Health-related quality of life and healthcare costs of symptoms and cardiovascular disease events in patients with atrial fibrillation: a longitudinal analysis of 27 countries from the EURObservational Research Programme on Atrial Fibrillation general long-term registry.

AIMS: We examine the effects of symptoms and cardiovascular disease (CVD) events on health-related quality of life (HRQOL) and healthcare costs in a European population with atrial fibrillation (AF). METHODS AND RESULTS: In the EURObservational Research Programme on AF long-term general registry, AF patients from 250 centres in 27 European countries were enrolled and followed for 2 years. We used fixed effects models to estimate the association of symptoms and CVD events on HRQOL and annual healthcare costs. We found significant decrements in HRQOL in AF patients in whom ST-segment elevation myocardial infarction (STEMI) [-0.075 (95% confidence interval -0.144, -0.006)], angina or non-ST-elevation myocardial infarction (NSTEMI) [-0.037 (-0.071, -0.003)], new-onset/worsening heart failure [-0.064 (-0.088, -0.039)], bleeding events [-0.031 (-0.059, -0.003)], thromboembolic events [-0.071 (-0.115, -0.027)], mild symptoms [0.037 (-0.048, -0.026)], or severe/disabling symptoms [-0.090 (-0.108, -0.072)] occurred during the follow-up. During follow-up, annual healthcare costs were associated with an increase of €11 718 (€8497, €14 939) in patients with STEMI, €5823 (€4757, €6889) in patients with angina/NSTEMI, €3689 (€3219, €4158) in patients with new-onset or worsening heart failure, €3792 (€3315, €4270) in patients with bleeding events, and €3182 (€2483, €3881) in patients with thromboembolic events, compared with AF patients without these events. Healthcare costs were primarily driven by inpatient costs. There were no significant differences in HRQOL or healthcare resource use between EU regions or by sex. CONCLUSION: Symptoms and CVD events are associated with a high burden on AF patients and healthcare systems throughout Europe.

Economic burden of cardiovascular diseases in the European Union: a population-based cost study.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) impacts significantly health and social care systems as well as society through premature mortality and disability, with patients requiring care from relatives. Previous pan-European estimates of the economic burden of CVD are now outdated. This study aims to provide novel, up-to-date evidence on the economic burden across the 27 European Union (EU) countries in 2021. METHODS: Aggregate country-specific resource use data on morbidity, mortality, and health, social and informal care were obtained from international sources, such as the Statistical Office of the European Communities, enhanced by data from the European Society of Cardiology Atlas programme and patient-level data from the Survey of Health, Ageing and Retirement in Europe. Country-specific unit costs were used, with cost estimates reported on a per capita basis, after adjustment for price differentials. RESULTS: CVD is estimated to cost the EU €282 billion annually, with health and long-term care accounting for €155 billion (55%), equalling 11% of EU-health expenditure. Productivity losses accounted for 17% (€48 billion), whereas informal care costs were €79 billion (28%). CVD represented a cost of €630 per person, ranging from €381 in Cyprus to €903 in Germany. Coronary heart disease accounted for 27% (€77 billion) and cerebrovascular diseases for 27% (€76 billion) of CVD costs. CONCLUSIONS: This study provides contemporary estimates of the wide-ranging impact of CVD on all aspects of the economy. The data help inform evidence-based policies to reduce the impact of CVD, promoting care access and better health outcomes and economic sustainability.

Strange, Rare and Peculiar Symptoms of COVID-19 Cases Managed by Practitioners of the Homeopathy Help Network.

BACKGROUND: More than 670 million people have been infected by COVID-19. This case series reports 8 of 55 cases in a broader study of COVID-positive clients who sought homeopathic care for symptoms. Existing studies of homeopathy and COVID-19 have sometimes failed to employ the underpinning theoretical framework of homeopathy-the genus epidemicus. Special focus has been placed on standout symptoms not often reported in conventional medical outlets, known among homeopaths as "strange, rare and peculiar" (SRP) symptoms. The Homeopathy Help Network (HHN) team of practitioners noted SRP symptoms across dozens of cases and studied how they shifted collectively as different variants of the virus emerged. METHODS: COVID-positive individuals self-selected for individualized care for their symptoms using homeopathy. They received tele-health consultations and individualized homeopathy interventions in an out-patient homeopathy clinical setting. Clients were seen by individual professional homeopathy practitioners and students under supervision working at the HHN in the United States. Cases for the series were hand-picked with the aim of being an average representation of the more than 4,000 COVID-positive cases seen by members of the HHN. Cases in the full compendium are grouped according to a predominant case feature: Multiple remedies, Posology, Time ill, Single remedy resolution, Hospitalization and, in this case series, SRP symptoms. RESULTS: SRP symptoms included: continually on the verge of unconsciousness; dark green stools; very low pulse alternating with tachycardia; sensation of strong or burning chemical smells; sensation of inhaling water through the nose; recurring electric shock sensations in head or extremities; yellow-green stools. CONCLUSION: Collective SRP symptoms from the pandemic provided the opportunity to study the hallmark features of COVID-19 in depth. The importance of these symptoms highlights the applicability of Hahnemannian principles and good case-taking practices.

