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Patient-reported outcome monitoring in a routine paediatric oncology setting: challenges and opportunities.
No full textFeasibility randomised controlled trial of a guided workbook intervention to support work-related goals among cancer survivors in the UK.
No full textOBJECTIVES
Employment following illness is associated with better physical and psychological functioning. This study aimed to assess the feasibility and acceptability of a theoretically led workbook intervention designed to support patients with cancer returning to work.
DESIGN
Parallel-group randomised controlled trial with embedded qualitative interviews.
SETTING
Oncology clinics within four English National Health Service Trusts.
PARTICIPANTS
Patients who had received a diagnosis of breast, gynaecological, prostate or colorectal cancer and who had been receiving treatment for a minimum of two weeks.
INTERVENTION
A self-guided WorkPlan workbook designed to support patients with cancer to return to work with fortnightly telephone support calls to discuss progress. The control group received treatment as usual and was offered the workbook at the end of their 12-month follow-up.
OUTCOME MEASURES
We assessed aspects of feasibility including eligibility, recruitment, data collection, attrition, feasibility of the methodology, acceptability of the intervention and potential to calculate cost-effectiveness.
RESULTS
The recruitment rate of eligible patients was 44%; 68 participants consented and 58 (85%) completed baseline measures. Randomisation procedures were acceptable, data collection methods (including cost-effectiveness data) were feasible and the intervention was acceptable to participants. Retention rates at 6-month and 12-month follow-up were 72% and 69%, respectively. At 6-month follow-up, 30% of the usual care group had returned to full-time or part-time work (including phased return to work) compared with 43% of the intervention group. At 12 months, the percentages were 47% (usual care) and 68% (intervention).
CONCLUSIONS
The findings confirm the feasibility of a definitive trial, although further consideration needs to be given to increasing the participation rates among men and black and ethnic minority patients diagnosed with cancer.
TRIAL REGISTRATION NUMBER
ISRCTN56342476; Pre-results
Randomized controlled study of the prediction of diminutive/small colorectal polyp histology using didactic versus computer-based self-learning module in gastroenterology trainees.
No full textBACKGROUND AND AIM
The aim of this randomized trial was to evaluate the performance of self-training versus didactic training in order to increase the diagnostic accuracy of diminutive/small colonic polyp histological prediction by trainees.
METHODS
Sixteen trainees reviewed 78 videos (48 iSCAN-OE and 30 NBI) of diminutive/small polyps in a pretraining assessment. Trainees were randomized to receive computer-based self-learning (n = 8) or didactic training (n = 8) using identical teaching materials and videos. The same 78 videos, in a different randomized order, were assessed. The NICE (NBI International Colorectal Endoscopic) and SIMPLE (Simplified Identification Method for Polyp Labeling during Endoscopy) classification systems were used to classify diminutive/small polyps.
RESULTS
A higher proportion of high-confidence predictions of polyps was made by the self-training group versus the didactic group using both the SIMPLE classification (77.1% [95% CI 73.4-80.3] vs 69.9% [95% CI 66.1-73.5%] [P = 0.005]) and the NICE classification (77% [95% CI 73.2-80.4%] vs 69.8% [95% CI 66-73.4%] [P = 0.006]). When using NICE, sensitivity of the self-training group compared with the didactic group was 72% versus 83% (P = 0.0005), and the accuracy was 66.1% versus 69.1%. The training improved the confidence of participants and SIMPLE was preferred over NICE.
CONCLUSION
Self-learning for the prediction of diminutive/small polyp histology is a method of training that can achieve results similar to didactic training. Availability of adequate self-learning teaching modules could enable widespread implementation of optical diagnosis in clinical practice
Factors Associated With Outcomes of Patients With Primary Sclerosing Cholangitis and Development and Validation of a Risk Scoring System.
No full textWe sought to identify factors that are predictive of liver transplantation or death in patients with primary sclerosing cholangitis (PSC), and to develop and validate a contemporaneous risk score for use in a real-world clinical setting. Analyzing data from 1,001 patients recruited to the UK-PSC research cohort, we evaluated clinical variables for their association with 2-year and 10-year outcome through Cox-proportional hazards and C-statistic analyses. We generated risk scores for short-term and long-term outcome prediction, validating their use in two independent cohorts totaling 451 patients. Thirty-six percent of the derivation cohort were transplanted or died over a cumulative follow-up of 7,904 years. Serum alkaline phosphatase of at least 2.4 × upper limit of normal at 1 year after diagnosis was predictive of 10-year outcome (hazard ratio [HR] = 3.05; C = 0.63; median transplant-free survival 63 versus 108 months; P < 0.0001), as was the presence of extrahepatic biliary disease (HR = 1.45; P = 0.01). We developed two risk scoring systems based on age, values of bilirubin, alkaline phosphatase, albumin, platelets, presence of extrahepatic biliary disease, and variceal hemorrhage, which predicted 2-year and 10-year outcomes with good discrimination (C statistic = 0.81 and 0.80, respectively). Both UK-PSC risk scores were well-validated in our external cohort and outperformed the Mayo Clinic and aspartate aminotransferase-to-platelet ratio index (APRI) scores (C statistic = 0.75 and 0.63, respectively). Although heterozygosity for the previously validated human leukocyte antigen (HLA)-DR*03:01 risk allele predicted increased risk of adverse outcome (HR = 1.33; P = 0.001), its addition did not improve the predictive accuracy of the UK-PSC risk scores. Conclusion: Our analyses, based on a detailed clinical evaluation of a large representative cohort of participants with PSC, furthers our understanding of clinical risk markers and reports the development and validation of a real-world scoring system to identify those patients most likely to die or require liver transplantation
Modeling graft loss in patients with donor-specific antibody at baseline using the Birmingham-Mayo (BirMay) predictor: Implications for clinical trials.
