Locality Aware Zeroing: Exploiting Both Hardware and Software Semantics

Memory safety defends against inadvertent and malicious misuse of memory that may compromise program correctness and security. A critical element of memory safety is zero initialization. The direct cost of zero initialization is surprisingly high: up to 12.7%, with average costs ranging from 2.7 to 4.5% on a high performance virtual machine on IA32 architectures. Zero initialization also incurs indirect costs due to its memory bandwidth demands and cache displacement effects. Existing virtual machines either: a) minimize direct costs by zeroing in large blocks, or b) minimize indirect costs by zeroing in the allocation sequence, which reduces cache displacement and bandwidth. This paper evaluates the two widely used zero initialization designs, showing that they make different tradeoffs to achieve very similar performance. Our analysis inspires three better designs: (1) bulk zeroing with cache-bypassing (non-temporal) instructions to reduce the direct and indirect zeroing costs simultaneously, (2) concurrent non-temporal bulk zeroing that exploits parallel hardware to move work off the application's critical path, and (3) adaptive zeroing, which dynamically chooses between (1) and (2) based on available hardware parallelism. The new software strategies offer speedups sometimes greater than the direct overhead, improving total performance by 3% on average. Our findings invite additional optimizations and microarchitectural support.

Shifts in migration and border control policies may increase the likelihood of trauma exposure related to child–parent separation and result in costs to the health system and society. In the present study, we estimated direct and indirect costs per child as well as overall cohort costs of border control policies on migrant children and adolescents who were separated from their parents, detained, and placed in the custody of the United States following the implementation of the 2018 Zero Tolerance Policy. Economic modeling techniques, including a Markov process and Monte Carlo simulation, based on data from the National Child Traumatic Stress Network's Core Data Set (N = 458 migrant youth) and published studies were used to estimate economic costs associated with three immigration policies: No Detention, Family Detention, and Zero Tolerance. Clinical evaluation data on mental health symptoms and disorders were used to estimate the initial health state and risks associated with additional trauma exposure for each scenario. The total direct and indirect costs per child were conservatively estimated at $33,008, $33,790, and $34,544 after 5 years for No Detention, Family Detention, and Zero Tolerance, respectively. From a health system perspective, annual estimated spending increases ranged from $1.5 million to $14.9 million for Family Detention and $2.8 million to $29.3 million for Zero Tolerance compared to baseline spending under the No Detention scenario. Border control policies that increase the likelihood of child and adolescent trauma exposure are not only morally troubling but may also create additional economic concerns in the form of direct health care costs and indirect societal costs.

Cost of Care of Rare Hematologic Disorders in the United States: Call to Action for Policy Supporting Pharmacologic Innovation

Aim: Although seriously injured patients account for a high medical as well as socioeconomic burden of disease in the German health care system, there are only very few data describing the costs that arise between the days of accident and occupational reintegration. With this study, a comprehensive cost model is developed that describes the direct, indirect and intangible costs of an accident and their relationship with socioeconomic background of the patients.Methods: This study included 113 patients who each had at least two injuries and a total Abbreviated Injury Scale (AIS) greater than or equal to five. We calculated the direct, indirect and intangible costs that arose between the day of the accident and occupational reintegration. Direct costs were the treatment costs at hospitals and rehabilitation centers. Indirect costs were calculated using the human capital approach on the basis of the work days lost due to injury, including sickness allowance benefits. Intangible costs were assessed using the Short Form Survey (SF-36) and represented in non-monetary form. Following univariate analysis, a bivariate analysis of the above costs and the patients’ sociodemographic and socioeconomic characteristics was performed. Results: At an average Injury Severity Score (ISS) of 19.2, the average direct cost per patient were €35,661. An average of 185.2 work days were lost, resulting in indirect costs of €17,205. The resulting total costs per patient were €50,431. A bivariate analysis showed that the costs for hospital treatment were 58% higher in patients who graduated from lower secondary school [Hauptschule] (ISS 19.5) than in patients with qualification for university admission [Abitur] (ISS 19.4). Conclusions: The direct costs of treating trauma patients at the hospital appear to be lower in patients with a higher level of education than in the comparison group with a lower educational level. Because of missing data, the calculated indirect costs can merely represent a general trend, so that the bivariate analysis can only be seen as a starting point for further studies.

