The STAR care pathway for patients with chronic pain after total knee replacement: four-year follow-up of a randomised controlled trial.

BACKGROUND: The Support and Treatment After Replacement (STAR) care pathway is a clinically important and cost-effective intervention found to improve pain outcomes over one year for people with chronic pain three months after total knee replacement (TKR). We followed up STAR trial participants to evaluate the longer-term clinical- and cost-effectiveness of this care pathway. METHODS: Participants who remained enrolled on the trial at one year were contacted by post at a median of four years after randomisation and invited to complete a questionnaire comprising the same outcomes collected during the trial. We captured pain (co-primary outcome using the Brief Pain Inventory (BPI) pain severity and interference scales; scored 0-10, best to worst), function, neuropathic characteristics, emotional aspects of pain, health-related quality of life, and satisfaction. Electronic hospital informatics data on hospital resource use for the period of one to four years post-randomisation were collected from participating hospital sites. The economic evaluation took an National Health Service (NHS) secondary care perspective, with a four-year time horizon. RESULTS: Overall, 226/337 (67%) of participants returned completed follow-up questionnaires, yielding adjusted between-group differences in BPI means of -0.42 (95% confidence interval, CI (-1.07, 0.23); p = 0.20) for pain severity and - 0.64 (95% CI -1.41, 0.12); p = 0.10) for pain interference. Analysis using a multiple imputed data set (n = 337) showed an incremental net monetary benefit in favour of the STAR care pathway of £3,525 (95% CI -£990 to £8,039) at a £20,000/QALY willingness-to-pay threshold, leading to a probability that the intervention was cost-effective of 0.94. CONCLUSIONS: The magnitude of the longer-term benefits of the STAR care pathway are uncertain due to attrition of trial participants; however, there is a suggestion of some degree of sustained clinical benefit at four years. The care pathway remained cost-effective at four years. TRIAL REGISTRATION: ISRCTN: 92,545,361.

The effectiveness and cost-effectiveness of a group domestic abuse perpetrator programme: protocol for a randomised controlled trial.

BACKGROUND: In contrast to evidence for interventions supporting victim/survivors of domestic violence and abuse (DVA), the effectiveness of perpetrator programmes for reduction of abuse is uncertain. This study aims to estimate the effectiveness and cost-effectiveness of a perpetrator programme for men. METHODS: Pragmatic two-group individually randomised controlled trial (RCT) with embedded process and economic evaluation. Five centres in southwest England and South Wales aim to recruit 316 (reduced from original target of 366) male domestic abuse perpetrators. These will be randomised 2:1 to a community-based domestic abuse perpetrator programme (DAPP) or usual care comparator with 12-month follow-up. Female partners/ex-partners will be invited to join the study. The intervention for men comprises 23 weekly sessions of a group programme delivered in voluntary sector domestic abuse services. The intervention for female partners/ex-partners is one-to-one support from a safety worker. Men allocated to usual care receive no intervention; however, they are free to access other services. Their partners/ex-partners will be signposted to support services. Data is collected at baseline, and 4, 8 and 12 months' follow-up. The primary outcome is men's self-reported abusive behaviour measured by the Abusive Behaviour Inventory (ABI-29) at 12 months. Secondary measures include physical and mental health status and resource use alongside the abuse measure ABI (ABI-R) for partners/ex-partners and criminal justice contact for men. A mixed methods process evaluation and qualitative study will explore mechanisms of effectiveness, judge fidelity to the intervention model using interviews and group observations. The economic evaluation, over a 1-year time horizon from three perspectives (health and social care, public sector and society), will employ a cost-consequences framework reporting costs alongside economic outcomes (Quality-Adjusted Life Years derived from EQ-5D-5L, SF-12 and CHU-9D, and ICECAP-A) as well as the primary and other secondary outcomes. DISCUSSION: This trial will provide evidence of the (cost)effectiveness of a DAPP. The embedded process evaluation will further insights in the experiences and contexts of participants and their journey through a perpetrator programme, and the study will seek to address the omission in other studies of economic evaluations. TRIAL REGISTRATION: ISRCTN15804282, April 1, 2019.

