A rapid priority setting exercise combining existing, emergent evidence with stakeholder knowledge identified broad topic uncertainties.

OBJECTIVES: The project aimed to rapidly identify priority topic uncertainties as a first step to identify future systematic review questions of pertinence to key international fecal incontinence (FI) stakeholders (patients, carers, health care professionals, policy makers and voluntary, community, or social enterprise representatives). The paper's aim is to share our methods, experience, and learning with other groups planning to deliver a rapid priority setting exercise. STUDY DESIGN AND SETTING: An evidence gap map incorporated three evidence streams: emerging evidence identified through horizon scanning; existing evidence identified through systematic searches of bibliographic databases; and FI stakeholder insights collected through an international survey. The evidence gap map was presented during an online workshop with stakeholders, where they shared their expertize to expand, refine, and rank topic uncertainties using ideation techniques, focus group discussions, consensus techniques, and online polling. RESULTS: The multistep methods used to deliver this priority setting exercise resulted in identification of broad priority topic uncertainties. The methods appear to have high acceptability and engagement with participants but await full evaluation. CONCLUSION: This project successfully followed robust methodology, building upon frameworks from published priority setting and evidence gap mapping projects while incorporating strong patient and public involvement components.

Interventions for treating obstetric fistula: An evidence gap map.

Obstetric fistula is prevalent in low- and middle-income countries, with between 50,000 and 100,000 new cases each year. The World Health Organization aims to eradicate it by 2030 but a clear idea of the extant evidence is unavailable. This evidence map compiled evidence on treatments for obstetric fistula to identify potential knowledge gaps. The protocol for this work was published on the Open Science Framework (DOI: 10.17605/OSF.IO/H7J35). A survey was developed, piloted and distributed online through organisations with an interest in obstetric fistula and snowballing. Results informed the evidence map framework. Searches were run on MEDLINE, Embase, CENTRAL, Global Index Medicus and ScanMedicine on 16 February 2022 to identify potentially eligible systematic reviews, randomised controlled trials, cohort studies and case-control studies. Forward and backward citation chaining was undertaken on relevant systematic reviews and included studies. Studies were screened, coded and assessed for risk of bias by a single reviewer, with a second checking a proportion. The evidence map results were compared to survey results. Thirty-nine people responded to the survey, half of which were clinicians. Of 9796 records identified, 37 reports of 28 studies were included in the evidence map. Many included studies were at some risk of bias; for observational studies, this was predominantly due to lack of controlling for confounders. Most studies (71%) assessed surgical interventions alone. Reporting on other intervention types was limited. Regarding outcome measures most important to survey respondents, 24 studies reported on cure/improvement in obstetric fistula and 20 on cure/improvement in urinary incontinence. Reporting on quality of life, faecal incontinence and sexual function was limited. There is currently little robust evidence to guide patients and practitioners on the most effective treatment option for obstetric fistula. Further research is required to address evidence gaps identified.

Clinical and cost effectiveness of endoscopic bipolar radiofrequency ablation for the treatment of malignant biliary obstruction: a systematic review.

