Health-related quality of life among transthyretin amyloid cardiomyopathy patients.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR CM) is a progressive and severe heart disease with physical and psychological implications. The Nordic PROACT study was conducted to investigate the health-related quality of life (HRQoL) in ATTR CM patients. METHODS AND RESULTS: The Nordic PROACT study was a cross-sectional non-interventional study conducted in 12 cardiology hospital clinics across Norway, Sweden, Finland and Denmark. Men and women aged ≥18 years diagnosed with symptomatic ATTR CM were included. The investigator provided information on medical history, biomarkers, current treatment, co-morbidities and disease severity according to the New York Heart Association (NYHA) class and the National Amyloidosis Centre (NAC) staging. Patients completed the HRQoL questionnaires in the form of the Kansas City Cardiomyopathy Questionnaire (KCCQ), the EQ-5D-5L index with Visual Analog Scale (VAS), and the Major Depression Inventory (MDI). A total of 169 patients (mean ± SD age 77.7 ± 6.2 years) were included. Ninety-two per cent were men. Seventy-six per cent had wildtype ATTR CM (ATTRwt CM) and 15% had a hereditary form of ATTR CM (ATTRv CM) while 9% were genetically unclassified. Most patients were in NYHA class II (54%) and NAC stage 1 (53%). Participation in randomized clinical trials (RCT) was noted in 58% of the patients. The 169 ATTR CM patients had a mean ± SD KCCQ score of 64.3 ± 23.1 for total symptom score, 64.8 ± 20.9 for overall summary score (OSS) and 65.1 ± 21.5 for clinical summary score. The EQ-5D-5L total utility score was 0.8 ± 0.2 and the EQ-5D-5L VAS score was 62.9 ± 20.6. The vast majority (89%) did not report any signs of depression. Patients with ATTRv CM had a higher KCCQ OSS as compared with ATTRwt CM, while EQ-5D-5L utility score, EQ-5D-5L VAS and MDI were similar. Non-RCT participants had a poorer HRQoL as compared with RCT participants as reflected in lower KCCQ OSS and EQ-5D-5L VAS scores and a higher MDI score. Patients with higher NYHA classes and NAC disease stages had a poorer HRQoL as demonstrated by lower KCCQ and EQ-5D-5L scores and higher MDI scores. Correlation between KCCQ, EQ-5D-5L and MDI and the covariate NYHA class remained significant (P < 0.05) after adjusting for multiple testing. CONCLUSIONS: KCCQ scores were lower than previously reported for patients with other heart diseases of non-ATTR CM origin. The HRQoL measures correlated well to NYHA class and NAC disease stage. The prevalence of depression appeared to be low.

Impact of new cancer medicine - real-world evidence from Danish register study of lung cancer patients.

BACKGROUND: Lung cancer (LC) is the leading cause of cancer deaths worldwide. Several new treatments have become available in recent decades, but little research exists on the impact of these on productivity, early retirement and survival for LC patients and their spouses. This study evaluates the effect of new medicines on productivity, early retirement and survival for LC patients and their spouses. METHODS: Data from the period 1 January 2004-31 December 2018 were collected from complete Danish registers. LC cases diagnosed before approval of first targeted therapy (19 June 2006, Before patients) were compared with those who received at least one new cancer treatment, diagnosed after this date (After patients). Subgroup analyses based on cancer stage, and epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutation were conducted. Linear regression and cox regression were used to estimate the outcomes including productivity, unemployment, early retirement, and mortality. Spouses of Before and After patients were compared on earnings, sick leave, early retirement, and healthcare utilisation. RESULTS: The study population comprised of 4,350 patient (2,175 After/2,175 Before). Patients who received new treatments had a significantly reduced risk of death (Hazard ratio = 0.76, Confidence interval: 0.71 - 0.82) and reduced risk of early retirement (Hazard ratio: 0.54, Confidence interval: 0.38 - 0.79). No significant differences in earnings, unemployment, or sick leave were found. Spouses of Before patients had a higher cost of healthcare services after diagnosis compared to spouses of After patients. For productivity, early retirement and sick leave, no significant differences were found between the spouse groups. CONCLUSION: Patients who received innovative new treatments had reduced risk of death and reduced risk of early retirement. Spouses of LC patients who received new treatments had lower healthcare costs in the years following diagnosis. All findings indicate that recipients of new treatments had reduced burden of illness.

