Developing an Intervention for Fall-Related Injuries in Dementia (DIFRID): an integrated, mixed-methods approach

Background Falls in people with dementia can result in a number of physical and psychosocial consequences. However, there is limited evidence to inform how best to deliver services to people with dementia following a fall. The aim of the DIFRID study was to determine the feasibility of developing and implementing a new intervention to improve outcomes for people with dementia with fall-related injuries; this encompasses both short-term recovery and reducing the likelihood of future falls. This paper details the development of the DIFRID intervention. Methods The intervention was designed using an integrated, mixed-methods approach. This involved a realist synthesis of the literature and qualitative data gathered through interviews and focus groups with health and social care professionals (n=81). An effectiveness review and further interviews and observation were also conducted and are reported elsewhere. A modified Delphi panel approach with 24 experts was then used to establish a consensus on how the findings should translate into a new intervention. After feedback from key stakeholders (n=15) on the proposed model, the intervention was manualised and training developed. Results We identified key components of a new intervention covering three broad areas: • Ensuring that the circumstances of rehabilitation are optimised for people with dementia • Compensating for the reduced ability of people with dementia to self-manage • Equipping the workforce with the necessary skills and information to care for this patient group Consensus was achieved on 54 of 69 statements over two rounds of the Delphi surveys. The statements were used to model the intervention and finalise the accompanying manual and protocol for a feasibility study. Stakeholder feedback was generally positive and the majority of suggested intervention components were approved. The proposed outcome was a 12-week complex multidisciplinary intervention primarily based at the patient’s home. Conclusions A new intervention has been developed to improve outcomes for people with dementia following a fall requiring healthcare attention. The feasibility of this intervention is currently being tested. Trial registration ISRCTN41760734 (16/11/2015

Primary trabeculectomy versus primary glaucoma eye drops for newly diagnosed advanced glaucoma:TAGS RCT

Funding Information: Declared competing interests of authors: Anthony J King declares receiving honoraria payments from Thea Pharmaceutical (Keele, UK) and Allergan Pharmaceutical (Dublin, Ireland) for speaking at educational meetings. Augusto Azuara-Blanco declares membership of the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Prioritisation Committee B (2020–present). Jennifer Burr declares membership of the NIHR HTA Clinical Evaluations and Trials Committee (2010–14). David Garway-Heath reports grants from NIHR for the HTA programme 12/35/38 during the conduct of the study; personal fees from Aerie Pharmaceuticals (Bedminster, NJ, USA), Allergan Pharmaceuticals, Bausch & Lomb (Rochester, NY, USA), Omikron (Beirut, Lebanon) and OptoVue (Fremont, CA, USA); personal fees and non-financial support from Carl Zeiss Meditec (Jena, Germany) and CenterVue (Padova, Italy); grants from Pfizer Inc. (New York, NY, USA) and Alcon Research Institute (Geneva, Switzerland); grants and personal fees from Santen Pharmaceutical (Osaka, Japan); and research equipment from Heidelberg Engineering (Heidelberg, Germany) and Topcon (Tokyo, Japan) outside the submitted work. David Garway-Heath also declared membership of the NIHR HTA Clinical Evaluations and Trials Committee (2014–17). John Norrie reports grants from University of Aberdeen and University of Edinburgh during the conduct of the study; and reports being a past and present member of the following: HTA Commissioning Sub-Board (EOI), NIHR Clinical Trials Unit Standing Advisory Committee, NIHR HTA and Efficacy and Mechanism Evaluation (EME) Editorial Board, Pre-Exposure Prophylaxis Impact Review Panel, EME Strategy Advisory Committee, EME Funding Committee Members, EME Funding Committee Sub-Group Remit and Comp Check, HTA General Committee, HTA Funding Committee Policy Group (formerly CSG) and the HTA Commissioning Committee. John Norrie also reports the HTA Post-funding Committee Teleconference (2016–19) and Covid Reviewing 2020. Luke Vale reports grants from NIHR HTA programme 12/35/38 during the conduct of the study. Luke Vale was also a member of the NIHR HTA Clinical Trials and Evaluation Panel from 2014 to 2018. John M Sparrow reports grants from NIHR HTA programme 12/35/38 during the conduct of the study, and was the previous chairperson of the National Institute for Health and Care Excellence Glaucoma Guideline Committee guideline published in 2017. Keith Barton reports personal fees from Allergan Pharmaceuticals, Alcon Pharmaceuticals, Laboratoires Thea (Clermont-Ferrand, France), EyeTechCare (Rillieux-la-Pape, France), Glaukos (San Clemente, CA, USA), Kowa Pharmaceuticals (Montgomery, AL, USA), Ivantis Inc. (Irvine, CA, USA), pH Pharma (South San Francisco, CA, USA), iStar Medical (Wavre, Belgium), Radiance Therapeutics (Tucson, AZ, USA) and EyeD Pharma (Liège, Belgium), grants from Allergan and Laboratoires Thea, stock from Vision Medical Events Ltd (London, UK), International Glaucoma Surgery Registry (London, UK) and MedEther Ophthalmology (London, UK), and a patent from Advanced Ophthalmic Implants outside the submitted work. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 72. See the NIHR Journals Library website for further project information. The research reported in this issue of the journal was funded by the HTA programme as project number 12/35/38. The contractual start date was in January 2014. The draft report began editorial review in February 2020 and was accepted for publication in December 2020. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.Peer reviewedPublisher PD

