Author: Jason Curtis

Caveolin-1 in renal disease (2018)

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Type of publication:
Journal article

Author(s):
*Chand S.

Citation:
Scientific Journal of Genetics and Gene Therapy. 2018 July: 007-014.

Abstract:
Caveolin-1 is the essential structural formation for lipid raft formation. It has been ascribed to several
disease processes in humans due to its ubiquitous distribution. Patients with chronic kidney disease suffer
great morbidity and mortality where manipulation of caveolin-1 could lead to new potential therapeutic
targets in this patient group. This review highlights caveolin-1 structure, signalling and provides examples
of studies of caveolin-1 single nucleotide polymorphism in chronic kidney disease.

Link to full-text [no password required]

Risk Prediction for Acute Kidney Injury in Acute Medical Admissions in the UK (2019)

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Type of publication:
Journal article

Author(s):
The RISK investigators [including *Chand, S ]

Citation:
QJM: An International Journal of Medicine, Volume 112, Issue 3, March 2019, Pages 197–205

Abstract:
Background
Acute Kidney Injury (AKI) is associated with adverse outcomes; therefore identifying patients who are at risk of developing AKI in hospital may lead to targeted prevention.

Aim
We undertook a UK-wide study in acute medical units (AMUs) to define those who develop hospital-acquired AKI (hAKI); to determine risk factors associated with hAKI and to assess the feasibility of developing a risk prediction score.

Design
Prospective multi-centre cohort study across 72 AMUs in the UK.

Methods
Data collected from all patients who presented over a 24-h period. Chronic dialysis, community-acquired AKI (cAKI) and those with fewer than two creatinine measurements were excluded. Primary outcome was the development of h-AKI.

Results
Two thousand four hundred and fourty-six individuals were admitted to the seventy-two participating centres. Three hundred and eighty-four patients (16%) sustained AKI of whom two hundred and eighty-seven (75%) were cAKI and ninety-seven (25%) were hAKI. After exclusions, chronic kidney disease [Odds Ratio (OR) 3.08, 95% Confidence Interval (CI) 1.96–4.83], diuretic prescription (OR 2.33, 95% CI 1.5–3.65), a lower haemoglobin concentration and elevated serum bilirubin were independently associated with development of hAKI. Multi-variable model discrimination was only moderate (c-statistic 0.75).

Conclusions
AKI in AMUs is common and associated with worse outcomes, with the majority of cases community acquired. Only a small proportion of patients develop hAKI. Prognostic risk factor modelling demonstrated only moderate discrimination implying that widespread adoption of such an AKI clinical risk score across all AMU admissions is not currently justified. More targeted risk assessment or automated methods of calculating individual risk may be more appropriate alternatives.

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Risk-Based Maintenance of Medical Devices for use with Humans (2018)

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Type of publication:
Dissertation

Author(s):
*Nigel Watkinson

Citation:
University of Derby

Abstract:
Medical devices continue to increase in quantity and complexity, and as they have a direct correlation with human health and safety their correct use and operation is paramount. This includes effective maintenance to retain serviceability and extend service life. Hospital Clinical Engineering departments are responsible for developing and operating Equipment Management Programs to ensure the safety and reliability of devices whilst optimising lifecycle costs for the organisation. Maintenance of engineering assets traditionally involves following manufacturers predetermined servicing activity at fixed intervals; however, alternative approaches have been employed in many engineering industries to optimise maintenance management resources with reduced risk. Risk-based maintenance (RBM) strategies being the most recent development are evaluated in this paper to consider their appropriateness with medical devices in UK hospitals. A mixed methods approach is used for the research study with a literature review of RBM in engineering industries, analysis of a survey of 74 UK medical engineering professionals and equipment service data
from local organisation. The current and future position of RBM is discussed including development of RBM methodology to be employed with medical devices in UK hospitals.

The study identifies strong endorsement of RBM principles by medical engineering professionals, including widespread employment of RBM, yet with no standardisation. Opposition to RBM is also encountered in favour of traditional approaches with variations in attitude to risk. Recommendations include collaboration of UK professionals for further research and development of medical device specific RBM with standardisation of methodology and approach with engagement of healthcare regulatory authorities.

