Author: Jason Curtis

A stroke-like presentation due to balo concentric sclerosis (2018)

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Type of publication:
Conference abstract

Author(s):
*Albuidair A.

Citation:
European Stroke Journal; May 2018; vol. 3, Supp 1

Abstract:
Background and Aims: A young woman presented with a 'stroke like' episode subsequently found to be due to a rare form of multiple sclerosis, Balo concentric sclerosis (BCS). Method: A literature search was conducted (5/ 1/2018) using the key words: 'Balo concentric sclerosis ' and 'Stroke ' finding only 30 PUbMed and 5 Medline references respectively. Few case reports exist of such a presentation. Results: The Hungarian neuropathologist Josef Balo published a case report in 1928 of a young man with a new hemiparesis who was found at autopsy to have lesions described as encephalitis periaxialis concerntrica. With the advent of MRI, imaging characteristically shows an onion ring or whorled appearance. Recently it has been classified to lie within the spectrum of atypical idiopathic inflammatory demyelinating disorders, and practically is considered as a form of relapsing-remitting MS. It is more common in Chinese and Filipino populations with an estimated 2:1 female predilection with on-going uncertainty as to the relative role of genetic or environmental predespositions. We describe a 33 year old lady presenting acutely with left arm heaviness, incoordination and paraesthesia. She had no vascular risk factors and no relevant past medical or family history. MRI confirmed a classical BCS ringed lesion within the white matter of the right frontal gyrus, Lumbar puncture showed raised lymphocytes and oligoclonal bands. Conclusion: Stroke-like presentations are not uncommonly found to be due to MS but rarely of the atypical BCS type. BCS shows a characteristic onion ring appearance on MRI.

Validating the portal population of the United Kingdom Multiple Sclerosis Register (2018)

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Type of publication:
Journal article

Author(s):
Middleton R.M.; Rodgers W.J.; Akbari A.; Tuite-Dalton K.; Lockhart-Jones H.; Griffiths D.; Noble D.G.; Jones K.H.; Ford D.V.; Chataway J.; Schmierer K.; Rog D.; Galea I.; Al-Din A.; Craner M.; Evangelou N.; Harman P.; Harrower T.; Hobart J.; Husseyin H.; Kasti M.; Kipps C.; McDonnell G.; *Owen C.; Pearson O.; Rashid W.; Wilson H.

Citation:
Multiple Sclerosis and Related Disorders; Aug 2018; vol. 24 ; p. 3-10

Abstract:
 The UK Multiple Sclerosis Register (UKMSR) is a large cohort study designed to capture 'real world' information about living with multiple sclerosis (MS) in the UK from diverse sources. The primary source of data is directly from people with Multiple Sclerosis (pwMS) captured by longitudinal questionnaires via an internet portal. This population's diagnosis of MS is self-reported and therefore unverified. The second data source is clinical data which is captured from MS Specialist Treatment centres across the UK. This includes a clinically confirmed diagnosis of MS (by Macdonald criteria) for consented patients. A proportion of the internet population have also been consented at their hospital making comparisons possible. This dataset is called the 'linked dataset'. The purpose of this paper is to examine the characteristics of the three datasets: the selfreported portal data, clinical data and linked data, in order to assess the validity of the self-reported portal data. The internet (n = 11,021) and clinical (n = 3,003) populations were studied for key shared characteristics. We found them to be closely matched for mean age at diagnosis (clinical = 37.39, portal = 39.28) and gender ratio (female %, portal = 73.1, clinical = 75.2). The Two Sample Kolmogorov-Smirnov test was for the continuous variables to examine is they were drawn from the same distribution. The null hypothesis was rejected only for age at diagnosis (D = 0.078, p < 0.01). The populations therefore, were drawn from different distributions, as there are more patients with relapsing disease in the clinical cohort. In all other analyses performed, the populations were shown to be drawn from the same distribution. Our analysis has shown that the UKMSR portal population is highly analogous to the entirely clinical (validated) population. This supports the validity of the self-reported diagnosis and therefore that the portal population can be utilised as a viable and valid cohort of people with Multiple Sclerosis for study.

