Staff Publication

Outcomes of two trials of oxygen-saturation targets in preterm infants (2016)

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Type of publication:
Journal article

Author(s):
Tarnow-Mordi W., Stenson B., Kirby A., Juszczak E., Donoghoe M., *Deshpande S., Morley C., King A., Doyle L.W., Fleck B.W., Davis P.G., Halliday H.L., Hague W., Cairns P., Darlow B.A., Fielder A.R., Gebski V., Marlow N., Simmer K., Tin W., Ghadge A., Williams C., Keech A., Wardle S.P., Kecskes Z., Kluckow M., Gole G., Evans N., Malcolm G., Luig M., Wright I., Stack J., Tan K., Pritchard M., Gray P.H., Morris S., Headley B., Dargaville P., Simes R.J., Brocklehurst P.

Citation:
New England Journal of Medicine, February 2016, vol./is. 374/8(749-760)

Abstract:
BACKGROUND The safest ranges of oxygen saturation in preterm infants have been the subject of debate. METHODS In two trials, conducted in Australia and the United Kingdom, infants born before 28 weeks' gestation were randomly assigned to either a lower (85 to 89%) or a higher (91 to 95%) oxygen-saturation range. During enrollment, the oximeters were revised to correct a calibration-algorithm artifact. The primary outcome was death or disability at a corrected gestational age of 2 years; this outcome was evaluated among infants whose oxygen saturation was measured with any study oximeter in the Australian trial and those whose oxygen saturation was measured with a revised oximeter in the U.K. trial. RESULTS After 1135 infants in Australia and 973 infants in the United Kingdom had been enrolled in the trial, an interim analysis showed increased mortality at a corrected gestational age of 36 weeks, and enrollment was stopped. Death or disability in the Australian trial (with all oximeters included) occurred in 247 of 549 infants (45.0%) in the lower-target group versus 217 of 545 infants (39.8%) in the higher-target group (adjusted relative risk, 1.12; 95% confidence interval [CI], 0.98 to 1.27; P = 0.10); death or disability in the U.K. trial (with only revised oximeters included) occurred in 185 of 366 infants (50.5%) in the lower-target group versus 164 of 357 infants (45.9%) in the higher-target group (adjusted relative risk, 1.10; 95% CI, 0.97 to 1.24; P = 0.15). In post hoc combined, unadjusted analyses that included all oximeters, death or disability occurred in 492 of 1022 infants (48.1%) in the lower-target group versus 437 of 1013 infants (43.1%) in the higher-target group (relative risk, 1.11; 95% CI, 1.01 to 1.23; P = 0.02), and death occurred in 222 of 1045 infants (21.2%) in the lower-target group versus 185 of 1045 infants (17.7%) in the higher-target group (relative risk, 1.20; 95% CI, 1.01 to 1.43; P = 0.04). In the group in which revised oximeters were used, death or disability occurred in 287 of 580 infants (49.5%) in the lower-target group versus 248 of 563 infants (44.0%) in the higher-target group (relative risk, 1.12; 95% CI, 0.99 to 1.27; P = 0.07), and death occurred in 144 of 587 infants (24.5%) versus 99 of 586 infants (16.9%) (relative risk, 1.45; 95% CI, 1.16 to 1.82; P = 0.001). CONCLUSIONS Use of an oxygen-saturation target range of 85 to 89% versus 91 to 95% resulted in nonsignificantly higher rates of death or disability at 2 years in each trial but in significantly increased risks of this combined outcome and of death alone in post hoc combined analyses. (Funded by the Australian National Health and Medical Research Council and others; BOOST-II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry number, ACTRN12605000055606.).

Link to more details or full-text: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=00006024-201602250-00011&LSLINK=80&D=ovft

Partial breast radiotherapy for women with early breast cancer: First results of local recurrence data for IMPORT LOW (CRUK/06/003) (2016)

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Type of publication:
Conference abstract

Author(s):
Coles C., *Agrawal R., Ah-See M.L., Algurafi H., Alhasso A., Brunt A.M., Chan C., Griffin C., Harnett A., Hopwood P., Kirby A., Sawyer E., Syndikus I., Titley J., Tsang Y., Wheatley D., Wilcox M., Yarnold J., Bliss J.M.

