Author: Jason Curtis

A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy (2019)

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Type of publication:
Randomised controlled trial

Author(s):
A. Coomarasamy, A.J. Devall, V. Cheed, H. Harb, L.J. Middleton, I.D. Gallos, H. Williams, A.K. Eapen, T. Roberts, C.C. Ogwulu, I. Goranitis, J.P. Daniels, A. Ahmed, R. Bender‑Atik, K. Bhatia, C. Bottomley, J. Brewin, M. Choudhary, F. Crosfill, S. Deb, W.C. Duncan, A. Ewer, K. Hinshaw, T. Holland, F. Izzat, J. Johns, K. Kriedt, M.-A. Lumsden, P. Manda, J.E. Norman, N. Nunes, C.E. Overton, S. Quenby, S. Rao, J. Ross, A. Shahid, *M. Underwood , N. Vaithilingam, L. Watkins, C. Wykes, A. Horne, and D. Jurkovic

Citation:
New England Journal of Medicine 2019;380:p.1815-24.

Abstract:
BACKGROUND
Bleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy.
METHODS
We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data.
RESULTS
A total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P=0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P=0.08). The incidence of adverse events did not differ significantly between the groups.
CONCLUSIONS
Among women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439.)

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Pre-transplant Nurse Led Education Clinic (2019)

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Type of publication:
Poster presentation

Author(s):
*Dean S, *Rogers C, *Chand S

Citation:
Joint British Transplant Society and NHS Blood and Transplant Annual Congress 6th – 8th March 2019, Harrogate Convention Centre

Abstract:
Introduction: Locally, there is a 40% pre-emptive renal transplant listing rate, between 2013-2016; and 22% for living donor pre-emptive 2014-2017. Thus we needed to revise our processes. After returning from the tertiary transplant centre, patient feedback including their shock of what was required and their follow-up arrangements, and they felt under-prepared from their local education.
Methods: By creating a separate renal pre-transplant education clinic, we aim to improve the education and experience of potential recipients and donors in order to improve or transplantation rates. This clinic was started in August 2016. It was also important to rationalise the time of the single transplant nurse more effectively.
Results: The nurse was able to stop time wasted travelling between individual consultant clinics, catching patients in an adhoc manner, and time wasted travelling between hospital sites. There was an increase of 20% over a 18 months period of patients transplant listed. Patients feedback has been qualitatively positive after their tertiary centre assessments, with noone reporting feeling under-prepared or shocked from the information and requirements if transplanted. Discussion: The nurse led clinic has been successful and we would like to share this model with other units. Other surprising benefits have included patients being better prepared for their transplantation clinic assessment at the tertiary assessment. Potential living donor assessments and any initial investigations have been identified and performed in a more timely manner. The clinic has also allowed to unmask and address unmet psychological and social needs prior to being assessed for transplantation and thus reducing the psychological burden post-transplantation.

Genetic Deletion of the Lipid Raft Protein Caveolin-1 Leads to Worsening Renal Fibrosis (2018)

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Type of publication:
Journal article

Author(s):
*Chand S , Hazeldine J, Smith S, Borrows R.

Citation:
Journal of Clinical Nephrology and Renal Care 2018 Jun;4(1):037

Abstract:
Background
Renal disease is a major global public health issue. Renal interstitial fibrosis is the characteristic histopathological finding in all progressive renal disease. Caveolin-1 is the essential structural protein for lipid rafts called caveolae that are ubiquitously distributed among fibroblasts, endothelial and epithelial cells. Caveolin-1 acts as an intracellular signalling pathway chaperone in fibrotic disease. Presently, caveolin-1 expression is associated with more severe renal disease in human and previous murine studies. In non-renal fibrosis, caveolin-1 protects against fibrosis. The purpose of this study was to investigate if caveolin-1 knockout led to an increased fibrotic phenotype using the unilateral ureteric obstruction model of renal fibrosis.
Methods
Using 2 time-points of the unilateral ureteric obstruction model, wild-type and caveolin-1 knockout mouse kidneys were analysed for caveolin-1 expression and markers of fibrosis using histology, Gomori staining, real-time quantified polymerase chain reaction, Western blotting and confocal microscopy.
Results
Confocal microscopy shows caveolin-1 staining mainly in glomerulus, lining of tubules as well as the vasculature. There was increased caveolin-1 expression the longer the unilateral obstruction occurred as well as in the contralateral compensating non-obstructed kidney. Caveolin-1 knockout had less fibrosis at day 3 histologically but more at day 14 as compared to wild-type. There were significantly more F4/80 positive staining cells at day 3 and day 14 in the wild-type injured kidney as compared to the caveolin-1 knockout mouse.
Conclusion
Caveolin-1 knockout leads to a worse fibrosis upon unilateral ureteric obstruction. Caveolin-1 expression manipulation timing remains to be elucidated in reducing renal fibrosis.

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Strategies for investigating the genetics of chronic kidney 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 4(1): 004-006.

Abstract:
This short review describes the strategies employed for investigating genetic variation in chronic kidney disease as well as highlighting potential shortfalls that should be overcome in future studies.

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