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial.

BACKGROUND: Anterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability. METHODS: We did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score-4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367. FINDINGS: Between Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5-13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications. INTERPRETATION: Surgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management. FUNDING: The UK National Institute for Health Research Health Technology Assessment Programme.

Should the nail plate be replaced or discarded after nail bed repair in children? Nail bed INJury Analysis (NINJA) randomised controlled trial: a health economic and statistical analysis plan.

BACKGROUND: Nail bed trauma is one of the most common surgically treated paediatric hand injuries in the UK. Despite surgeons generally expressing a preference to replace the nail plate after repairing the nail bed, there is limited evidence to support this practice. We describe a statistical and health economic analysis plan (SHEAP) for the Nail bed INJury Analysis (NINJA) randomised controlled trial. METHODS/DESIGN: NINJA is a multicentre, pragmatic, superiority, parallel group randomised controlled trial of the treatment of nail bed injury in participants 16 years old or younger. The study aims to evaluate the efficacy and cost-effectiveness of replacing the nail plate compared to discarding it following the repair of a nail bed injury. Surgical site infection at 7-10 days post-randomisation and cosmetic appearance of the nail are the co-primary outcomes for NINJA. Surgical site infection at 7-10 days post-randomisation will be evaluated using a logistic regression model adjusting for site as the sole stratification factor and allowing for intra-site correlation. Cosmetic appearance will be assessed via the newly developed Oxford Finger Nail Appearance Score and will be evaluated by use of a Mann-Whitney U test. An ordinal logistic regression model will also be used to assess the Oxford Finger Nail Appearance Score, adjusting for site and allowing for intra-site correlation. Secondary outcomes are measured at 7-10 days and 4 months and include the EQ-5D-Y questionnaire, pain at first dressing change, cost-effectiveness, late surgical site infection, and participant/parent satisfaction with nail healing. Missing primary outcome data will be summarised by treatment arm and investigated through a sensitivity analysis. Full details of the planned methods of analysis and descriptive statistics are described in this paper. The NINJA study protocol has been published previously. DISCUSSION: The planned analysis strategy for the NINJA trial has been set out here to reduce the risk of reporting bias and data-driven analysis. Any deviations from the SHEAP described in this paper will be detailed and justified fully in the final report of the trial. TRIAL REGISTRATION: ISRCTN, ISRCTN44551796 . Registered on 23 April 2018.

Comparison of the clinical and cost effectiveness of two management strategies (rehabilitation versus surgical reconstruction) for non-acute anterior cruciate ligament (ACL) injury: study protocol for the ACL SNNAP randomised controlled trial.

BACKGROUND: Anterior cruciate ligament (ACL) rupture is a common knee injury that can lead to poor quality of life, decreased activity and increased risk of secondary osteoarthritis of the knee. Management of patients with a non-acute ACL injury can include a non-surgical (rehabilitation) or surgical (reconstruction) approach. However, insufficient evidence to guide treatment selection has led to high variation in treatment choice for patients with non-acute presentation of ACL injury. The objective of the ACL SNNAP trial is to determine in patients with non-acute anterior cruciate ligament deficiency (ACLD) whether a strategy of non-surgical management (rehabilitation) (with option for later ACL reconstruction only if required) is more clinically effective and cost effective than a strategy of surgical management (reconstruction) without prior rehabilitation with all patients followed up at 18 months. METHODS: The study is a pragmatic, multi-centre, superiority, randomised controlled trial with two-arm parallel groups and 1:1 allocation. Patients with a symptomatic non-acute ACL deficient knee will be randomised to either non-surgical management (rehabilitation) or surgical management (reconstruction). We aim to recruit 320 patients from approximately 30 secondary care orthopaedic units from across the United Kingdom. Randomisation will occur using a web-based randomisation system. Blinding of patients and clinicians to treatment allocation will not be possible because of the nature of the interventions. Participants will be followed up via self-reported questionnaires at 6, 12 and 18 months. The primary outcome is the Knee injury and Osteoarthritis Outcome Score (KOOS) at 18 months post randomisation. Secondary outcomes will include a return to sport/activity, intervention-related complications, patient satisfaction, expectations of activity, generic health quality of life, knee specific quality of life and resource usage. DISCUSSION: At present, no evidence-based treatment of non-acute ACL deficiency exists, particularly in the NHS. Moreover, little consensus exists on the management approach for these patients. The proposed trial will address this gap in knowledge regarding the clinical and cost effectiveness of ACL treatment and inform future standards of care for this condition. TRIAL REGISTRATION: ISRCTN: 10110685. Registered on 16 November 2016. ClinicalTrials.gov: NCT02980367. Registered in December 2016.

