2019

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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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.

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.

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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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Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study) (2019)

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Type of publication:
Journal article

Author(s):

Schmidinger M.; Bamias A.; Procopio G.; Hawkins R.; Sanchez A.R.; Vazquez S.; *Srihari N.; Kalofonos H.; Bono P.; Pisal C.B.; Hirschberg Y.; Dezzani L.; Ahmad Q.; Jonasch E.; Gimeno R.A.; Herranz U.A.; Ardavanis A.; Ashraf S.A.; Barone C.; Bella S.R.; Belz H.; Companario E.B.; Bolling C.; Bothe K.; Carteni G.; Espinosa J.C.; Clausse M.; Confente C.; Coskun H.; Herrero G.C.; Demey W.; D'hondt R.; Santasusana M.D.; Doshi G.; Elkiran E.; Facchini G.; Fein L.; Calvo O.F.; Flaherty A.; Fountzilas G.; Fruehauf J.; Diaz E.G.; Garcia R.; Dominguez R.G.; Ghosn M.; Glorieux P.; Goebell P.J.; Gutierrez L.G.-A.; Gonzalez M.; Green N.B.; Arnau M.G.; Harich H.-D.; Hegele A.; Perez C.H.; Herrmann E.; Horniniger W.J.; Hutson T.E.; Janetschek G.; Kalantari H.; Klausmann M.; Kolin M.; Krause S.; Kroening H.; Sorrosal J.J.L.; Lazaro M.; Lema M.; Lema M.L.; Lin J.; Lueck A.; Lybaert W.; Magi A.; Marina V.A.; Rey J.P.M.; Matus G.; Melear J.; Gonzalez B.M.; Milella M.; Montalar J.; Ferrandis J.M.; Nathan P.; Nechushtan H.; Nusch A.; Ojamaa K.; Oksuzoglu B.; Ozkan M.; Papazisis K.; Passalacqua R.; Pe'er A.; Gracia J.L.P.; Pichler A.; Pokker H.; Porta C.; Rauchenwald M.; Richardet M.E.; Richey S.L.; Garcia J.M.R.; Rudolph R.; Sabbatini R.; Salmon J.-P.; Lobera C.S.; Sarid D.L.; Saylors G.B.; Schrijvers D.; Schulze M.; Sevilay A.; Shumaker G.G.; Siemer S.; de Prado y Otero D.S.; Stoiber F.; Rodriguez C.S.; Varela M.S.; Vasanthan S.; Estevez S.V.; Vehling-Kaiser U.; Vogelzang N.; Weiss H.; Whenham N.; Wyendaele W.; Yildiz R.; Yucel I.; Zarba J.J.; Zarkar A.; Zhong W.; Ziem P.

Citation:
The Oncologist; Apr 2019; vol. 24 (no.4); p. 491-497

Abstract:
BACKGROUND Real-world data are essential to accurately assessing efficacy and toxicity of approved agents in everyday practice. PRINCIPAL, a prospective, observational study, was designed to confirm the real-world safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC).SUBJECTS, MATERIALS, AND METHODS Patients with clear cell advanced/metastatic RCC and a clinical decision to initiate pazopanib treatment within 30 days of enrollment were eligible. Primary objectives included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity (RDI) and its effect on treatment outcomes, change in health-related quality of life (HRQoL), and safety. We also compared characteristics and outcomes of clinical-trial-eligible (CTE) patients, defined using COMPARZ trial eligibility criteria, with those of non-clinical-trial-eligible (NCTE) patients. Secondary study objectives were to evaluate clinical efficacy, safety, and RDI in patient subgroups.RESULTS Six hundred fifty-seven patients were enrolled and received ≥1 dose of pazopanib. Median PFS and OS were 10.3 months (95% confidence interval [CI], 9.2-12.0) and 29.9 months (95% CI, 24.7 to not reached), respectively, and the ORR was 30.3%. HRQoL showed no or little deterioration over time. Treatment-related serious adverse events (AEs) and AEs of special interest occurred in 64 (9.7%), and 399 (60.7%) patients, respectively. More patients were classified NCTE than CTE (85.2% vs. 14.8%). Efficacy of pazopanib was similar between the two groups. CONCLUSION PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting. IMPLICATIONS FOR PRACTICE PRINCIPAL is the largest (n = 657) prospective, observational study of pazopanib in patients with advanced/metastatic renal cell carcinoma, to the authors' knowledge. Consistent with clinical trial results that often contain specific patient types, the PRINCIPAL study demonstrated that the effectiveness and safety of pazopanib is similarly safe and effective in patients with advanced kidney cancer in a real-world clinical setting. The PRINCIPAL study showed that patients with advanced kidney cancer who are treated with first-line pazopanib generally do not show disease progression for approximately 10 months and generally survive for nearly 30 months.