Primary trabeculectomy for advanced glaucoma : pragmatic multicentre randomised controlled trial (TAGS)

Funding: The project was funded by the National Institute of Health Research (NIHR) Health Technology Assessment (HTA) Programme (project number 12/35/38). The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The funders had no role in considering the study design or in the collection, analysis, or interpretation of data; writing the report; or the decision to submit the article for publication. The views expressed herein are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Acknowledgments Sponsor representative: Pauline Hyman-Taylor (from February 2019), Natalie McGregor (March 2015 to February 2019), Audrey Athlan (from July 2014 to March 2015), Joanne Thornhill (from 2013 to July 2014). Patient and public involvement representative: Rick Walsh, Russel Young. CHaRT Trial Office: Mark Forrest (from 2015), Gladys McPherson (until 2015). CHaRT Trial Office data coordinator: Pauline Garden. Health economists: Eoin Maloney (until 2015), Mehdi Javanbakht (until June 2019).All participants in the trial, staff, and members of the TAGS Investigator Group responsible for recruitment in the clinical centres.Peer reviewedPublisher PD

Best-practice prevention alone or with conventional or biological caries management for 3- to 7-year-olds:the FiCTION three-arm RCT

Background Historically, lack of evidence for effective management of decay in primary teeth has caused uncertainty, but there is emerging evidence to support alternative strategies to conventional fillings, which are minimally invasive and prevention orientated. Objectives The objectives were (1) to assess the clinical effectiveness and cost-effectiveness of three strategies for managing caries in primary teeth and (2) to assess quality of life, dental anxiety, the acceptability and experiences of children, parents and dental professionals, and caries development and/or progression. Design This was a multicentre, three-arm parallel-group, participant-randomised controlled trial. Allocation concealment was achieved by use of a centralised web-based randomisation facility hosted by Newcastle Clinical Trials Unit. Setting This trial was set in primary dental care in Scotland, England and Wales. Participants Participants were NHS patients aged 3–7 years who were at a high risk of tooth decay and had at least one primary molar tooth with decay into dentine, but no pain/sepsis. Interventions Three interventions were employed: (1) conventional with best-practice prevention (local anaesthetic, carious tissue removal, filling placement), (2) biological with best-practice prevention (sealing-in decay, selective carious tissue removal and fissure sealants) and (3) best-practice prevention alone (dietary and toothbrushing advice, topical fluoride and fissure sealing of permanent teeth). Main outcome measures The clinical effectiveness outcomes were the proportion of children with at least one episode (incidence) and the number of episodes, for each child, of dental pain or dental sepsis or both over the follow-up period. The cost-effectiveness outcomes were the cost per incidence of, and cost per episode of, dental pain and/or dental sepsis avoided over the follow-up period. Results A total of 72 dental practices were recruited and 1144 participants were randomised (conventional arm, n = 386; biological arm, n = 381; prevention alone arm, n = 377). Of these, 1058 were included in an intention-to-treat analysis (conventional arm, n = 352; biological arm, n = 352; prevention alone arm, n = 354). The median follow-up time was 33.8 months (interquartile range 23.8–36.7 months). The proportion of children with at least one episode of pain or sepsis or both was 42% (conventional arm), 