Nocturnal temperature-controlled laminar airflow device for adults with severe allergic asthma: the LASER RCT.

BACKGROUND: Severe asthma exacerbations are costly to patients and the NHS, and occur frequently in severely allergic patients. OBJECTIVE: To ascertain whether or not nocturnal temperature-controlled laminar airflow (TLA) device usage over 12 months can reduce severe exacerbations and improve asthma control and quality of life compared with a placebo device, while being cost-effective and acceptable to adults with severe allergic asthma. DESIGN: A pragmatic, multicentre, randomised, double-blind, placebo-controlled, parallel-group, superiority trial with qualitative interviews. The trial included an internal pilot with qualitative focus groups. SETTING: Fourteen hospitals in the UK that manage patients with severe asthma. PARTICIPANTS: Adults (16-75 years) with severe, poorly controlled, exacerbation-prone asthma despite high-intensity treatment, and who are sensitised to a perennial indoor aeroallergen. INTERVENTION: Nocturnal, home-based TLA treatment using an Airsonett® (Airsonett AB, Ängelholm, Sweden) device. The comparator was a placebo device that was identical to the active device except that it did not deliver the laminar airflow. Participants were allocated 1 : 1 to TLA therapy or placebo, minimised by site, origin of case, baseline severe exacerbation frequency, maintenance oral corticosteroid use and pre-bronchodilator forced expiratory volume in 1 second. MAIN OUTCOME MEASURES: Primary outcome - frequency of severe asthma exacerbations occurring within the 12-month follow-up period, defined as worsening of asthma requiring systemic corticosteroids [≥ 30 mg of prednisolone or equivalent daily (or ≥ 50% increase in dose if on maintenance dose of ≥ 30 mg of prednisolone)] for ≥ 3 days. Secondary outcomes - changes in asthma control, lung function, asthma-specific and global quality of life for participants, adherence to the intervention, device acceptability, health-care resource use and cost-effectiveness. RESULTS: Between May 2014 and January 2016, 489 patients consented to participate in the trial, of whom 249 failed screening and 240 were randomised (n = 119 in the treatment group and n = 121 in the placebo group); all were analysed. In total, 202 participants (84%) reported use of the device for 9-12 months. Qualitative analyses showed high levels of acceptability. The mean [standard deviation (SD)] rate of severe exacerbations did not differ between groups [active 1.39 (1.57), placebo 1.48 (2.03); risk ratio 0.92, 95% CI 0.66 to 1.27; p = 0.616]. There were no significant differences in secondary outcomes for lung function, except for a reduction in mean daily peak expiratory flow [mean (SD) difference 14.7 l/minute (7.35 l/minute), 95% CI 0.32 to 29.1 l/minute; p = 0.045) for those in the active device group. There were no differences in asthma control or airway inflammation and no serious harms related to the device. No significant difference between the groups in quality-adjusted life-years gained over 1 year was observed. In addition, there was no difference in generic or disease-specific health-related quality of life overall, although statistically significant higher quality of life at month 6 was observed. Increases in quality of life were not sufficient to offset the annual costs associated with use of the TLA device. LIMITATIONS: Missing outcome data could have resulted in an underestimation of exacerbations and rendered the study inconclusive. CONCLUSIONS: Within the limits of the data, no consistent benefits of the active device were demonstrated, and the differences observed were not sufficient to make the device cost-effective. The types of patients who may benefit from the TLA device, and the reasons for large reductions in exacerbation frequency in severe asthma trials, which also incorporate other methods of recording exacerbations, need to be explored. TRIAL REGISTRATION: Current Controlled Trials ISRCTN46346208. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 29. See the NIHR Journals Library website for further project information.

