Risk-based Target Research Articles

Risk-Based Targeting of Animals for Ancillary Testing during a Bovine Tuberculosis Breakdown Is Associated with a Reduced Time to Test Failure: Indirect Evidence of Mycobacterium bovis Exposure?

Bovine tuberculosis (bTB) continues to have significant economic and veterinary health impacts on cattle herds where the disease remains endemic. The continual tailoring of policies to address such maintenance requires an in-depth analysis of national data, underpinning new control strategies. In Ireland, when outbreaks occur, ancillary testing of herd mates deemed to be at the highest risk of exposure to reactors is undertaken using the interferon gamma (GIF) test. This highest risk cohort was hypothesised to be of a higher future risk despite this ancillary testing. We used a dataset from Ireland to model bovine test failure to the comparative tuberculin skin test using a survival analysis (observations: 39,248). Our primary exposure of interest was whether an animal that tested negative had a GIF test after the disclosure of infection within a herd during a bTB breakdown. There was evidence that animals with a negative GIF test during a breakdown had an increased risk of failing a test relative to other animals from the same herds without this exposure. The time to failure was 48.8% (95%CI: 38.3-57.5%) shorter for the exposed group relative to the unexposed group during a two-year follow-up period (2019-2022; time ratio: 0.51; 95%CI: 0.43-0.62; p < 0.001). The results from this study suggest that animals who were GIF-tested, having been deemed to have a higher risk of exposure, subsequently had shorter time-to-test failure periods. The absolute numbers of failure are small (only 2.5% of animals go on to fail during 2-year follow-up). Importantly, however, a high proportion of these high-risk herds included in the dataset failed at least one test at the follow-up (21/54 herds), impacting breakdown duration or recurrence. Such risk-informed targeting of animals could be utilised in future control policies, though further research is warranted.

Implementation of risk-based lipid-lowering therapies in older (age ≥ 65 years) and very-old adults (age ≥ 75 years) with ischemic heart disease in the greater Salzburg region.

Introduction: European guidelines recommend the implementation of lipid-lowering therapies (LLTs) in adults (≥ 65years) with established atherosclerotic cardiovascular disease (ASCVD) and for risk-based primary prevention in older adults (≤ 75years), yet their use in very-old adults (> 75years) is controversial, discretionary, and oriented on the presence of risk factors. The aim of this retrospective study is to assess guideline-directed LLT implementation and low-density lipoprotein cholesterol (LDL-C) target achievement in high-/very-high-risk older/very-old adults (65-74 and ≥ 75years) at presentation for ST-segment elevation myocardial infarction (STEMI) and also to assess evidence-based care delivery to older adults in our region. Methods: All STEMI patients with available LDL-C and total cholesterol presenting for treatment at a large tertiary center in Salzburg, Austria, 2018-2020, were screened (n = 910). High-risk/very-high-risk patients (n = 369) were classified according to European guidelines criteria and divided into cohorts by age: < 65years (n = 152), 65-74years (n = 104), and ≥ 75years (n = 113). Results: Despite being at high-/very-high-risk, prior LLT use was < 40% in the total cohort, with no significant difference by age. Statin monotherapy predominated; 20%-23% of older/very-old adults in the entire cohort were using low-/moderate-intensity stains, 11%-13% were using high-intensity statins, 4% were on ezetimibe therapy, and none were taking proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. In the secondary prevention cohort, 53% of older/very-old patients used prior LLTs. Significantly higher percentages of older/oldest ASCVD patients (43% and 49%) met LDL-C targets < 70mg/dL compared to patients < 65years (29%; p = 0.033), although just 22% and 30% of these older groups attained stricter LDL-C targets of < 55mg/dL. Low LLT uptake (16%) among older adults aged 64-74years for primary prevention resulted in 17% and 10% attainment of risk-based LDL-C targets < 70mg/dL and < 55mg/dL, respectively. Oldest adults (≥ 75years) in both primary and secondary prevention groups more often met risk-based targets than older and younger adults, despite predominantly receiving low-/moderate-intensity statin monotherapy. Conclusion: Secondary prevention was sub-optimal in our region. Less than half of older/very-old adults with established ASCVD met LDL-C targets at the time of STEMI, suggesting severe care-delivery deficits in LLT implementation. Shortcomings in initiation of risk-based LLTs were also observed among high-/very-high-risk primary prevention patients < 75years, with the achievement of risk-based LDL-C targets in 10%-48% of these patients.