40% (biological arm) and 45% (prevention alone arm). There was no evidence of a difference in incidence or episodes of pain/sepsis between arms. When comparing the biological arm with the conventional arm, the risk difference was –0.02 (97.5% confidence interval –0.10 to 0.06), which indicates, on average, a 2% reduced risk of dental pain and/or dental sepsis in the biological arm compared with the conventional arm. Comparing the prevention alone arm with the conventional arm, the risk difference was 0.04 (97.5% confidence interval –0.04 to 0.12), which indicates, on average, a 4% increased risk of dental pain and/or dental sepsis in the prevention alone arm compared with the conventional arm. Compared with the conventional arm, there was no evidence of a difference in episodes of pain/sepsis among children in the biological arm (incident rate ratio 0.95, 97.5% confidence interval 0.75 to 1.21, which indicates that there were slightly fewer episodes, on average, in the biological arm than the conventional arm) or in the prevention alone arm (incident rate ratio 1.18, 97.5% confidence interval 0.94 to 1.48, which indicates that there were slightly more episodes in the prevention alone arm than the conventional arm). Over the willingness-to-pay values considered, the probability of the biological treatment approach being considered cost-effective was approximately no higher than 60% to avoid an incidence of dental pain and/or dental sepsis and no higher than 70% to avoid an episode of pain/sepsis. Conclusions There was no evidence of an overall difference between the three treatment approaches for experience of, or number of episodes of, dental pain or dental sepsis or both over the follow-up period

Dual bronchodilators in Bronchiectasis study (DIBS): protocol for a pragmatic, multicentre, placebo-controlled, three-arm, double-blinded, randomised controlled trial studying bronchodilators in preventing exacerbations of bronchiectasis

INTRODUCTION: Bronchiectasis is a long-term lung condition, with dilated bronchi, chronic inflammation, chronic infection and acute exacerbations. Recurrent exacerbations are associated with poorer clinical outcomes such as increased severity of lung disease, further exacerbations, hospitalisations, reduced quality of life and increased risk of death. Despite an increasing prevalence of bronchiectasis, there is a critical lack of high-quality studies into the disease and no treatments specifically approved for its treatment. This trial aims to establish whether inhaled dual bronchodilators (long acting beta agonist (LABA) and long acting muscarinic antagonist (LAMA)) taken as either a stand-alone therapy or in combination with inhaled corticosteroid (ICS) reduce the number of exacerbations of bronchiectasis requiring treatment with antibiotics during a 12 month treatment period. METHODS: This is a multicentre, pragmatic, double-blind, randomised controlled trial, incorporating an internal pilot and embedded economic evaluation. 600 adult patients (≥18 years) with CT confirmed bronchiectasis will be recruited and randomised to either inhaled dual therapy (LABA+LAMA), triple therapy (LABA+LAMA+ICS) or matched placebo, in a 2:2:1 ratio (respectively). The primary outcome is the number of protocol defined exacerbations requiring treatment with antibiotics during the 12 month treatment period. ETHICS AND DISSEMINATION: Favourable ethical opinion was received from the North East-Newcastle and North Tyneside 2 Research Ethics Committee (reference: 21/NE/0020). Results will be disseminated in peer-reviewed publications, at national and international conferences, in the NIHR Health Technology Assessments journal and to participants and the public (using lay language). TRIAL REGISTRATION NUMBER: ISRCTN15988757