Clinical Outcomes in Chronic Conditions: Findings from a Homeopathy Teaching Clinic using the MYCaW Instrument.

BACKGROUND: The Academy of Homeopathy Education is a US-based accredited teaching institution offering homeopathy education services to professional and medically licensed homeopathy students. This study reports on clinical outcomes from the teaching clinic from 2020 to 2021. METHODS: Data collected using the patient-generated outcome measure, the Measure Yourself Concerns and Wellbeing (MYCaW), were anonymized. Mean MYCaW values for initial and subsequent consultations were analyzed for the degree of change across the intervention period in 38 clients. Each client listed up to two complaints. MYCaW scores between initial and subsequent consultations were analyzed for the degree of change (delta) across the intervention period. RESULTS: A total of 95 body system-related symptoms were analyzed for change in intensity following the homeopathic intervention. Statistically significant improvements in the intensity of main symptoms were observed between initial and subsequent follow-ups. The main symptom scores showed a mean change in intensity (delta MYCaW) of -0.79 points (95% confidence interval (CI), -1.29 to -0.29; p = 0.003) at first follow-up, a mean change of -1.67 points (95% CI, -2.34 to -0.99; p = 0.001) at second follow-up compared with the initial visit, and a mean change of -1.93 points (95% CI, -3.0 to -0.86; p = 0.008) at third follow-up compared with the initial visit. For clients with four or more follow-ups, the mean delta MYCaW was -1.57 points (95% CI, -2.86 to -0.28; p = 0.039). CONCLUSION: Statistically significant improvements as well as some clinically meaningful changes in symptom intensity were found across a diverse group of individuals with a variety of long-term chronic conditions. The improvement was evident across different body systems and different levels of chronicity. There are limitations to the generalizability of the study due to the research design. Further research and investigation are warranted given the promising results of this work.

Single versus multiple arterial grafting in diabetic patients at 10 years: the Arterial Revascularization Trial.

AIMS: To evaluate the impact of multiple arterial grafting (MAG) vs. single arterial grafting (SAG) in a post hoc analysis of 10-year outcomes in patients with diabetes mellitus (DM) from the Arterial Revascularization Trial (ART). METHODS AND RESULTS: The primary endpoint was all-cause mortality and the secondary endpoint was a composite of major adverse cardiac events (MACE) at 10-year follow-up. Patients were stratified by diabetes status (non-DM and DM) and grafting strategy (MAG vs. SAG). A total of 3020 patients were included in the analysis; 716 (23.7%) had DM. Overall, 55.8% non-DM patients received MAG and 44.2% received SAG, while 56.6% DM patients received MAG and 43.4% received SAG. The use of MAG compared with SAG was associated with lower 10-year mortality for both non-DM [17.7 vs. 21.0%, adjusted hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.72-1.06] and DM patients (21.5 vs. 29.9%, adjusted HR 0.65, 95% CI 0.48-0.89; P for interaction = 0.12). For both groups, the rate of 10-year MACE was also lower for MAG vs. SAG. Overall, deep sternal wound infections (DSWIs) were uncommon but more frequent in the MAG vs. SAG group in both non-DM (3.3 vs. 2.1%) and DM patients (7.9 vs. 4.8%). The highest rates of DSWI were in insulin-treated patients receiving MAG (9.6 vs. 6.3%, when compared with SAG). CONCLUSION: In this post hoc analysis of the ART, MAG was associated with substantially lower mortality rates at 10 years after coronary artery bypass grafting in patients with DM. Patients with DM receiving MAG had a higher incidence of DSWI, especially if insulin dependent.

Attitudes To and Uptake of Repertory Software in Homeopathy Clinical Practice-Results of an International Survey.