Evaluating risk-based allocation strategies for PCSK9 inhibitors: results from a simulation study in a contemporary ASCVD cohort

Abstract Background/Aim Targeting PCSK9 inhibitors (PCSK9i) to patients with high LDL-cholesterol (LDL-C) as well as a high cardiovascular event rate yields the highest therapeutic effect and is thus reasonable from a health economic perspective. The current European dyslipidaemia guideline determines PCSK9i eligibility solely by LDL-C, whereas guidelines from the US/the UK additionally use a set of clinical risk factors. Such selection criteria require evaluation. Methods We determined the cardiovascular event rate and calculated the cost/preventable cardiovascular event for PCSK9i initiation in the target populations according to three scenarios: (i) European Society of Cardiology (ESC) 2019 dyslipidaemia guideline (PCSK9i recommended for all patients with residual LDL-C &amp;gt;55 mg/dl), (ii) American Heart Association/American College of Cardiology (AHA/ACC) 2018 cholesterol guideline (use of PCSK9i restricted to patients with residual LDL-C &amp;gt;70 mg/dl and clinical risk factors) and (iii) UK National Institute for Health and Care (NICE) recommendation (use of PCSK9i restricted to patients with residual LDL-C &amp;gt;155 mg/dl or &amp;gt;135 mg/dl with clinical risk factors). A Monte Carlo simulation taking into account statin intolerance was used to simulate uptitration of lipid lowering medications according to the different scenarios. Analyses were based on patients with atherosclerotic cardiovascular disease (ASCVD) from a contemporary all-comers cohort recruited at a large tertiary care center in Germany. Major adverse cardiovascular events (MACE, defined as the composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) were recorded over a median follow-up of 4.2 years. Results We included 1922 patients with ASCVD (mean age 69.3 years, median baseline LDL-C 86.0 mg/dl, 75.0% male). Eligibility for PCSK9i was simulated to be 39.6% (ESC 2019), 6.2% (AHA/ACC 2018) and 1.4% (NICE). The 3 year cardiovascular event rates in the corresponding PCSK9i target populations were 11.4%, 13.8% and 13.8% respectively. Event rate differences were driven by a higher rate of non-fatal myocardial infarction in the risk-based target populations (5.2%, 8.2%, 7.2%). Annual cost/preventable event differed by up to a factor 3 (689,000 €, 515,000 € and 215,000 €), driven mainly by pre-PCSK9i LDL-C levels in the different target populations (68.8 mg/dl, 76.0 mg/dl and 182.7 mg/dl). (Table 1) Conclusion The AHA/ACC and NICE guidelines, based on both residual LDL-C and clinical risk factors, reduced the eligibility for PCSK9i as well as the cost/preventable cardiovascular event compared to the ESC guideline. However, the clinical criteria used for risk classification yielded limited discrimination for the identification of subpopulations at highest cardiovascular risk. Development of accurate risk prediction tools and their integration into risk-based allocation strategies, both requisites for a cost-effective use of PCSK9i, remain a challenge.Table 1

Post-COVID ventilation design: Infection risk-based target ventilation rates and point source ventilation effectiveness

Post-COVID ventilation design: Infection risk-based target ventilation rates and point source ventilation effectiveness

Remedial effectiveness of a pond biomanipulation: Habitat value and concentrations of polychlorinated biphenyls in fish

The fish and plant communities in a pond contaminated with polychlorinated biphenyls (PCBs) in East Tennessee, USA, were manipulated to reduce ecological and human-health risk associated with exposure to the chemical contaminants. We evaluated the success of the remedial action using a habitat valuation approach, as well as measuring PCB concentrations in fish. Risk reduction objectives included: alter the fish community to favor fish that do not resuspend, bioaccumulate, or biomagnify PCBs; stabilize contaminated sediments to improve water quality; and stabilize shoreline soils and enhance riparian habitat. Fish targeted for removal included gizzard shad, largemouth bass, and nonnative carp. Reduced PCB concentrations in fish have characterized the new bluegill-dominated community, although a weir-overtopping event led to the need for additional removals of gizzard shad and largemouth bass. Sunfish abundance is high, as was intended. Moreover, amphibian and waterbird diversities have increased in the years following biomanipulation, possibly owing to improvements in the riparian zone and increased structural (vegetation) complexity in both the aquatic and terrestrial environment. Thus, the remedial action has improved aspects of habitat value, and PCB concentrations in sunfish have dropped below the remediation level (risk-based target value) for this pond (1 µg/g in fish fillets or 2.3 µg/g in whole body fish).

