The Disease Burden and Societal Costs of Hereditary Angioedema.

BACKGROUND: According to the current treatment guidelines, the goals of treatment of patients with hereditary angioedema (HAE) are to achieve total control of the disease and to normalize patients' lives. OBJECTIVE: This study aims to establish the entire burden of HAE comprising disease control, treatment satisfaction, reductions in quality of life, and societal costs. METHODS: Adult patients with HAE under treatment at the Dutch national center of reference completed a cross-sectional survey in 2021. The survey consisted of different questionnaires: angioedema-specific questionnaires (4-week Angioedema Activity Score and Angioedema Control Test), quality of life questionnaires (Angioedema Quality of Life [AE-QoL] questionnaire and EQ-5D-5L), the Treatment Satisfaction Questionnaire for Medication (TSQM), and societal costs questionnaires (iMTA Medical Consumption Questionnaire and iMTA Productivity Cost Questionnaire). RESULTS: The response rate was 78% (69 of 88). The entire sample had a mean Angioedema Activity Score of 16.61, and 36% of participants had poorly controlled disease as expressed by the Angioedema Control Test. The mean quality of life in the entire sample was 30.99 as expressed by the AE-QoL and 0.873 as expressed by the EQ-5D-5L utility value. Utilities dropped by 0.320 points during an angioedema attack. TSQM scores ranged from 66.67 to 75.00 across its 4 domains. On average, total costs per year incurred €22,764, predominantly existing of HAE-medication costs. Total costs showed substantial variation between patients. CONCLUSIONS: This study describes the entire burden of HAE among Dutch patients comprising disease control, quality of life, treatment satisfaction, and societal costs. These results can inform cost-effectiveness analyses that can aid reimbursement decisions for HAE treatments.

Real-world evidence in health technology assessment of high-risk medical devices: Fit for purpose?

Health technology assessment (HTA) of medical devices (MDs) increasingly rely on real-world evidence (RWE). The aim of this study was to evaluate the type and the quality of the evidence used to assess the (cost-)effectiveness of high risk MDs (Class III) by HTA agencies in Europe (four European HTA agencies and EUnetHTA), with particular focus on RWE. Data were extracted from HTA reports on the type of evidence demonstrating (cost-)effectiveness, and the quality of observational studies of comparative effectiveness using the Good Research for Comparative Effectiveness principles. 25 HTA reports were included that incorporated 28 observational studies of comparative effectiveness. Half of the studies (46%) took important confounding and/or effect modifying variables into account in the design and/or analyses. The most common way of including confounders and/or effect modifiers was through multivariable regression analysis. Other methods, such as propensity score matching, were rarely employed. Furthermore, meaningful analyses to test key assumptions were largely omitted. Resulting recommendations from HTA agencies on MDs is therefore (partially) based on evidence which is riddled with uncertainty. Considering the increasing importance of RWE it is important that the quality of observational studies of comparative effectiveness are systematically assessed when used in decision-making.

Costs of Persons with Dementia Living in Nursing Homes in The Netherlands.

BACKGROUND: Disease modifying treatments (DMTs) currently under development for Alzheimer's disease, have the potential to prevent or postpone institutionalization and more expensive care and might delay institutionalization of persons with dementia. OBJECTIVE: The current study estimates costs of living in a nursing home for persons with dementia in the Netherlands to help inform economic evaluations of future DMTs. METHODS: Data were collected during semi-structured interviews with healthcare professionals and from the financial administration of a healthcare organization with several nursing homes. Personnel costs were calculated using a bottom-up approach by valuing the time estimates. Non-personnel costs were calculated using information from the financial administration of the healthcare organization. RESULTS: Total costs of a person with dementia per 24 hours, including both care staff and other healthcare providers, were € 151 for small-scale living wards and € 147 for independent living wards. Non-personnel costs were € 37 per day. CONCLUSION: This study provides Dutch estimates for total healthcare costs per day for institutionalized persons with dementia. These cost estimates can be used in cost-effectiveness analyses for future DMTs in dementia.

Acoustic Indoor Localization Augmentation by Self-Calibration and Machine Learning.

An acoustic transmitter can be located by having multiple static microphones. These microphones are synchronized and measure the time differences of arrival (TDoA). Usually, the positions of the microphones are assumed to be known in advance. However, in practice, this means they have to be manually measured, which is a cumbersome job and is prone to errors. In this paper, we present two novel approaches which do not require manual measurement of the receiver positions. The first method uses an inertial measurement unit (IMU), in addition to the acoustic transmitter, to estimate the positions of the receivers. By using an IMU as an additional source of information, the non-convex optimizers are less likely to fall into local minima. Consequently, the success rate is increased and measurements with large errors have less influence on the final estimation. The second method we present in this paper consists of using machine learning to learn the TDoA signatures of certain regions of the localization area. By doing this, the target can be located without knowing where the microphones are and whether the received signals are in line-of-sight or not. We use an artificial neural network and random forest classification for this purpose.