Conservative management versus tonsillectomy in adults with recurrent acute tonsillitis in the UK (NATTINA) : a multicentre, open-label, randomised controlled trial

This study was funded by the NIHR Health Technology Assessment programme (12/146/06).Background Tonsillectomy is regularly performed in adults with acute tonsillitis, but with scarce evidence. A reduction in tonsillectomies has coincided with an increase in acute adult hospitalisation for tonsillitis complications. We aimed to assess the clinical effectiveness and cost-effectiveness of conservative management versus tonsillectomy in patients with recurrent acute tonsillitis. Methods This pragmatic multicentre, open-label, randomised controlled trial was conducted in 27 hospitals in the UK. Participants were adults aged 16 years or older who were newly referred to secondary care otolaryngology clinics with recurrent acute tonsillitis. Patients were randomly assigned (1:1) to receive tonsillectomy or conservative management using random permuted blocks of variable length. Stratification by recruiting centre and baseline symptom severity was assessed using the Tonsil Outcome Inventory-14 score (categories defined as mild 0–35, moderate 36–48, or severe 49–70). Participants in the tonsillectomy group received elective surgery to dissect the palatine tonsils within 8 weeks after random assignment and those in the conservative management group received standard non-surgical care during 24 months. The primary outcome was the number of sore throat days collected during 24 months after random assignment, reported once per week with a text message. The primary analysis was done in the intention-to-treat (ITT) population. This study is registered with the ISRCTN registry, 55284102. Findings Between May 11, 2015, and April 30, 2018, 4165 participants with recurrent acute tonsillitis were assessed for eligibility and 3712 were excluded. 453 eligible participants were randomly assigned (233 in the immediate tonsillectomy group vs 220 in the conservative management group). 429 (95%) patients were included in the primary ITT analysis (224 vs 205). The median age of participants was 23 years (IQR 19–30), with 355 (78%) females and 97 (21%) males. Most participants were White (407 [90%]). Participants in the immediate tonsillectomy group had fewer days of sore throat during 24 months than those in the conservative management group (median 23 days [IQR 11–46] vs 30 days [14–65]). After adjustment for site and baseline severity, the incident rate ratio of total sore throat days in the immediate tonsillectomy group (n=224) compared with the conservative management group (n=205) was 0·53 (95% CI 0·43 to 0·65;Publisher PDFPeer reviewe

Tonsillectomy compared with conservative management in patients over 16 years with recurrent sore throat:the NATTINA RCT and economic evaluation