Non-selective distribution of infectious disease prevention may outperform risk-based targeting

Epidemic control often requires optimal distribution of available vaccines and prophylactic tools, to protect from infection those susceptible. Well-established theory recommends prioritizing those at the highest risk of exposure. But the risk is hard to estimate, especially for diseases involving stigma and marginalization. We address this conundrum by proving that one should target those at high risk only if the infection-averting efficacy of prevention is above a critical value, which we derive analytically. We apply this to the distribution of pre-exposure prophylaxis (PrEP) of the Human Immunodeficiency Virus (HIV) among men-having-sex-with-men (MSM), a population particularly vulnerable to HIV. PrEP is effective in averting infections, but its global scale-up has been slow, showing the need to revisit distribution strategies, currently risk-based. Using data from MSM communities in 58 countries, we find that non-selective PrEP distribution often outperforms risk-based, showing that a logistically simpler strategy is also more effective. Our theory may help design more feasible and successful prevention.

Deconvoluting Thermodynamics from Biology in the Aquatic Food Web Model.

Bioaccumulation of hydrophobic pollutants in an aquatic food web is governed by exposure concentrations in sediment and water phases and by complex trophic interactions among the various species. We demonstrate that biological interactions and exposure from the chemical environment can be deconvoluted for aquatic food webs to allow clearer assessments of the role of thermodynamic drivers from the sediment and surface water phases. We first demonstrate the feasibility of this deconvolution mathematically for hypothetical food webs with 3 and 4 interacting species and for more realistic real-world food webs with >10 species of aquatic organisms (i.e., the freshwater lake food web in Western Lake Erie [ON, Canada] and the marine food web in New Bedford Harbor [MA, USA]). Our results show both mathematically (for the simple food webs) and computationally (for the more complex food webs) that a deconvoluted food web model parameterized for site-specific conditions can predict the bioaccumulation of polychlorinated biphenyls in aquatic organisms same as existing complex food web models. The merit of this approach is that once the thermodynamic and biological contributions to food web bioaccumulation are computed for an ecosystem, the deconvoluted model provides a relatively simple approach for calculating concentrations of chemicals in organisms for a range of possible surface water and sedimentary concentrations. This approach is especially useful for calculating bioaccumulation of pollutants from freely dissolved concentrations measured using passive sampling devices or predicted by fate and transport models. The deconvoluted approach makes it possible to develop regulatory guidelines for a set of surface water and sediment (or porewater) concentration combinations for a water body that is able to achieve a risk-based target for fish concentration.Environ Toxicol Chem 2021;40:2145-2155. © 2021 SETAC.

Cleanup and Restoration of 1000-ha of Oiled Mangroves, Bodo, Eastern Niger Delta, Nigeria

ABSTRACT A 1000 ha (2471 ac) area around the community of Bodo in Rivers State, Nigeria, was affected by two large pipeline spills in 2008 and numerous smaller discharges between 2009 and present, primarily related to oil theft, transport and indigenous refining. This paper describes the remediation of affected environments which represents the largest cleanup and restoration of a mangrove ecosystem due to oil-related damage ever undertaken and serves as a potential model for other areas of the Niger Delta similarly affected. Cleanup activities include: (1) raking / mixing of surface sediments to break up a thick algal mat and removal of heavily polluted dead mangrove debris while lesser-oiled (most common) debris is broken up and left in place to aid re-establishment of mangrove plants and animal life used as a food source by the Bodo Community; (2) pressure flushing using ambient water from adjacent channels; (3) compressed air with water from a barge-mounted system, (4) use of hard boom and sorbents around the work area to capture off-floating oil, and (5) manual collection of floating oil using sorbents and hand bailers, followed by transfer to a central collection point and disposal at a government approved facility. High-volume low-pressure flushing system proved effective in releasing much of the deeply penetrated oil without damaging the sedimentary structure of the mangrove platform. Innovative methods are continually being sought. After confirmation of cleanup requirements, former mangrove areas (~860 ha, 2125 ac) will be planted with mangrove seedlings to phytoremediate remaining oil. Close-out criteria are based upon visual assessment followed by chemical sampling to meet government approved risk-based site-specific target levels. Potential major impediments to the successful completion of this Project are community unrest, security issues and reoiling from illegal activities and pipeline operations.