Suspicion, screening, and diagnosis of wild-type transthyretin amyloid cardiomyopathy: a systematic literature review.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt CM) is a more common disease than previously thought. Awareness of ATTRwt CM and its diagnosis has been challenged by its unspecific and widely distributed clinical manifestations and traditionally invasive diagnostic tools. Recent advances in echocardiography and cardiac magnetic resonance (CMR), non-invasive diagnosis by bone scintigraphy, and the development of disease-modifying treatments have resulted in an increased interest, reflected in multiple publications especially during the last decade. To get an overview of the scientific knowledge and gaps related to patient entry, suspicion, diagnosis, and systematic screening of ATTRwt CM, we developed a framework to systematically map the available evidence of (i) when to suspect ATTRwt CM in a patient, (ii) how to diagnose the disease, and (iii) which at-risk populations to screen for ATTRwt CM. Articles published between 2010 and August 2021 containing part of or a full diagnostic pathway for ATTRwt CM were included. From these articles, data for patient entry, suspicion, diagnosis, and screening were extracted, as were key study design and results from the original studies referred to. A total of 50 articles met the inclusion criteria. Of these, five were position statements from academic societies, while one was a clinical guideline. Three articles discussed the importance of primary care providers in terms of patient entry, while the remaining articles had the cardiovascular setting as point of departure. The most frequently mentioned suspicion criteria were ventricular wall thickening (44/50), carpal tunnel syndrome (42/50), and late gadolinium enhancement on CMR (43/50). Diagnostic pathways varied slightly, but most included bone scintigraphy, exclusion of light-chain amyloidosis, and the possibility of doing a biopsy. Systematic screening was mentioned in 16 articles, 10 of which suggested specific at-risk populations for screening. The European Society of Cardiology recommends to screen patients with a wall thickness ≥12 mm and heart failure, aortic stenosis, or red flag symptoms, especially if they are >65 years. The underlying evidence was generally good for diagnosis, while significant gaps were identified for the relevance and mutual ranking of the different suspicion criteria and for systematic screening. Conclusively, patient entry was neglected in the reviewed literature. While multiple red flags were described, high-quality prospective studies designed to evaluate their suitability as suspicion criteria were lacking. An upcoming task lies in defining and evaluating at-risk populations for screening. All are steps needed to promote early detection and diagnosis of ATTRwt CM, a prerequisite for timely treatment.

Correlations of fatigue in Danish patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis.

OBJECTIVE: To describe fatigue in relation to disease-specific and socioeconomic factors and to test possible correlations between fatigue and work impairment, quality of life, pain, sleep, depression, and physical functioning in people with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). METHODS: A questionnaire-based cross-sectional survey collecting patient characteristics such as disease characteristics, socioeconomic factors and patient-reported outcomes (PROs) from patients with RA, PsA and axSpA in Denmark. PRO scales included the FACIT-Fatigue sub-scale, Work Productivity and Activity Impairment scale (WPAI), EuroQol (EQ-5D), Medical Outcomes Study Sleep Scale (MOS), Major Depression Inventory (MDI), and Health Assessment Questionnaire (HAQ). Respondents were recruited via routine visits to the outpatient rheumatology clinic; information on diagnosis, treatment and disease activity was collected from medical journals by trained nurses. RESULTS: 487 patients participated in the study. Fatigue was more present in women, experienced patients, and patients who changed medication in the past 12 months, who were unemployed, who had less education, and who had lower household income. There was no statistically significant difference between mean fatigue in the three diagnostic groups (p = 0.08). Fatigue correlated with all included PROs (Pearson correlation coefficients, p<0.0001). Stratifying for diagnosis and adjusting for socioeconomic factors did not change the conclusion. CONCLUSION: In a stable, representative group of patients with RA, PsA and axSpA, we found significant correlations between fatigue and work impairment, quality of life, pain, sleep, depression and physical functioning. Fatigue cannot be perceived as a single problem, but rather as a symptom that affects broadly.

Diagnostic and lifetime hospital costs of patients suffering from wild-type transthyretin amyloid cardiomyopathy in Denmark.

