered regardless of previous interferon and ribavirin exposure (Table presented).

Coronary heart disease mortality in treated Familial Hypercholesterolaemia: Update of the UK Simon Broome FH Register (2017)

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Type of publication:
Conference abstract

Author(s):
Humphries S.E.; Cooper J.A.; Seed M.; *Capps N.; Durrington P.N.; Jones B.; McDowell I.F.W.; Soran H.; Neil

Citation:
Atherosclerosis Supplements; 2017; vol. 28, Pages 41-46

Abstract:
Background: Guidelines for the management of patients with Familial Hypercholesterolaemia (FH) recommend the use of high intensity statin therapy to reduce subsequent risk of Coronary Heart Disease (CHD). Here we compare changes in CHD mortality in patients with heterozygous (FH) pre 1992 before lipid-lowering therapy with statins was used routinely, and in the periods 1992-2008 and 2008 till the present. Methods: Analysis used 1903 Definite (DFH) and 1650 Possible (PFH) patients (51% women) aged 20-79 years, recruited from 21 lipid clinics in the United Kingdom and followed prospectively between 1980-1991 (6627 personyears) 1992-2008 (43117 person-years) and 2009-2016 (17317 person-years). The excess CHD standardised mortality ratio (SMR) compared to the population in England and Wales was calculated (with 95% Confidence intervals). Results: There were 252 deaths from CHD. Overall, treated DFH patients had a higher CHD SMR than PFH patients (post 1991 35% higher 2.40 (2.00-2.86) vs 1.78 (1.44-2.19) p = 0.03). In treated DFH patients with previous CHD the CHD SMR was significantly elevated at all time periods but in men fell from a 4.83-fold excess (2.32-8.89) pre-1992 to 4.66 (3.46-6.14) in 1992-2008 and 2.51 (1.01-5.17) post 2008, while in women these values were 7.23 (2.65-15.73), 4.42 (2.70-6.82) and 6.34 (2.06-14.81)). In treated DFH men with no previous CHD the CHD SMR fell over the three time periods, and was not significantly elevated post 2008 (0.89 (0.29-2.08), but in women the SMR remained significantly elevated (post 2008 3.65 (1.75-6.72)). Conclusions: The data confirm the major benefit in CHD mortality associated with statin treatment, but suggest that FH patients with pre-existing disease, and women with FH may not be being treated adequately.

Impact of PCSK9 inhibitors Alirocumab and Evolocumab on total & LDL cholesterol in clinical practice (2017)

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Type of publication:
Conference abstract

Author(s):
*Capps N.

Citation:
Atherosclerosis Supplements; 2017; vol. 28, e13

Abstract:
Background: The PCSK9 inhibitors Alirocumab (Al) and Evolocumab (Ev) were recently recommended for use in the NHS on the basis of NICE TA393 and 394 respectively. Clinical trials of both drugs show rapid, significant and continued reductions in total (TC) and LDL cholesterol (LDLC), however confirmation of their efficacy in UK clinical practice is required. Methods: The first patients in the hospital lipid clinic treated with Al 75 mg (14) or Ev 140 mg (13), with pre and post initiation (after 2-3 injections) fasting bloods, were evaluated. All results are in mmol/L. Results: 19 patients had Familial Hypercholesterolaemia, 9 classed by NICE as high or very high risk. Of the remaining 8 patients 5 were HR and 3 VHR. Overall mean TC and LDLC fell from 7.83 to 5.04 and 5.8 to 3.0, ie by 36 and 48%. For Alirocumab 75 mg mean TC and LDLC fell from 8.21 to 5.71 and 6.20 to 3.48, ie by 30 and 44%; individual reductions were 10 to 45% for TC and 13 to 62% for LDLC. For Evolocumab 140 mg mean TC and LDLC fell from 7.41 to 4.32 and 5.33 to 2.44, reductions of 42 and 54%; individual reductions were 32 to 55% for TC and 45 to 69% for LDLC. LDLC fell below 2.0 in 6 patients (Al 1, Ev 5), the lowest to 1.4 mmol/L. Conclusions: The data confirm the rapid and significant reductions in TC and LDLC with Al and Ev in previously difficult to treat patients, however many still had LDLC higher than ideal. This cohort did not contain patients treated with 150 mg Al, or by both drugs, so a direct comparison is not reported.