Infliximab induction regimes in steroid refractory acute severe colitis: A multi-centre retrospective cohort study with propensity score analysis (2019)

Type of publication:
Conference abstract

Author(s):
Sebastian S.; Myers S.; Syed N.; Argyriou K.; Samuel S.; Moran G.; Martin G.; Allen P.B.; *Los L.; *Butterworth J.; Fiske J.; Limdy J.; Ranjan R.; Dhar A.; Cooper B.; Shenoy A.H.; Patel N.; Subramanian S.; Goodoory V.; Shaikh F.; Shenderey R.; Ching H.L.; Lobo A.; Jayasooriya N.; Parkes G.; Brooks J.; Raine T.

Citation:
Journal of Crohn’s and Colitis; Mar 2019; vol. 13

Abstract:
Background: While infliximab is used as rescue therapy for steroid refractory acute severe colitis (ASUC),
between 30 and 40% of patients do not respond and undergo colectomy. Accelerated induction regimes of
infliximab have been proposed to improve response rates. We aimed to evaluate colectomy rates in steroid
refractory ASUC patients receiving standard induction (SI) vs. accelerated induction (AI) of infliximab.
Method(s): Data collected on hospitalised patients receiving rescue therapy for steroid refractory ASUC. The choice of rescue therapy was at the discretion of the treating clinician. Accelerated induction (AI) was defined as receiving second dose of infliximab within 8 days of first rescue therapy or receiving front loading dose of 10 mg/kg. Our primary outcome was the short-term (in-patient, 30 days and 90 days) colectomy rate. Secondary outcomes were 12-month colectomy rates, length of hospital stay (LOS), and complication rates. We used a propensity score analysis with optimal calliper matching using a priori defined high-risk covariates at the start of rescue therapy (albumin, CRP, CRP-albumin ratio, haemoglobin nadir and pancolitis) to reduce potential provider selection bias.
Result(s): A total of 131 patients receiving infliximab rescue therapy were included, of whom 102 patients
received SI and 29 received AI. There was no difference in age, duration of diagnosis, age at rescue therapy,
Montreal class or use of steroids, 5ASAs or thiopurines prior to index admission. In the unmatched overall
cohort, there was no difference in colectomy during index admission (13% vs. 20%, p = 0.26), 30-day colectomy (18% vs. 20%, p = 0.45), 90-day colectomy (20% vs. 24%, p = 0.38) or 6 month colectomy (25% vs. 27%, p = 0.49). The LOS was shorter in the SI group (14.87 +/- 8.1 days vs. 19.31 +/- 5.8 days, p = 0.007). In patients who underwent colectomy, there were no differences in complications or serious infection rates. In the propensity score-matched cohort of 52 patients, there was no difference in overall colectomy rates between SI and AI groups (57% vs. 31%, p = 0.09), but the index admission colectomy (53% vs. 23%, p = 0.045) and 30-day colectomy (57% vs. 27%, p = 0.048) rates were higher in those receiving SI. There was no significant difference in LOS between SI and AI groups (23.6 +/- 4.3 vs. 18.2 +/- 7.1 days, p = 0.09) or in overall complication and infection rates but there was a mortality in AI group.
Conclusion(s): In this retrospective cohort study, there was no difference in overall colectomy rates in ASUC patients receiving different induction dosing regimens of infliximab. However, using propensity score matching, the short-term colectomy rates appear to be better in those receiving accelerated induction regime. A prospective study to confirm findings is planned.

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MON-112 Home Haemodialysis (HHD) with low dialysate volume (LDV) – The green benefit (2019)

Type of publication:
Conference abstract

Author(s):
*Nair, S.; Gautier J.

