| 1. |
- Garg, Manik, et al.
(författare)
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Tumour gene expression signature in primary melanoma predicts long-term outcomes
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Adjuvant systemic therapies are now routinely used following resection of stage III melanoma, however accurate prognostic information is needed to better stratify patients. We use differential expression analyses of primary tumours from 204 RNA-sequenced melanomas within a large adjuvant trial, identifying a 121 metastasis-associated gene signature. This signature strongly associated with progression-free (HR = 1.63, p = 5.24 × 10−5) and overall survival (HR = 1.61, p = 1.67 × 10−4), was validated in 175 regional lymph nodes metastasis as well as two externally ascertained datasets. The machine learning classification models trained using the signature genes performed significantly better in predicting metastases than models trained with clinical covariates (pAUROC = 7.03 × 10−4), or published prognostic signatures (pAUROC < 0.05). The signature score negatively correlated with measures of immune cell infiltration (ρ = −0.75, p < 2.2 × 10−16), with a higher score representing reduced lymphocyte infiltration and a higher 5-year risk of death in stage II melanoma. Our expression signature identifies melanoma patients at higher risk of metastases and warrants further evaluation in adjuvant clinical trials.
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| 2. |
- Beard, David J., et al.
(författare)
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Considerations and methods for placebo controls in surgical trials (ASPIRE guidelines)
- 2020
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Ingår i: The Lancet. - 0140-6736. ; 395:10226, s. 828-838
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Forskningsöversikt (refereegranskat)abstract
- Placebo comparisons are increasingly being considered for randomised trials assessing the efficacy of surgical interventions. The aim of this Review is to provide a summary of knowledge on placebo controls in surgical trials. A placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. This Review outlines what a placebo control entails and present understanding of this tool in the context of surgery. We consider when placebo controls in surgery are acceptable (and when they are desirable) in terms of ethical arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be done and interpreted. Use of placebo controls is justified in randomised controlled trials of surgical interventions provided there is a strong scientific and ethical rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with high risk of bias, particularly because of the placebo effect. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. This Review forms an outline for best practice and provides guidance, in the form of the Applying Surgical Placebo in Randomised Evaluations (known as ASPIRE) checklist, for those considering the use of a placebo control in a surgical randomised controlled trial.
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| 3. |
- Beard, David J., et al.
(författare)
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Placebo comparator group selection and use in surgical trials : The aspire project including expert workshop
- 2021
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Ingår i: Health Technology Assessment. - 1366-5278. ; 25:53
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. Objectives: To provide a summary of knowledge on placebo controls in surgical trials and to summarise any recommendations for designers, evaluators and funders of placebo-controlled surgical trials. Design: To carry out a state-of-the-art workshop and produce a corresponding report involving key stakeholders throughout. Setting: A workshop to discuss and summarise the existing knowledge and to develop the new guidelines. Results: To assess what a placebo control entails and to assess the understanding of this tool in the context of surgery is considered, along with when placebo controls in surgery are acceptable (and when they are desirable). We have considered ethics arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be carried out and interpreted. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with a high risk of bias, particularly because of the placebo effect. Conclusions: The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. An outline for best practice was produced in the form of the Applying Surgical Placebo in Randomised Evaluations (ASPIRE) guidelines for those considering the use of a placebo control in a surgical randomised controlled trial. Limitations: Although the workshop participants involved international members, the majority of participants were from the UK. Therefore, although every attempt was made to make the recommendations applicable to all health systems, the guidelines may, unconsciously, be particularly applicable to clinical practice in the UK NHS. Future work: Future work should evaluate the use of the ASPIRE guidelines in making decisions about the use of a placebo-controlled surgical trial. In addition, further work is required on the appropriate nomenclature to adopt in this space.
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| 4. |
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| 5. |
- Howick, Jeremy, et al.
(författare)
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Effects of empathic and positive communication in healthcare consultations: a systematic review and meta-analysis
- 2018
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Ingår i: Journal of the Royal Society of Medicine. - : Sage Publications. - 0141-0768 .- 1758-1095. ; 111:7, s. 240-252
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPractitioners who enhance how they express empathy and create positive expectations of benefit could improve patient outcomes. However, the evidence in this area has not been recently synthesised.ObjectiveTo estimate the effects of empathy and expectations interventions for any clinical condition.DesignSystematic review and meta-analysis of randomised trials.Data sourceSix databases from inception to August 2017.Study selectionRandomised trials of empathy or expectations interventions in any clinical setting with patients aged 12 years or older.Review methodsTwo reviewers independently screened citations, extracted data, assessed risk of bias and graded quality of evidence using GRADE. Random effects model was used for meta-analysis.ResultsWe identified 28 eligible (n = 6017). In seven trials, empathic consultations improved pain, anxiety and satisfaction by a small amount (standardised mean difference −0.18 [95% confidence interval −0.32 to −0.03]). Twenty-two trials tested the effects of positive expectations. Eighteen of these (n = 2014) reported psychological outcomes (mostly pain) and showed a modest benefit (standardised mean difference −0.43 [95% confidence interval −0.65 to −0.21]); 11 (n = 1790) reported physical outcomes (including bronchial function/ length of hospital stay) and showed a small benefit (standardised mean difference −0.18 [95% confidence interval −0.32 to −0.05]). Within 11 trials (n = 2706) assessing harms, there was no evidence of adverse effects (odds ratio 1.04; 95% confidence interval 0.67 to 1.63). The risk of bias was low. The main limitations were difficulties in blinding and high heterogeneity for some comparisons.ConclusionGreater practitioner empathy or communication of positive messages can have small patient benefits for a range of clinical conditions, especially pain.Protocol registrationCochrane Database of Systematic Reviews (protocol) DOI: 10.1002/14651858.CD011934.pub2.
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| 6. |
- Howick, Jeremy, et al.
(författare)
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Positive "framing" as a powerful medication for pain : A meta-analysis of randomized trials
- 2016
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Ingår i: European Journal of Integrative Medicine. - : Elsevier. - 1876-3820 .- 1876-3839. ; 8, s. 57-59
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A growing body of evidence suggests that positive framing–inducing positive expectations about the outcome of treatments can reduce pain symptoms. However there is no pooled estimate of the effect size of positive framing for treating pain. Such an estimate is useful to understand the extent to which positive expectations can enhance usual care.Methods: We extracted data from a recent systematic review of interventions that modified all "context factors" (including but not limited to) inducing positive expectations) in adults suffering from pain. The systematic review concluded that positive expectations were effective, but did not pool the results so no effect size was provided. Two authors independently extracted data from the studies and conducted the analysis. Our primary outcome was patient self-reported pain.Results: 10 randomized trials were eligible for meta-analysis. In the trials with continuous outcomes the standardized effect size was −0.39 (95% confidence interval −0.68 to −0.10, p = 0.009, I2 = 79%), suggesting reduced pain on average in groups in which positive expectations were induced. The effect size was similar in magnitude but was not statistically significant when we excluded studies deemed to have a high risk of bias (standard effect size −0.31, 95% CI −0.65 to 0.02, p = 0.07, I2 = 77%).Conclusion: The effect of inducing positive expectations is comparable to the effects of some pharmacological drugs. However many of the studies had a high risk of bias, and heterogeneity was significant. Future research is warranted including investigating ways to implement this evidence into patient care in an ethical way.
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