Reaching consensus on reporting patient and public involvement (PPI) in research: methods and lessons learned from the development of reporting guidelines

INTRODUCTION: Patient and public involvement (PPI) is inconsistently reported in health and social care research. Improving the quality of how PPI is reported is critical in developing a higher quality evidence base to gain a better insight into the methods and impact of PPI. This paper describes the methods used to develop and gain consensus on guidelines for reporting PPI in research studies (updated version of the Guidance for Reporting Patient and Public Involvement (GRIPP2)). METHODS: There were three key stages in the development of GRIPP2: identification of key items for the guideline from systematic review evidence of the impact of PPI on health research and health services, a three-phase online Delphi survey with a diverse sample of experts in PPI to gain consensus on included items and a face-to-face consensus meeting to finalise and reach definitive agreement on GRIPP2. Challenges and lessons learnt during the development of the reporting guidelines are reported. DISCUSSION: The process of reaching consensus is vital within the development of guidelines and policy directions, although debate around how best to reach consensus is still needed. This paper discusses the critical stages of consensus development as applied to the development of consensus for GRIPP2 and discusses the benefits and challenges of consensus development

Identifying back pain subgroups: developing and applying approaches using individual patient data collected within clinical trials

There 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

The GRIPP 2 reporting checklists: tools to improve reporting of patient and public involvement in research

Background: While the PPI evidence base has expanded over the last decade, the quality of reporting within papers is often inconsistent, limiting our understanding of how it works, in what context, for whom and why. Objective: To develop international consensus on the key items to report to enhance the quality, transparency and consistency of the PPI evidence base. To collaboratively involve patients as research partners at all stages in the development of GRIPP 2. Methods: The EQUATOR method for developing reporting guidelines was utilised. The original GRIPP (Guidance for Reporting Involvement of Patients and the Public) checklist was revised, based on updated systematic review evidence. A three round Delphi survey was used to develop consensus on items to be included in the guideline. A subsequent face-to-face meeting produced agreement on items not reaching consensus during the Delphi process. Results: 143 participants agreed to participate in round 1, with an 86% (123/143) response for round 2 and a 78% (112/143) response for round 3. The Delphi survey identified the need for long-form (LF) and short-form (SF) versions. GRIPP2-LF includes 34 items on aims, definitions, concepts and theory, methods, stages and nature of involvement, context, capture or measurement of impact, outcomes, economic assessment and reflections, and is suitable for studies where the main focus is PPI. GRIPP2-SF includes 5 items on aims, methods, results, outcomes and critical perspective and is suitable for studies where PPI is a secondary focus. Conclusions: GRIPP2-LF and GRIPP2-SF represent the first international evidence-based, consensus-informed guidance for reporting patient and public involvement in research. Both versions of GRIPP2 aim to improve the quality, transparency and consistency of the international PPI evidence base, to ensure PPI practice is based on the best evidence. GRIPP 2 is co-published with Research Involvement and Engagement

Clinical sub-phenotypes of Staphylococcus aureus bacteraemia

Background: Staphylococcus aureus bacteraemia (SAB) is a clinically heterogeneous disease. The ability to identify sub-groups of patients with shared traits (sub-phenotypes) is an unmet need that could allow patient stratification for clinical management and research. We aimed to test the hypothesis that clinically-relevant sub-phenotypes can be reproducibly identified amongst patients with SAB. Methods: We studied three cohorts of hospitalised adults with monomicrobial SAB: a UK retrospective observational study (Edinburgh cohort, n=458), the UK ARREST randomised trial (n=758), and the Spanish SAFO randomised trial (n=214). Latent class analysis was used to identify sub-phenotypes using routinely-collected clinical data, without considering outcomes. Mortality and microbiologic outcomes were then compared between sub-phenotypes. Results: Included patients had predominantly methicillin-susceptible SAB (1366/1430,95.5%). We identified five distinct, reproducible clinical sub-phenotypes: (A) SAB associated with older age and comorbidity, (B) nosocomial intravenous catheter-associated SAB in younger people without comorbidity, (C) community-acquired metastatic SAB, (D) SAB associated with chronic kidney disease, and (E) SAB associated with injection drug use. Survival and microbiologic outcomes differed between the sub-phenotypes. 84-day mortality was highest in sub-phenotype A, and lowest in B and E. Microbiologic outcomes were worse in sub-phenotype C. In a secondary analysis of the ARREST trial, adjunctive rifampicin was associated with increased 84-day mortality in sub-phenotype B and improved microbiologic outcomes in sub-phenotype C. Conclusions: We have identified reproducible and clinically-relevant sub-phenotypes within SAB, and provide proof-of-principle of differential treatment effects. Through clinical trial enrichment and patient stratification, these sub-phenotypes could contribute to a personalised medicine approach to SAB

