Obesity and Weight Loss Strategies for Patients With Heart Failure.

Obesity is a common comorbidity among patients with heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF), with the strongest pathophysiologic link of obesity being seen for HFpEF. Lifestyle measures are the cornerstone of weight loss management, but sustainability is a challenge, and there are limited efficacy data in the heart failure (HF) population. Bariatric surgery has moderate efficacy and safety data for patients with preoperative HF or left ventricular dysfunction and has been associated with reductions in HF hospitalizations and medium-term mortality. Antiobesity medications historically carried concerns for cardiovascular adverse effects, but the safety and weight loss efficacy seen in general population trials of glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide/GLP-1 agonists are highly encouraging. Although there are safety concerns regarding GLP-1 agonists in advanced HFrEF, trials of the GLP-1 agonist semaglutide for treatment of obesity have confirmed safety and efficacy in patients with HFpEF.

Prevalence and patterns of neuropathic pain in people with chronic post-surgical pain after total knee arthroplasty.

Aims: The aim of this study was to describe the prevalence and patterns of neuropathic pain over one year in a cohort of patients with chronic post-surgical pain at three months following total knee arthroplasty (TKA). Methods: Between 2016 and 2019, 363 patients with troublesome pain, defined as a score of ≤ 14 on the Oxford Knee Score pain subscale, three months after TKA from eight UK NHS hospitals, were recruited into the Support and Treatment After Replacement (STAR) clinical trial. Self-reported neuropathic pain and postoperative pain was assessed at three, nine, and 15 months after surgery using the painDETECT and Douleur Neuropathique 4 (DN4) questionnaires collected by postal survey. Results: Symptoms of neuropathic pain were common among patients reporting chronic pain at three months post-TKA, with half reporting neuropathic pain on painDETECT (191/363; 53%) and 74% (267/359) on DN4. Of those with neuropathic pain at three months, half continued to have symptoms over the next 12 months (148/262; 56%), one-quarter had improved (67/262; 26%), and for one-tenth their neuropathic symptoms fluctuated over time (24/262; 9%). However, a subgroup of participants reported new, late onset neuropathic symptoms (23/262; 9%). Prevalence of neuropathic symptoms was similar between the screening tools when the lower cut-off painDETECT score (≥ 13) was applied. Overall, mean neuropathic pain scores improved between three and 15 months after TKA. Conclusion: Neuropathic pain is common in patients with chronic pain at three months after TKA. Although neuropathic symptoms improved over time, up to half continued to report painful neuropathic symptoms at 15 months after TKA. Postoperative care should include screening, assessment, and treatment of neuropathic pain in patients with early chronic postoperative pain after TKA.

Artificial intelligence based left ventricular ejection fraction and global longitudinal strain in cardiac amyloidosis.

BACKGROUND: Assessment of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) plays a key role in the diagnosis of cardiac amyloidosis (CA). However, manual measurements are time consuming and prone to variability. We aimed to assess whether fully automated artificial intelligence (AI) calculation of LVEF and GLS provide similar estimates and can identify abnormalities in agreement with conventional manual methods, in patients with pre-clinical and clinical CA. METHODS: We identified 51 patients (age 80 ± 10 years, 53% male) with confirmed CA according to guidelines, who underwent echocardiography before and/or at the time of CA diagnosis (median (IQR) time between observations 3.87 (1.93, 5.44 years). LVEF and GLS were quantified from the apical 2- and 4-chamber views using both manual and fully automated methods (EchoGo Core 2.0, Ultromics). Inter-technique agreement was assessed using linear regression and Bland-Altman analyses and two-way ANOVA. The diagnostic accuracy and time for detecting abnormalities (defined as LVEF ≤ 50% and GLS ≥ -15.1%, respectively) using AI was assessed by comparisons to manual measurements as a reference. RESULTS: There were no significant differences in manual and automated LVEF and GLS values in either pre-CA (p = .791 and p = .105, respectively) or at diagnosis (p = .463 and p = .722). The two methods showed strong correlation on both the pre-CA (r = .78 and r = .83) and CA echoes (r = .74 and r = .80) for LVEF and GLS, respectively. The sensitivity and specificity of AI-derived indices for detecting abnormal LVEF were 83% and 86%, respectively, in the pre-CA echo and 70% and 79% at CA diagnosis. The sensitivity and specificity of AI-derived indices for detecting abnormal GLS was 82% and 86% in the pre-CA echo and 100% and 67% at the time of CA diagnosis. There was no significant difference in the relationship between LVEF (p = .99) and GLS (p = .19) and time to abnormality between the two methods. CONCLUSION: Fully automated AI-calculated LVEF and GLS are comparable to manual measurements in patients pre-CA and at the time of CA diagnosis. The widespread implementation of automated LVEF and GLS may allow for more rapid assessment in different disease states with comparable accuracy and reproducibility to manual methods.

