Incremental Life Research Articles

Characterization of polycyclic aromatic hydrocarbon (PAHs) source profiles in urban PM2.5 fugitive dust: A large-scale study for 20 Chinese cites

Polycyclic aromatic hydrocarbons (PAHs) in road dust (RD) and construction dust (CD) in PM2.5 were quantified in the samples collected in 20 Chinese cities. The PAHs profiles in urban PM2.5 fugitive dusts were determined and their potential health risks were evaluated. Seven geographical regions in China were identified as northwest China (NWC), the North China Plain (NCP), northeast China (NEC), central China (CC), south China (SC), southwest China (SWC), and east China (EC). The overall average concentrations of total quantified PAHs (ΣPAHs) were 23.2 ± 18.9 and 22.8 ± 29.6 μg·g−1 in RD and CD of PM2.5, indicating that severe PAHs pollution to urban fugitive dusts in China. The differences of ΣPAHs between RD and CD were minor in northern and central regions of China but much larger in southern and east regions. The ƩPAHs for RD displayed a pattern of “high in northern and low in southern”, and characterized by large abundance of high molecular weights (HMWs) PAHs, indicating that vehicle emission was the predominant pollution origin. Additionally, higher diagnostic ratios of fluoranthene/(fluoranthene + pyrene) in NCP, CC, and SWC suggest critical contributions of biomass burning and coal combustion for RD in these areas. In comparison, gasoline combustion was the major pollution source for CD PAHs in NWC, NCP, NEC, and CC, whereas industrial emissions such as cement production and iron smelting had strong impacts in the heavy industrial regions. The total benzo[a]pyrene (BaP) carcinogenic potency concentrations (BaPTEQ) for RD and CD both showed the lowest in SC (0.05 and 0.07, respectively) and the highest in NCP (10.99 and 7.67, respectively). The highest and lowest incremental life cancer risks (ILCR) were found in NCP and SC, coinciding with the spatial distributions of ambient PAHs levels. The total CD-related cancer risks for adults and children (~10−4) suggest high potential health risks in NCP, SWC, and NWC, whereas the evaluated values in EC and SC indicate virtual safety (≤10−6).

A comprehensive risk assessment of human inhalation exposure to atmospheric halogenated flame retardants and organophosphate esters in an urban zone

Inhalation exposure to flame retardants used as additives to minimize fire risk and plasticizers is ubiquitous in human daily activities, but has not been adequately assessed. To address this research gap, the present study conducted an assessment of human health risk for four age groups through inhalation exposure to size fractionated particle-bound and gaseous halogenated flame retardants (polybrominated diphenyl ethers (PBDEs) and alternative halogenated flame retardants (AHFRs)) and organophosphate esters (OPEs) at indoor and outdoor environments (school, office, and residence) in three districts of a megacity (Guangzhou, China). Results demonstrated that OPEs were the dominant components among all targets. Indoor daily intakes of PBDEs and OPEs were 13–16 times greater than outdoor levels for all age groups. Gaseous OPEs contributed significantly greater than particle-bound compounds to daily intakes of all target compounds. Based on the different life scenarios, hazard quotient (HQ) and incremental life cancer risk (ILCR) from adults exposure to PBDEs and OPEs in indoor and outdoor settings were the greatest, followed by adolescents, children, and seniors. The estimated HQ and ILCR for all age groups both indoors and outdoors were lower than the safe level (HQ = 1 and ILCR = 10−6), indicating that the potential health risk for local residents in Guangzhou via inhalation exposure to atmospheric halogenated flame retardants and OPEs was low.

PMD9 CONTINUOUS POSITIVE AIRWAY PRESSURE DEVICE COMPARED TO USUAL CARE FOR SEVERE OBSTRUCTIVE SLEEP APNEA: A COST-EFFECTIVENESS ANALYSIS