BACKGROUND: Despite the substantial size of the maturing complementary medicine (CM) industry, the technologies used by practitioners have received little research attention. In the clinical delivery of homeopathy services, repertory software can be employed to cross-reference client symptoms with numerous databases, making the process of seeking a clinical intervention quicker and more accurate. The purpose of the study is to learn about the quantitative patterns of usage, uptake and attitudes to repertory software amongst professional homeopaths. METHODS: An online cross-sectional survey of 15 questions was completed by practicing professional homeopaths between August 2016 and May 2017, using non-probability snowball sampling. Questions gathered demographic information, reflections and attitudes on the use of electronic repertories in clinical homeopathy practice. RESULTS: In total, 59% of respondents reported using software regularly in practice and 71% found that it adds clear value in their work. Sixty-eight percent of respondents learned about repertory software during homeopathy training, and 47% were introduced to software when they began clinical practice. Lack of sufficient training is a very important barrier to the use of repertory software, indicating that more robust and accessible software training is needed for practitioners. Many respondents agreed with a statement that repertory software represents good value for money and yet 46% agreed that it is cost prohibitive for most practitioners, signaling a challenge for software companies. Few respondents reported regularly using more than three of the most common repertory features. CONCLUSION: This preliminary study presents some potentially significant uptake, usage and attitude markers that stand to shed light on the practice of homeopathy and the place of emerging technologies such as repertory software. Ultimately, more research is needed to help identify and address the challenges, risks and tensions around integration of practice-enhancing technologies in CM educational and clinical settings to best serve the diverse and changing needs of practitioners.

Progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of patients with rotator cuff disorders (GRASP): a multicentre, pragmatic, 2 × 2 factorial, randomised controlled trial.

BACKGROUND: Corticosteroid injections and physiotherapy exercise programmes are commonly used to treat rotator cuff disorders but the treatments' effectiveness is uncertain. We aimed to compare the clinical effectiveness and cost-effectiveness of a progressive exercise programme with a single session of best practice physiotherapy advice, with or without corticosteroid injection, in adults with a rotator cuff disorder. METHODS: In this pragmatic, multicentre, superiority, randomised controlled trial (2 × 2 factorial), we recruited patients from 20 UK National Health Service trusts. We included patients aged 18 years or older with a rotator cuff disorder (new episode within the past 6 months). Patients were excluded if they had a history of significant shoulder trauma (eg, dislocation, fracture, or full-thickness tear requiring surgery), neurological disease affecting the shoulder, other shoulder conditions (eg, inflammatory arthritis, frozen shoulder, or glenohumeral joint instability), received corticosteroid injection or physiotherapy for shoulder pain in the past 6 months, or were being considered for surgery. Patients were randomly assigned (centralised computer-generated system, 1:1:1:1) to progressive exercise (≤6 sessions), best practice advice (one session), corticosteroid injection then progressive exercise, or corticosteroid injection then best practice advice. The primary outcome was the Shoulder Pain and Disability Index (SPADI) score over 12 months, analysed on an intention-to-treat basis (statistical significance set at 1%). The trial was registered with the International Standard Randomised Controlled Trial Register, ISRCTN16539266, and EuDRACT, 2016-002991-28. FINDINGS: Between March 10, 2017, and May 2, 2019, we screened 2287 patients. 708 patients were randomly assigned to progressive exercise (n=174), best practice advice (n=174), corticosteroid injection then progressive exercise (n=182), or corticosteroid injection then best practice advice (n=178). Over 12 months, SPADI data were available for 166 (95%) patients in the progressive exercise group, 164 (94%) in the best practice advice group, 177 (97%) in the corticosteroid injection then progressive exercise group, and 175 (98%) in the corticosteroid injection then best practice advice group. We found no evidence of a difference in SPADI score between progressive exercise and best practice advice when analysed over 12 months (adjusted mean difference -0·66 [99% CI -4·52 to 3·20]). We also found no evidence of a difference between corticosteroid injection compared with no injection when analysed over 12 months (-1·11 [-4·47 to 2·26]). No serious adverse events were reported. INTERPRETATION: Progressive exercise was not superior to a best practice advice session with a physiotherapist in improving shoulder pain and function. Subacromial corticosteroid injection provided no long-term benefit in patients with rotator cuff disorders. FUNDING: UK National Institute for Health Research Technology Assessment Programme.

Bilateral versus Single Internal-Thoracic-Artery Grafts at 10 Years.