Cost-Effectiveness of Group-Based Outpatient Physical Therapy After Total Knee Replacement: Results From the Economic Evaluation Alongside the ARENA Multicenter Randomized Controlled Trial.

OBJECTIVE: To assess the cost-utility and cost-effectiveness of a group-based outpatient physical therapy intervention delivered 6 weeks after primary total knee replacement (TKR) compared with usual care, alongside the Activity-Orientated Rehabilitation Following Knee Arthroplasty (ARENA) multicenter, randomized, controlled trial. METHODS: The economic analyses were performed from the perspective of the health and social care payer. We collected resource use for health and social care and productivity losses and patient outcomes for 12 months after surgery to derive costs and quality-adjusted life years (QALYs). Results were expressed in incremental cost-effectiveness ratios (ICERs), and incremental net monetary benefit statistics (INMBs) for a society willingness-to-pay (WTP) threshold of £20,000 per QALY gained, with sensitivity analyses to model specification and perspective. RESULTS: The cost of the ARENA physical therapy classes was mean ± SD £179 ± 39 per patient. Treatment in the year following surgery cost was, on average, £1,739 (95% confidence interval [95% CI] -£742, £4,221) per patient in the intervention group (n = 89), which was an additional £346 (95% CI £38, £653) per patient compared with usual care (n = 91) (£1,393 [95% CI -£780, £3,568]). QALY benefits were 0.0506 higher (95% CI 0.009, 0.09) in the intervention group, corresponding to an additional 19 days in "perfect health." The ICER for the intervention group was £6,842 per QALY gained, and the INMB was £665 (95% CI £139, £1,191), with a 92% probability of being cost-effective, and no less than 73% in all sensitivity analysis scenarios. CONCLUSION: The addition of group-based outpatient physical therapy classes to usual care improves quality of life and is a cost-effective treatment option following TKR for a society WTP threshold of £20,000 per QALY gained.

The STAR care pathway for patients with pain at 3 months after total knee replacement: a multicentre, pragmatic, randomised, controlled trial.

BACKGROUND: Approximately 20% of people experience chronic pain after total knee replacement, but effective treatments are not available. We aimed to evaluate the clinical effectiveness and cost-effectiveness of a new care pathway for chronic pain after total knee replacement. METHODS: We did an unmasked, parallel group, pragmatic, superiority, randomised, controlled trial at eight UK National Health Service (NHS) hospitals. People with chronic pain at 3 months after total knee replacement surgery were randomly assigned (2:1) to the Support and Treatment After Replacement (STAR) care pathway plus usual care, or to usual care alone. The STAR intervention aimed to identify underlying causes of chronic pain and enable onward referrals for targeted treatment through a 3-month post-surgery assessment with an extended scope practitioner and telephone follow-up over 12 months. Co-primary outcomes were self-reported pain severity and pain interference in the replaced knee, assessed with the Brief Pain Inventory (BPI) pain severity and interference scales at 12 months (scored 0-10, best to worst) and analysed on an as-randomised basis. Resource use, collected from electronic hospital records and participants, was valued with UK reference costs. Quality-adjusted life-years (QALYs) were calculated from EQ-5D-5L responses. This trial is registered with ISRCTN, ISRCTN92545361. FINDINGS: Between Sept 6, 2016, and May 31, 2019, 363 participants were randomly assigned to receive the intervention plus usual care (n=242) or to receive usual care alone (n=121). Participants had a median age of 67 years (IQR 61 to 73), 217 (60%) of 363 were female, and 335 (92%) were White. 313 (86%) patients provided follow-up data at 12 months after randomisation (213 assigned to the intervention plus usual care and 100 assigned to usual care alone). At 12 months, the mean between-group difference in the BPI severity score was -0·65 (95% CI -1·17 to -0·13; p=0·014) and the mean between-group difference in the BPI interference score was -0·68 (-1·29 to -0·08; p=0·026), both favouring the intervention. From an NHS and personal social services perspective, the intervention was cost-effective (greater improvement with lower cost), with an incremental net monetary benefit of £1256 (95% CI 164 to 2348) at £20 000 per QALY threshold. One adverse reaction of participant distress was reported in the intervention group. INTERPRETATION: STAR is a clinically effective and cost-effective intervention to improve pain outcomes over 1 year for people with chronic pain at 3 months after total knee replacement surgery. FUNDING: National Institute for Health Research.

Screening to Identify Postoperative Pain and Cross-Sectional Associations Between Factors Identified in This Process With Pain and Function, Three Months After Total Knee Replacement.