The GRIPP 2 reporting checklists: tools to improve reporting of patient and public involvement in research

Background: While the PPI evidence base has expanded over the last decade, the quality of reporting within papers is often inconsistent, limiting our understanding of how it works, in what context, for whom and why. Objective: To develop international consensus on the key items to report to enhance the quality, transparency and consistency of the PPI evidence base. To collaboratively involve patients as research partners at all stages in the development of GRIPP 2. Methods: The EQUATOR method for developing reporting guidelines was utilised. The original GRIPP (Guidance for Reporting Involvement of Patients and the Public) checklist was revised, based on updated systematic review evidence. A three round Delphi survey was used to develop consensus on items to be included in the guideline. A subsequent face-to-face meeting produced agreement on items not reaching consensus during the Delphi process. Results: 143 participants agreed to participate in round 1, with an 86% (123/143) response for round 2 and a 78% (112/143) response for round 3. The Delphi survey identified the need for long-form (LF) and short-form (SF) versions. GRIPP2-LF includes 34 items on aims, definitions, concepts and theory, methods, stages and nature of involvement, context, capture or measurement of impact, outcomes, economic assessment and reflections, and is suitable for studies where the main focus is PPI. GRIPP2-SF includes 5 items on aims, methods, results, outcomes and critical perspective and is suitable for studies where PPI is a secondary focus. Conclusions: GRIPP2-LF and GRIPP2-SF represent the first international evidence-based, consensus-informed guidance for reporting patient and public involvement in research. Both versions of GRIPP2 aim to improve the quality, transparency and consistency of the international PPI evidence base, to ensure PPI practice is based on the best evidence. GRIPP 2 is co-published with Research Involvement and Engagement

The GRIPP 2 reporting checklists: tools to improve reporting of patient and public involvement in research

Background: While the PPI evidence base has expanded over the last decade, the quality of reporting within papers is often inconsistent, limiting our understanding of how it works, in what context, for whom and why. Objective: To develop international consensus on the key items to report to enhance the quality, transparency and consistency of the PPI evidence base. To collaboratively involve patients as research partners at all stages in the development of GRIPP 2. Methods: The EQUATOR method for developing reporting guidelines was utilised. The original GRIPP (Guidance for Reporting Involvement of Patients and the Public) checklist was revised, based on updated systematic review evidence. A three round Delphi survey was used to develop consensus on items to be included in the guideline. A subsequent face-to-face meeting produced agreement on items not reaching consensus during the Delphi process. Results: 143 participants agreed to participate in round 1, with an 86% (123/143) response for round 2 and a 78% (112/143) response for round 3. The Delphi survey identified the need for long-form (LF) and short-form (SF) versions. GRIPP2-LF includes 34 items on aims, definitions, concepts and theory, methods, stages and nature of involvement, context, capture or measurement of impact, outcomes, economic assessment and reflections, and is suitable for studies where the main focus is PPI. GRIPP2-SF includes 5 items on aims, methods, results, outcomes and critical perspective and is suitable for studies where PPI is a secondary focus. Conclusions: GRIPP2-LF and GRIPP2-SF represent the first international evidence-based, consensus-informed guidance for reporting patient and public involvement in research. Both versions of GRIPP2 aim to improve the quality, transparency and consistency of the international PPI evidence base, to ensure PPI practice is based on the best evidence. GRIPP 2 is co-published with Research Involvement and Engagement