BACKGROUND: Multiple arterial grafts may result in longer survival than single arterial grafts after coronary-artery bypass grafting (CABG) surgery. We evaluated the use of bilateral internal-thoracic-artery grafts for CABG. METHODS: We randomly assigned patients scheduled for CABG to undergo bilateral or single internal-thoracic-artery grafting. Additional arterial or vein grafts were used as indicated. The primary outcome was death from any cause at 10 years. The composite of death from any cause, myocardial infarction, or stroke was a secondary outcome. RESULTS: A total of 1548 patients were randomly assigned to undergo bilateral internal-thoracic-artery grafting (the bilateral-graft group) and 1554 to undergo single internal-thoracic-artery grafting (the single-graft group). In the bilateral-graft group, 13.9% of the patients received only a single internal-thoracic-artery graft, and in the single-graft group, 21.8% of the patients also received a radial-artery graft. Vital status was not known for 2.3% of the patients at 10 years. In the intention-to-treat analysis at 10 years, there were 315 deaths (20.3% of the patients) in the bilateral-graft group and 329 deaths (21.2%) in the single-graft group (hazard ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.12; P=0.62). Regarding the composite outcome of death, myocardial infarction, or stroke, there were 385 patients (24.9%) with an event in the bilateral-graft group and 425 patients (27.3%) with an event in the single-graft group (hazard ratio, 0.90; 95% CI, 0.79 to 1.03). CONCLUSIONS: Among patients who were scheduled for CABG and had been randomly assigned to undergo bilateral or single internal-thoracic-artery grafting, there was no significant between-group difference in the rate of death from any cause at 10 years in the intention-to-treat analysis. Further studies are needed to determine whether multiple arterial grafts provide better outcomes than a single internal-thoracic-artery graft. (Funded by the British Heath Foundation and others; Current Controlled Trials number, ISRCTN46552265 .).

Is comprehensive geriatric assessment hospital at home a cost-effective alternative to hospital admission for older people?

BACKGROUND: hospital level healthcare in the home guided by comprehensive geriatric assessment (CGA) might provide a less costly alternative to hospitalisation for older people. OBJECTIVE: to determine the cost-effectiveness of CGA admission avoidance hospital at home (HAH) compared with hospital admission. DESIGN/INTERVENTION: a cost-effectiveness study alongside a randomised trial of CGA in an admission avoidance HAH setting, compared with admission to hospital. PARTICIPANTS/SETTING: older people considered for a hospital admission in nine locations across the UK were randomised using a 2:1 randomisation schedule to admission avoidance HAH with CGA (N = 700), or admission to hospital with CGA when available (N = 355). MEASUREMENTS: quality adjusted life years, resource use and costs at baseline and 6 months; incremental cost-effectiveness ratios were calculated. The main analysis used complete cases. RESULTS: adjusting for baseline covariates, HAH was less costly than admission to hospital from a health and social care perspective (mean -£2,265, 95% CI: -4,279 to -252), and remained less costly with the addition of informal care costs (mean difference -£2,840, 95% CI: -5,495 to -185). There was no difference in quality adjusted survival. Using multiple imputation for missing data, the mean difference in health and social care costs widened to -£2,458 (95% CI: -4,977 to 61) and societal costs remained significantly lower (-£3,083, 95% CI: -5,880 to -287). There was little change to quality adjusted survival. CONCLUSIONS: CGA HAH is a cost-effective alternative to admission to hospital for selected older people.

Is Comprehensive Geriatric Assessment Admission Avoidance Hospital at Home an Alternative to Hospital Admission for Older Persons? : A Randomized Trial.

BACKGROUND: Delivering hospital-level care with comprehensive geriatric assessment (CGA) in the home is one approach to deal with the increased demand for bed-based hospital care, but clinical effectiveness is uncertain. OBJECTIVE: To assess the clinical effectiveness of admission avoidance hospital at home (HAH) with CGA for older persons. DESIGN: Multisite randomized trial. (ISRCTN registry number: ISRCTN60477865). SETTING: 9 hospital and community sites in the United Kingdom. PATIENTS: 1055 older persons who were medically unwell, were physiologically stable, and were referred for a hospital admission. INTERVENTION: Admission avoidance HAH with CGA versus hospital admission with CGA when available using 2:1 randomization. MEASUREMENTS: The primary outcome of living at home was measured at 6 months. Secondary outcomes were new admission to long-term residential care, death, health status, delirium, and patient satisfaction. RESULTS: Participants had a mean age of 83.3 years (SD, 7.0). At 6-month follow-up, 528 of 672 (78.6%) participants in the CGA HAH group versus 247 of 328 (75.3%) participants in the hospital group were living at home (relative risk [RR], 1.05 [95% CI, 0.95 to 1.15]; P = 0.36); 114 of 673 (16.9%) versus 58 of 328 (17.7%) had died (RR, 0.98 [CI, 0.65 to 1.47]; P = 0.92); and 37 of 646 (5.7%) versus 27 of 311 (8.7%) were in long-term residential care (RR, 0.58 [CI, 0.45 to 0.76]; P < 0.001). LIMITATION: The findings are most applicable to older persons referred from a hospital short-stay acute medical assessment unit; episodes of delirium may have been undetected. CONCLUSION: Admission avoidance HAH with CGA led to similar outcomes as hospital admission in the proportion of older persons living at home as well as a decrease in admissions to long-term residential care at 6 months. This type of service can provide an alternative to hospitalization for selected older persons. PRIMARY FUNDING SOURCE: The National Institute for Health Research Health Services and Delivery Research Programme (12/209/66).