To estimate the incremental cost-effectiveness ratio (ICER) of incorporating continuous positive airway pressure device (CPAP) for the treatment of patients with severe obstructive sleep apnea (OSA), compared to the usual care in the Brazilian Private Healthcare System (PHS). A Markov model was constructed with the following health states: Event-free OSA, non-fatal stroke, non-fatal myocardial infarction (MI) and death, in addition to the events: traffic accident, MI and stroke. Eligible population consisted of patients with severe OSA (apnea-hypopnea index ≥ 30) in PHS. The analysis considered a lifetime horizon with a discount of 5% for costs and clinical outcomes. Direct medical costs for each health state/event were considered, as well as the cost of device acquisition/maintenance and medical follow-up of patients. Probabilistic sensitivity analyses were performed to explore parametric uncertainties. CPAP treatment is more expensive and more effective than the usual care, presenting 2.85 incremental life years and 3.21 incremental quality-adjusted life-years (QALY) and a cost of BRL 19,255. ICER was BRL 6,733/life years gained and BRL 5,995/QALY. That means the payer would disburse BRL 6,733 to promote one additional year of life and BRL 5,995 to promote an additional quality-adjusted life year for the patient using CPAP. Deterministic results are corroborated by the probabilistic analyses. OSA has a major impact on patients’ health, resulting in high costs for the health system. Although it is indicated for the treatment of patients with severe disease, treatment with CPAP is not available in the Brazilian PHS. This study shows that CPAP is a potential device to promote health benefits at low costs for payers. Although there is no cost-effectiveness threshold in Brazil, it is known that ICERs here presented are considered low for the analyzed outcomes.

Abstract 198: Lifetime Clinical Benefit of Folic Acid Therapy for Primary Prevention of Stroke in Patients with Hypertension - Projection Based on the CSPPT

Background: The CSPPT (China Stroke Primary Prevention Trial) demonstrated a significant risk reduction of first stroke in hypertensive patients treated with EPFA (enalapril plus folic acid) compared to those with enalapril alone, but the life time clinical benefit associated with the use of EPFA is unknown. In this study, we evaluated and quantified the net lifetime clinical benefit of EPFA vs. enalapril alone via assessing stroke-fee life expectancy. Methods: By establishing adjusted models for competing risks and an age-based time scale using data from 19, 053 participants of the CSPPT, we estimated lifetime incremental stroke-free life expectancy for EPFA vs. enalapril alone. Results: Compared with enalapril alone, lifetime EPFA treatment projected a mean stroke-free survival gain of 1.75 months, with an interquartile range months from 0.96 to 4.06 months and the maximum gain up to 12.95 months ( Table 1 ). Subgroup analysis showed greater gain in stroke-free survival in younger male patients, and those with lower baseline folate levels, higher systolic blood pressure, higher total cholesterol and blood glucose, and with methylenetetrahydrofolate reductase (MTHFR) C677T CT or TT genotype; the net benefit of stroke-free life expectancy varies from 3.5 months to 5.3 months among subgroup ( Figure 1 ). Conclusions: Our analyses projected that compared with enalapril alone, enalapril plus folic acid treatment in patients with hypertension is associated with a modest gain in lifetime stroke-free life expectancy. Younger male patients and those with lower baseline folate levels, and higher systolic blood pressure, total cholesterol and blood glucose, and the MTHFR C677T CT or TT genotype are expected to benefit most from the treatment.

Determination of polycyclic aromatic hydrocarbon content in heat-treated meat retailed in Egypt: Health risk assessment, benzo[a]pyrene induced mutagenicity and oxidative stress in human colon (CaCo-2) cells and protection using rosmarinic and ascorbic acids

This study was undertaken to estimate the concentrations of the formed polycyclic aromatic hydrocarbons (PAHs) in heat-treated (boiled, pan-fried and grilled) meats collected from Egypt. Dietary intakes and cancer risks of PAHs among Egyptian adults were calculated. Benzo[a]pyrene (B[a]P)-induced mutagenicity and oxidative stress in human colon (CaCo-2) cell line and mechanisms behind such effects were also investigated. Finally, protection trials using rosmarinic (RMA) and ascorbic acids (ASA) were carried out. The results indicated formation of PAHs at high levels in the heat-treated meats. Calculated incremental life time cancer risk among Egyptian adults were 7.05179E−07, 7.00604 E−06 and 1.86069 E−05 due to ingestion of boiled, pan-fried and grilled meats, respectively. B[a]P-exposed CaCo-2 cells had high abilities for mutagenicity (490.05 ± 21.37 His + revertants) and production of reactive oxygen species. RMA and ASA protected CaCo-2 cells via reduction of B[a]P-induced mutagenicity and oxidative stress and upregulation of phase II detoxification enzymes and xenobiotic transporters.