A Harmonised Risk-based Approach for the Carcinogens and Mutagens Directive/Ein harmonisiertes Risikokonzept für die Krebsrichtlinie

The risk of occupational cancer is still a matter of concern for occupational safety and health in Europe. The authors propose transparency of residual risks of Binding Occupational Exposure Limit Values (BOELV) for carcinogens and the establishment of a risk-based approach in Directive 2004/37/EC, the Carcinogens and Mutagens Directive, as important steps to further minimise the risk of occupational cancer. BOELV from the EU in their current form do not clearly identify residual risks as such. This may lead to a false sense of safety for employers and employees. Based on the good experience with a risk-based approach in Germany and other European countries, the authors support the introduction of a harmonised risk-based target level for carcinogens in the European Union.

Goal attainment in cardiovascular prevention in diabetes: Results of the Brazilian diabetes study

Background and Aims: Cardiovascular disease (CVD) is the leading cause of death in individuals with type 2 diabetes (T2D). Achievement of strict LDL, blood pressure (BP), and glycated hemoglobin (A1c) targets has been pursued as a compelling strategy to tackle residual CV risk. Nevertheless, this approach remains challenged by the low achievement rates of these goals. This study explored how often T2D individuals reach their risk-based targets.

A Comparison of Immunosuppression Regimens in Hand, Face, and Kidney Transplantation

BackgroundAuthors have speculated that vascularized composite allotransplantation (VCA) recipients may require greater maintenance immunosuppression than solid organ transplant (SOT) recipients due to the higher antigenicity of skin. However, detailed comparisons of VCA and SOT immunosuppression regimens have been limited. MethodsHand and face VCA recipient immunosuppression data were collected through a systematic literature review. Kidney recipient data were obtained through a retrospective chart review of the authors’ institution. Prednisone and mycophenolate mofetil (MMF) doses were compared between VCA and kidney recipients at predefined follow-up intervals (<1, 1-5, and >5 y). Tacrolimus target trough levels (TTTL) were compared at follow-up intervals of 1-5 and >5 y, and stratified into our institution’s kidney transplant risk-based target ranges (4-6 ng/mL, 6-8 ng/mL) or higher (>8 ng/mL). ResultsImmunosuppression data were available for 57 VCA and 98 kidney recipients. There were no significant differences in prednisone doses between groups at all follow-up intervals. VCA recipient mean MMF dose was significantly greater at <1-y (1.71 ± 0.58 versus 1.16 ± 0.55 gm/d; P = 0.01). For VCA recipients, there was a significant difference (P = 0.02) in TTTL distribution over the three predefined therapeutic ranges (4-6 ng/mL, 6-8 ng/mL, and >8 ng/mL) between 1 and 5 y (24.0%, 20.0%, 56.0%, respectively) and >5 y (28.6%, 42.9%, 28.6%). ConclusionsAt longer follow-up, VCA and kidney recipients receive comparable MMF/prednisone doses, and most VCA recipients are treated with TTTL similar to kidney recipients. Further research may improve our understanding of VCA’s complex risk/benefit ratio, and enhance informed consent.

Complex Systems Model of Dynamic Mechanisms of Early Childhood Caries Development

Early childhood caries (ECC) is a largely preventable condition that occurs when children develop caries in their primary teeth before the age of six. National trends of ECC indicate that prevalence is decreasing, but disparities between various sociodemographic groups may be increasing, despite intervention efforts. Dynamic mechanisms in caries development are hypothesized to be responsible for the observed population distributions of disease. Agent-based models (ABMs) have been utilized to explore similar hypotheses in many areas of health research. Therefore, we developed an ABM of ECC development mechanisms and examined population outcomes of hypothetical preventive intervention scenarios. We found that risk-based targeting had minimal impact on population averages or disparities and was largely due to the strength of the dynamic mechanisms among those considered to be at high caries risk. Universally increasing intervention access reduced population caries prevalence, but increased disparities between different groups of caries risk profiles. We show that population distributions of ECC can emerge as a result of dynamic mechanisms that have been shown to drive disease development. Understanding the effectiveness of a proposed intervention in relation to the hypothesized mechanism(s) that contributes to the outcome of interest is critical to future efforts to address population disparities in ECC.

Translating antibiotic prescribing into antibiotic resistance in the environment: A hazard characterisation case study.