No full textPredicting which renal allografts will fail and the likely cause of failure is important in clinical trial design to either enrich patient populations to be or as surrogate efficacy endpoints for trials aimed at improving long-term graft survival. This study tests our previous Birmingham-Mayo model (termed the BirMay Predictor) developed in a low-risk kidney transplant population in order to predict the outcome of patients with donor specific alloantibody (DSA) at the time of transplantation and identify new factors to improve graft loss prediction in DSA+ patients. We wanted define ways to enrich the population for future therapeutic intervention trials. The discovery set included 147 patients from Mayo Cohort and the validation set included 111 patients from the Paris Cohort-all of whom had DSA at the time of transplantation. The BirMay predictor performed well predicting 5-year outcome well in DSA+ patients (Mayo C statistic = 0.784 and Paris C statistic = 0.860). Developing a new model did not improve on this performance. A high negative predictive value of greater than 90% in both cohorts excluded allografts not destined to fail within 5 years. We conclude that graft-survival models including histology predict graft loss well, both in DSA+ cohorts as well as DSA- patients
Development and Validation of a Combined Hypoxia and Immune Prognostic Classifier for Head and Neck Cancer.
No full textPURPOSE
Intratumoral hypoxia and immunity have been correlated with patient outcome in various tumor settings. However, these factors are not currently considered for treatment selection in head and neck cancer (HNC) due to lack of validated biomarkers. Here we sought to develop a hypoxia-immune classifier with potential application in patient prognostication and prediction of response to targeted therapy.
EXPERIMENTAL DESIGN
A 54-gene hypoxia-immune signature was constructed on the basis of literature review. Gene expression was analyzed using the The Cancer Genome Atlas (TCGA) HNC dataset ( = 275) and validated using two independent cohorts ( = 130 and 123). IHC was used to investigate the utility of a simplified protein signature. The spatial distribution of hypoxia and immune markers was examined using multiplex immunofluorescence staining.
RESULTS
Unsupervised hierarchical clustering of TCGA dataset (development cohort) identified three patient subgroups with distinct hypoxia-immune phenotypes and survival profiles: hypoxia/immune, hypoxia/immune, and mixed, with 5-year overall survival (OS) rates of 71%, 51%, and 49%, respectively ( = 0.0015). The prognostic relevance of the hypoxia-immune gene signature was replicated in two independent validation cohorts. Only PD-L1 and intratumoral CD3 protein expression were associated with improved OS on multivariate analysis. Hypoxia/immune and hypoxia/immune tumors were overrepresented in "inflamed" and "immune-desert" microenvironmental profiles, respectively. Multiplex staining demonstrated an inverse correlation between CA-IX expression and prevalence of intratumoral CD3 T cells ( = -0.5464; = 0.0377), further corroborating the transcription-based classification.
CONCLUSIONS
We developed and validated a hypoxia-immune prognostic transcriptional classifier, which may have clinical application to guide the use of hypoxia modification and targeted immunotherapies for the treatment of HNC
The Impact of Advanced Patient Age on Mortality after Allogeneic Hematopoietic Cell Transplantation for Non-Hodgkin Lymphoma: A Retrospective Study by the European Society for Blood and Marrow Transplantation Lymphoma Working Party.
No full textMore than 60% of patients with non-Hodgkin lymphoma (NHL) are age >60 years at presentation. The purpose of this study was to compare the potential risks and benefits of allogeneic hematopoietic cell transplantation (alloHCT) in elderly patients with NHL with younger patients in a large sample, also taking into account comorbidity information. All patients age ≥18 years who had undergone alloHCT from a matched sibling or unrelated donor for NHL between 2003 and 2013 and were registered with the European Society for Blood and Marrow Transplantation were eligible for the study. The primary study endpoint was 1-year nonrelapse mortality (NRM). A total of 3919 patients were eligible and were categorized by age: young (Y), 18 to 50 y (n = 1772); middle age (MA), 51 to 65 y (n = 1967); or old (O), 66 to 77 y (n = 180). Follicular lymphoma was present in 37% of the patients; diffuse large B cell lymphoma, in 30%; mantle cell lymphoma, in 21%, and peripheral T cell lymphoma, in 11%. At the time of alloHCT, 85% of the patients were chemosensitive and 15% were chemorefractory. With a median follow-up of 4.5 years in survivors, NRM at 1 year was 13% for the Y group. 20% for the MA group, and 33% for the O group (P 65 y provides similar NHL control as seen in younger patients but is associated with a higher NRM that is not fully explained by comorbidity. Thus, although alloHCT is feasible and effective in very old patients, the increased NRM risk must be taken into account when assessing the indication for alloHCT for NHL in this age group
Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial.
No full textBACKGROUND
Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH.
METHODS
In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6.
FINDINGS
Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group).
INTERPRETATION
Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes.
FUNDING
Intercept Pharmaceuticals
Effect of blood volume on analytical bias in dried blood spots prepared for newborn screening external quality assurance.
No full textDried blood spots (DBS) are used for the analysis of more than 2000 biomarkers. We assessed a range of analyte concentrations and diameters of DBS. DBS samples were created by the application of increasing volumes of whole blood prepared by the UK NEQAS Quality Assurance Laboratory. Samples were analyzed in four separate laboratories. Volumes less than 25 μl (8 mm) and more than 75 μl (14 mm) created unsatisfactory analytical biases. Results obtained from peripheral subpunches tended to be higher than those from a central subpunch. DBS diameters formed from nonvolumetric application of blood to filter paper can be used to assess whether measurement bias will be within acceptable limits according to the analyte being quantified. DBS received for newborn screening in the UK with diameters less than 8 mm and those more than 14 mm should be rejected