Citation:
Kidney International Reports; Jul 2019; vol. 4 (no. 7), S350

Abstract:
Introduction: Man-made greenhouse gas emissions have impacted climate changes significantly. This has
adversely affected human health presently and has serious implications for future generations. Healthcare
industry itself contributes towards these carbon footprints. In England, 3.2% of the total CO2 emissions are accounted for by the healthcare industry alone producing 18 million tons CO2eq emissions. National Health Services (NHS) England CO2 emissions exceeds the total emissions from all aircraft departing from Heathrow, the largest European airport. Dialysis patient care accounts for 62.5% of the carbon footprint of a renal service. In UK, the prevalence rate of dialysis patients is 440 patients per million population, that is 25,261 haemodialysis (HD) patients in 2016. 1256 patients received dialysis at home. In-centre HD undertaking dialysis 4 hours 3 times/week, consumes more than 55,000 Litres of water/patient/year and contributes 3,818 kgCO2eq to the carbon footprint. A LDV system may have less emissions compared to traditional machines.
Method(s): This footprint is influenced more by frequency of treatments rather than duration. On average in Europe, patients using NxStage System One (NSO) dialyse 5.7 times for 2.6 hours/week with 24.3 Litres of dialysate/session to deliver a 2.61 stdKt/V. Based on manufacturers data, we calculated fluids volume, weight and energy required with NSO and we compared with requirements to deliver 3 times/week HD or the same clearance with traditional machines (3.5 times/week to deliver a 2.6 stdKt/V in the same patient).
Result(s): Reduced water usage NSO with PureFlow allows to prepare dialysate in-situ. It includes deionization technology and converts 1 Litre source water to 1 Litre of ultrapure dialysate as against traditional osmosis water systems which have a conversion rate of around 50%. Frequent therapy as above utilizes 7377 Litres of source water/year, only 13% of the 56,160 Litres of water used in centre HD and 12% of the 59,717 Litres of water required to deliver the same clearance with a traditional system. Low shipping volume of dialysate concentrates Fluids is the main contributor to shipping volumes in dialysis supplies. PureFlow system allows a minimal shipping volume of 422 Litres of concentrate including buffer per patient-year vs. 702-780 Litres of acid concentrate (dilution 1/43 or 1/35) in conventional HD or 819-910 Liters to deliver the same clearance as with NSO. PureFlow concentrate equals 1.5ton and 0.8m3 per patient-year. Conventional therapy equals 0.9-1.1 ton and 1.4-1.7 m3 (dilution 1/43 or 1/35) of acid concentrate. Delivering the same clearance with a traditional system equals 1.0-1.2 ton and 1.6-2.0 m3. Less energy consumption NSO with PureFlow utilizes 8.2-10.7 kwh to deliver 6 sessions/week. This is 28% less than 29.6-52.9 kwh to deliver 3 sessions/week with a traditional system. If one includes the energy used for water treatment which amounts to 32.5-63.2 kwh/week without heat disinfection, PureFlow usage is less than 20% of this.
Conclusion(s): Despite increased frequency, HHD with LDV is a much greener option for dialysis patients and significantly reduces the carbon footprint. Such systems are the order of the day where one is constantly looking for effective greener options in delivering treatments for our patients.

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A randomised, multi-centre, double-blind, placebo-controlled study of a targeted release oral cyclosporine formulation in the treatment of mild-to-moderate ulcerative colitis: Efficacy results (2019)

Type of publication:
Conference abstract

Author(s):
Bloom S.; Iqbal T.; Nwokolo C.; *Smith M.; O’Donoghue D.; Hall J.; Dzyngel B.