Full-text available [NHS OpenAthens account required]

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Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception (2019)

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Type of publication:
Randomised controlled trial

Author(s):
Dhillon-Smith, Rima K; Middleton, Lee J; Sunner, Kirandeep K; Cheed, Versha; Baker, Krys; Farrell-Carver, Samantha; Bender-Atik, Ruth; Agrawal, Rina; Bhatia, Kalsang; Edi-Osagie, Edmond; Ghobara, Tarek; Gupta, Pratima; Jurkovic, Davor; Khalaf, Yacoub; MacLean, Marjory; McCabe, Christopher; Mulbagal, Khashia; Nunes, Natalie; Overton, Caroline; Quenby, Siobhan; Rai, Raj; Raine-Fenning, Nick; Robinson, Lynne; Ross, Jackie; *Sizer, Andrew; Small, Rachel; Tan, Alex; *Underwood, Martyn ; Kilby, Mark D; Boelaert, Kristien; Daniels, Jane; Thangaratinam, Shakila; Chan, Shiao Y; Coomarasamy, Arri

Citation:
The New England Journal of Medicine Apr 2019; 380 (no. 14); p. 1316-1325

Abstract:
BACKGROUND Thyroid peroxidase antibodies are associated with an increased risk of miscarriage and preterm birth, even when thyroid function is normal. Small trials indicate that the use of levothyroxine could reduce the incidence of such adverse outcomes. METHODS We conducted a double-blind, placebo-controlled trial to investigate whether levothyroxine treatment would increase live-birth rates among euthyroid women who had thyroid peroxidase antibodies and a history of miscarriage or infertility. A total of 19,585 women from 49 hospitals in the United Kingdom underwent testing for thyroid peroxidase antibodies and thyroid function. We randomly assigned 952 women to receive either 50 μg once daily of levothyroxine (476 women) or placebo (476 women) before conception through the end of pregnancy. The primary outcome was live birth after at least 34 weeks of gestation. RESULTS The follow-up rate for the primary outcome was 98.7% (940 of 952 women). A total of 266 of 470 women in the levothyroxine group (56.6%) and 274 of 470 women in the placebo group (58.3%) became pregnant. The live-birth rate was 37.4% (176 of 470 women) in the levothyroxine group and 37.9% (178 of 470 women) in the placebo group (relative risk, 0.97; 95% confidence interval [CI], 0.83 to 1.14, P = 0.74; absolute difference, -0.4 percentage points; 95% CI, -6.6 to 5.8). There were no significant between group differences in other pregnancy outcomes, including pregnancy loss or preterm birth, or in neonatal outcomes. Serious adverse events occurred in 5.9% of women in the levothyroxine group and 3.8% in the placebo group (P = 0.14). CONCLUSIONS The use of levothyroxine in euthyroid women with thyroid peroxidase antibodies did not result in a higher rate of live births than placebo. (Funded by the United Kingdom National Institute for Health Research; TABLET Current Controlled Trials number, ISRCTN15948785.).

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