The environment receives antibiotics through a combination of direct application (e.g., aquaculture and fruit production), as well as indirect release through pharmaceutical manufacturing, sewage and animal manure. Antibiotic concentrations in many sewage-impacted rivers are thought to be sufficient to select for antibiotic resistance genes. Yet, because antibiotics are nearly always found associated with antibiotic-resistant faecal bacteria in wastewater, it is difficult to distinguish the selective role of effluent antibiotics within a ‘sea’ of gut-derived resistance genes. Here we examine the potential for macrolide and fluoroquinolone prescribing in England to select for resistance in the River Thames catchment, England. We show that 64% and 74% of the length of the modelled catchment is chronically exposed to putative resistance-selecting concentrations (PNEC) of macrolides and fluoroquinolones, respectively. Under current macrolide usage, 115 km of the modelled River Thames catchment (8% of total length) exceeds the PNEC by 5-fold. Similarly, under current fluoroquinolone usage, 223 km of the modelled River Thames catchment (16% of total length) exceeds the PNEC by 5-fold. Our results reveal that if reduced prescribing was the sole mitigating measure, that macrolide and fluoroquinolone prescribing would need to decline by 77% and 85%, respectively, to limit resistance selection in the catchment. Significant reductions in antibiotic prescribing are feasible, but innovation in sewage-treatment will be necessary for achieving substantially-reduced antibiotic loads and inactivation of DNA-pollution from resistant bacteria. Greater confidence is needed in current risk-based targets for antibiotics, particularly in mixtures, to better inform environmental risk assessments and mitigation.

The prediction formula and a risk-based sensor scheduling method in target detection with guiding information

Sensor scheduling is used to improve the sensing performance in the estimation of targets' states. However, few papers are on the sensor scheduling for target detection with guiding information. This letter can remedy this deficiency. A risk-based target detection method with guiding information is provided firstly, based on which, the sensor scheduling approach is aiming at reducing the risk and uncertainty in target detection, namely risk-based sensor scheduling method. What should be stressed is that the Prediction Formula in sensor scheduling is proposed. Lastly, some examples are conducted to stress the effectiveness of this proposed method.

Social network analysis and risk assessment: An example of introducing an exotic animal disease in Italy

Exotic animal diseases are transboundary hazards, characterized by their capability to cover global distances, affecting animal health and welfare with significant economic losses. Their prevention is complex and requires the dynamic management of potential entry points, transmission pathways, and preventative barriers. The well-timed detection of an undefined or unexpected (exotic or re-emerging) threat could minimize the consequences due to onward transmission. As a fit for purpose framework, OIE developed the import risk assessment i.e. a risk assessment model focusing on the entrance of an exotic disease into a geographical area with naïve hosts. In this paper, we propose an improvement of the model by integrating it with Social Network Analysis (SNA) accounting for within-country animal movements. Our integrated model has been used as a combined tool to better estimate the spatial probability of the introduction of at least one affected animal in Italian provinces using Bluetongue (BT) as an example. Starting from international country-specific BT prevalence data, the model estimated the probability of introduction to Italy via two different routes of release i.e. the import of infected animals or the release of infected vectors either associated with imported livestock or through windborne dispersion from Africa. The conventional OIE model estimating the probability of BT entering Italy assuming the same release probability for every Italian province was paralleled by a model integrated with outputs from SNA to account for different release probability among provinces based on animal movements. The conventional model predicted a remarkable homogeneity in the risk among the provinces with some peaks only visible during the warmest months. The model incorporating the network analysis predicted the highest risk to be in the North Eastern region of Italy but also highlighted the likely occurrence in a couple of Southern provinces, an output mirroring past occurrence of BT in Italy. Moreover, the sensitivity analysis highlighted the main role for a couple of model parameters i.e. the probability for a vector to become infected and the vaccine coverage, thus suggesting that an extra effort in vaccine campaigns could be envisaged. The ability to measure animal movements by SNA can allow the identification of geographical risk hot spots and therefore the risk-based targeting of the surveillance system.

Risk-based targeting of adjuvant pregabalin treatment in laparoscopic cholecystectomy: a randomized, controlled trial.