Citation:
Journal of Crohn’s and Colitis; Mar 2019; vol. 13

Abstract:
Background: Cyclosporine (CsA) is an effective treatment for patients with acute severe ulcerative colitis (UC), and studies have shown that it has an impact on disease activity comparable to the anti-TNF agent,
infliximab.1,2 Concerns regarding systemic toxicities have limited its role to short-term induction therapy and as a bridge to other therapies. ST-0529 is a novel low dose, controlled release formulation of CsA. A Phase 1 dose-ranging study demonstrated that tissue concentrations improved when it is given twice daily (BID).3
Methods: A total of 118 subjects with mild (baseline DAI < 6) or moderate (baseline DAI >= 6) UC were
randomised 1:1 to receive 75 mg ST-0529 once daily or placebo (53 and 65 patients, respectively) for 4 weeks in a multi-centre, randomised, double-blind, placebo-controlled, Phase IIa study. Patients using UC medications (eg low-dose steroids, 5-aminosalicylates, and immunomodulatory agents) on screening could continue them if agreed to maintain a stable dosing regimen during the study. The primary objective was to evaluate the efficacy of ST-0529 in inducing clinical remission (DAI score <=2, with no individual score >1 and rectal bleeding subscore of 0 or 1). The secondary objectives included clinical response, mucosal and histological healing, safety, and tolerability.
Result(s): A numerical although not statistically significant advantage of ST-0529 over placebo was found for rates of clinical remission (ST-0529: 13.2%; placebo: 6.3%, p = 0.2211) and clinical response (ST-0529: 30.2%; placebo: 18.8%, p = 0.1923). There were no differences between the treatment groups for mucosal and histological healing. ST-0529 was safe and well-tolerated. A post hoc subgroup analysis was performed to evaluate effects by disease severity. Clinical remission and clinical response rates in subjects with moderate (baseline DAI >=6) and mild (baseline DAI <6) disease (ITT, N = 118)
Conclusion(s): In this pilot study, ST-0529 given once daily, was safe, well tolerated, and showed a numerically higher, but not statistically significant difference in remission rate in patients with mild-to-moderate UC compared with placebo after 4 weeks of treatment. In the post hoc analysis, differences in the clinical response between treatment subgroups achieved statistical significance in some subgroups, the largest clinical response rate in moderate UC patients taking 5-aminosalicylates and/or steroids. These preliminary data, added to the data from a Phase 1 study, support further development of ST-0529 as a treatment for the induction and maintenance of remission in UC patients with moderate to severe disease. (Table Presented).

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Reflective doctors and cool babies (2019)

Type of publication:
Conference abstract

Author(s):
*Charlesworth D.; Cunningham S.; Dudley L.; Bentley F.; Oguntimehin J.; Fairclough S.

Citation:
BJOG: An International Journal of Obstetrics and Gynaecology; Jun 2019; vol. 126 ; p. 45

Abstract:
Introduction In 2014, the RCOG launched the ‘Each Baby Counts’ initiative which included the aim of reducing the number of neonates who are left severely disabled by preventable incidents in labour. The initial report concluded that a different outcome may have been achieved in 76% of cases if different care had been received. Around the same time, reflective practice among doctors faced a significant challenge secondary to negative perceptions of its use in litigation, and resilience continued to be tested as work pressures, insufficient staff numbers, and public perceptions continued to increase. With the interplay between all these factors being crucial in achieving the state of experiential learning necessary to achieve the EBC goals, we look at a different method for reflective practice and quality improvement. Methods In 2015, we launched a series of measures inspired by EBC to reduce our rates of neonates requiring therapeutic hypothermia. One key component of our programme was a change in how our RCAs were undertaken. We changed RCA leads to include staff at all levels from across the multidisciplinary team, promoted a reflective journey and thematic analysis, changed our meetings to include staff recommended by the EBC report to achieve a more multidisciplinary and inclusive representation, promoted team learning, and fed back via casebased, reflective teaching. We then undertook a 48-month retrospective audit from 01/2015 to 12/2018 to see if we had improved care. Results In 2015, our therapeutic hypothermia annual incidence was 12, 11 in 2016, 7 in 2017, and 2 by 12/2018. Thematic analysis of our cases revealed a change in precipitating factors from preventable to unpredictable, and we subsequently increased the proportion of cases in which we concluded we could not improve the end outcome (though learning was identified in all). Staff empowerment increased, hierarchies flattened, and our ability to identify key targeted improvements increased to facilitate change and drive improvement. Conclusion We discovered that, if conducted well, with reflection as a key component, and the aim to promote a culture of learning and becoming, RCA can be used as a powerful teaching tool in training, and to promote improved patient care. As more staff engaged in our new RCA process, feedback indicated an increase in resilience and a more open culture of learning, unhindered by more traditional elements of reflective learning.