Cost-effectiveness analysis of lenvatinib treatment for patients with unresectable hepatocellular carcinoma (uHCC) compared with sorafenib in Japan

BackgroundLenvatinib demonstrated a treatment effect on overall survival by the statistical confirmation of non-inferiority to sorafenib for the first-line treatment of uHCC. The objective of this study was to evaluate the cost-effectiveness of lenvatinib compared with sorafenib for patients with uHCC in Japan.MethodsA partitioned-survival model was developed to estimate the cost-effectiveness of lenvatinib versus sorafenib when treating uHCC patients over a lifetime horizon and considering total public healthcare expenditure. Efficacy and safety data were extracted from the REFLECT trial. Utility values were derived from the European Quality-of-Life 5-Dimension Questionnaire, conducted with patients enrolled in the REFLECT trial. Direct medical costs, such as primary drug therapy, outpatient visits, diagnostic tests, hospitalization, post-progression therapy, and adverse-event treatments, were included. Cost parameters unavailable in the clinical trial or publications were obtained based on the consolidated clinical standards from a Delphi panel of four Japanese medical experts.ResultsFor lenvatinib versus sorafenib, the incremental cost was − 406,307 Japanese Yen (JPY), and the incremental life years and quality-adjusted life years (QALYs) were 0.27 and 0.23, respectively. Thus, lenvatinib dominated sorafenib, due to the mean incremental cost-effectiveness ratio falling in the fourth quadrant, conferring more benefit at lower costs compared with sorafenib. The probabilistic sensitivity analysis showed that 81.3% of the simulations were favorable to lenvatinib compared with sorafenib, with a payer’s willingness-to-pay-per-QALY of 5 million JPY.ConclusionsLenvatinib was cost-effective compared with sorafenib for the first-line treatment of uHCC in Japan.

Quantitative relationship between weld defect characteristic and fatigue crack initiation life for high-cycle fatigue property

In this paper, the effect of interior defects on high cycle fatigue (HCF) life of welded joint made by narrow-gap arc welding was investigated. The HCF tests were conducted with a stress ratio (R) of −1 at room temperature, including two specimens pre-tested with R=0.1. Interior defect fatigue crack origins (IDFCO) like inclusion and pore were studied by fracture surface observation. The crack initiation life (Ni), non-ignorable for short-life specimens, was obtained by excluding the long crack propagation life within the fish-eye area. The traditional threshold value of stress intensity factor at R=0 (ΔKth,0) can be regarded as a suitable parameter for fatigue life partition by considering the incremental life in the near-threshold regime. The fatigue initiation life is mainly affected by the applied stress level and projection area of defect. The defect shape plays an important role in the stress distribution at the defect-matrix interface, which is also indirectly affected by defect size due to elastic anisotropy and inhomogeneous microstructure. The combined effect of defect shape and size may induce multi-cracks formation at the defect-matrix interface. A new numerical model considering the multi-cracks formation effect was proposed to predict the fatigue initiation life, which agrees with the experimental results.

Measurement of health-related quality by multimorbidity groups in primary health care

BackgroundIncreased life expectancy in Western societies does not necessarily mean better quality of life. To improve resources management, management systems have been set up in health systems to stratify patients according to morbidity, such as Clinical Risk Groups (CRG). The main objective of this study was to evaluate the effect of multimorbidity on health-related quality of life (HRQL) in primary care.MethodsAn observational cross-sectional study, based on a representative random sample (n = 306) of adults from a health district (N = 32,667) in east Spain (Valencian Community), was conducted in 2013. Multimorbidity was measured by stratifying the population with the CRG system into nine mean health statuses (MHS). HRQL was assessed by EQ-5D dimensions and the EQ Visual Analogue Scale (EQ VAS). The effect of the CRG system, age and gender on the utility value and VAS was analysed by multiple linear regression. A predictive analysis was run by binary logistic regression with all the sample groups classified according to the CRG system into the five HRQL dimensions by taking the “healthy” group as a reference. Multivariate logistic regression studied the joint influence of the nine CRG system MHS, age and gender on the five EQ-5D dimensions.ResultsOf the 306 subjects, 165 were female (mean age of 53). The most affected dimension was pain/discomfort (53%), followed by anxiety/depression (42%). The EQ-5D utility value and EQ VAS progressively lowered for the MHS with higher morbidity, except for MHS 6, more affected in the five dimensions, save self-care, which exceeded MHS 7 patients who were older, and MHS 8 and 9 patients, whose condition was more serious. The CRG system alone was the variable that best explained health problems in HRQL with 17%, which rose to 21% when associated with female gender. Age explained only 4%.ConclusionsThis work demonstrates that the multimorbidity groups obtained by the CRG classification system can be used as an overall indicator of HRQL. These utility values can be employed for health policy decisions based on cost-effectiveness to estimate incremental quality-adjusted life years (QALY) with routinely e-health data.Patients under 65 years with multimorbidity perceived worse HRQL than older patients or disease severity. Knowledge of multimorbidity with a stronger impact can help primary healthcare doctors to pay attention to these population groups.