To estimate the current and future economic burdens of Type 1 and Type 2 diabetes in the UK. A top-down approach was used to estimate costs for 2010/2011 from aggregated data sets and literature. Prevalence and population data were used to project costs for 2035/2036. Direct health costs were estimated from data on diagnosis, lifestyle interventions, ongoing treatment and management, and complications. Indirect costs were estimated from data on mortality, sickness, presenteeism (potential loss of productivity among people who remain in work) and informal care. Diabetes cost approximately £ 23.7bn in the UK in 2010/2011: £ 9.8bn in direct costs (£1bn for Type 1 diabetes and £ 8.8bn for Type 2 diabetes) and £ 13.9bn in indirect costs (£ 0.9bn and £ 13bn). In real terms, the 2035/2036 cost is estimated at £ 39.8bn: £ 16.9bn in direct costs (£ 1.8bn for Type 1 diabetes and £ 15.1bn for Type 2 diabetes) and £ 22.9bn in indirect costs (£ 2.4bn and £ 20.5bn). Sensitivity analysis applied to the direct costs produced a range of costs: between £ 7.9bn and £ 11.7bn in 2010/2011 and between £ 13.8bn and £20bn in 2035/2036. Diabetes currently accounts for approximately 10% of the total health resource expenditure and is projected to account for around 17% in 2035/2036. Type 1 and Type 2 diabetes are prominent diseases in the UK and are a significant economic burden. Data differentiating between the costs of Type 1 and Type 2 diabetes are sparse. Complications related to the diseases account for a substantial proportion of the direct health costs. As prevalence increases, the cost of treating complications will grow if current care regimes are maintained.

This study was undertaken to calculate epilepsy-related direct, indirect, and total costs in adult patients with active epilepsy (ongoing unprovoked seizures) in Germany and to analyze cost components and dynamics compared to previous studies from 2003, 2008, and 2013. This analysis was part of the Epi2020study. Direct and indirect costs related to epilepsy were calculated with a multicenter survey using an established and validated questionnaire with a bottom-up design and human capital approach over a 3-month period in late 2020. Epilepsy-specific costs in the German health care sector from 2003, 2008, and 2013 were corrected for inflation to allow for a valid comparison. Data on the disease-specific costs for 253 patients in 2020 were analyzed. The mean total costs were calculated at €5551 (±€5805, median = €2611, range = €274-€21667) per 3months, comprising mean direct costs of €1861 (±€1905, median = €1276, range = €327-€13158) and mean indirect costs of €3690 (±€5298, median = €0, range = €0-€11925). The main direct cost components were hospitalization (42.4%), antiseizure medication (42.2%), and outpatient care (6.2%). Productivity losses due to early retirement (53.6%), part-time work or unemployment (30.8%), and seizure-related off-days (15.6%) were the main reasons for indirect costs. However, compared to 2013, there was no significant increase of direct costs (-10.0%), and indirect costs significantly increased (p<.028, +35.1%), resulting in a significant increase in total epilepsy-related costs (p<.047, +20.2%). Compared to the 2013study population, a significant increase of cost of illness could be observed (p=.047). The present study shows that disease-related costs in adult patients with active epilepsy increased from 2013 to 2020. As direct costs have remained constant, this increase is attributable to an increase in indirect costs. These findings highlight the impact of productivity loss caused by early retirement, unemployment, working time reduction, and seizure-related days off.

264. Economic impact of revision operations for adjacent segment disease of the cervical spine

This study assessed quality of life, direct and indirect healthcare costs related to ankylosing spondylitis (AS). This study included 650 prevalent AS patients visiting seven centers at tertiary healthcare institutions in Turkey who were interviewed using a standard questionnaire to determine annual direct and indirect healthcare costs. Eligible patients were age ≥18 years with AS for at least 12 months. Direct costs were categorized as inpatient, outpatient and pharmacy, and AS-related consultation. Indirect costs were categorized as workday loss, additional AS-related costs, and caregiver costs. Clinical outcome measures were obtained, including Patients’ Global Disease Activity (Pt-GDA); visual analog scale (Pain-VAS) for pain; Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Functional Index (BASFI), and Metrology Index (BASMI) scores, and EuroQoL 5 dimension (EQ-5D) health status survey scores. Mean (€4,335.20) and median (€5,671.00) annual costs per patient were calculated. Pharmacy costs (€4,032.73) were highest among overall expenditures, followed by additional AS-related consultation (€2,480.38), outpatient (€225.02), and inpatient costs (€29.98). Over half of AS patients (54.8 %) experienced work loss. Related average annual costs were €414.16, based on income level. 10.3 % of AS patients incurred an additional €2,008.07 in 1 year. 6.8 % of patients required caregivers and incurred €778.70 in average annual patient paid costs. Mean Pt-GDA, Pain-VAS, EQ-5D, BASDAI, BASFI, and BASMI scores were 4.4, 40.5, 62.7, 3.6, 3.1, and 2.9, respectively. Direct and indirect AS-related costs are high and represent a considerable economic burden on Turkish AS patients.