Effect of Transcatheter Aortic Valve Implantation vs Surgical Aortic Valve Replacement on All-Cause Mortality in Patients With Aortic Stenosis: A Randomized Clinical Trial.

Importance: Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement and is the treatment of choice for patients at high operative risk. The role of TAVI in patients at lower risk is unclear. Objective: To determine whether TAVI is noninferior to surgery in patients at moderately increased operative risk. Design, Setting, and Participants: In this randomized clinical trial conducted at 34 UK centers, 913 patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk due to age or comorbidity were enrolled between April 2014 and April 2018 and followed up through April 2019. Interventions: TAVI using any valve with a CE mark (indicating conformity of the valve with all legal and safety requirements for sale throughout the European Economic Area) and any access route (n = 458) or surgical aortic valve replacement (surgery; n = 455). Main Outcomes and Measures: The primary outcome was all-cause mortality at 1 year. The primary hypothesis was that TAVI was noninferior to surgery, with a noninferiority margin of 5% for the upper limit of the 1-sided 97.5% CI for the absolute between-group difference in mortality. There were 36 secondary outcomes (30 reported herein), including duration of hospital stay, major bleeding events, vascular complications, conduction disturbance requiring pacemaker implantation, and aortic regurgitation. Results: Among 913 patients randomized (median age, 81 years [IQR, 78 to 84 years]; 424 [46%] were female; median Society of Thoracic Surgeons mortality risk score, 2.6% [IQR, 2.0% to 3.4%]), 912 (99.9%) completed follow-up and were included in the noninferiority analysis. At 1 year, there were 21 deaths (4.6%) in the TAVI group and 30 deaths (6.6%) in the surgery group, with an adjusted absolute risk difference of -2.0% (1-sided 97.5% CI, -∞ to 1.2%; P < .001 for noninferiority). Of 30 prespecified secondary outcomes reported herein, 24 showed no significant difference at 1 year. TAVI was associated with significantly shorter postprocedural hospitalization (median of 3 days [IQR, 2 to 5 days] vs 8 days [IQR, 6 to 13 days] in the surgery group). At 1 year, there were significantly fewer major bleeding events after TAVI compared with surgery (7.2% vs 20.2%, respectively; adjusted hazard ratio [HR], 0.33 [95% CI, 0.24 to 0.45]) but significantly more vascular complications (10.3% vs 2.4%; adjusted HR, 4.42 [95% CI, 2.54 to 7.71]), conduction disturbances requiring pacemaker implantation (14.2% vs 7.3%; adjusted HR, 2.05 [95% CI, 1.43 to 2.94]), and mild (38.3% vs 11.7%) or moderate (2.3% vs 0.6%) aortic regurgitation (adjusted odds ratio for mild, moderate, or severe [no instance of severe reported] aortic regurgitation combined vs none, 4.89 [95% CI, 3.08 to 7.75]). Conclusions and Relevance: Among patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, TAVI was noninferior to surgery with respect to all-cause mortality at 1 year. Trial Registration: isrctn.com Identifier: ISRCTN57819173.

Postoperative Atrial Fibrillation and Long-Term Risk of Stroke After Isolated Coronary Artery Bypass Graft Surgery.

BACKGROUND: Postoperative atrial fibrillation (pAF) after coronary artery bypass grafting is a common complication. Whether pAF is associated with an increased risk of cerebrovascular accident (CVA) remains uncertain. We investigated the association between pAF and long-term risk of CVA by performing a post hoc analysis of 10-year outcomes of the ART (Arterial Revascularization Trial). METHODS: For the present analysis, among patients enrolled in the ART (n=3102), we excluded those who did not undergo surgery (n=25), had a history of atrial fibrillation (n=45), or had no information on the incidence of pAF (n=9). The final population consisted of 3023 patients, of whom 734 (24.3%) developed pAF with the remaining 2289 maintaining sinus rhythm. Competing risk and Cox regression analyses were used to investigate the association between pAF and the risk of CVA. RESULTS: At 10 years, the cumulative incidence of CVA was 6.3% (4.6%-8.1%) versus 3.7% (2.9%-4.5%) in patients with pAF and sinus rhythm, respectively. pAF was an independent predictor of CVA at 10 years (hazard ratio, 1.53 [95% CI, 1.06-2.23]; P=0.025) even when CVAs that occurred during the index admission were excluded from the analysis (hazard ratio, 1.47 [95% 1.02-2.11]; P=0.04). CONCLUSIONS: Patients with pAF after coronary artery bypass grafting are at higher risk of CVA. These findings challenge the notion that pAF is a benign complication.