Allergies (along with viruses) are common triggers of asthma exacerbations or 'attacks', which can cause suffering and frequent visits to the general practitioner or hospital. A new machine known as a temperature-controlled laminar airflow device, which remains at the bedside and is switched on every night, filters out allergy particles in the air of a patient's breathing zone, allowing their lungs to rest in clean air overnight. We tested whether or not this machine could improve the lives of those with severe allergic asthma. We recruited 240 people across 14 centres that treat severe asthma across the UK; approximately half received the active device and the other half received a machine that looked exactly the same but did not remove the allergens (a 'placebo' machine). One in five participants was recruited using newer methods of social media such as Facebook (Facebook, Inc., Menlo Park, CA, USA) and Twitter (Twitter, Inc., San Francisco, CA, USA). Participants found the machine easy to use and to live with and there were no significant side effects. The number of attacks reduced a lot in both participants using the active device and those who used the placebo device ­ two participants in five did not suffer any attacks during the trial. However, there was no difference in the number of attacks between the two groups. This might have been because participants did not record everything that happened to them. There was no difference in measurements showing how well the lungs were working, nor in participants' quality of life after 1 year of participating in the trial. Those who were interviewed told us that the study visits and questionnaires could be burdensome, although it was helpful to think more about their asthma. An improvement was seen in one aspect of participants' breathing as well as in their quality of life after 6 months of using the machine, but these potential health benefits could not outweigh the cost of the machine.

Multicomponent Interventions Reduce High-Risk Medications for Delirium in Hospitalized Older Adults.

Delirium threatens the functional independence and cognitive capacity of patients. Medications, especially those with strong anticholinergic effects, have been implicated as a preventable cause of delirium. We evaluated the effect of multicomponent interventions aimed at reducing the use of 9 target medications in hospitalized older adults at risk of delirium. This continuous quality improvement program was undertaken at a tertiary care facility and 4 community hospitals in a hospital system. We included 21, 541 hospital admissions with patients aged 70 and older on acute care medical or surgical units from the preintervention (2012) period, and 27,764 from the postintervention (2015) period. Implemented interventions include formulary and policy changes, technology-assisted medication review, age-conditional order set modifications, best practice alerts, and education. The proportion of hospital admissions with individual's receiving at least 1 target medication declined from 45.6% to 31.3% (relative reduction (RR)=31.4%) from before to after the intervention, meaning that target medication exposure was avoided in approximately 4,000 older adults. The greatest effect was observed for zolpidem (11.2% to 5.3%, RR=52.6%) and diphenhydramine (12.9% to 7.1%, RR=45%). Furthermore, the mean number of doses administered during all hospital admissions was reduced for 7 of 9 medications. Multicomponent interventions implemented in our hospital system were effective at reducing exposure to target medications in hospitalized older adults at risk of delirium. These systematic changes applied throughout the medication use process are sustained today.

Outcomes and Resource Use of Sepsis-associated Stays by Presence on Admission, Severity, and Hospital Type.

OBJECTIVE: To establish a baseline for the incidence of sepsis by severity and presence on admission in acute care hospital settings before implementation of a broad sepsis screening and response initiative. METHODS: A retrospective cohort study using hospital discharge abstracts of 5672 patients, aged 18 years and above, with sepsis-associated stays between February 2012 and January 2013 at an academic medical center and 5 community hospitals in Texas. RESULTS: Sepsis was present on admission in almost 85% of cases and acquired in-hospital in the remainder. The overall inpatient death rate was 17.2%, but was higher in hospital-acquired sepsis (38.6%, medical; 29.2%, surgical) and Stages 2 (17.6%) and 3 (36.4%) compared with Stage 1 (5.9%). Patients treated at the academic medical center had a higher death rate (22.5% vs. 15.1%, P<0.001) and were more costly ($68,050±184,541 vs. $19,498±31,506, P<0.001) versus community hospitals. CONCLUSIONS: Greater emphasis is needed on public awareness of sepsis and the detection of sepsis in the prehospitalization and early hospitalization period. Hospital characteristics and case mix should be accounted for in cross-hospital comparisons of sepsis outcomes and costs.