Background: Early evidence suggests that using radiofrequency ablation as an adjunct to standard care (i.e. endoscopic retrograde cholangiopancreatography with stenting) may improve outcomes in patients with malignant biliary obstruction. Objectives: To assess the clinical effectiveness, cost-effectiveness and potential risks of endoscopic bipolar radiofrequency ablation for malignant biliary obstruction, and the value of future research. Data sources: Seven bibliographic databases, three websites and seven trials registers were searched from 2008 until 21 January 2021. Review methods: The study inclusion criteria were as follows: patients with biliary obstruction caused by any form of unresectable malignancy; the intervention was reported as an endoscopic biliary radiofrequency ablation to ablate malignant tissue that obstructs the bile or pancreatic ducts, either to fit a stent (primary radiofrequency ablation) or to clear an obstructed stent (secondary radiofrequency ablation); the primary outcomes were survival, quality of life or procedure-related adverse events; and the study design was a controlled study, an observational study or a case report. Risk of bias was assessed using Cochrane tools. The primary analysis was meta-analysis of the hazard ratio of mortality. Subgroup analyses were planned according to the type of probe, the type of stent (i.e. metal or plastic) and cancer type. A de novo Markov model was developed to model cost and quality-of-life outcomes associated with radiofrequency ablation in patients with primary advanced bile duct cancer. Insufficient data were available for pancreatic cancer and secondary bile duct cancer. An NHS and Personal Social Services perspective was adopted for the analysis. A probabilistic analysis was conducted to estimate the incremental cost-effectiveness ratio for radiofrequency ablation and the probability that radiofrequency ablation was cost-effective at different thresholds. The population expected value of perfect information was estimated in total and for the effectiveness parameters. Results: Sixty-eight studies (1742 patients) were included in the systematic review. Four studies (336 participants) were combined in a meta-analysis, which showed that the pooled hazard ratio for mortality following primary radiofrequency ablation compared with a stent-only control was 0.34 (95% confidence interval 0.21 to 0.55). Little evidence relating to the impact on quality of life was found. There was no evidence to suggest an increased risk of cholangitis or pancreatitis, but radiofrequency ablation may be associated with an increase in cholecystitis. The results of the cost-effectiveness analysis were that the costs of radiofrequency ablation was £2659 and radiofrequency ablation produced 0.18 quality-adjusted life-years, which was more than no radiofrequency ablation on average. With an incremental cost-effectiveness ratio of £14,392 per quality-adjusted life-year, radiofrequency ablation was likely to be cost-effective at a threshold of £20,000 per quality-adjusted life-year across most scenario analyses, with moderate uncertainty. The source of the vast majority of decision uncertainty lay in the effect of radiofrequency ablation on stent patency. Limitations: Only 6 of 18 comparative studies contributed to the survival meta-analysis, and few data were found concerning secondary radiofrequency ablation. The economic model and cost-effectiveness meta-analysis required simplification because of data limitations. Inconsistencies in standard reporting and study design were noted. Conclusions: Primary radiofrequency ablation increases survival and is likely to be cost-effective. The evidence for the impact of secondary radiofrequency ablation on survival and of quality of life is limited. There was a lack of robust clinical effectiveness data and, therefore, more information is needed for this indication. Future work: Future work investigating radiofrequency ablation must collect quality-of-life data. High-quality randomised controlled trials in secondary radiofrequency ablation are needed, with appropriate outcomes recorded. Study registration: This study is registered as PROSPERO CRD42020170233. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 7. See the NIHR Journals Library website for further project information.

The bile and pancreatic ducts transport fluids to the intestines to help people digest their food properly. Some types of cancer can cause these ducts to become totally or partially blocked. We wanted to know if endoscopic radiofrequency ablation is safe and works well to treat people who have one of these blockages that cannot be removed by surgery. Radiofrequency ablation burns away a blockage by hitting it with radio waves. Endoscopic means that the radio waves are directed to the blockage using a thin, tube-like wire with a camera at the end. During radiofrequency ablation, a person might have a small tube called a stent put into their bile or pancreatic duct to keep it open or to replace an already blocked stent.

We searched for research studies that looked at (1) whether or not radiofrequency ablation was able to remove blockages from the ducts, (2) if radiofrequency ablation allowed people to live longer, (3) if patients had a better quality of life after radiofrequency ablation, (4) if radiofrequency ablation caused any side effects and (5) how much it costs to treat people with radiofrequency ablation.

We found that treatment with radiofrequency ablation before giving a person a stent helped them to live a little longer with their cancer. We did not find any evidence that radiofrequency ablation increased pain or swelling in the bile duct or pancreatic duct. Radiofrequency ablation might cause more swelling in the gall bladder than having a stent without radiofrequency ablation, but there was not enough research available for us to be certain of this.

Radiofrequency ablation before inserting a stent could be a safe option to add to treatment of bile and pancreatic duct blockages caused by cancer. There is limited research evidence and so we are unable to recommend radiofrequency ablation as a treatment for standard clinical practice.

Economic evaluations of interventions to prevent and control health-care-associated infections: a systematic review.

Almost 9 million health-care-associated infections have been estimated to occur each year in European hospitals and long-term care facilities, and these lead to an increase in morbidity, mortality, bed occupancy, and duration of hospital stay. The aim of this systematic review was to review the cost-effectiveness of interventions to limit the spread of health-care-associated infections), framed by WHO infection prevention and control core components. The Embase, National Health Service Economic Evaluation Database, Database of Abstracts of Reviews of Effects, Health Technology Assessment, Cinahl, Scopus, Pediatric Economic Database Evaluation, and Global Index Medicus databases, plus grey literature were searched for studies between Jan 1, 2009, and Aug 10, 2022. Studies were included if they reported interventions including hand hygiene, personal protective equipment, national-level or facility-level infection prevention and control programmes, education and training programmes, environmental cleaning, and surveillance. The British Medical Journal checklist was used to assess the quality of economic evaluations. 67 studies were included in the review. 25 studies evaluated methicillin-resistant Staphylococcus aureus outcomes. 31 studies evaluated screening strategies. The assessed studies that met the minimum quality criteria consisted of economic models. There was some evidence that hand hygiene, environmental cleaning, surveillance, and multimodal interventions were cost-effective. There were few or no studies investigating education and training, personal protective equipment or monitoring, and evaluation of interventions. This Review provides a map of cost-effectiveness data, so that policy makers and researchers can identify the relevant data and then assess the quality and generalisability for their setting.