Cost-Effectiveness of Dopamine Agonists and Monoamine Oxidase B Inhibitors in Early Parkinson's Disease.

BACKGROUND: The PD MED study reported small but persistent benefits in patient-rated mobility scores and quality of life from initiating therapy with levodopa compared with levodopa-sparing therapies in early Parkinson's disease (PD). OBJECTIVES: The objective was to estimate the cost-effectiveness of levodopa-sparing therapy (dopamine agonists or monoamine oxidase type B inhibitors compared with levodopa alone. METHODS: PD MED is a pragmatic, open-label randomized, controlled trial in which patients newly diagnosed with PD were randomly assigned between levodopa-sparing therapy (dopamine agonists or monoamine oxidase type B inhibitors ) and levodopa alone. Mean quality-adjusted life-years and costs were calculated for each participant. Differences in mean quality-adjusted life-years and costs between levodopa and levodopa-sparing therapies and between dopamine agonists and monoamine oxidase type B inhibitors were estimated using linear regression. RESULTS: Over a mean observation period of 4 years, levodopa was associated with significantly higher quality-adjusted life-years (difference, 0.18; 95% CI, 0.05-0.30; P < 0.01) and lower mean costs (£3390; £2671-£4109; P < 0.01) than levodopa-sparing therapies, the difference in costs driven by the higher costs of levodopa-sparing therapies. There were no significant differences in the costs of inpatient, social care, and institutional care between arms. There was no significant difference in quality-adjusted life-years between those allocated dopamine agonists and monoamine oxidase type B inhibitors (0.02; -0.17 to 0.13 in favor of dopamine agonists; P = 0.81); however costs were significantly lower for those allocated monoamine oxidase type B inhibitors (£2321; £1628-£3015; P < 0.01) because of the higher costs of dopamine agonists. There were no significant differences between arms for other costs. CONCLUSIONS: Initial treatment with levodopa is highly cost-effective compared with levodopa-sparing therapies. Monoamine oxidase type B inhibitors, as initial levodopa-sparing therapy was more cost-effective, with similar quality-adjusted life-years but lower costs than dopamine agonists. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Estimating risk factor progression equations for the UKPDS Outcomes Model 2 (UKPDS 90).

OBJECTIVES: To estimate 13 equations that predict clinically plausible risk factor time paths to inform the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model version 2 (UKPDS-OM2). METHODS: Data from 5102 UKPDS participants from the 20-year trial, and the 4031 survivors with 10 years further post-trial follow-up, were used to derive equations for the time paths of 13 clinical risk factors: HbA1c , systolic blood pressure, LDL-cholesterol, HDL-cholesterol, BMI, micro- or macro-albuminuria, creatinine, heart rate, white blood cell count, haemoglobin, estimated glomerular filter rate, atrial fibrillation and peripheral vascular disease (PVD). The incidence of events and death predicted by the UKPDS-OM2 when informed by the new risk factor equations was compared with the observed cumulative rates up to 25 years. RESULTS: The new equations were based on 24 years of follow-up and up to 65,252 person-years of data. Women were associated with higher values of all continuous risk factors except for haemoglobin. Older age and higher BMI at diagnosis were associated with higher rates of PVD (HR 1.06 and 1.02), atrial fibrillation (HR 1.10 and 1.08) and micro- or macro-albuminuria (HR 1.01 and 1.18). Smoking was associated with higher rates of developing PVD (HR 2.38) and micro- and macro-albuminuria (HR 1.39). The UKPDS-OM2, informed by the new risk factor equations, predicted event rates for complications and death consistent with those observed. CONCLUSIONS: The new equations allow risk factor time paths beyond observed data, which should improve modelling of long-term health outcomes for people with type 2 diabetes when using the UKPDS-OM2 or other models.

The impact of symptoms on quality of life before and after diagnosis of coeliac disease: the results from a Polish population survey and comparison with the results from the United Kingdom.