Background and aims Pain is the most common reason for delayed discharge after day-case laparoscopic cholecystectomy. This study investigates a simple five-item questionnaire in evaluating the risk of postoperative pain in day-case cholecystectomy and the efficacy and safety of single-dose preoperative pregabalin on patients with multiple risk factors for pain. There are no previous studies on targeting adjuvant pain treatment based on the individual risk factors like the preoperative state of anxiety, acute or chronic pain, and the expectation of pain in day-case surgery. Methods One hundred and thirty patients scheduled for day-case laparoscopic cholecystectomy were evaluated with a five-item questionnaire assessing the risk for postoperative pain. The patients with multiple risk factors (n=60) were randomized to receive either pregabalin 150 mg or placebo, 1 h before surgery. The primary outcome was abdominal pain intensity on numerical rating scale (NRS) 1 h after surgery. Pain, analgesic consumption and adverse effects during first three postoperative days, and the length of hospital stay were also recorded. Results Pregabalin 150 mg given as an adjuvant analgesic preoperatively did not decrease postoperative abdominal pain or opioid consumption in the first hour after surgery compared to placebo in a preselected group of patients with multiple risk factors for postoperative pain (p=0.31). Preoperative anxiety assessed with a scale of 0-10 had a positive association with postoperative pain (p=0.045). Conclusions and implications This was the first trial on systematically selecting patients with a high-risk factor profile for postoperative pain as a target for a preventive adjuvant analgesic intervention. Although numerous previous studies have identified various risk factors, including those used in the current trial, it seems to be challenging to use these risk factors as predictive tools for targeting adjuvant analgesics in day-case surgery. Preoperative anxiety has a positive association with postoperative pain in day-case laparoscopic cholecystectomy, and this should be taken into account when treating these patients.

Risk-Based Critical Concentrations of Legionella pneumophila for Indoor Residential Water Uses

Legionella spp. is a key contributor to the United States waterborne disease burden. Despite potentially widespread exposure, human disease is relatively uncommon, except under circumstances where pathogen concentrations are high, host immunity is low, or exposure to small-diameter aerosols occurs. Water quality guidance values for Legionella are available for building managers but are generally not based on technical criteria. To address this gap, a quantitative microbial risk assessment (QMRA) was conducted using target risk values in order to calculate corresponding critical concentrations on a per-fixture and aggregate (multiple fixture exposure) basis. Showers were the driving indoor exposure risk compared to sinks and toilets. Critical concentrations depended on the dose response model (infection vs clinical severity infection, CSI), risk target used (infection risk vs disability adjusted life years [DALY] on a per-exposure or annual basis), and fixture type (conventional vs water efficient or "green"). Median critical concentrations based on exposure to a combination of toilet, faucet, and shower aerosols ranged from ∼10-2 to ∼100 CFU per L and ∼101 to ∼103 CFU per L for infection and CSI dose response models, respectively. As infection model results for critical L. pneumophila concentrations were often below a feasible detection limit for culture-based assays, the use of CSI model results for nonhealthcare water systems with a 10-6 DALY pppy target (the more conservative target) would result in an estimate of 12.3 CFU per L (arithmetic mean of samples across multiple fixtures and/or over time). Single sample critical concentrations with a per-exposure-corrected DALY target at each conventional fixture would be 1.06 × 103 CFU per L (faucets), 8.84 × 103 CFU per L (toilets), and 14.4 CFU per L (showers). Using a 10-4 annual infection risk target would give a 1.20 × 103 CFU per L mean for multiple fixtures and single sample critical concentrations of 1.02 × 105, 8.59 × 105, and 1.40 × 103 CFU per L for faucets, toilets, and showers, respectively. Annual infection risk-based target estimates are in line with most current guidance documents of less than 1000 CFU per L, while DALY-based guidance suggests lower critical concentrations might be warranted in some cases. Furthermore, approximately <10 CFU per mL L. pneumophila may be appropriate for healthcare or susceptible population settings. This analysis underscores the importance of the choice of risk target as well as sampling program considerations when choosing the most appropriate critical concentration for use in public health guidance.