Rapid priority setting exercise on faecal incontinence for Cochrane Incontinence.

OBJECTIVE: This rapid priority setting exercise aimed to identify, expand, prioritise and explore stakeholder (patients, carers and healthcare practitioners) topic uncertainties on faecal incontinence (FI). DESIGN: An evidence gap map (EGM) was produced to give a visual overview of emerging trial evidence; existing systematic review-level evidence and FI stakeholder topic uncertainties derived from a survey. This EGM was used in a knowledge exchange workshop that promoted group discussions leading to the prioritisation and exploration of FI stakeholder identified topic uncertainties. RESULTS: Overall, a mismatch between the existing and emerging evidence and key FI stakeholder topic uncertainties was found. The prioritised topic uncertainties identified in the workshop were as follows: psychological support; lifestyle interventions; long-term effects of living with FI; education; constipation and the cultural impact of FI. When these six prioritised topic uncertainties were explored in more depth, the following themes were identified: education; impact and burden of living with FI; psychological support; healthcare service improvements and inconsistencies; the stigma of FI; treatments and management; culturally appropriate management and technology and its accessibility. CONCLUSIONS: Topic uncertainties identified were broad and wide ranging even after prioritisation. More research is required to unpick the themes emerging from the in-depth discussion and explore these further to achieve a consensus on deliverable research questions.

Systemic Hypertension in Pediatric Veno-Venous Extracorporeal Membrane Oxygenation.

Systemic hypertension (HTN) is a recognized complication of veno-venous (VV) extracorporeal membrane oxygenation (ECMO) in children. We sought to determine the prevalence and associated features of HTN in a retrospective cohort of children (>1 year old) supported with VV ECMO from January 2015 to July 2019 at our institution. Patient and ECMO-related characteristics were reviewed, including intensive care unit (ICU) length of stay (LOS), ECMO duration, corticosteroids and nephrotoxic medication exposure, acute kidney injury (AKI), overall fluid balance, and transfusion data. We analyzed 23 children (43% female) with a median age of 8.5 years (interquartile range [IQR] = 4-14.5). Median ICU LOS was 26 days (IQR = 15-47) with a median ECMO duration of 288 hours (IQR = 106-378) and a mortality rate of 35%. HTN was diagnosed in 87% subjects at a median of 25 ECMO hours (IQR = 9-54) of whom 55% were hypertensive >50% of their ECMO duration. AKI and fluid overload were documented in >50% of cohort. All but two subjects received at least one nephrotoxic medication, and nearly all received corticosteroids. Our data demonstrate that HTN is present in a preponderance of children supported with VV ECMO and appears within the first 3 days of cannulation. Underlying etiology is likely multifactorial.

Antithrombin Dose Optimization in Extracorporeal Membrane Oxygenation in Infants.

Anticoagulation in extracorporeal membrane oxygenation (ECMO) is challenging, with significant morbidity and mortality associated with thrombotic complications. Unfractionated heparin (UFH) is commonly used, which depends on native antithrombin (AT) function to exert anticoagulant effects. Antithrombin deficiency is common in infants on ECMO and replacement with AT concentrate may be warranted. However, dosing recommendations in this population are limited. We conducted a retrospective review of patients <1 year of age who received recombinant AT (ATryn) while on UFH and ECMO between January 1, 2010 and December 31, 2017. Commonly used dosing equations were assessed to determine their ability to predict postdose AT levels. Patient AT levels were compared with equation-predicted postdose AT levels to determine a correlation. A total of 102 doses in 41 patients were used for analysis. Baseline mean AT level was 43% (±13%) and mean AT doses were 134 units (±58.1 units) or 40.5 units/kg (±18.7 units/kg). Median increase in the AT level was 8% (interquartile range 2-17%) with a mean postdose level of 52.6% (±14.2%). Weight-based dosing poorly correlated with postdose AT levels (r2 = 0.082). Postdose levels were best predicted when using an equation that included desired change in the AT level from baseline, the patient's weight, and added weight from the volume of the ECMO circuit (r2 = 0.427). Prospective studies are needed to evaluate optimal dosing strategies, safety, and efficacy of AT in this population.

Context-Responsive Anticoagulation Reduces Complications in Pediatric Extracorporeal Membrane Oxygenation.