A comparison of follow-up rates of women with gestational diabetes before and after the updated National Institute for Health and Care Excellence guidance advocating routine follow-up, and the association with neighbourhood deprivation (2019)

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Type of publication:
Journal article

Author(s):
Sebastian Walsh, Mahmoud Mahmoud, Htwe Htun, *Sheena Hodgett, *David Barton

Citation:
British Journal of Diabetes 2019;19:[epub ahead of publication]

Abstract:
Background: Gestational diabetes mellitus (GDM) occurs in one in every 23 UK pregnancies. GDM identifies the mother as high-risk for development of type 2 diabetes. The National Institute for Health and Care Excellence (NICE) published updated guidance in February 2015 recommending routine follow-up of women with GDM.

Aims: This cohort study compared follow-up rates of women with GDM before and after the updated guidance. We also investigated for an association between follow-up rates and deprivation.

Methods: Participants were identified from the database of the GDM service of two English hospitals and were organised into two cohorts: ‘pre-guidance’ (2012–2015) and ‘post-guidance’ (2015–2016). Using the recommendations of the NICE guidance as the follow-up standard, we used the hospitals’ computer system to compare follow-up rates of the two cohorts. The English Indices of Deprivation split the country into 32,844 small areas and rank them in order of deprivation such that 1 is the most deprived area and 32,844 is the least deprived. We compared the patients’ postcodes against the English Indices of Deprivation to investigate the relative levels of neighbourhood deprivation of those followed up compared with those not followed up. The Z statistic was used to test for statistical significance.

Results: 535 participants were included (pre-guidance n=306, post-guidance n=229). Baseline average age (pre-guidance 32.2 years, post-guidance 32.5 years), body mass index (30.7 kg/m2, 30.9 kg/m2) and fasting glucose (4.9 mmol/L, 4.8 mmol/L) were all comparable between cohorts. The follow-up rate improved from 60.5% in the pre-guidance group to 69.9% in the post-guidance group. The median deprivation rank of those followed up was 14,565 compared with 13,393 in those not followed up. This difference was not found to be significant.

Conclusion: A higher proportion of women with GDM were followed up with screening for type 2 diabetes after the updated NICE guidance in 2015 recommended routine follow-up. Across the study, over a third of women were not followed up. There was no statistically significant difference in the deprivation levels of those women followed up compared with those not followed up.

TPS-calculated vs. measured dose around a prosthetic hip implant (2018)

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Type of publication:
Poster presentation

Author(s):
*Maryke Fox, *Mike Alexander

Citation:
IPEM Medical Physics & Engineering Conference & Biennial Radiotherapy Meeting Proceedings, York, UK. September 2018

Abstract:
An increasing number of patients presenting for prostate radiotherapy have prosthetic hips. It is well known
that modern treatment planning systems are unable to accurately model dose in the vicinity of high density
prostheses. This work sought to characterise how dose is modelled by the Eclipse TPS around a hip prosthesis in a water phantom by comparing the modelled dose with dose measured by a Farmer chamber and find estimate dose due to scatter. Transmission, lateral scatter and back scatter were measured at a range of distances from the prosthesis and compared to the Eclipse modelled dose. It was found that dose distal to the prosthesis was underestimated by over 20%, backscatter was not modelled at all by Eclipse but lateral scatter was adequately modelled. The dose due to backscatter and lateral scatter from the prosthesis were not significant contributors to dose. These results indicate that planners should avoid treating through prosthetic hips, and that dose due to scatter was unlikely to cause ill effects.

Link to poster [PDF]

Cleavage stage or blastocyst transfer- Which is better? (2019)

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Type of publication:
Book chapter

Author(s):
*Jason Kasraie

Citation:
Kasraie, J. (2019). Cleavage Stage or Blastocyst Transfer: Which Is Better? In G. Kovacs & L. Salamonsen (Eds.), How to Prepare the Endometrium to Maximize Implantation Rates and IVF Success (pp. 91-103). Cambridge: Cambridge University Press.

Abstract:
Embryo transfer is the last step in the IVF treatment cycle, yet the one with the highest failure rate. This book provides a practical review of all aspects of endometrial receptivity, including histological, hormonal, biochemical and immunological, to enable specialists to make evidence-based decisions that influence success rates.