The objective of the study was to quantify the direct and indirect incremental costs of epoetin alpha (EPO) therapy for anemia in pre-dialysis chronic kidney disease (CKD). Using employer claims data from January 1998 to January 2005, direct (medical and pharmacy) and indirect (sick leave and disability) costs were compared between CKD-anemic patients treated with EPO before dialysis (n = 199) and those not treated with an erythropoiesis-stimulating therapy (EST) (n = 196). Among the results, incremental direct and indirect cost savings for EPO-treated patients were $1443 and $328 per member per month (PMPM) (p < 0.001), respectively, compared to non-EST-treated patients with anemia. After multivariate adjustments, direct and indirect costs remained significantly lower by $852 and $308 PMPM (p < 0.001), respectively, for the EPO-treated group. Direct costs during the first 6 months of dialysis also were significantly lower for the EPO-treated group (who received EPO before dialysis), by $1515 PMPM (p = 0.0267, in multivariate regression). In conclusion, anemic CKD patients treated with EPO before dialysis had significantly lower direct and indirect costs compared to non-EST-treated patients.

PND36 HEALTHCARE COSTS ASSOCIATED WITH ALZHEIMER’S DISEASE IN THE US AND EU-5: A SYSTEMATIC LITERATURE REVIEW

To examine what direct and indirect societal costs are associated with decreased visual acuity (VA). Nationally representative sample of 8028 Finnish adults aged 30 years or older with survey data and clinical examination including VA assessment was evaluated. These data were linked with multiple national registers to capture health care services utilization during 1999-2013. All direct and indirect costs were calculated using prevalence-based bottom-up approach and adjusted for age, sex, and comorbidities with generalized linear models. The results in 2019 cost level are presented according to VA groups at baseline per person, and with population estimates. Total direct health care costs ranged from 1996 €/year/person for those with VA ≥1.0 to 3277 €/year/person for those with weak (0.32-0.5) VA. The increase in direct costs was notable even before the onset of visual impairment. Indirect costs showed monotonously increasing trend with decreasing VA. At the population level, the additional annual direct costs associated with decreased VA were estimated at 1.9 billion €. Only 2% or less of the additional costs are due to increased direct eye-related secondary health care usage. Estimated additional annual national indirect costs were 1.2 billion €. In addition to those with visual impairment or blindness, health care need, and societal costs are elevated even among those with adequate VA. We conclude, that focusing on prevention of VA decrease would not only help sustain the patients' quality of life but could also reduce the future societal costs.

Fracture nonunion represents a major complication in orthopaedic surgery, occurring in 5% to 10% of fracture patients. Fracture nonunions are associated with pain and loss of function, and lead to a substantial socioeconomic burden. The present retrospective cohort study analyzed direct and indirect costs and length of hospital stay, number of surgical procedures, and hospital (re-)admissions of nonunion patients. Data from 18- to 65-year-old patients surgically treated for lower limb fractures and nonunions in a German level I trauma centre between 2012 and 2018 were analyzed. A total of 193 patients with nonunion were included, and 2,511 patients with fractures served as the control group. Direct costs were calculated using reimbursement according to the diagnosis-related group (DRG). Indirect costs were calculated including daily sickness allowance and productivity loss. The median healing time of nonunion patients was 45 weeks. Treatment expenses showed a 2.6-fold increase in direct costs, a 3.3-fold increase in indirect costs, and a 3.3-fold increase in total costs for nonunion patients compared to the control group. As every patient with a nonunion suffered from a fracture prior to nonunion treatment, costs were calculated by adding the median direct costs of €10,487 (IQR 9,173 to 15,262), median daily sickness allowance of €23,046 (IQR 14,892 to 36,264), median productivity loss of €85,714 (IQR 60,949 to 126,650), and median total socioeconomic burden of €123,334 (IQR 88,630 to 176,329). Nonunions not only pose a significant burden on the injured individual and on healthcare systems, but also have a substantial socioeconomic impact. High direct and indirect costs illustrate that healing complications need to be detected and addressed as early as possible.

Soft bandage vs rigid immobilisation in pediatric distal radius torus fractures: A cost and patient burden analysis - A retrospective cohort study.