Citation:
European Journal of Cancer, April 2016, vol./is. 57/(S4)

Abstract:
Background: IMPORT LOW is a randomised, multi-centre phase III trial testing partial breast radiotherapy (RT) using intensity modulated RT in women with low risk early stage breast cancer, for whom late complications of RT are the dominant hazard rather than local recurrence (LR). Materials and Methods: Women age >50 who had breast conservation surgery, for invasive adenocarcinoma (excluding classical lobular carcinoma) pT1-2 (<3 cm) N0-1, any grade, with minimum microscopic margins of ge;2 mm, were eligible. Patients were randomised (1:1:1) to 40Gy/15F to whole breast (control); 36Gy/15F to whole breast and 40Gy/15Fr to partial breast (test 1); or 40Gy/15F to partial breast (test 2). The primary endpoint is local tumour control in the ipsilateral breast. 1935 patients were required to exclude 2.5% inferiority for each test group (80% power, one-sided alpha 2.5%) assuming 2.5% local recurrence (LR) rate at 5 years in the control group. Key secondary endpoints were late adverse effects measured using a combination of clinical, photographic and patient self-assessments. Analysis was by intention to treat. Results: 2018 patients were recruited from 05/2007 to 09/2010 from 30 UK RT centres (675 control, 674 test 1, 669 test 2). Baseline characteristics were balanced with median age 63 (IQR 58-68); 43%, 47% and 10% were tumour grade 1, 2 and 3; 3% were pN+. Median follow-up is 68.3 (IQR 60.3-73.4) months. The 5-year rate of LR was 1.1% (95% CI 0.5, 2.3), 0.2% (95% CI 0.02, 1.2) and 0.5% (95% CI 0.2-1.4) in the control, test 1 and test 2 groups respectively. Absolute treatment differences in LR with control compared with test 1 is -0.83% (95% CI -1.04, 0.18) and -0.69% (-0.99, 0.44) compared with test 2. For each of the test groups non-inferiority, assessed against the pre-specified 2.5% threshold was demonstrated. Conclusions: At 5 years, partial breast RT was shown to be non-inferior to whole breast RT in women with low risk early breast cancer. LR rates were very low in all treatment groups and moderate and marked normal tissue events were also low across all groups. Follow-up is ongoing and 10 year LR rates will be reported. (Figure Presented).

Failure-Free Survival and Radiotherapy in Patients With Newly Diagnosed Nonmetastatic Prostate Cancer: Data From Patients in the Control Arm of the STAMPEDE Trial (2016)

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Type of publication:
Journal article

Author(s):
James, Nicholas D, Spears, Melissa R, Clarke, Noel W, Dearnaley, David P, Mason, Malcolm D, Parker, Christopher C, Ritchie, Alastair W S, Russell, J Martin, Schiavone, Francesca, Attard, Gerhardt, de Bono, Johann S, Birtle, Alison, Engeler, Daniel S, Elliott, Tony, Matheson, David, O'Sullivan, Joe, Pudney, Delia, *Srihari, Narayanan, Wallace, Jan, Barber, Jim, Syndikus, Isabel, Parmar, Mahesh K B, Sydes, Matthew R, STAMPEDE Investigators

Citation:
JAMA oncology, Mar 2016, vol. 2, no. 3, p. 348-357

Abstract:
The natural history of patients with newly diagnosed high-risk nonmetastatic (M0) prostate cancer receiving hormone therapy (HT) either alone or with standard-of-care radiotherapy (RT) is not well documented. Furthermore, no clinical trial has assessed the role of RT in patients with node-positive (N+) M0 disease. The STAMPEDE Trial includes such individuals, allowing an exploratory multivariate analysis of the impact of radical RT. To describe survival and the impact on failure-free survival of RT by nodal involvement in these patients. Cohort study using data collected for patients allocated to the control arm (standard-of-care only) of the STAMPEDE Trial between October 5, 2005, and May 1, 2014. Outcomes are presented as hazard ratios (HRs) with 95% CIs derived from adjusted Cox models; survival estimates are reported at 2 and 5 years. Participants were high-risk, hormone-naive patients with newly diagnosed M0 prostate cancer starting long-term HT for the first time. Radiotherapy is encouraged in this group, but mandated for patients with node-negative (N0) M0 disease only since November 2011. Long-term HT either alone or with RT, as per local standard. Planned RT use was recorded at entry. Failure-free survival (FFS) and overall survival. A total of 721 men with newly diagnosed M0 disease were included: median age at entry, 66 (interquartile range [IQR], 61-72) years, median (IQR) prostate-specific antigen level of 43 (18-88) ng/mL. There were 40 deaths (31 owing to prostate cancer) with 17 months' median follow-up. Two-year survival was 96% (95% CI, 93%-97%) and 2-year FFS, 77% (95% CI, 73%-81%). Median (IQR) FFS was 63 (26 to not reached) months. Time to FFS was worse in patients with N+ disease (HR, 2.02 [95% CI, 1.46-2.81]) than in those with N0 disease. Failure-free survival outcomes favored planned use of RT for patients with both N0M0 (HR, 0.33 [95% CI, 0.18-0.61]) and N+M0 disease (HR, 0.48 [95% CI, 0.29-0.79]). Survival for men entering the cohort with high-risk M0 disease was higher than anticipated at study inception. These nonrandomized data were consistent with previous trials that support routine use of RT with HT in patients with N0M0 disease. Additionally, the data suggest that the benefits of RT extend to men with N+M0 disease. clinicaltrials.gov Identifier: NCT00268476; ISRCTN78818544.