Link to more details

Trial of atorvastatin for the primary prevention of cardiovascular events in patients with rheumatoid arthritis (TRACE RA): A multicenter, randomized, placebo controlled trial (2019)

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Type of publication:
Journal article

Author(s):
Kitas GD, Nightingale P, Armitage J, Sattar N, Belch JJF, Symmons DPM; TRACE RA consortium.

Collaborators (137) Kitas G, Belch J, Symmons D, Williams H, Vasishta S, Storey R, Nightingale P, Bruce I, Durrington P, McInnes I, Nightingale P, Sattar N, Situnayake D, Struthers A, Lowe G, Armitage J, Fox K, Haskard D, Dore C, Bosworth A, Kitas G, Belch J, Symmons D, Williams H, Frenneaux M, Edwards C, Emberson J, Bax D, Cobbe S, Stott D, Sturrock R, Macfarlane P, Klocke R, Pullar T, Knight S, Rowe I, Kumar P, Goodson N, Mulherin D, Brzeski M, Gardiner P, Situnayake D, Walker D, Callaghan R, Allen M, McCarey D, George E, Deighton C, Kirkham B, Teh LS, Luqmani R, Chakravarty K, Nixon J, Richards S, Scott D, Woolf T, Prouse P, Packham J, Davies M, DeLord D, O'Neill T, Pande I, Harvie J, Watts R, Rankin E, Papasavvas G, Emery P, Sinha A, Dasgupta B, Bruce I, Creamer P, Zoma A, Walsh D, Van-Laar J, *Capps N, Cairns A, Marguerie C, Kumar N, Abernethy R, Lillicrap M, Ralston S, Makadsi R, Hopkinson N, Tan S, Akil M, Ahmad Y, Adler M, Bukhari M, Sanders P, Roussou E, Binymin K, Hassan A, Hughes R, O'Reilly D, Sainsbury P, Richmond R, Malgorzata M, Nisar M, McEntergart A, Roy D, Marks J, Batley M, McKenna F, Irani M, Harris H, Smyth A, Tunn E, Young A, Thomas J, Hall F, Marshall T, Rao C, Baburaj K, Dixey J, Gendi N, Birrell F, Chelliah G, Teh LS, Morgan A, Fishman D, Knights S, Coady D, Makadsi R, Smith B, Harrison B, Walker D, Siebert S, Chan A, Putchakayala K, Al-Ansari A, Gough A, Naz S, Kumar N, Pyne D, Mahmud T, Patel Y, Isdale A.

Citation:
Arthritis Rheumatol. 2019 Apr 15. doi: 10.1002/art.40892. [Epub ahead of print]

Abstract:
OBJECTIVE:

Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVE in RA patients.

METHODS:

Randomized, double-blind, placebo-controlled trial designed for 80% power at p<0.05 to detect a 32% CVE risk reduction based on an estimated 1.8% per annum (pa) event rate. Patients aged >50 years or with RA duration >10 years; without clinical atherosclerosis, diabetes, or myopathy; received atorvastatin 40mg daily or matching placebo. Primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary/tertiary endpoints included plasma lipids and safety.

RESULTS:

3002 patients (mean age 61 years, 74% female) were followed for a median 2.51 years (IQR 1.90-3.49) [7,827 patient-years] – early termination was due to lower than expected event rate (0.77% pa). Among patients allocated atorvastatin 24/1504 (1.6%) had a primary endpoint, compared with 36/1498 (2.4%) on placebo (hazard ratio 0.66, 95%CI 0.39-1.11, p=0.115); adjusted hazard ratio (0.60, 95%CI 0.32-1.15, p=0.127). At trial end, patients on atorvastatin had 0.77±0.04 mmol/L lower LDL-cholesterol compared to placebo (p<0.0001); CRP (mg/L) was also significantly lower on atorvastatin than placebo (2.59 (0.94-6.08) vs. 3.60 (1.47-7.49) – p<0.0001). CVE risk reduction per mmol/L LDLc reduction was 42% (95%CI -14%-70%). Adverse events in the atorvastatin (298 (19.8%)) and placebo (292 (19.5%)) groups were similar.

CONCLUSION:

Atorvastatin 40mg daily was safe and resulted in significantly greater reduction of LDLc than placebo in patients with RA. The 40% (adjusted) CVE risk reduction is consistent with the Cholesterol Treatment Trialists' Collaboration meta-analysis of statin effects in other populations.

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