BACKGROUND: Coeliac disease (CD) is characterised by diverse clinical symptoms, which may cause diagnostic problems and reduce the patients' quality of life. A study conducted in the United Kingdom (UK) revealed that the mean time between the onset of coeliac symptoms and being diagnosed was above 13 years. This study aimed to analyse the diagnostic process of CD in Poland and evaluate the quality of life of patients before and after CD diagnosis. In addition, results were compared to the results of the original study conducted in the UK. METHODS: The study included 2500 members of the Polish Coeliac Society. The patients were asked to complete a questionnaire containing questions on socio-demographic factors, clinical aspects and quality of life, using the EQ-5D questionnaire. Questionnaires received from 796 respondents were included in the final analysis. RESULTS: The most common symptoms reported by respondents were bloating (75%), abdominal pain (72%), chronic fatigue (63%) and anaemia (58%). Anaemia was the most persistent symptom, with mean duration prior to CD diagnosis of 9.2 years, whereas diarrhoea was observed for the shortest period (4.7 years). The mean duration of any symptom before CD diagnosis was 7.3 years, compared to 13.2 years in the UK. CD diagnosis and the introduction of a gluten-free diet substantially improved the quality of life in each of the five EQ-5D-5L health dimensions: pain and discomfort, anxiety and depression, usual activities, self-care and mobility (p < 0.001), the EQ-Index by 0.149 (SD 0.23) and the EQ-VAS by 30.4 (SD 28.3) points. CONCLUSIONS: Duration of symptoms prior to the diagnosis of CD in Poland, although shorter than in the UK, was long with an average of 7.3 years from first CD symptoms. Faster CD diagnosis after the onset of symptoms in Polish respondents may be related to a higher percentage of children in the Polish sample. Introduction of a gluten-free diet improves coeliac patients' quality of life. These results suggest that doctors should be made more aware of CD and its symptoms across all age groups.

Obtaining EQ-5D-5L utilities from the disease specific quality of life Alzheimer's disease scale: development and results from a mapping study.

PURPOSE: The Quality of Life Alzheimer's Disease Scale (QoL-AD) is commonly used to assess disease specific health-related quality of life (HRQoL) as rated by patients and their carers. For cost-effectiveness analyses, utilities based on the EQ-5D are often required. We report a new mapping algorithm to obtain EQ-5D indices when only QoL-AD data are available. METHODS: Different statistical models to estimate utility directly, or responses to individual EQ-5D questions (response mapping) from QoL-AD, were trialled for patient-rated and proxy-rated questionnaires. Model performance was assessed by root mean square error and mean absolute error. RESULTS: The response model using multinomial regression including age and sex, performed best in both the estimation dataset and an independent dataset. CONCLUSIONS: The recommended mapping algorithm allows researchers for the first time to estimate EQ-5D values from QoL-AD data, enabling cost-utility analyses using datasets where the QoL-AD but no utility measures were collected.

Cost and quality-of-life impacts of community treatment orders (CTOs) for patients with psychosis: economic evaluation of the OCTET trial.

PURPOSE: Current RCT and meta-analyses have not found any effect of community treatment orders (CTOs) on hospital or social outcomes. Assumed positive impacts of CTOs on quality-of-life outcomes and reduced hospital costs are potentially in conflict with patient autonomy. Therefore, an analysis of the cost and quality-of-life consequences of CTOs was conducted within the OCTET trial. METHODS: The economic evaluation was carried out comparing patients (n = 328) with psychosis discharged from involuntary hospitalisation either to treatment under a CTO (CTO group) or voluntary status via Section 17 leave (non-CTO group) from the health and social care and broader societal perspectives (including cost implication of informal family care and legal procedures). Differences in costs and outcomes defined as quality-adjusted life years (QALYs) based on the EQ-5D-3L or capability-weighted life years (CWLYs) based on the OxCAP-MH were assessed over 12 months (£, 2012/13 tariffs). RESULTS: Mean total costs from the health and social care perspective [CTO: £35,595 (SD: £44,886); non-CTO: £36,003 (SD: £41,406)] were not statistically significantly different in any of the analyses or cost categories. Mental health hospitalisation costs contributed to more than 85% of annual health and social care costs. Informal care costs were significantly higher in the CTO group, in which there were also significantly more manager hearings and tribunals. No difference in health-related quality of life or capability wellbeing was found between the groups. CONCLUSION: CTOs are unlikely to be cost-effective. No evidence supports the hypothesis that CTOs decrease hospitalisation costs or improve quality of life. Future decisions should consider impacts outside the healthcare sector such as higher informal care costs and legal procedure burden of CTOs.

Quality of life in the FOXFIRE, SIRFLOX and FOXFIRE-global randomised trials of selective internal radiotherapy for metastatic colorectal cancer.

