BackgroundPoor nutrition in the first months after oesophago-gastric resection is a contributing factor to the reduced quality of life seen in these patients. The aim of this pilot and feasibility study was to ascertain the feasibility of conducting a multi-centre randomised controlled trial to evaluate routine home enteral nutrition in these patients.MethodsPatients undergoing oesophagectomy or total gastrectomy were randomised to either six weeks of home feeding through a jejunostomy (intervention), or treatment as usual (control). Intervention comprised overnight feeding, providing 50 % of energy and protein requirements, in addition to usual oral intake. Primary outcome measures were recruitment and retention rates at six weeks and six months. Nutritional intake, nutritional parameters, quality of life and healthcare costs were also collected. Interviews were conducted with a sample of participants, to ascertain patient and carer experiences.ResultsFifty-four of 112 (48 %) eligible patients participated in the study over the 20 months. Study retention at six weeks was 41/54 patients (76 %) and at six months was 36/54 (67 %). At six weeks, participants in the control group had lost on average 3.9 kg more than participants in the intervention group (95 % confidence interval [CI] 1.6 to 6.2). These differences remained evident at three months (mean difference 2.5 kg, 95 % CI −0.5 to 5.6) and at six months (mean difference 2.5 kg, 95 % CI −1.2 to 6.1). The mean values observed in the intervention group for mid arm circumference, mid arm muscle circumference, triceps skin fold thickness and right hand grip strength were greater than for the control group at all post hospital discharge time points. The economic evaluation suggested that it was feasible to collect resource use and EQ-5D data for a full cost-effectiveness analysis. Thematic analysis of 15 interviews identified three main themes related to the intervention and the trial: 1) a positive experience, 2) the reasons for taking part, and 3) uncertainty of the study process.ConclusionsThis study demonstrated that home enteral feeding by jejunostomy was feasible, safe and acceptable to patients and their carers. Whether home enteral feeding as ’usual practice’ is a cost-effective therapy would require confirmation in an appropriately powered, multi-centre study.Trial registrationUK Clinical Research Network ID 12447 (main trial, first registered 30 May 2012); UK Clinical Research Network ID 13361 (qualitative substudy, first registered 30 May 2012); ClinicalTrials.gov NCT01870817 (first registered 28 May 2013)

Results from extensive cruises in the years 2000 and 2001 throughout distinct ecohydrodynamic regions of the central and southern North Sea are presented and used to generate estimates of gross primary production and new production. An undulating CTD fitted with a fluorometer was towed over a distance of 12,000 kms. Fluorescence data were used to determine the chlorophyll distribution and derive estimates of phytoplankton biomass. These results were combined with estimates of primary production (new and regenerated) from experiments from one cruise in order to estimate gross production for a greater geographical extent. Results from repeat inter-annual transects showed that the strength of the thermocline and the associated deep chlorophyll maximum were variable. However, when the primary production was integrated over the 15-40 m depth, the variability between years was low. While the depth and strength of the deep chlorophyll maximum varied across the region, a deep chlorophyll maximum (DCM) is a consistent and widespread feature of this region at around 30 m depth. In 2001 the calculated average primary production rate in summer for the whole area surveyed was 0. 91 g C m day. This daily production equates to ~130 g C m for the summer stratified period. In the offshore stratified regions around the Dogger Bank and Eastern Central North Sea primary production of 64 g C m associated with the deep chlorophyll maximum (15-40 m) accounted for 60 % of total primary production during the summer stratified period (after the spring bloom). Approximately 66 % of new production in these areas occurred in the DCM. This study shows the extent of the DCM in the North Sea and demonstrates its importance in sustaining primary production after the spring bloom. © 2013 UK Crown

Total word count including appendix: 93,499 ii ABSTRACT BackgroundThere is good evidence that therapist delivered interventions have modest beneficial effects for people with low back pain (LBP). Identification of subgroups of people with LBP who may benefit from these different treatment approaches is an important research priority. Aim and objectivesOverall aim was to improve the clinical and cost-effectiveness of LBP treatment by providing patients, their clinical advisors, and health service purchasers with better information about which participants are most likely to benefit from which treatment To achieve these objectives required substantial methodological work including the development and evaluation of some novel statistical approaches. This programme of work was not designed to analyse main effect of interventions and no such interpretations should be made.iii MethodsFirstly, we reviewed the literature on treatment moderators and subgroups. We initially invited investigators of trials of therapist-delivered interventions for LBP with >179 participants to share their data with us; some further smaller trials offered to us were also included. Using these trials we developed a repository of individual participant data of therapist delivered interventions for LBP. Using this dataset we sought to identify which participant characteristics, if any, predict response to different treatments (moderators) for clinical and cost effectiveness outcomes.We did an ANCOVA to identify potential moderators to apply in our main analyses.Subsequently we developed and applied three methods of subgroup identification; recursive partitioning (interaction trees and subgroup identification based on a differential effect search), adaptive risk group refinement, and an individual participant data indirect network meta-analysis to identify sub-groups defined by multiple parameters. ResultsWe included data from 19 randomised controlled trials with 9,328 participants (mean age 49 years, 57% females). Our prespecified analyses using recursive partitioning and adaptive risk group refinement performed well and allowed us to identify some subgroups. The differences in the effect size in the different subgroups were typically small, and unlikely to be clinically meaningful. Increasing baseline severity on the outcome of interest was the strongest driver of sub-group identification that we identified. Additionally we explored the application of Bayesian indirect network metaanalysis. This method produced varying probabilities that a particular treatment choice would be most likely to be effective for a specific patient profile. ConclusionThese data lack clinical or cost-effectiveness justification for the use of baseline characteristics in the development of subgroups for back pain. The methodological developments from this work have the potential to be applied in other clinical areas.iv The pooled repository database will serve as a valuable resource to the LBP research community. FundingFunding from the NIHR Programme Grants for Ap...