Bioaccumulation of Polycyclic Aromatic Hydrocarbon (PAH) in a bivalve (Arca senilis- blood cockles) and health risk assessment.

Concentration of PAH in bivalves (Arca senilis) and human health risks due to consumption was examined in samples collected from southern Nigeria and analysed using gas chromatography. Mean PAH concentration (ngkg−1) ranged from 12.0 ± 5.0–5500.0 ± 1000 with a significant difference (p < 0.001) while total PAH ranged from 3000.0-16,000.0. Concentrations (ngkg−1) of PAH4 varied from 250 to 15268.0 while concentrations of PAH8 ranged from 542.0 to 15620.7 with significant difference (p < 0.001). Diagnostic ratios for PAH source distinction suggested mixture of petrogenic and pyrogenic sources. Dietary daily intake-DDI (ng/kg/day) of individual PAHs ranged from 1.04 to 9.86 while DDI for PAH4 and PAH8 were 340.8 and 379.8 respectively. Carcinogenic potencies (ngkg−1) varied from 0.012 to 900.0 for individual PAH while carcinogenic toxic equivalent (TEQs) values were 1916.2, 572.49 and 1914.4 for total PAH, PAH4 and PAH8 respectively. The Excess cancer risk (ECR) for individual PAHs, PAH4 and PAH8 were all <10-6. DDI and ECR values obtained were below USEPA threshold concentration/limits indicating minimal health risk concerns while PAH4 and PAH8 concentrations were also below the EU regulatory limits (30 μg kg−1) for PAH4. The margin of exposures were above the 10,000 critical limit proposed by EFSA while incremental life cancer risk (ILCR) value (10-5 - 10-9) also suggests low potential health risk for consumers of the sea food. The screening value (SV) was 0.095 but lower than observed TEQs values indicating potential health concerns. The study concluded that consumers of bivalves (Arca senilis) in southern Nigeria generally have minimal health risk concern via consumption but regular monitoring is required to detect changes.

PMD89 - COST-EFFECTIVENESS OF OXIGEN THERAPY WITH C-PAP FOR THE TREATMENT OF OBSTRUCTIVE SLEEP APNOEA SYNDROME (OSA) VERSUS THE STANDARD OF CARE IN THE MEXICAN PUBLIC HEALTH CARE SYSTEM

The Obstructive sleep apnoea (OSA) is characterised by repeated episodes of apnoea and hypopnea during sleep, loud snoring and excessive daytime sleepiness; its main cause is the collapse of the upper airway during sleep. OSA is associated with an increased risk of cardiovascular events and reduction of life expectancy. The most common treatment for OSA is the continuous positive airway pressure (C-PAP); the positive pressure prevents upper airway collapse, applied through a face mask during sleep. To predict clinical endpoints and costs over a 5-year time horizon, a decision analytic model (Markov) was developed. The model has two main health states disease progression: death and alive; and all the patients alive in each cycle face the probability of non-fatal cardiovascular events. A non-treatment strategy was identified as the comparator in the Mexican Public Health System. Progression to death and the probability of non-fatal cardiovascular events were identified from a literature review. Costs were taken from public available sources considering direct medical costs only. Results were presented as incremental cost per life years gained in national currency. With an incremental savings per patient of 39,593 MXN and an incremental effectiveness of 0.496 life-years gained, C-PAP showed to be a dominant treatment versus the no intervention strategy in the 5-year temporal horizon scenario being able to generate savings and incremental life years gained in comparison with the non-treatment strategy. C-PAP represents a cost-effective strategy for the treatment of obstructive sleep apnea syndrome when compared with the current available treatment options in the Mexican public healthcare system. The results signals an opportunity for the public healthcare institutions in Mexico to offer a better perspective for OSA patients while reducing its expenditure in managing these patients.