Purpose: We sought to determine the impact of a comprehensive, context-responsive anticoagulation and transfusion guideline on bleeding and thrombotic complication rates and blood product utilization during extracorporeal membrane oxygenation (ECMO). Design: Single-center, observational pre- and post-implementation cohort study. Setting: Academic pediatric hospital. Patients: Patients in the PICU, CICU, and NICU receiving ECMO support. Interventions: Program-wide implementation of a context-responsive anticoagulation and transfusion guideline. Measurements: Pre-implementation subjects consisted of all patients receiving ECMO between January 1 and December 31, 2012, and underwent retrospective chart review. Post-implementation subjects consisted of all ECMO patients between September 1, 2013, and December 31, 2014, and underwent prospective data collection. Data collection included standard demographic and admission data, ECMO technical specifications, non-ECMO therapies, coagulation parameters, and blood product administration. A novel grading scale was used to define hemorrhagic complications (major, intermediate, and minor) and major thromboembolic complications. Main Results: Seventy-six ECMO patients were identified: 31 during the pre-implementation period and 45 in the post-implementation period. The overall observed mortality was 33% with no difference between groups. Compared to pre-implementation, the post-implementation group experienced fewer major hemorrhagic and major thrombotic complications and less severe hemorrhagic complications and received less RBC transfusion volume per kg. Conclusions: Use of a context-responsive anticoagulation and transfusion guideline was associated with a reduction in hemorrhagic and thrombotic complications and reduced RBC transfusion requirements. Further evaluation of guideline content, compliance, performance, and sustainability is needed.

Primary Care Transformation.

Primary care transformation will usher in a new era of advanced team-based care with extensive roles beyond the physician to build authentic healing relationships with patients. Smart technology will support these relationships, empower and engage patients, and build confidence that their health care team will take excellent care of them. Investments need to shift from catastrophic hospital-based care to proactive prevention and wellness, pushing us to think of health beyond health care. Systems need to build a culture of continuous improvement, supported by data-driven improvement science, and keep a sharp focus on the patient experience of care.

Evaluation of an established learning portfolio.

BACKGROUND: The trainee-held learning portfolio is integral to the foundation programme in the UK. In the Northern Deanery, portfolio assessment is standardised through the Annual Review of Competence Progression (ARCP) process. In this study we aimed to establish how current trainees evaluate portfolio-based learning and ARCP, and how these attitudes may have changed since the foundation programme was first introduced. METHODS: Deanery-wide trainee attitudes were surveyed by an electronic questionnaire in 2009 and compared with perceptions recorded during the pilot phase (2004-2005). RESULTS: Many trainees continue to view the e-portfolio negatively. Indeed, significantly fewer trainees in 2009 thought that the e-portfolio was a 'good idea' or a 'worthwhile investment of time' than in 2005. Trainees remain unconvinced about the educational value of the e-portfolio: fewer trainees in 2009 regarded it as a tool that might help focus on training or recognise individual strengths and weaknesses. Issues around unnecessary bureaucracy persist. Current trainees tend to understand how to use the e-portfolio, but many did not know how much, or what evidence to collect. Few supervisors were reported to provide useful guidance on the portfolio. ARCP encouraged portfolio completion but did not give meaningful feedback to drive future learning. DISCUSSION: Continued support is needed for both trainees and supervisors in portfolio-building skills and in using the e-portfolio as an educational tool. Trainee-tailored feedback is needed to ensure that portfolio-based assessment promotes lifelong, self-directed and reflective learners.

A prospective study of neurocognitive changes 15 years after chronic inhalant abuse.

AIMS: In a previous study, neurological and cognitive deficits reflecting central nervous system (CNS) disruption from chronic inhalant abuse showed substantial recovery after 2 years' abstinence. Functional recovery was progressive, with recovery rates dependent on the degree of impairment prior to abstinence, and severity and duration of initial abuse. Persistent deficits occurred in those with previous 'lead encephalopathy' from leaded petrol abuse. The current study examined recovery in the same cohort 15 years after baseline. DESIGN: Prospective cohort design. SETTING: Two remote Aboriginal communities in Arnhem Land, Australia. PARTICIPANTS: Using baseline group classifications, 27 healthy controls, 60 ex-chronic inhalant abusers and an additional 17 with previous lead encephalopathy were assessed. MEASUREMENTS: Standard neurological, ocular-motor and cognitive functions and blood lead levels. FINDINGS: Chronic (non-encephalopathic) inhalant abusers showed elevated blood lead levels and abnormal scores on most tasks at baseline. At 2 years' abstinence, blood lead was reduced but remained elevated and most scores had normalized. By 15 years, blood lead and all performance scores were equivalent to healthy controls for this group (P > 0.05). The encephalopathic group was more severely impaired on all scores at baseline and showed little improvement, if any, across all tests after both 2 and 15 years' abstinence. Blood lead for this group declined, and was not significantly different to controls after 15 years. CONCLUSIONS: Some inhalant abusers experience severe and persistent neurological deficits, suggesting irrecoverable damage attributable to lead encephalopathy. In the absence of this encephalopathy long-term abstinence from inhalants may allow recovery of normal brain function.