A survey of management of vulvar disorders in the primary health care setting in an urban area of England (2018)

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Type of publication:
Journal article

Author(s):
*Kandanearachchi P.; *Sahu B.; *Antonakou A.; *Papoutsis D.

Citation:
Archives of Hellenic Medicine; 2018; vol. 35 (no. 3); p. 405-411

Abstract:
OBJECTIVE To determine the frequency of consultation for vulvar diseases in the primary health care setting, and their investigation and management patterns, and to identify the training needs of general practitioners (GPs) in vulvar disease. METHOD A survey was conducted using a 13-item questionnaire handed out to GPs during their regional post-graduate seminars in the area of Shropshire in the West Midlands in England. RESULTS Of 120 questionnaires distributed, a total of 107 responses were received (response rate: 89.1%). Of the participants, 67.3% reported that they see more than 5 patients per month with vulvar symptoms, and 24.6% that they see more than 5 patients per month with recurrent vulvar symptoms. The predominant symptom was pruritus vulvae (77.5%), with 94.5% of practitioners considering lichen sclero-sus as the most likely diagnosis. For recurrent pruritus vulvae a gynecological referral was made in most cases (86%). In contrast, when there was vulvar pain, only few practitioners would refer the patient to a gynecologist (8.4%) or a dermatologist (17.3%). Only 41.1% of GPs had ever received any kind of training, with all (100%) agreeing that formal training in the diagnosis and management of vulvar diseases would benefit their care of their patients. CONCLUSIONS This survey showed that a substantial number of women consult their GP with vulvar symptoms. A variety of approaches were reported in the diagnosis and management of these cases. All the GPs agreed that there is a need for formal training in vulvar disease.

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Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol (2018)

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Type of publication:
Journal article

Author(s):
Sydes, M R; Spears, M R; Mason, M D; Clarke, N W; Dearnaley, D P; de Bono, J S; Attard, G; Chowdhury, S; Cross, W; Gillessen, S; Malik, Z I; Jones, R; Parker, C C; Ritchie, A W S; Russell, J M; Millman, R; Matheson, D; Amos, C; Gilson, C; Birtle, A; Brock, S; Capaldi, L; Chakraborti, P; Choudhury, A; Evans, L; Ford, D; Gale, J; Gibbs, S; Gilbert, D C; Hughes, R; McLaren, D; Lester, J F; Nikapota, A; O'Sullivan, J; Parikh, O; Peedell, C; Protheroe, A; Rudman, S M; Shaffer, R; Sheehan, D; Simms, M; *Srihari, N; Strebel, R; Sundar, S; Tolan, S; Tsang, D; Varughese, M; Wagstaff, J; Parmar, M K B; James, N D; STAMPEDE Investigators

Citation:
Annals of Oncology : Official Journal of the European Society for Medical Oncology; May 2018; vol. 29 (no. 5); p. 1235-1248

Abstract:
 Background Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC+AAP versus SOC+DocP. Method Recruitment to SOC+DocP and SOC+AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for≥2years and RT to the primary tumour. Stratified randomisation allocated pts 2:1:2 to SOC; SOC+docetaxel 75mg/m2 3-weekly×6+prednisolone 10mg daily; or SOC+abiraterone acetate 1000mg+prednisolone 5mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC+AAP, and HR>1 favours SOC+DocP. Results A total of 566 consenting patients were contemporaneously randomised: 189 SOC+DocP and 377 SOC+AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66years and median PSA 56ng/ml. With median follow-up 4years, 149 deaths were reported. For overall survival, HR=1.16 (95% CI 0.82-1.65); failure-free survival HR=0.51 (95% CI 0.39-0.67); progression-free survival HR=0.65 (95% CI 0.48-0.88); metastasis-free survival HR=0.77 (95% CI 0.57-1.03); prostate cancer-specific survival HR=1.02 (0.70-1.49); and symptomatic skeletal events HR=0.83 (95% CI 0.55-1.25). In the safety population, the proportion reporting≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC+DocP, and 40%, 7% and 1% SOC+AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm. Conclusions This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs.Trial registration Clinicaltrials.gov: NCT00268476.