MO4 - COMPARING MIXTURE CURE MODELS WITH STANDARD PARAMETRIC MODELS WITHIN THREE- AND FIVE-STATE PARTITION SURVIVAL FRAMEWORKS

Mixture cure models (MCMs) can differentiate between survival of cured and uncured patients. Published cost-effectiveness analyses apply the aggregated survival from MCMs, so do not differentiate between cured and uncured survival. This study compares a standard partition survival framework (PSF) with three health states based on Weibull models for progression-free survival (PFS) and overall survival (OS) to PSFs with three- and five health states in which Weibull MCMs are implemented for PFS and OS. The five-state MCM PSF included the following health states; PFS cured, progressed disease (PD) cured, PFS uncured, PD uncured, death. In the five-state model, cured patients were assumed to have general population utility values and no treatment and disease monitoring costs from the point of cure. PSFs were compared based on lifetime incremental costs and effects. The incremental life years, QALYs and costs for the three-state PSF based on standard Weibull models were 1.59, 1.33 and 4,488, respectively. For the three-state PSF with MCMs the corresponding numbers were 1.65, 1.39 and 4,629 and for the five-state PSF with MCMs 1.65, 1.42 and 1,816, respectively. The MCMs predicted cure rates for active and placebo arms of 36.7% and 25.7% for PFS and 43.6% and 34.0% for OS, respectively. The difference between the three-state PSFs with and without MCMs is explained by the longer predicted survival tails. The difference between the three-state and five-state PSFs is explained by the differentiation in utilities and costs of cured versus uncured patients. If cure is clinically plausible and there is a difference in utilities and costs of cured versus uncured patients, the five-state PSF based on MCMs more accurately describes the decision problem than a standard three-state PSF. For the five-state PSF, it is important to validate the difference between the PFS and OS cure rates are patients cured after progression.

PCN170 - COST-EFFECTIVENESS OF TISAGENLECLEUCEL IN PEDIATRIC AND YOUNG ADULT PATIENTS WITH RELAPSED OR REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: A CANADIAN SOCIETAL PERSPECTIVE

Tisagenlecleucel, a CD19-directed genetically modified autologous T-cell immunocellular therapy is pending regulatory approval for the treatment of pediatric and young adult patients with relapsed or refractory (r/r) B-cell acute lymphoblastic leukemia (pALL). The current study assessed the cost-utility of tisagenlecleucel in comparison with salvage chemotherapy for the treatment of r/r B-cell pALL from a Canadian societal perspective. The model included three health states: event free survival (EFS), progressive disease, and death. Using the partitioned survival model approach, the proportions of patients in each health state were determined by the area under the curves based on the fitted overall survival (OS) and EFS trial curves. The model used literature of ALL long-term survivors to inform the mortality risk after year 5 and conservatively assumed no difference in mortality risk across treatments. A 70-year time horizon was used to capture all the relevant costs and benefits associated with the treatments. Both costs and benefits were discounted at 1.5% per year. The model comparator was salvage chemotherapy. Costs, health state utility and treatment-related disutility inputs were obtained from Canada-specific databases and literature Tisagenlecleucel was associated with incremental life year (LY) gains of 13.46 years, incremental quality-adjusted life years (QALYs) gains of 11.74 years and an incremental cost of $135,758 when compared to salvage chemotherapy. The incremental cost-effectiveness ratio (ICER) for tisagenlecleucel vs. salvage chemotherapy was $11,567 per QALY gained. Deterministic and probabilistic sensitivity analyses supported the base-case findings and contributed to the robustness of the economic case. Tisagenlecleucel represents a clinically significant advancement in the management of r/r B-cell pALL and fulfils the unmet needs for this difficult-to-treat patient population. Compared with the current standard of care, tisagenlecleucel greatly prolonged survival, EFS, improved quality of life and is a cost-effective option for the treatment of r/r B-cell pALL.

Seasonal occurrence and cancer risk assessment of polycyclic aromatic hydrocarbons in street dust from the Novi Sad city, Serbia