Optimizing Evaluation of Patients with Low-to-Intermediate-Risk Acute Chest Pain: A Randomized Study Comparing Stress Myocardial Perfusion Tomography Incorporating Stress-Only Imaging Versus Cardiac CT.

UNLABELLED: The purpose of this study was to determine whether stress myocardial perfusion (SPECT) optimized with stress-only (SO) imaging is comparable to cardiac CT angiography (CTA) for evaluating patients with acute chest pain (ACP). METHODS: This was a prospective randomized observational study in 598 ACP patients who underwent CTA versus SPECT. The primary endpoint was length of hospital stay, and secondary endpoints were test feasibility, time to diagnosis, diagnostic accuracy, radiation exposure, and overall cost. Median follow-up was 6.5 mo, with a 3.8% cardiac event rate defined as death or an acute coronary syndrome. RESULTS: Of 2,994 patients screened, 1,703 (56.9%) were not candidates for CTA because of prior cardiac disease (41%) or imaging contraindications (16%). Time to diagnosis (8.1 ± 8.5 vs. 9.4 ± 7.4 h) and length of hospital stay (19.7 ± 27.8 vs. 23.5 ± 34.4 h) were significantly shorter with CTA than with SPECT (P = 0.002). However, time to diagnosis (7.0 ± 6.2 vs. 6.8 ± 5.9 h, P = 0.20), length of stay (15.5 ± 17.2 vs. 16.7 ± 15.3 h, P = 0.36), and hospital costs ($4,242 ± $3,871 vs. $4,364 ± 1781, P = 0.86) were comparable with CTA versus SO SPECT, respectively. SO was also superior to conventional SPECT regarding all of the above metrics and significantly reduced radiation exposure (5.5 ± 4.4 vs. 12.5 ± 2.7 mSv, P < 0.0001). CONCLUSION: Stress SPECT when optimized with SO imaging is similar to CTA in time to diagnosis, length of hospital stay, and cost, with improved prognostic accuracy and less radiation exposure. Our results emphasize the importance of SO imaging, particularly in low-intermediate-risk emergency room patients who are a population likely to have a normal test result.

Reductions in Sepsis Mortality and Costs After Design and Implementation of a Nurse-Based Early Recognition and Response Program.

BACKGROUND: Sepsis is a leading cause of death, but evidence suggests that early recognition and prompt intervention can save lives. In 2005 Houston Methodist Hospital prioritized sepsis detection and management in its ICU. In late 2007, because of marginal effects on sepsis death rates, the focus shifted to designing a program that would be readily used by nurses and ensure early recognition of patients showing signs suspicious for sepsis, as well as the institution of prompt, evidence-based interventions to diagnose and treat it. METHODS: The intervention had four components: organizational commitment and data-based leadership; development and integration of an early sepsis screening tool into the electronic health record; creation of screening and response protocols; and education and training of nurses. Twice-daily screening of patients on targeted units was conducted by bedside nurses; nurse practitioners initiated definitive treatment as indicated. Evaluation focused on extent of implementation, trends in inpatient mortality, and, for Medicare beneficiaries, a before-after (2008-2011) comparison of outcomes and costs. A federal grant in 2012 enabled expansion of the program. RESULTS: By year 3 (2011) 33% of inpatients were screened (56,190 screens in 9,718 unique patients), up from 10% in year 1 (2009). Inpatient sepsis-associated death rates decreased from 29.7% in the preimplementation period (2006-2008) to 21.1% after implementation (2009-2014). Death rates and hospital costs for Medicare beneficiaries decreased from preimplementation levels without a compensatory increase in discharges to postacute care. CONCLUSION: This program has been associated with lower inpatient death rates and costs. Further testing of the robustness and exportability of the program is under way.