A "systems medicine" approach to the study of non-alcoholic fatty liver disease (2016)

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Type of publication:
Journal article

Author(s):
Petta, Salvatore; Valenti, Luca; Bugianesi, Elisabetta; Targher, Giovanni; *Bellentani, Stefano ; Bonino, Ferruccio; Special Interest Group on Personalised Hepatology of the Italian Association for the Study of the Liver (AISF), Special Interest Group on Personalised Hepatology of the Italian Association for the Study of the Liver AISF (2016)

Citation:
Digestive and Liver Disease, Mar 2016, vol. 48, no. 3, p. 333-342

Abstract:
The prevalence of fatty liver (steatosis) in the general population is rapidly increasing worldwide. The progress of knowledge in the physiopathology of fatty liver is based on the systems biology approach to studying the complex interactions among different physiological systems. Similarly, translational and clinical research should address the complex interplay between these systems impacting on fatty liver. The clinical needs drive the applications of systems medicine to re-define clinical phenotypes, assessing the multiple nature of disease susceptibility and progression (e.g. the definition of risk, prognosis, diagnosis criteria, and new endpoints of clinical trials). Based on this premise and in light of recent findings, the complex mechanisms involved in the pathology of fatty liver and their impact on the short- and long-term clinical outcomes of cardiovascular, metabolic liver diseases associated with steatosis are presented in this review using a new "systems medicine" approach. A new data set is proposed for studying the impairments of different physiological systems that have an impact on fatty liver in different subsets of subjects and patients. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Reducing medication (TTOs) delays when patients are ready to leave hospital (2016)

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Type of publication:
Post on the Academy of Fab NHS Stuff website

Author(s):
Nick Holding

Citation:
Academy of Fab NHS Stuff (www.fabnhsstuff.net/), February 2016

Abstract:
It’s a commonly held belief that patient discharge medication and discharge summaries are a cause of delays to patients leaving hospital.

Last year we tested to what extent this was a problem, confirm or dispel myths, and work with teams to find ways to improve turnaround times of medication.

We found that the process could be broken down into 4 key cycles of work:

1. Pharmacist generating the medication request (average 1.5hrs)

2. Prescription in queue waiting to be picked (average 1hr)

3. Prescription collection in Pharmacy Dept (average 50 mins)

4. Delivery of medication back to the patient (average 1hr)

Overall lead time to turnaround medication was therefore 4hrs 40mins. One of our roles in this was to help the teams that carry out the work, improve the work. So with this in mind we presented our findings to ward and pharmacy teams and ran a workshop to identify a number of improvement ideas which we would test and measure their effectiveness using Plan, Do, Study, Act (PDSA) cycles.

The teams came up with 3 simple ideas that they wanted to try out.

1. Pharmacist on daily ward round to improve communication and reduce delays in generating prescription

2. Separate work line in pharmacy for outpatient and inpatient activity to reduce delays in the picking queue

3. Introduce a direct delivery service to wards from pharmacy to reduce delivery times of medication

Testing the concepts and ideas Using PDSA cycles we planned a series of improvement weeks where we tested out the various concepts and measured the impact. Our aim was to develop a proof of concept which could then be explored further and introduced appropriately. By doing a number of simple steps we found that in after the first improvement week we reduced the turnaround time from 4hrs 40mins to 2hrs 30mins. By retesting, refining and introducing the other ideas in the second improvement week, the teams reduced the turnaround time further down to 1hr 30mins

Therefore, in conclusion, by truly understanding the current state, allowing the teams that carry out the work to improve the work, and giving them the space and time to test out their ideas, we showed that we can significantly reduce delays that patient experience when they are ready to leave hospital.

Link to more details or full-text: http://www.fabnhsstuff.net/2016/02/24/reducing-medication-ttos-delays-patients-ready-leave-hospital/

Taking Board Meetings outside the room (2016)

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Type of publication:
Post on the Academy of Fab NHS Stuff website

Author(s):
Adrian Osborne

Citation:
Academy of Fab NHS Stuff (www.fabnhsstuff.net/), March 2016

Abstract:
Trust Board meetings sometimes aren’t the most engaging or interactive of experiences, and any meeting that takes place in one place in one town will be limited in the number of people it can reach.

At The Shrewsbury and Telford Hospital NHS Trust (SATH) we’re on a journey, using social media to take our meetings outside the room and bring communities (real and virtual) into the room.

Link to more details or full-text: http://www.fabnhsstuff.net/2016/03/16/taking-board-meetings-outside-room/