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Giant Circumflex Artery Aneurysm with a Coronary Sinus Fistula (2018)

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Type of publication:
Journal article

Author(s):
Libertini, Richard; *Walbridge, David; Jones, Hefin R; Gunning, Mark; Satur, Christopher Mr

Citation:
The Annals of Thoracic Surgery; May 2018 [online]

Abstract:
Giant coronary artery aneurysms (GCCAA) are extremely rare entities, and of the circumflex artery we are aware of only 13 case reports. We therefore provide this case report to add evidence of the natural history and pathophysiology and describe successful surgical treatment of the condition.

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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Coronary heart disease mortality in treated familial hypercholesterolaemia: Update of the UK Simon Broome FH register (2018)

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Type of publication:
Journal article

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

Citation:
Atherosclerosis; Jul 2018; vol. 274 ; p. 41-46

Abstract:
 Background and aims: Patients with familial hypercholesterolaemia (FH) have an elevated 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 2008-2016. Methods: 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 and 2016 for 67,060 person-years. The CHD standardised mortality ratio (SMR) compared to the population in England and Wales was calculated (with 95% Confidence intervals). Results: There were 585 deaths, including 252 from CHD. Overall, the observed 2.4-fold excess coronary mortality for treated DFH post-1991 was significantly higher than the 1.78 excess for PFH (35% 95% CI 3%-76%). In patients with DFH and established coronary disease, there was a significant excess coronary mortality in all time periods, but in men it was reduced 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 the corresponding values were 7.23 (2.65-15.73), 4.42 (2.70-6.82) and 6.34 (2.06-14.81). Primary prevention in men with DFH resulted in a progressive reduction in coronary mortality over the three time-periods, with no excess mortality evident post-2008 (0.89 (0.29-2.08)), although in women the excess persisted (post-2008 3.65 (1.75-6.72)). Conclusions: The results confirm the benefit of statin treatment in reducing CHD mortality, but suggest that FH patients with pre-existing CHD and women with FH may not be treated adequately.

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.

How accurate is glycated haemoglobin in patients with liver cirrhosis? A case series (2018)

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Type of publication:
Conference abstract

Author(s):
*Basavaraju N.; *Rangan S.; *Singh P.; *Moulik P

Citation:
Diabetic Medicine; Mar 2018; vol. 35 ; S1

Abstract:
Introduction: Glycated haemoglobin (HbA1c) is the gold standard for monitoring glycaemic control in patients with diabetes. We present three cases of chronic liver disease where HbA1c may be misleading. Case 1: A 71-year-old Caucasian woman with liver cirrhosis due to hepatitis C, Type 2 diabetes, previous bladder tuberculosis and chronic kidney disease stage 3 was evaluated in clinic. Her capillary glucose (CG) was 6 to 9 mmol/l, no hypoglycaemia. She was anaemic; HbA1c was low at 34mmol/mol. Fructosamine was elevated at 296umol/l (205 to 285). Case 2: A 38-year-old Caucasian man with alcoholic liver cirrhosis, portal hypertension, and Type 2 diabetes was admitted with haematemesis. His CG was 10 to 14 mmol/l and HbA1c 26mmol/mol. He had iron deficiency anaemia, deranged liver enzymes and renal function. Fructosamine was normal at 246umol/l. Case 3: A 65-year-old Caucasian woman with non-alcoholic steatohepatosis/cirrhosis, portal hypertension, Type 2 diabetes, iron deficiency anaemia was admitted with melena. Her CG was 12 to 14mmol/l and HbA1c 44mmol/mol. Results showed acute kidney injury, deranged liver enzymes, normal albumin but low haemoglobin. Fructosamine is awaited. All patients required insulin for management of their diabetes. Discussion: The degree of glycation (glucose binding to N-terminal valine of HbA) is dependent on glycation rate, glucose availability and lifespan of red blood cells. Reference range of HbA1c is based on normal lifespan of RBC. There are very limited studies in evaluating the accuracy of HbA1c in chronic liver disease (CLD). Multiple factors can shorten RBC survival in CLD, including anaemia, portal hypertension, hypersplenism, variceal bleeding, resulting in falsely low HbA1c. Fructosamine, glycated albumin can also be inaccurate. Capillary glucose monitoring should guide glycaemic management.

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