BACKGROUND: The place of tonsillectomy in the management of sore throat in adults remains uncertain.OBJECTIVES: To establish the clinical effectiveness and cost-effectiveness of tonsillectomy, compared with conservative management, for tonsillitis in adults, and to evaluate the impact of alternative sore throat patient pathways.DESIGN: This was a multicentre, randomised controlled trial comparing tonsillectomy with conservative management. The trial included a qualitative process evaluation and an economic evaluation.SETTING: The study took place at 27 NHS secondary care hospitals in Great Britain.PARTICIPANTS: A total of 453 eligible participants with recurrent sore throats were recruited to the main trial.INTERVENTIONS: Patients were randomised on a 1 : 1 basis between tonsil dissection and conservative management (i.e. deferred surgery) using a variable block-stratified design, stratified by (1) centre and (2) severity.MAIN OUTCOME MEASURES: The primary outcome measure was the total number of sore throat days over 24 months following randomisation. The secondary outcome measures were the number of sore throat episodes and five characteristics from Sore Throat Alert Return, describing severity of the sore throat, use of medications, time away from usual activities and the Short Form questionnaire-12 items. Additional secondary outcomes were the Tonsil Outcome Inventory-14 total and subscales and Short Form questionnaire-12 items 6 monthly. Evaluation of the impact of alternative sore throat patient pathways by observation and statistical modelling of outcomes against baseline severity, as assessed by Tonsil Outcome Inventory-14 score at recruitment. The incremental cost per sore throat day avoided, the incremental cost per quality-adjusted life-year gained based on responses to the Short Form questionnaire-12 items and the incremental net benefit based on costs and responses to a contingent valuation exercise. A qualitative process evaluation examined acceptability of trial processes and ramdomised arms.RESULTS: There was a median of 27 (interquartile range 12-52) sore throats over the 24-month follow-up. A smaller number of sore throats was reported in the tonsillectomy arm [median 23 (interquartile range 11-46)] than in the conservative management arm [median 30 (interquartile range 14-65)]. On an intention-to-treat basis, there were fewer sore throats in the tonsillectomy arm (incident rate ratio 0.53, 95% confidence interval 0.43 to 0.65). Sensitivity analyses confirmed this, as did the secondary outcomes. There were 52 episodes of post-operative haemorrhage reported in 231 participants undergoing tonsillectomy (22.5%). There were 47 re-admissions following tonsillectomy (20.3%), 35 relating to haemorrhage. On average, tonsillectomy was more costly and more effective in terms of both sore throat days avoided and quality-adjusted life-years gained. Tonsillectomy had a 100% probability of being considered cost-effective if the threshold for an additional quality-adjusted life year was £20,000. Tonsillectomy had a 69% probability of having a higher net benefit than conservative management. Trial processes were deemed to be acceptable. Patients who received surgery were unanimous in reporting to be happy to have received it.LIMITATIONS: The decliners who provided data tended to have higher Tonsillectomy Outcome Inventory-14 scores than those willing to be randomised implying that patients with a higher burden of tonsillitis symptoms may have declined entry into the trial.CONCLUSIONS: The tonsillectomy arm had fewer sore throat days over 24 months than the conservative management arm, and had a high probability of being considered cost-effective over the ranges considered. Further work should focus on when tonsillectomy should be offered. National Trial of Tonsillectomy IN Adults has assessed the effectiveness of tonsillectomy when offered for the current UK threshold of disease burden. Further research is required to define the minimum disease burden at which tonsillectomy becomes clinically effective and cost-effective.TRIAL REGISTRATION: This trial is registered as ISRCTN55284102.FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/146/06) and is published in full in Health Technology Assessment; Vol. 27, No. 31. See the NIHR Funding and Awards website for further award information. </p

Clinical effectiveness of septoplasty versus medical management for nasal airways obstruction:multicentre, open label, randomised controlled trial

OBJECTIVE: To assess the clinical effectiveness of septoplasty.DESIGN: Multicentre, randomised controlled trial.SETTING: 17 otolaryngology clinics in the UK's National Health Service.PARTICIPANTS: 378 adults (≥18 years, 67% men) newly referred with symptoms of nasal obstruction associated with septal deviation and at least moderate symptoms of nasal obstruction (score &gt;30 on the Nasal Obstruction and Symptom Evaluation (NOSE) scale).INTERVENTIONS: Participants were randomised 1:1 to receive either septoplasty (n=188) or defined medical management (n=190, nasal steroid and saline spray for six months), stratified by baseline symptom severity and sex.MAIN OUTCOME MEASURES: The primary outcome measure was patient reported score on the Sino-Nasal Outcome Test-22 (SNOT-22) at six months, with 9 points defined as the minimal clinically important difference. Secondary outcomes included quality of life and objective nasal airflow measures.RESULTS: Mean SNOT-22 scores at six months were 19.9 (95% confidence interval 17.0 to 22.7) in the septoplasty arm (n=152, intention-to-treat population) and 39.5 (36.1 to 42.9) in the medical management arm (n=155); an estimated 20.0 points lower (better) for participants randomised to receive septoplasty (95% confidence interval 16.4 to 23.6, P&lt;0.001, adjusted for baseline continuous SNOT-22 score and the stratification variables sex and baseline NOSE severity categories). Greater improvement in SNOT-22 scores was predicted by higher baseline symptom severity scores. Quality of life outcomes and nasal airflow measures (including peak nasal inspiratory flow and absolute inhalational nasal partitioning ratio) improved more in participants in the septoplasty group. Readmission to hospital with bleeding after septoplasty occurred in seven participants (4% of 174 who had septoplasty), and a further 20 participants (12%) required antibiotics for infections.CONCLUSIONS: Septoplasty is a more effective intervention than a defined medical management regimen with a nasal steroid and saline spray in adults with nasal obstruction associated with a deviated nasal septum.TRIAL REGISTRATION: ISRCTN Registry ISRCTN16168569.</p