Reducing opioid use for chronic pain with a group-based intervention

Importance Opioid use for chronic nonmalignant pain can be harmful. Objective To test whether a multicomponent, group-based, self-management intervention reduced opioid use and improved pain-related disability compared with usual care. Design, Setting, and Participants Multicentered, randomized clinical trial of 608 adults taking strong opioids (buprenorphine, dipipanone, morphine, diamorphine, fentanyl, hydromorphone, methadone, oxycodone, papaveretum, pentazocine, pethidine, tapentadol, and tramadol) to treat chronic nonmalignant pain. The study was conducted in 191 primary care centers in England between May 17, 2017, and January 30, 2019. Final follow-up occurred March 18, 2020. Intervention Participants were randomized 1:1 to either usual care or 3-day–long group sessions that emphasized skill-based learning and education, supplemented by 1-on-1 support delivered by a nurse and lay person for 12 months. Main Outcomes and Measures The 2 primary outcomes were Patient-Reported Outcomes Measurement Information System Pain Interference Short Form 8a (PROMIS-PI-SF-8a) score (T-score range, 40.7-77; 77 indicates worst pain interference; minimal clinically important difference, 3.5) and the proportion of participants who discontinued opioids at 12 months, measured by self-report. Results Of 608 participants randomized (mean age, 61 years; 362 female [60%]; median daily morphine equivalent dose, 46 mg [IQR, 25 to 79]), 440 (72%) completed 12-month follow-up. There was no statistically significant difference in PROMIS-PI-SF-8a scores between the 2 groups at 12-month follow-up (−4.1 in the intervention and −3.17 in the usual care groups; between-group difference: mean difference, −0.52 [95% CI, −1.94 to 0.89]; P = .15). At 12 months, opioid discontinuation occurred in 65 of 225 participants (29%) in the intervention group and 15 of 208 participants (7%) in the usual care group (odds ratio, 5.55 [95% CI, 2.80 to 10.99]; absolute difference, 21.7% [95% CI, 14.8% to 28.6%]; P < .001). Serious adverse events occurred in 8% (25/305) of the participants in the intervention group and 5% (16/303) of the participants in the usual care group. The most common serious adverse events were gastrointestinal (2% in the intervention group and 0% in the usual care group) and locomotor/musculoskeletal (2% in the intervention group and 1% in the usual care group). Four people (1%) in the intervention group received additional medical care for possible or probable symptoms of opioid withdrawal (shortness of breath, hot flushes, fever and pain, small intestinal bleed, and an overdose suicide attempt). Conclusions and Relevance In people with chronic pain due to nonmalignant causes, compared with usual care, a group-based educational intervention that included group and individual support and skill-based learning significantly reduced patient-reported use of opioids, but had no effect on perceived pain interference with daily life activities. Trial Registration isrctn.org Identifier: ISRCTN4947093

Stable DNA triple helix formation using oligonucleotides containing 2'-aminoethoxy,5-propargylamino-U

We have prepared oligonucleotides containing the novel base analogue 2'-aminoethoxy,5-proparaylamino-U in place of thymidine and examined their ability to form intermolecular and intramolecular triple helices by DNase I footprinting and thermal melting studies. The results were compared with those for oligonucleotides containing 5-propargylamino-dU and 2'-aminoethoxy-T. We find that the bis-substituted derivative produces a large increase in triplex stability, much greater than that produced by either of the monosubstituted analogues, which are roughly equipotent with each other. Intermolecular triplexes with 9-mer oligonucleotides containing three or four base modifications generate footprints at submicromolar concentrations even at pH 7.5, in contrast to the unmodified oligonucleotide, which failed to produce a footprint at pH 5.0, even at 30 muM. UV- and fluorescence melting studies with intramolecular triplexes confirmed that the bis-modified base produces a much greater increase in T-m than either modification alone

Data dossier on 'Solidarity in Europe'

State of the Union 10-12 May 2018, FlorenceThe main Data Dossier on ‘Solidarity in Europe’ offers key statistics and data visualisations on each of the six topics of the EUI’s The State of the Union 2018 conference to provide a first insight into each area, namely Economic, Monetary and Fiscal Policies; Social Investment; European Defence and Security; Migration; Climate Change and Energy; and Development. The contents and data narrative have been conceptualised and written by the GlobalStat team, with the contribution of Anton Hemerijck for text on Social Investment. Based on this, Christian Dietrich, a data scientist and graphic designer, has developed and designed the magnificent data visualisations