An approach for collection of nearfield groundwater samples in submerged limestone caverns

Walls of submerged caves feeding Florida springs are often lined with a heavy mat of filamentous bacteria, many of which are able to oxidize reduced sulfur in groundwater migrating from the porous bedrock into the cave conduit. To determine changes in water chemistry as water passes through the microbial mat, a simple device made from standard well screen and sealed with a rubber stopper and controllable vents was installed in a hole drilled in the wall of the cave passage. The sampler was sealed in place with marine epoxy. We measured anions in water from the sampler and from the water-filled conduit taken just outside the sampler. Most anions measured viz., Cl−, NO3−, and PO43−, increased slightly between the matrix and conduit waters. However, traces of sulfide were measured in the water from the rock matrix, but not in the conduit. SO42− concentrations in the conduit were about twice that measured in the water from the sampler, about 22 and 11 mg SO42− L−1, respectively, providing further evidence that sulfur oxidation is an important process in the bacterial mats attached to the limestone surfaces in these caves. An additional use of the sampling device is to measure discharge from the local bedrock into the cave conduit.Keywords: sulfur oxidation, bacteria, acid dissolution, groundwater chemistry.DOI:10.3986/ac.v42i2-3.664

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

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

Facet-joint injections for people with persistent non-specific low back pain (FIS) : study protocol for a randomised controlled feasibility trial

BACKGROUND: The role of injections of therapeutic substances into the back as treatment for low back pain is unclear. Facet joint injections are widely used despite the absence of evidence of sustained benefit. We hypothesise that facet joint injections might facilitate engagement with physiotherapist-led, best usual care (a combined physical and psychological programme) and is a clinically and cost-effective treatment for people with suspected low back pain of facet joint origin. METHODS/DESIGN: We present here the protocol for a randomised controlled feasibility trial for a main trial to test the above hypotheses. Patients referred to secondary care with persistent non-specific low back pain will be screened and invited to take part in the study. Those who meet the eligibility criteria will be invited for a physiotherapy assessment to confirm trial eligibility and for baseline data collection. All participants (n = 150) will be offered the best usual care package with physical and psychological components. Those randomised into the intervention arm (n = 75) will, in addition, receive intra-articular facet joint injections with local anaesthetic and steroids. Primary outcome data will be collected using daily and then weekly text messaging service for a pain score on a 0-10 scale. Questionnaire follow-up will be at 3, 6, and 12 months. Evaluation of trial processes and health economic analyses, including a value of information analysis, will be undertaken. The process evaluation will be mixed methods and will include the views of all stakeholders. DISCUSSION: Whilst this trial is a feasibility study it is currently one of the largest trials in this area. The outcomes will provide some evidence on the use of facet joint injections for patients with clinically diagnosed facet joint pain. TRIAL REGISTRATION: EudraCT identifier 2014-000682-50

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

Reducing Opioid Use for Chronic Pain With a Group-Based Intervention: A Randomized Clinical Trial

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: ISRCTN49470934

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

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

Testing a support programme for opioid reduction for people with chronic non-malignant pain: The I-WOTCH randomised controlled trial protocol

Introduction: Chronic non-malignant pain has a major impact on the wellbeing, mood and productivity of those affected. Opioids are increasingly being prescribed to manage this type of pain, but the increasing risk of other disabling symptoms, and their effectiveness for this type of pain has been questioned. This trial is designed to implement and evaluate a patient-centred intervention targeting withdrawal of strong opioids in patients with chronic pain. . Methods and analysis: A pragmatic, multi–centre, randomised controlled trial will assess the clinical and cost-effectiveness of a group-based multicomponent intervention combined with individualised clinical facilitator led support for the management of chronic non-malignant pain against the control intervention (self-help booklet and relaxation CD). An embedded process evaluation will examine fidelity of delivery and investigate experiences of the intervention. The twoprimary outcomes are activities of daily living (measured by PROMIS Pain Interference Short Form (8A)) and opioid use. The secondary outcomes are pain severity, quality of life, sleep quality, self-efficacy, adverse events, and NHS health care resource use. Participants are followed up at four, eight, and 12 months, with a primary endpoint of 12 months. Between-group differences will indicate effectiveness; we are looking for a difference of 3.5 points on our pain interference outcome (scale 40-77). We will undertake an NHS perspective cost-effectiveness analysis using Quality Adjusted Life Years. Ethics: Full approval was given by Yorkshire & The Humber - South Yorkshire Research Ethics Committee on September 13th, 2016 (16/YH/0325). Appropriate local approvals were sought for each area in which recruitment was undertaken. The current protocol version is 1.6. date 19th December 2018. Dissemination: Publication of results in peer reviewed journals, including the development and theoretical framework of the intervention, will inform the scientific and clinical community. We will disseminate results to patient participants and study facilitators in a study newsletter as well as a lay summary of results on the study website. Trial registration: This trial is registered with an International Standard Randomised Controlled Trial Number (ISRCTN) Register. ISRCTN number: 49470934 (06 Feb 2017