Selective internal radiotherapy (SIRT) is a liver-directed treatment involving the injection of yttrium-90 microspheres into the blood supply of liver tumours. There are very few studies assessing health-related quality of life (HRQOL) in patients treated with SIRT. Patients with liver metastases from colorectal cancer (CRC) were randomised in the FOXFIRE (FFr; ISRCTN83867919), SIRFLOX (SF; NCT00724503) and FOXFIRE-Global (FFrG; NCT01721954) trials of first-line oxaliplatin-fluorouracil (FOLFOX) chemotherapy combined with SIRT versus FOLFOX alone. HRQOL was assessed using the three-level EQ-5D, European Organisation for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) and EORTC Colorectal Liver Metastases cancer module (EORTC QLQ-LMC21) at baseline, ≤3 months, 6 months, 12 months and annually thereafter from randomisation, and at disease progression. Analyses were conducted on an intention-to-treat basis. In total, 554 patients were randomised to SIRT + FOLFOX and 549 patients to FOLFOX alone. HRQOL was statistically significant lower in SIRT + FOLFOX patients ≤3 months after SIRT administration in all three instruments, particularly global health, physical and role functioning and symptoms of fatigue, nausea/vomiting and appetite loss. By accepted thresholds, these differences were deemed not clinically important. Differences between SIRT + FOLFOX and FOLFOX alone over the 2-year follow up and at disease progression were also not clinically important. Although there is some decrease in HRQOL for up to 3 months following SIRT, the addition of SIRT to FOLFOX chemotherapy does not change HRQOL to a clinically important degree in metastatic CRC patients.

Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial.

BACKGROUND: The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer, a disease affecting younger patients, is rapidly increasing. Cetuximab, an epidermal growth factor receptor inhibitor, has been proposed for treatment de-escalation in this setting to reduce the toxicity of standard cisplatin treatment, but no randomised evidence exists for the efficacy of this strategy. METHODS: We did an open-label randomised controlled phase 3 trial at 32 head and neck treatment centres in Ireland, the Netherlands, and the UK, in patients aged 18 years or older with HPV-positive low-risk oropharyngeal cancer (non-smokers or lifetime smokers with a smoking history of <10 pack-years). Eligible patients were randomly assigned (1:1) to receive, in addition to radiotherapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m2 on days 1, 22, and 43 of radiotherapy) or intravenous cetuximab (400 mg/m2 loading dose followed by seven weekly infusions of 250 mg/m2). The primary outcome was overall severe (grade 3-5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. This trial is registered with the ISRCTN registry, number ISRCTN33522080. FINDINGS: Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group). Overall (acute and late) severe (grade 3-5) toxicity did not differ significantly between treatment groups at 24 months (mean number of events per patient 4·8 [95% CI 4·2-5·4] with cisplatin vs 4·8 [4·2-5·4] with cetuximab; p=0·98). At 24 months, overall all-grade toxicity did not differ significantly either (mean number of events per patient 29·2 [95% CI 27·3-31·0] with cisplatin vs 30·1 [28·3-31·9] with cetuximab; p=0·49). However, there was a significant difference between cisplatin and cetuximab in 2-year overall survival (97·5% vs 89·4%, hazard ratio 5·0 [95% CI 1·7-14·7]; p=0·001) and 2-year recurrence (6·0% vs 16·1%, 3·4 [1·6-7·2]; p=0·0007). INTERPRETATION: Compared with the standard cisplatin regimen, cetuximab showed no benefit in terms of reduced toxicity, but instead showed significant detriment in terms of tumour control. Cisplatin and radiotherapy should be used as the standard of care for HPV-positive low-risk patients who are able to tolerate cisplatin. FUNDING: Cancer Research UK.

Can the cardiovascular risk reductions observed with empagliflozin in the EMPA-REG OUTCOME trial be explained by concomitant changes seen in conventional cardiovascular risk factor levels?

AIM: To perform post-hoc analyses of the EMPA-REG OUTCOME trial examining the degree to which empagliflozin-induced changes in conventional cardiovascular (CV) risk factors might explain the observed CV benefits. MATERIALS AND METHODS: We estimated 3-year EMPA-REG OUTCOME CV event rates using a type 2 diabetes-specific clinical outcomes simulation model applied to annual patient-level data. Variables included were atrial fibrillation, smoking, albuminuria, HDL cholesterol, LDL cholesterol, systolic blood pressure, glycated haemoglobin, heart rate, white cell count, haemoglobin, estimated glomerular filtration rate, and histories of ischaemic heart disease, heart failure, amputation, blindness, renal failure, stroke, myocardial infarction or diabetic ulcer. Multiple simulations were performed for each participant to minimize uncertainty and optimize confidence interval precision around CV risk point estimates. Observed and simulated cardiovascular relative risk reductions were compared. RESULTS: Model-predicted relative risk reductions were smaller than those observed in the trial, with empagliflozin-associated changes in conventional CV risk factor values appearing to explain only 12% of the observed relative risk reduction for all-cause death (4% of 32%), 7% for CV death (3% of 39%) and 15% for heart failure (4% of 29%). CONCLUSIONS: Empagliflozin-associated changes in conventional CV risk factors in EMPA-REG OUTCOME appear to explain only a small proportion of the CV and all-cause death reductions observed. Alternative risk-reduction mechanisms need to be explored to determine if the observed CV risk changes can be explained by other factors, or possibly by a direct drug-specific effect.