OBJECTIVE: To describe the screening and recruitment process of a randomized trial and evaluate associations with knee pain and function 3 months after total knee replacement (TKR). METHODS: In order to screen for a multicenter trial, a total of 5,036 patients were sent the Oxford Knee Score (OKS) questionnaire 10 weeks post-TKR. Patients who reported pain in their replaced knee (score of ≤14 on the OKS pain component) completed a second OKS questionnaire 12 weeks post-TKR. Those patients who were still experiencing pain 12 weeks post-TKR completed a detailed questionnaire 13 weeks post-TKR. These data were used to characterize pain in a cross-sectional analysis. Multivariable regression was performed in order to identify factors associated with pain and function at 13 weeks post-TKR. RESULTS: We received OKS questionnaires from 3,058 of 5,063 TKR patients (60%), and 907 of the 3,058 (30%) reported pain in their replaced knee 10 weeks post-TKR. By 12 weeks, 179 of 553 patients (32%) reported improved pain (score of >14 on the OKS pain component). At 13 weeks, 192 of 363 patients (53%) who completed a detailed questionnaire reported neuropathic pain, 94 of 362 (26%) reported depression symptoms, and 95 of 363 (26%) anxiety symptoms. More severe pain at 13 weeks postoperatively was associated with poorer general health, poorer physical health, more pain worry, and lower satisfaction with surgery outcome. More severe functional limitation was associated with higher levels of depression, more pain worry, lower satisfaction with surgery outcome, and higher pain acceptance. CONCLUSION: Screening after TKR identified individuals with pain. We identified several potential targets (physical and mental health outcomes, acceptance of pain, and quality of life) for tailored intervention to improve outcomes for patients. Future trials of multidisciplinary interventions warranted.

Effectiveness and cost-effectiveness of the PLAN-A intervention, a peer led physical activity program for adolescent girls: results of a cluster randomised controlled trial.

BACKGROUND: Physical activity is associated with improved health. Girls are less active than boys. Pilot work showed that a peer-led physical activity intervention called PLAN-A was a promising method of increasing physical activity in secondary school age girls. This study examined the effectiveness and cost-effectiveness of the PLAN-A intervention. METHODS: We conducted a cluster randomised controlled trial with Year 9 (13-14 year old) girls recruited from 20 secondary schools. Schools were randomly assigned to the PLAN-A intervention or a non-intervention control group after baseline data collection. Girls nominated students to be peer leaders. The top 18 % of girls nominated by their peers in intervention schools received three days of training designed to prepare them to support physical activity. Data were collected at two time points, baseline (T0) and 5-6 months post-intervention (T1). Participants wore an accelerometer for seven days to assess the primary outcome of mean weekday minutes of moderate-to-vigorous physical activity (MVPA). Multivariable mixed effects linear regression was used to estimate differences in the primary outcome between the two arms on an Intention-to-Treat (ITT) basis. Resource use and quality of life were measured and a within trial economic evaluation from a public sector perspective was conducted. RESULTS: A total of 1558 girls were recruited to the study. At T0, girls in both arms engaged in an average of 51 min of MVPA per weekday. The adjusted mean difference in weekday MVPA at T1 was - 2.84 min per day (95 % CI = -5.94 to 0.25) indicating a slightly larger decline in weekday MVPA in the intervention group. Results were broadly consistent when repeated using a multiple imputation approach and for pre-specified secondary outcomes and sub-groups. The mean cost of the PLAN-A intervention was £2817 per school, equivalent to £31 per girl. Economic analyses indicated that PLAN-A did not lead to demonstrable cost-effectiveness in terms of cost per unit change in QALY. CONCLUSIONS: This study has shown that the PLAN-A intervention did not result in higher levels of weekday MVPA or associated secondary outcomes among Year 9 girls. The PLAN-A intervention should not be disseminated as a public health strategy. TRIAL REGISTRATION: ISRCTN14539759 -31 May, 2018.

Development of a tool for coding safety-netting behaviours in primary care: a mixed-methods study using existing UK consultation recordings.

BACKGROUND: Safety netting is recommended in a variety of clinical settings, yet there are no tools to record clinician safety-netting communication behaviours. AIM: To develop and assess the inter-rater reliability (IRR) of a coding tool designed to assess safety-netting communication behaviours in primary care consultations. DESIGN AND SETTING: A mixed-methods study using an existing dataset of video-and audio-recorded UK primary care consultations. METHOD: Key components that should be assessed in a coding tool were identified using the published literature and relevant guidelines. An iterative approach was utilised to continuously refine and generate new codes based on the application to real-life consultations. After the codebook had been generated, it was applied to 35 problems in 24 consultations independently by two coders. IRR scores were then calculated. RESULTS: The tool allows for the identification and quantification of the key elements of safety-netting advice including: who initiates the advice and at which stage of the consultation; the number of symptoms or conditions the patient is advised to look out for; what action patients should take and how urgently; as well as capturing how patients respond to such advice plus important contextual codes such as the communication of diagnostic uncertainty, the expected time course of an illness, and any follow-up plans. The final tool had substantial levels of IRR with the mean average agreement for the final tool being 88% (κ = 0.66). CONCLUSION: The authors have developed a novel tool that can reliably code the extent of clinician safety-netting communication behaviours.