Representative Landscapes in the Forested Area of Canada

Canada is a large nation with forested ecosystems that occupy over 60% of the national land base, and knowledge of the patterns of Canada’s land cover is important to proper environmental management of this vast resource. To this end, a circa 2000 Landsat-derived land cover map of the forested ecosystems of Canada has created a new window into understanding the composition and configuration of land cover patterns in forested Canada. Strategies for summarizing such large expanses of land cover are increasingly important, as land managers work to study and preserve distinctive areas, as well as to identify representative examples of current land-cover and land-use assemblages. Meanwhile, the development of extremely efficient clustering algorithms has become increasingly important in the world of computer science, in which billions of pieces of information on the internet are continually sifted for meaning for a vast variety of applications. One recently developed clustering algorithm quickly groups large numbers of items of any type in a given data set while simultaneously selecting a representative—or “exemplar”—from each cluster. In this context, the availability of both advanced data processing methods and a nationally available set of landscape metrics presents an opportunity to identify sets of representative landscapes to better understand landscape pattern, variation, and distribution across the forested area of Canada. In this research, we first identify and provide context for a small, interpretable set of exemplar landscapes that objectively represent land cover in each of Canada’s ten forested ecozones. Then, we demonstrate how this approach can be used to identify flagship and satellite long-term study areas inside and outside protected areas in the province of Ontario. These applications aid our understanding of Canada’s forest while augmenting its management toolbox, and may signal a broad range of applications for this versatile approach

Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority trial.

OBJECTIVE: To test and compare the efficacy of methenamine hippurate for prevention of recurrent urinary tract infections with the current standard prophylaxis of daily low dose antibiotics. DESIGN: Multicentre, open label, randomised, non-inferiority trial. SETTING: Eight centres in the UK, recruiting from June 2016 to June 2018. PARTICIPANTS: Women aged ≥18 years with recurrent urinary tract infections, requiring prophylactic treatment. INTERVENTIONS: Random assignment (1:1, using permuted blocks of variable length via a web based system) to receive antibiotic prophylaxis or methenamine hippurate for 12 months. Treatment allocation was not masked and crossover between arms was allowed. MAIN OUTCOME MEASURE: Absolute difference in incidence of symptomatic, antibiotic treated, urinary tract infections during treatment. A patient and public involvement group predefined the non-inferiority margin as one episode of urinary tract infection per person year. Analyses performed in a modified intention-to-treat population comprised all participants observed for at least six months. RESULTS: Participants were randomly assigned to antibiotic prophylaxis (n=120) or methenamine hippurate (n=120). The modified intention-to-treat analysis comprised 205 (85%) participants (antibiotics, n=102 (85%); methenamine hippurate, n=103 (86%)). Incidence of antibiotic treated urinary tract infections during the 12 month treatment period was 0.89 episodes per person year (95% confidence interval 0.65 to 1.12) in the antibiotics group and 1.38 (1.05 to 1.72) in the methenamine hippurate group, with an absolute difference of 0.49 (90% confidence interval 0.15 to 0.84) confirming non-inferiority. Adverse reactions were reported by 34/142 (24%) in the antibiotic group and 35/127 (28%) in the methenamine group and most reactions were mild. CONCLUSION: Non-antibiotic prophylactic treatment with methenamine hippurate might be appropriate for women with a history of recurrent episodes of urinary tract infections, informed by patient preferences and antibiotic stewardship initiatives, given the demonstration of non-inferiority to daily antibiotic prophylaxis seen in this trial. TRIAL REGISTRATION: ISRCTN70219762