To prospectively evaluate the health economic burden of patients with Parkinson's disease (PD) in Germany over a 6-month observation period and to identify the predictors of these costs. Direct and indirect costs were evaluated in 145 patients with PD (mean age 67.3 +/- 9.6 years). PD patients were recruited from an outpatient department for movement disorders, a specialised PD clinic, two office-based neurologists and general practitioners, all located in Germany, and were enrolled between January and June 2000. Relevant economic data were documented in a patient diary over the 6-month period. Clinical evaluations (Unified Parkinson's Disease Rating Scale [UPDRS]) were performed at baseline and at 3 and 6 months. Costs were derived from various German medical economic resources. Costs were calculated from the perspective of healthcare and transfer payment providers and the individual patient. Indirect costs for lost productivity were also calculated. Costs are presented as means +/- standard deviation (SD). Multivariate regression analyses were performed to identify independent cost predictors. Costs are in year 2000-02 values. We estimated average per patient direct, indirect and total costs for the 6-month observation period. The costs from the perspective of statutory health insurance (Gesetzliche Krankenkversicherung [GKV]) consisted of direct medical costs 1370 euro +/- 3240 euro, including rehabilitation (420 euro +/- 1630 euro), hospitalisation (710 euro +/-2520 euro), outpatient treatment (40 euro +/- 30 euro), ancillary treatment (190 euro +/- 280 euro) and ambulatory diagnostic procedures (10 euro +/-30 euro). In addition, parkinsonian drug costs were 1520 euro +/-euro1250. Non-medical direct costs calculated from the GKV perspective were estimated to be euro480 +/-euro1710, which included transportation (10 euro+/- 20 euro), special equipment (420 euro +/- 1640 euro), social/home-help services (10 euro +/-110 euro) and sickness benefit (40 euro +/- 540 euro). The total medical (including drug costs) and non-medical direct costs for the GKV were 3380 euro +/- 4230 euro. Univariate predictors for GKV direct costs included occurrence of motor complications and falls, disease severity, nightmares and dementia. However, multivariate analyses only suggested disease severity and health-related quality of life as significant predictors. For nursing insurance, payments of 1330 euro +/- 2890 euro were calculated. For retirement insurance, payments were 650 euro +/- 1510 euro and there were patient (or caregiver) costs of 1490 euro +/- 2730 euro. Total indirect costs amounted to 3180 euro +/-6480 euro. According to our study, PD puts a high financial burden on society and underscores the need for further economic and medical research to optimise treatment for PD.

Pneumococcal infection prevention in children of the first 5 years of life in Russia is of high importance due to high morbidity and mortality. The goal of the study is pharmacoeconomic assessment of first year of life infants vaccination program by 13-valent conjugate pneumococcal vaccine (PCV13) for both routine vaccination by 3 doses and for selected vaccination of premature (born before 32 week of pregnancy) children by 4 doses. Modeling based on clinical trials and epidemiology data results has been established. The costs of Medical care have been obtained from the 2011 State Insurance tariff in St.Petersburg. Analysis has been done from the position of the Health Care system (only direct medical costs) and from the social perspective (analysis of direct medical and indirect costs) with 10 and 20 years horizon and for the full length of life. In routine vaccination scenario and in case of investing to the Health Care system for 10 years cost effectiveness of PCV13 in general population of children including herd effect is 44,2K rubles/1 additional life year gained for direct medical costs only. In direct and indirect costs estimating vaccination is dominating – so, not only decreasing the incidence and morbidity but cost-saving for 2,1K rubles per patient. Study horizon extension (prolongation of the period when the State is ready to wait for the return of investment) is leading to the vaccination cost-effectiveness increase: without herd effect the cost/effectiveness is 505,1K rubles per 1 additional life year gained in 10 years horizon and 100,6K rubles in analysis for the full length of life. Selected vaccination of premature children is also cost effective as these children are at real high risk for Pneumococcal Infection – efficiency in 10 years horizon for direct medical costs is 131,2K rubles per 1 additional life year gained and for indirect and direct costs is 48,3K rubles per 1 additional life year gained. But it is important to mention that routine vaccination of all children during the first year of life is more efficient due to herd effect starting from the third year of the routine immunization start. According to the WHO recommendations efficiency of medical interventions can be assessed by comparison with the NDP – in Russia in 2012 this has been 316K rubles per citizen. Therefore, PCV13 can be recommended for inclusion and addition to the Russian National Immunization Calendar due to the high clinical effectiveness with appropriate cost-effectiveness even its’ implementation needs significant increase of budget investment to vaccination. Routine vaccination is economically more preferable and efficient in comparison to selected groups’ vaccination and will provide the return of investment and budget cost savings in 10 years period from the start.