An Integrated Approach to Flood Risk Management Management and Spatial Quality Enhancement for a Netherlands’ River Polder Area

In the previous paper, the aspect of including interventions from different flood risk safety layers is explained quite concisely. In this publication, an extended approach for the inclusion of interventions from different flood risk layers are described in more detail. The paper demonstrates how the Netherlands’ policy shift from a probability-based flood risk target to a risk-based flood risk target increased the range of interchangeable measures for flood risk protection. Though applying a risk-based mindset, the Netherlands’ flood risk reduction targets were, until recently, defined as probability-based safety standards. This resulted in a uniform dike-ring approach in which different dike-rings have different safety standards, based on, amongst others, the perceived economic value of the area, which are applied uniformly to the whole dike-ring. Within this probability reduction based system it is possible to define interchangeable flood risk management interventions at different locations, for instance, by proposing interventions of different scales, as demonstrated in the previous publication. The ‘Room for the River’ project is an example of providing alternative probability reduction measures, since both dike elevation and load reduction reduce the probability of a flood. However, applying risk-based flood risk targets conceptually considerably extends the amount of interchangeable flood risk measures. Not only does it, next to probability reduction measures, allow for the inclusion of consequence reduction measures (such as flood proofing buildings, elevating areas, and improving evacuation), but compared to the uniform dike-ring approach, it also allows for differentiations in probability standards per dike segment. This conceptually more fine-meshed perspective of the dike-ring extends the amount of variable locations for flood risk management interventions. In the research-by-design study described in this paper, the examined method for the aspect of ‘changing the layer of the flood risk intervention’ is applied to the Albasserwaard case study area. The paper demonstrates how the Netherlands’ recent shift from a probability standard target towards a risk-based target, by increasing the amount of interchangeable flood risk management interventions for the case study area, strengthens the possibility of deploying the developed method and the use of spatial quality as an ex-ante criterion.

Risk-based target reliability indices for quay walls

Design codes and standards rely on generalised target reliability indices. It is unclear, however, whether these indices are applicable to the specific risk-profile of marine structures. In this study, target reliability indices for quay walls were derived from various risk acceptance criteria, such as economic optimisation, individual risk (IR), societal risk (SR), the life quality index (LQI) and the social and environmental repercussion index (SERI). Important stochastic design variables in quay wall design, such as retaining height, soil strength and material properties, are largely time-independent, whereas other design variables are time-dependent. The extent to which a reliability problem is time variant affects the present value of future failure costs and the associated reliability optimum. A method was therefore developed to determine the influence of time-independent variables on the development of failure probability over time. This method can also be used to evaluate target reliability indices of other civil and geotechnical structures. The target reliability indices obtained for quay walls depend on failure consequences and marginal costs of safety investments. The results were used to elaborate the reliability framework of ISO 2394, and associated reliability levels are proposed for various consequence classes. The insights acquired were used to evaluate the acceptable probability of failure for different types of quay walls.

"Pay for Success" Financing and Home-Based Multicomponent Childhood Asthma Interventions: Modeling Results From the Detroit Medicaid Population.

Pay for Success has emerged as a potential financing mechanism for innovative and cost-effective prevention programs. In the PFS model, interventions that provide value to the public sector are implemented with financing from private investors who receive a payout from the government only if the metrics identified in a performance-based contract are met. In this nascent field, little has been written about the potential for and challenges of PFS initiatives that produce savings and/or value for Medicaid. In order to elucidate the basic economics of a PFS intervention in a Medicaid population, we modeled the potential impact of an evidence-based multicomponent childhood asthma intervention among low-income children enrolled in Medicaid in Detroit. We modeled outcomes and a comparative benefit-cost analysis in 3 risk-based target groups: (1) all children with an asthma diagnosis; (2) children with an asthma-related emergency department visit in the past year; and (3) children with an asthma-related hospitalization in the past year. Modeling scenarios for each group produced estimates of potential state and federal Medicaid savings for different types or levels of investment, the time frames for savings, and some overarching challenges. The PFS economics of a home-based asthma intervention are most viable if it targets children who have already experienced an expensive episode of asthma-related care. In a 7-year demonstration, the overall (undiscounted) modeled potential savings for Group 2 were $1.4 million for the federal Medicaid and $634,000 for the state Medicaid programs, respectively. Targeting children with at least 1 hospitalization in the past year (Group 3) produced estimated potential savings of $2.8 million to federal Medicaid and $1.3 million to state Medicaid. However, current Medicaid rules and regulations pose significant challenges for capturing federal Medicaid savings for PFS payouts. A multicomponent intervention that provides home remediation and medical case management to high-risk children with asthma has significant potential for PFS financing in urban Medicaid populations. However, there are significant administrative and payment challenges, including the limited ability to capture federal Medicaid savings and to use them as a source of investor repayment. Without some policy reform and clear guidance from the federal government, the financing burden of PFS outcome payments will be on the state Medicaid program or some other state-level funding source.