BackgroundTailoring is a frequent component of approaches for implementing clinical practice guidelines, although evidence on how to maximise the effectiveness of tailoring is limited. In England, overweight and obesity are common, and national guidelines have been produced by the National Institute for Health and Care Excellence. However, the guidelines are not routinely followed in primary care.MethodsA tailored implementation intervention was developed following an analysis of the determinants of practice influencing the implementation of the guidelines on obesity and the selection of strategies to address the determinants. General practices in the East Midlands of England were invited to take part in a cluster randomised controlled trial of the intervention. The primary outcome measure was the proportion of overweight or obese patients offered a weight loss intervention. Secondary outcomes were the proportions of patients with (1) a BMI or waist circumference recorded, (2) record of lifestyle assessment, (3) referred to weight loss services, and (4) any change in weight during the study period. We also assessed the mean weight change over the study period. Follow-up was for 9 months after the intervention. A process evaluation was undertaken, involving interviews of samples of participating health professionals.ResultsThere were 16 general practices in the control group, and 12 in the intervention group. At follow-up, 15.08 % in the control group and 13.19 % in the intervention group had been offered a weight loss intervention, odds ratio (OR) 1.16, 95 % confidence interval (CI) (0.72, 1.89). BMI/waist circumference measurement 42.71 % control, 39.56 % intervention, OR 1.15 (CI 0.89, 1.48), referral to weight loss services 5.10 % control, 3.67 % intervention, OR 1.45 (CI 0.81, 2.63), weight management in the practice 9.59 % control, 8.73 % intervention, OR 1.09 (CI 0.55, 2.15), lifestyle assessment 23.05 % control, 23.86 % intervention, OR 0.98 (CI 0.76, 1.26), weight loss of at least 1 kg 42.22 % control, 41.65 % intervention, OR 0.98 (CI 0.87, 1.09). Health professionals reported the interventions as increasing their confidence in managing obesity and providing them with practical resources.ConclusionsThe tailored intervention did not improve the implementation of the guidelines on obesity, despite systematic approaches to the identification of the determinants of practice. The methods of tailoring require further development to ensure that interventions target those determinants that most influence implementation.Trial registration ISRCTN07457585 Electronic supplementary materialThe online version of this article (doi:10.1186/s13012-016-0441-3) contains supplementary material, which is available to authorized users.

This pilot study suggests similar efficacy and safety but a cost difference favoring APC. A fully powered non-inferiority trial is appropriate to confirm these findings. (Clinical trial registration number: NCT01733719.).

The findings suggest that the Surviving Crying package may be effective in supporting the well-being and mental health of parents of excessively crying babies. Further, large-scale controlled trials of the package in NHS settings are warranted.

ObjectivesTo investigate the extent to which cluster sizes vary in stepped-wedge cluster randomised trials (SW-CRT) and whether any variability is accounted for during the sample size calculation and analysis of these trials.SettingAny, not limited to healthcare settings.ParticipantsAny taking part in an SW-CRT published up to March 2016.Primary and secondary outcome measuresThe primary outcome is the variability in cluster sizes, measured by the coefficient of variation (CV) in cluster size. Secondary outcomes include the difference between the cluster sizes assumed during the sample size calculation and those observed during the trial, any reported variability in cluster sizes and whether the methods of sample size calculation and methods of analysis accounted for any variability in cluster sizes.ResultsOf the 101 included SW-CRTs, 48% mentioned that the included clusters were known to vary in size, yet only 13% of these accounted for this during the calculation of the sample size. However, 69% of the trials did use a method of analysis appropriate for when clusters vary in size. Full trial reports were available for 53 trials. The CV was calculated for 23 of these: the median CV was 0.41 (IQR: 0.22–0.52). Actual cluster sizes could be compared with those assumed during the sample size calculation for 14 (26%) of the trial reports; the cluster sizes were between 29% and 480% of that which had been assumed.ConclusionsCluster sizes often vary in SW-CRTs. Reporting of SW-CRTs also remains suboptimal. The effect of unequal cluster sizes on the statistical power of SW-CRTs needs further exploration and methods appropriate to studies with unequal cluster sizes need to be employed.

Background. Experimental studies suggest that mechanical cell washing to remove pro-inflammatory components that accumulate in the supernatant of stored donor red blood cells (RBCs) might reduce inflammation and organ injury in transfused patients. Methods. Cardiac surgery patients at increased risk of large-volume RBC transfusion were eligible. Participants were randomized to receive either mechanically washed allogenic RBCs or standard care RBCs. The primary outcome was serum interleukin-8 measured at baseline and at four postsurgery time points. A mechanism substudy evaluated the effects of washing on stored RBCs in vitro and on markers of platelet, leucocyte, and endothelial activation in trial subjects. Results. Sixty adult cardiac surgery patients at three UK cardiac centres were enrolled between September 2013 and March 2015. Subjects received a median of 3.5 (interquartile range 2–5.5) RBC units, stored for a mean of 21 (sd 5.2) days, within 48 h of surgery. Mechanical washing reduced concentrations of RBC-derived microvesicles but increased cell-free haemoglobin concentrations in RBC supernatant relative to standard care RBC supernatant. There was no difference between groups with respect to perioperative serum interleukin-8 values [adjusted mean difference 0.239 (95% confidence intervals −0.231, 0.709), P=0.318] or concentrations of plasma RBC microvesicles, platelet and leucocyte activation, plasma cell-free haemoglobin, endothelial activation, or biomarkers of heart, lung, or kidney injury. Conclusions. These results do not support a hypothesis that allogenic red blood cell washing has clinical benefits in cardiac surgery. Clinical trial registration. ISRCTN 27076315.