This is the first investigation that identified seasonal occurrence, distribution and sources of 16 polycyclic aromatic hydrocarbons (PAHs) in 60 street dust samples collected within urban zone of Novi Sad, the second largest city in Serbia. The obtained results were further used for comprehensive assessment of carcinogenic risk of Serbian inhabitants exposed to PAHs present in street dust by the incremental lifetime cancer risk method. The total level of 16 PAHs ranged between 35 μg kg−1 and 2422 μg kg−1 in samples taken in summer and between 35 μg kg−1 and 587 μg kg−1 in samples taken in winter. In both seasons, 4-ring PAHs were the most dominant compounds and high molecular weight (HMW) PAHs had similar contribution (55% in summer and 65% in winter). The highest content was determined for fluoranthene (Fly) in both seasons (597 μg kg−1 in winter, 301 μg kg−1 in summer). The PAHs source apportionment was analyzed by principal component analysis (PCA) and diagnostic ratios, and combustion of petroleum seemed to be the main sources of the PAHs in street dust. The cancer risk level for children and adult were comparable for dermal contact and by ingestion, and ranged from 10−6 to 10−4 indicating a potential risk. Additionally, the total incremental life time cancer risk (ILCR) was assessed for children and adult population taking into account three possible exposure routs and the median total cancer risk was ˃10−5, with 7% of the samples having the risk ˃10−4 that should be considered of high concern with potential health problem. These results are the first of this kind for the whole Serbia and the Western Balkan region and can be considered as the base line for future research.

PSY57 - Belimumab for the Treatment of Adults Living with Active Systemic Lupus Erythematosus: A Cost-Effectiveness Analysis in Canada

To assess the cost effectiveness of belimumab IV or belimumab SC added to standard of care (SoC) for the treatment of adults with active systemic lupus erythematosus (SLE) who test positive for anti-double stranded DNA (Anti-dsDNA) and low complement (C3 or C4). A cost-effectiveness analysis (CEA) was conducted using a semi-Markov cohort model, described previously (Kelton et al. Value in Health, 2017). The analysis was run, from a private payer perspective and follows guidance from CADTH Guidelines for the Economic Evaluation of Health Technologies (4th Edition). The model estimates costs and clinical benefits for each treatment valued by life-years (LYs) and quality-adjusted life-years (QALYs). Health states are defined by treatment status (belimumab or SoC), total SDI score, and SDI cardiovascular (CV) damage (present or absent). The disease characteristics of the patients in each health state are based on the selected population and are updated each cycle. Total costs, life-years, and QALYS were accumulated annually over a lifetime time horizon. The Incremental Cost-Effectiveness Ratio (ICER) and Incremental Cost Utility Ratio (ICUR) were calculated. The lifetime incremental discounted costs, life years gained and QALYS gained for belimumab IV vs SoC were $70,792, 0.80, and 0.6957, respectively. The belimumab SC vs SoC analysis yielded an incremental cost of $70,770 and the same incremental life years and incremental QALYS gained as IV. The ICER for belimumab IV vs SoC was $88,493 while the ICUR was $101,757. The ICER for belimumab SC vs SOC was $88,465 and the ICUR was $101,726. Belimumab IV and SC increased survival and quality of life for a mean lifetime cost of about $70,800. Belimumab demonstrates an ICER that is comparable to other biologics available in the immunoinflammation therapeutic area.

Cost-effectiveness analysis of blue light cystoscopy with hexylaminolevulinate in transurethral resection of the bladder

Photodynamic diagnosis using the optical imaging agent hexaminolevulinate (HAL, Hexvix®, Ipsen Pharma GmbH, Ettlingen, Germany) as an adjunct to white light cystoscopy (WLC) during the initial transurethral resection of bladder tumours (TURB) improves the detection rate of bladder cancer and leads to fewer recurrences. Acost-effectiveness analysis was carried out in order to calculate the consequences for the German healthcare system. We combined ashort-term decision tree and aMarkov model to evaluate outcomes over along period of time. The alternatives investigated were HAL-assisted blue light cystoscopy (BLC) as adjunct to WLC (HAL + BLC/WLC) compared with WLC alone in patients undergoing TURB. HAL + BLC/WLC compared to WLC alone was associated with 0.07 incremental quality-adjusted life years (QALYs) and cost savings of 537 € per patient. HAL + BLC/WLC compared with WLC alone resulted in both cost savings and improved patient outcome rendering it the "dominant" strategy.