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A national survey on the uterotonic use for the prevention of postpartum haemorrhage (2019)

Type of publication:
Conference abstract

Author(s):
*Stephanou M.; Gallos I.; Coomarasamy A.

Citation:
BJOG: An International Journal of Obstetrics and Gynaecology; Jun 2019; vol. 126 ; p. 148-149

Abstract:
Objective: To map the current national practice of the first line uterotonic drug given for the prevention of
postpartum haemorrhage (PPH) at both vaginal and caesarean section deliveries. Design A prospective national survey was carried out by contacting maternity units by means of telephone contact. Survey questions were set out to evaluate the uterotonic drug of choice in accordance with local hospital policy which was then compared with national guidance.
Methods: Maternity units across England were identified using the NHS Maternity Statistics 2016-2017 data available from NHS Digital. 136 NHS trusts were identified and 143 maternity units were contacted. Responses were collected by means of telephone communication with each of the maternity units. Maternity governance leads were the first point of contact followed by labour ward coordinators and senior labour ward doctors. The Health Research Authority Ethics toolkit was applied and determined that Research and Ethics council approval was not required.
Results: All 143 maternity units identified were contacted to answer the survey. 118 (82.5%) responses were obtained for the uterotonic of choice used for the prevention of postpartum haemorrhage at vaginal birth, of which 75 (63.5%) maternity units administered oxytocin with ergometrine combination as the first-line uterotonic. 116 (81%) responses were collected for the uterotonic of choice at caesarean section, where 95 (81.9%) administered intravenous oxytocin as first line.
Conclusion: The National Institute of Clinical Excellence (NICE) and World Health Organization (WHO)
guidelines recommend oxytocin as the first-line uterotonic of choice for the prevention of postpartum
haemorrhage. This survey has shown that current UK practice conflicts with both international and national guidance, favouring oxytocin with ergometrine over oxytocin alone at vaginal birth. Postpartum haemorrhage is a significant cause of morbidity and mortality; it is recommended that further attention be paid towards the first line uterotonic agent used for the prevention of a PPH in line with the most current up to date evidence.

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The genetic and clinico-pathological profile of early-onset progressive supranuclear palsy (2019)

Type of publication:
Journal article

Author(s):
Jabbari E.; Woodside J.; Tan M.M.X.; Morris H.R.; Pavese N.; Bandmann O.; Ghosh B.C.P.; Massey L.A.; *Capps E.;Warner T.T.; Lees A.J.; Revesz T.; Holton J.L.; Williams N.M.; Grosset D.G.

Citation:
Movement Disorders; 2019 [epub ahead of print]

Abstract:
Background: Studies on early-onset presentations of progressive supranuclear palsy (PSP) have been limited to those where a rare monogenic cause has been identified. Here, we have defined early-onset PSP (EOPSP) and investigated its genetic and clinico-pathological profile in comparison with late-onset PSP (LOPSP) and Parkinson’s disease (PD).
Method(s): We included subjects from the Queen Square Brain Bank, PROSPECT-UK study, and Tracking
Parkinson’s study. Group comparisons of data were made using Welch’s t-test and Kruskal-Wallis analysis of variance. EOPSP was defined as the youngest decile of motor age at onset (<=55 years) in the Queen Square Brain Bank PSP case series.
Result(s): We identified 33 EOPSP, 328 LOPSP, and 2000 PD subjects. The early clinical features of EOPSP usually involve limb parkinsonism and gait freezing, with 50% of cases initially misdiagnosed as having PD. We found that an initial clinical diagnosis of EOPSP had lower diagnostic sensitivity (33%) and positive predictive value (38%) in comparison with LOPSP (80% and 76%) using a postmortem diagnosis of PSP as the gold standard. 3/33 (9%) of the EOPSP group had an underlying monogenic cause. Using a PSP genetic risk score (GRS), we showed that the genetic risk burden in the EOPSP (mean z-score, 0.59) and LOPSP (mean z-score, 0.48) groups was significantly higher (P < 0.05) when compared with the PD group (mean z-score, -0.08).
Conclusion(s): The initial clinical profile of EOPSP is often PD-like. At the group level, a PSP GRS was able to differentiate EOPSP from PD, and this may be helpful in future diagnostic algorithms.