Addressing Health System Values in Health Technology Assessment: The Use of Evidence-Informed Deliberative Processes.

Health technology assessment (HTA) is increasingly used around the globe to inform resource allocation decisions. Furthermore, the importance of using explicit and transparent criteria for coverage decision making in line with health system values has been acknowledged. However, the values of a health system are often not explicitly taken into account in the HTA process. This situation influences the allocation of scarce resources and could lead to a discord between the HTA outcome and the values of the health system. We describe how evidence-informed deliberative processes (EDPs) can help to improve this situation. EDPs are integrating two theoretical frameworks; multi-criteria decision-analysis and accountability for reasonableness. Through the use of EDPs, HTA agencies can ensure that health system values are more explicitly and consistently taken into account in the HTA process, enhancing the legitimacy of coverage decisions.

Identifying and Bounding Ethnic Neighborhoods.

This study presents three novel approaches to the question of how best to identify ethnic neighborhoods (or more generally, neighborhoods defined any aspect of their population composition) and to define their boundaries. It takes advantage of unusual data on the residential locations of all residents of Newark, NJ, in 1880 to avoid having to accept arbitrary administrative units (like census tracts) as the building blocks of neighborhoods. For theoretical reasons the street segment is chosen as the basic unit of analysis. All three methods use information on the ethnic composition of buildings or street segments and the ethnicity of their neighbors. One approach is a variation of k-functions calculated for each adult resident, which are then subjected to a cluster analysis to detect discrete patterns. The second is an application of an energy minimization algorithm commonly used to enhance digital images. The third is a Bayesian approach previously used to study county-level disability data. Results of all three methods depend on decisions about technical procedures and criteria that are made by the investigator. Resulting maps are roughly similar, but there is no one best solution. We conclude that researchers should continue to seek alternative methods, and that the preferred method depends on how one's conceptualization of neighborhoods matches the empirical approach.

Recognition of shapes by editing their shock graphs.

This paper presents a novel framework for the recognition of objects based on their silhouettes. The main idea is to measure the distance between two shapes as the minimum extent of deformation necessary for one shape to match the other. Since the space of deformations is very high-dimensional, three steps are taken to make the search practical: 1) define an equivalence class for shapes based on shock-graph topology, 2) define an equivalence class for deformation paths based on shock-graph transitions, and 3) avoid complexity-increasing deformation paths by moving toward shock-graph degeneracy. Despite these steps, which tremendously reduce the search requirement, there still remain numerous deformation paths to consider. To that end, we employ an edit-distance algorithm for shock graphs that finds the optimal deformation path in polynomial time. The proposed approach gives intuitive correspondences for a variety of shapes and is robust in the presence of a wide range of visual transformations. The recognition rates on two distinct databases of 99 and 216 shapes each indicate highly successful within category matches (100 percent in top three matches), which render the framework potentially usable in a range of shape-based recognition applications.

Renal failure due to acute nephrocalcinosis following oral sodium phosphate bowel cleansing.

Nephrocalcinosis is a chronic tubulointerstitial nephropathy characterized by tubular calcium phosphate deposition and slowly progressive renal insufficiency. We report a novel association of acute nephrocalcinosis and acute renal failure (ARF) with colonoscopy preceded by a bowel-cleansing regimen consisting of oral sodium phosphate solution (OSPS). A cohort of 5 patients (mean age, 69.2 years) had normal renal function (mean serum creatininem 0.9 mg/dL) before colonoscopy and presented with ARF (mean serum creatinine, 4.9 mg/dL) from 3 days to 2 months postcolonoscopy. Past medical history included hypertension in all 5 patients. Medications included an angiotensin-converting enzyme (ACE) inhibitor (ACE-I) or angiotensin receptor blocker (ARB) in 4 patients and diuretics in 2 patients. In all patients, colonoscopy was preceded by bowel cleansing with OSPS; OSPS was contraindicated in a single patient with hyperparathyroidism and was used at excessive doses in another. Renal biopsy specimens obtained from all 5 patients revealed diffuse tubular injury and abundant tubular deposition of calcium phosphate. Although the tubular injury involved all tubular segments, lectin and immunohistochemical staining disclosed calcium phosphate deposition confined to distal tubules and collecting ducts. At a mean of 5.8 weeks of postbiopsy follow-up, renal function was unchanged in 4 patients and mildly improved in 1 patient. We conclude that acute nephrocalcinosis is a seemingly rare complication of bowel cleansing with OSPS. The pathophysiology of acute nephrocalcinosis after treatment with OSPS likely involves transient hyperphosphatemia; volume depletion exacerbated by intercurrent ACE-I, ARB, and diuretic use; and elevated distal tubular phosphate and calcium concentrations. Greater awareness of this entity is needed to identify potential risk factors.