Assessment of airborne polycyclic aromatic hydrocarbons in a megacity of South China: Spatiotemporal variability, indoor-outdoor interplay and potential human health risk

Although a number of studies have assessed the occurrence of atmospheric polycyclic aromatic hydrocarbons (PAHs) in indoor environment, few studies have systemically examined the indoor-outdoor interplay of size-dependent particulate PAHs and potential health risk based on daily lifestyles. In the present study, size-dependent particle and gaseous samples were collected both indoors and outdoors within selected schools, offices and residences located in three districts of Guangzhou, China with different urbanization levels during the dry and wet weather seasons. Results from measurements of PAHs showed that higher total PAH concentrations occurred in residential areas than in other settings and in indoor than in outdoor environments. Compositional profiles and size distribution patterns of particle-bound PAHs were similar indoors and outdoors, predominated by 4-and 5-ring PAHs and the 0.56–1.0 μm particle fraction. Statistical analyses indicated that outdoor sources may have contributed to 38–99% and 62–100% of the variations for indoor particle-bound and gaseous PAH concentrations, respectively. Incremental life cancer risk (ILCR) from human exposure to indoor and outdoor PAHs based on different lifestyles followed the order of adults > children > adolescents > seniors. All average ILCR values for four age groups were below the lower limit of the Safe Acceptable Range (10−6). In addition, the ILCR value for adults (average: 7.2 × 10−7; 95% CI: 5.4 × 10−8‒2.5 × 10−6), estimated from outdoor air PAH levels with 24-h exposure time, was significantly higher than our assessment results (average: 5.9 × 10−7; 95% CI: 6.3 × 10−8‒1.9 × 10−6), suggesting the significance of assessing human inhalation exposure risks of indoor and outdoor PAHs in urban air based on daily lifestyles.

Effects of Flooding on the Sources, Spatiotemporal Characteristics and Human Health Risks of Polycyclic Aromatic Hydrocarbons in Floodplain Soils of the Lower Parts of the River Niger, Nigeria

ABSTRACTThe concentrations of the 16 US EPA polycyclic aromatic hydrocarbons (PAHs) were determined in the floodplain soils of the lower parts of the River Niger, Nigeria in 2013 and 2014 after recent flood waters had receded completely into the river channels. The aim of the research was to provide data on the spatiotemporal changes in the contamination levels, compositional patterns, sources and human health risks linked with exposure to PAHs in these soils through non-dietary ingestion, inhalation and dermal contact pathways. The PAHs in the soil samples were extracted by ultrasonication with hexane/dichloromethane, followed by clean-up on a silica gel/alumina column, and gas chromatography-mass spectrometry was used for their separation, detection and quantification. The concentrations of the 16 PAHs varied from 812 to 10,700 µg kg−1 in 2013 after an extreme flooding event, and from 12.2 to 2630 µg kg−1 in 2014 after a natural flooding event. The benzo[a]pyrene (BaP) potency factors and incremental life cancer risks (ILCR) were used to evaluate the risks of human exposure to PAHs in these soils. The average total ILCR values obtained for 2014 (a year after the extreme flooding) indicated that there was a probability of 443 children and 308 adults in a population of one million equally exposed individuals at risk of developing cancer or cancer-related illnesses in their lifetime as opposed to 6450 children and 4480 adults in 2013 immediately after the extreme flooding event. This study has shown that flooding events can cause significant variations in pollutant concentrations of floodplain soils that markedly alter human health risks.

Cost-effectiveness of enzyme replacement therapy with alglucosidase alfa in adult patients with Pompe disease

BackgroundPompe disease is a rare, progressive, metabolic disease, and the first treatable inheritable muscle disorder. Enzyme replacement therapy (ERT) with alglucosidase alfa is disease specific and the only medicinal product authorized for the treatment of Pompe disease. Costs of ERT are very high as for most orphan drugs. This study investigates the cost-effectiveness of ERT compared to supportive treatment in adult patients with Pompe disease.MethodsSurvival probabilities were estimated from an international observational dataset (n = 283) using a time-dependent Cox model. Quality of life was estimated on a Dutch observational dataset using a previously developed conceptual model which links clinical factors to quality of life. Costs included costs of ERT, costs of drug administration and other healthcare costs. Cost-effectiveness was estimated using a patient-level simulation model (n = 90), synthesising the information from underlying models for survival, quality of life and costs. The cost-effectiveness model estimated the (difference in) lifetime effects and costs for both treatments. Two scenarios were modelled: (1) a worse case scenario with no extrapolation of the survival gain due to ERT beyond the observed period (i.e. from 10 years onwards); and (2) a best case scenario with lifetime extrapolation of the survival gain due to ERT. Effects were expressed in (quality adjusted) life years (QALYs). Costs were discounted at 4.0% and effects at 1.5%.ResultsSubstantial increases in survival were estimated – discounted incremental life years of ERT ranged from 1.9 years to 5.4 years in the scenarios without and with extrapolation of survival gains beyond the observed period. Quality of life was also significantly better for patients receiving ERT. Incremental costs were considerable and primarily consisted of the costs of ERT. Incremental costs per QALY were €3.2 million for scenario 1 and €1.8 million for scenario 2.ConclusionsThe availability of extended, prospectively collected, longitudinal observational data on the most important input parameters required to construct a cost-effectiveness model is quite exceptional for orphan diseases. The cost-effectiveness model showed substantial survival gains from ERT. Despite these substantial gains, ERT was not cost-effective in the treatment of adult Pompe disease because of the high cost of treatment.