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Expanding the clinical spectrum of dermal hyperneury. Report of nine new cases and review of literature (2019)

Type of publication:
Journal article

Author(s):
Ieremia, Eleni; Marušić, Zlatko; Mudaliar, Vivek; *Kelly, Susan; Gonzalvo Rodriguez, Pablo; McNiff, Jennifer M; LeBoit, Philip E; Calonje, Eduardo

Citation:
Histopathology; Jun 2019 [epub ahead of print]

Abstract:
AIMS Dermal hyperneury is defined as the hypertrophy of small nerves in the dermis. It has been described in a variety of settings. We present a series of nine new cases with distinctive clinical presentation and review the existing literature. The aim of the study is to summarise the clinical, histopathological and immunohistochemical findings in a case series of dermal hyperneury with unique clinical presentation. METHODS AND RESULTS Nine cases were identified from the referral practice of one of the authors. Clinical characteristics, including demographic details were collated. The histopathological features and novel immunohistochemical findings were analysed. Four cases presented with multiple skin lesions. Clinical evaluation revealed no associated syndromic stigmata. The histology in all cases was that of dermal hyperneury. Immunohistochemistry for phosphatase and tensin homolog (PTEN) and RET was supportive of the lack of syndromic association. CONCLUSION The presentation of dermal hyperneury with multiple cutaneous lesions and no syndromic associations is distinctive and the study with PTEN and RET immunohistochemistry is previously undescribed. Comparison to recent reports of multiple nonsyndromic mucocutaneous neuromas is discussed.

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Preoperative anemia and outcomes in cardiovascular surgery: systematic review and meta-analysis (2019)

Type of publication:
Systematic Review

Author(s):
Padmanabhan, Hari; Siau, Keith; *Curtis, Jason; Ng, Alex; Menon, Shyam; Luckraz, Heyman; Brookes, Matthew J

Citation:
The Annals of Thoracic Surgery; Jun 2019 [epub ahead of print]

Abstract:
BACKGROUND Pre-operative anemia is common in patients scheduled for cardiac surgery. However, its effect on postoperative outcomes remains controversial. This meta-analysis aimed to clarify the impact of anemia on outcomes following cardiac surgery.METHODS A literature search was conducted on MEDLINE, Embase, Cochrane, and Web of Science databases. The primary outcome was 30-day postoperative or in-hospital mortality. Secondary outcomes included acute kidney injury (AKI), stroke, blood transfusion, and infection. A meta-analytic model was used to determine the differences in the above postoperative outcomes between anemic and non-anemic patients. RESULTS Out of 1103 studies screened, 22 met the inclusion criteria. A total of 23624 (20.6%) out of 114277 patients were anemic. Anemia was associated with increased mortality (odds ratio [OR] 2.74, 95% confidence interval [CI] 2.32-3.24; I2=69.6%; p<0?001), AKI (OR 3.13, 95% CI 2.37-4.12; I2=71.1%; p<0?001), stroke (OR 1.46, 95% CI 1.24-1.72; I2=21.6%; p<0?001), and infection (OR 2.65, 95% CI 1.98-3.55; I2=46.7%; p<0?001). More anemic patients were transfused than non-anemic (33.3 versus 11.9%). No statistically significant association was found between mortality and blood transfusion (OR 1.35, 95% CI 0.92-1.98; I2=83.7%; p=0.12) but we were not able to compare mortality with or without transfusion in those who were or were not anemic. CONCLUSIONS Preoperative anemia is associated with adverse outcomes following cardiac surgery. These findings support the addition of preoperative anemia to future risk prediction models, and as a target for risk modification.

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