AIMS: Wild-type transthyretin amyloid cardiomyopathy (ATTRwt) is a fast progressing and fatal disease associated with substantial delays in diagnosis. Between the first symptoms and diagnosis, patients are frequently hospitalized, primarily with cardiac symptoms. After diagnosis, patients continue to experience frequent hospital admissions. The objective of this study was to estimate the Danish diagnostic and lifetime hospital costs associated with the treatment of patients with ATTRwt both before and after they are diagnosed. MATERIALS AND METHODS: We developed a cost model for Danish hospital costs associated with ATTRwt, including the costs of diagnosis, cardiac implants, and hospital admissions covering inpatient hospitalization and outpatient hospital care (ambulatory and emergency services). The number of diagnoses, cardiac implants, inpatient hospitalization and outpatient hospital care were estimated based on published data. Estimates of the unit costs were based on publicly available Danish reference costs. We calculated the total hospital costs covering the median lifespan of patients from onset of symptoms, which is 13 months prior to diagnosis, to 52 months after diagnosis which is the median survival time after diagnosis. RESULTS: The average cost of diagnosing ATTRwt was USD 3,424 per patient; the average costs of cardiac implants were USD 1,851 per patient. Hospital admissions costs totaled USD 3,345 pre-diagnosis and USD 59,449 post-diagnosis per patient, on average. The total diagnostic and lifetime (65 months) hospital costs associated with ATTRwt were USD 68,069. CONCLUSIONS: Caring for patients with ATTRwt places a significant economic burden on the healthcare system. The study emphasizes the cost saving potential for medical interventions in this patient population.

Severity of fatigue in people with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis - Results of a cross-sectional study.

BACKGROUND: Despite improvements in treatment for rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (axSpA), several key unmet needs remain, such as fatigue. The objective of this study was to describe the severity of fatigue, disease characteristics and socioeconomic factors in people with RA, PsA and axSpA. METHODS: The study was designed as a cross-sectional survey collecting patient characteristics such as disease characteristics, socioeconomic factors and fatigue in people with RA, PsA and axSpA in Denmark. Respondents were consecutively recruited for the study over a six-month period in 2018 via routine visits to outpatient rheumatology clinics. Study nurses collected information on diagnosis, current disease-related treatment and disease activity from medical journals. People were invited to complete a questionnaire related to socioeconomic factors and containing the FACIT-Fatigue subscale. Descriptive statistics were analyzed using SAS. RESULTS: We invited 633 people to participate, and 488 (77%) completed the questionnaire. Women constituted 62% of respondents, and the mean age was 53.5 years. Respondents had on average been diagnosed between 11 and 15 years ago. Overall, 79% had no changes to their disease-related treatment during the past year, and the average disease activity as indicated by DAS28 for RA and PsA was 2.48 and 2.36, respectively, and BASDAI for axSpA was 28.40. Fatigue was present in all three diagnoses (mean: 34.31). The mean fatigue score varied from respondents answering that they suffered from no or little fatigue (mean: 45.48) to extreme fatigue (mean: 10.11). Analyses demonstrated that the respondents were not considerably different from nonrespondents, and the study population is considered representative compared with Danish RA and axSpA patients in the Danish National Rheumatology Registry, the DANBIO database. CONCLUSION: We found that the majority of the study population were fatigued (61%). They had low disease activity and few disease-related treatment changes.

Healthcare costs of fast-acting insulin analogues versus short-acting human insulin for Danish patients with type 2 diabetes on a basal-bolus regimen.

AIMS: Fast-acting insulin analogues (FAIAs) reduce hypoglycaemia and improve administration flexibility compared with short-acting human insulin (SHI). This analysis examines whether these benefits translate into cost offsets when comparing the total treatment costs for FAIA versus SHI used as basal-bolus therapy for treating type 2 diabetes (T2D). METHODS: Registry data covering the Danish population including demographic variables, prescription, hospital and primary care data formed the basis for analysis. To capture patients on basal-bolus therapy only, inclusion criteria were ≥2 prescriptions of either long-acting insulin analogues (LAIAs) or neutral protamine Hagedorn (NPH) insulin (basal component), and ≥2 prescriptions for either an FAIA or SHI (bolus component) during the inclusion period (1 January-31 December 2005). Patients using LAIAs (n = 521) or NPH (n = 2695) were analysed separately. Within each basal cohort, patients using FAIAs or SHI were matched regarding observable variables using propensity scores. Healthcare costs were analysed for a follow-up period (maximum 2 years post-inclusion). RESULTS: Within each cohort, matching produced groups with similar observed covariates. Overall direct healthcare costs in the LAIA cohort were €4183 and €5289 for FAIA and SHI, respectively. In the NPH cohort, costs were €4940 and €4699 for FAIA and SHI, respectively. For both basal cohorts, cost differences between FAIA and SHI were not statistically significant. LIMITATIONS: As the propensity score model cannot account for unobserved variables, conclusions of causality cannot be made. Moreover, exclusion of indirect costs and application of hospital contact charges accrued in the discharge year only may result in an underestimation of overall healthcare costs. CONCLUSION: Using matched cohorts, treating patients with T2D using basal-bolus regimens containing FAIAs was no more costly to the Danish healthcare system than regimens using SHI. FAIAs provide a flexible administration and optimal glucose control for a similar cost.