Assessment of Pollution, Sources, and Risks of Polycyclic Aromatic Hydrocarbons in Soil from Urban Parks in Xi'an City, China

A total of seventeen surface soil samples were collected from urban parks in Xi'an city. The concentration of sixteen priority polycyclic aromatic hydrocarbons (PAHs) were analyzed by high performance liquid chromatography (HPLC). In addition, the composition, source, pollution level and a risk assessment of PAHs in surface soil of park were evaluated. The results showed that the total concentrations of sixteen PAHs ranged from 0.362 to 1.336 μg·g-1, with a mean value of 0.591 μg·g-1. The concentration of seven carcinogenic PAHs (Σ7CPAHs) ranged from 0.051 to 0.528 μg·g-1, with a mean value of 0.181 μg·g-1. Compared to the ΣPAHs levels of other cities of China, the ΣPAHs in park surface soils in Xi'an are relatively low. PAHs in the soil samples were dominated by low molecular weight PAHs with 2 and 3 rings. The results of source analysis showed that the PAHs in park surface soil mainly originated from the combustion of fossil fuels, however, the source of PAHs in some samples is complex and from mixed sources, such as oil spills, oil burning, and incomplete combustion of coal and biomass. The ecological risks of PAHs in the surface soil were evaluated according to the soil quality guidelines to be ERL (effects range low) and ERM (effects range median), and these results showed that all samples, in general, were polluted. However, the potential ecological risks of PAHs were at a low level. The incremental life cancer risk (ILCR) assessment indicated that health risks for children and adults were both in a permissible range, however, the risks for children exposed to the soil were considerably higher than for adults. Dermal contact was the main exposure pathway that resulted in the relatively higher risk, followed by ingestion.

Cost-effectiveness of sacubitril/valsartan versus enalapril in patients with heart failure and reduced ejection fraction

Background: Sacubitril/valsartan reduces cardiovascular death and hospitalizations for heart failure (HF). However, decision-makers need to determine whether its benefits are worth the additional costs, given the low-cost generic status of traditional standard of care.Aims: To evaluate the cost-effectiveness of sacubitril/valsartan compared to enalapril in patients with HF and reduced ejection fraction, from the Singapore healthcare payer perspective.Methods: A Markov model was developed to project clinical and economic outcomes of sacubitril/valsartan vs enalapril for 66-year-old patients with HF over 10 years. Key health states included New York Heart Association classes I–IV and deaths; patients in each state incurred a monthly risk of hospitalization for HF and cardiovascular death. Sacubitril/valsartan benefits were modeled by applying the hazard ratios (HRs) in PARADIGM-HF trial to baseline probabilities. Primary model outcomes were total and incremental costs and quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) for sacubitril/valsartan relative to enalaprilResults: Compared to enalapril, sacubitril/valsartan was associated with an ICER of SGD 74,592 (USD 55,198) per QALY gained. A major driver of cost-effectiveness was the cardiovascular mortality benefit of sacubitril/valsartan. The uncertainty of this treatment benefit in the Asian sub-group was tested in sensitivity analyses using a HR of 1 as an upper limit, where the ICERs ranged from SGD 41,019 (USD 30,354) to SGD 1,447,103 (USD 1,070,856) per QALY gained. Probabilistic sensitivity analyses showed the probability of sacubitril/valsartan being cost-effective was below 1%, 12%, and 71% at SGD 20,000, SGD 50,000, and SGD 100,000 per QALY gained, respectively.Conclusions: At the current daily price sacubitril/valsartan may not represent good value for limited healthcare dollars compared to enalapril in reducing cardiovascular morbidity and mortality in HF in the Singapore healthcare setting. This study highlights the cost-benefit trade-off that healthcare professionals and patients face when considering therapy.