Risk-based public health impact assessment for drinking water contamination emergencies.

Chemical spills in surface waters pose a significant threat to public health and the environment. This study investigates the public health impacts associated with organic chemical spill emergencies and explores timely countermeasures deployable by drinking water facilities. Using a dynamic model of a typical multi-sourced New England drinking water treatment facility and its distribution network, this study assesses the impacts of various countermeasure deployment scenarios, including source switching, enhanced coagulation via poly­aluminum chloride (PACl), addition of powdered activated carbon (PAC), and temporary system shutdown. This study reveals that the deployment of multiple countermeasures yields the most significant reduction in total public health impacts, regardless of the demand and supply availability. With the combination PAC deployed first with other countermeasures proving to be the most effective strategies, followed by the combination of facility shutdowns. By understanding the potential public health impacts and evaluating the effectiveness of countermeasures, authorities can develop proactive plans, secure additional funding, and enhance their capacity to mitigate the consequences of such events. These insights contribute to safeguarding public health and improving the resilience of drinking water systems in the face of the ever-growing threat of chemical spills.

A spatial life cycle cost assessment of stormwater management systems.

Although widely implemented, the research and understanding of the economic impacts and benefits of green infrastructure (GI) systems remain limited. Currently, few studies have investigated the economics of GI systems from a spatial perspective and typically opportunity costs related to land and property tax were ignored. This study aims at bridging these gaps by investigating both the equivalent annual costs (EAC) and cost effectiveness of seven GI systems and compare them against local wastewater treatment facilities in five different US cities. To do this, we utilized capital and maintenance cost data obtained from GI systems that are currently installed at the University of New Hampshire. The costing data were then extrapolated across five different cities considering reported local material, land, tax, and labor rates. A system dynamics model was utilized to calculate the total stormwater reduction as well as the amounts of nitrogen and phosphorous removed by each GI system over its life cycle under a certain city setting. Based upon these outcomes, the cost effectiveness (CE) in terms of stormwater reduction, nitrogen treatment, and phosphorous treatment of the GI systems was calculated. Land and tax costs were found to be a significant component of the EAC for GI systems with larger footprints in cities with higher property values, accounting for up to 78% in some cities. The rankings of the GI systems differ significantly when different types of cost effectiveness are under consideration. The tree filter performs the best when the CE is calculated based on stormwater reductions, while the subsurface gravel wetland performs the best considering nitrogen treatment, and either the subsurface gravel wetland or the sand filter performs the best considering phosphorous treatment. Our study suggests recommendations of GI systems need to be made based on local needs and issues to achieve the most cost-effective solution.

A dynamic life cycle assessment of green infrastructures.

As stormwater and its associated nutrients continue to impair our nation's waterways, green infrastructures (GIs) are increasingly applied in urban and suburban communities as a means to control combined sewer system overflows and stormwater related pollutants. Although GIs have been widely studied for their life cycle impacts and benefits, most of these studies adopt a static approach which prevents that information from being scaled or transferred to different spatial and temporal settings. To overcome this limitation, this research utilizes a dynamic life cycle assessment (LCA) approach to evaluate seven different GIs by integrating a traditional LCA with a system dynamics model which simulates the daily loadings and treatments of nutrients by the GIs across a 30-year life span. A base model was first developed, calibrated, and validated for seven GIs that are currently installed on the campus of the University of New Hampshire. The base model was then expanded to assess different scenarios in terms of geographic locations, land uses, GI design sizes, and climate changes. Our results show these aforementioned factors have significant influences on GIs' life cycle performances, with life cycle nitrogen reductions varying -100.90 to 512.09kgNeq. and life cycle phosphorous reductions varying from -23.77 to 63.43kg P eq. Furthermore, nutrient loading thresholds exist for certain GIs to offset nutrient emissions from their construction and maintenance activities. Accordingly, an optimal GI design size can be estimated for a given spatial and temporal setting. Such thresholds and optimal sizes are important to be identified to inform the decision-making and future planning of GIs.

The Living Donor Collective: A Scientific Registry for Living Donors.

In the setting of an overall decline in living organ donation and new questions about long-term safety, a better understanding of outcomes after living donation has become imperative. Adequate information on outcomes important to donors may take many years to ascertain and may be evident only by comparing large numbers of donors with suitable controls. Previous studies have been unable to fully answer critical questions, primarily due to lack of appropriate controls, inadequate sample size, and/or follow-up duration that is too short to allow detection of important risks attributable to donation. The Organ Procurement and Transplantation Network does not follow donors long term and has no prospective control group with which to compare postdonation outcomes. There is a need to establish a national living donor registry and to prospectively follow donors over their lifetimes. In addition, there is a need to better understand the reasons many potential donors who volunteer to donate do not donate and whether the reasons are justified. Therefore, the US Health Resources and Services Administration asked the Scientific Registry of Transplant Recipients to establish a national registry to address these important questions. Here, we discuss the efforts, challenges, and opportunities inherent in establishing the Living Donor Collective.

The independent living donor advocate: a guidance document from the American Society of Transplantation's Living Donor Community of Practice (AST LDCOP).

The independent living donor advocate (ILDA) serves a mandated and supportive role in the care of the living organ donor, yet qualifications and role requirements are not clearly defined. Guidance comes from Centers for Medicare and Medicaid Services (CMS) Conditions for Transplant Center Participation and interpretive guidelines, Organ Procurement and Transplantation Network (OPTN) Policy and CMS and OPTN site surveys, yet interpretation of regulations varies. Herein, the AST Living Donor Community of Practice (LDCOP) offers seven recommendations to clarify and optimize the ILDA role: (a) the ILDA must have a certain skill set rather than a specific profession, (b) the ILDA must be educated and demonstrate competence in core knowledge components, (c) the ILDA's primary role is to assess components of informed consent, (d) centers must develop a transparent system to define ILDA independence, (e) the ILDA should have a reporting structure outside the transplant center, (f) the ILDA's role should be integrated throughout the donor care continuum, (g) the ILDA role should include a narrow "veto power." We address controversies in ILDA implementation, and offer pathways to maximize benefits and minimize limitations of approaches that may each meet regulatory requirements but confer different practice benefits. We propose a research agenda to explore the impact of the ILDA.

Emotional well-being of living kidney donors: findings from the RELIVE Study.

Following kidney donation, short-term quality of life outcomes compare favorably to US normative data but long-term effects on mood are not known. In the Renal and Lung Living Donors Evaluation Study (RELIVE), records from donations performed 1963-2005 were reviewed for depression and antidepressant use predonation. Postdonation, in a cross-sectional cohort design 2010-2012, donors completed the Patient Health Questionnaire (PHQ-9) depression screening instrument, the Life Orientation Test-Revised, 36-Item Short Form Health Survey and donation experience questions. Of 6909 eligible donors, 3470 were contacted and 2455 participated (71%). The percent with depressive symptoms (8%; PHQ-9>10) was similar to National Health and Nutrition Examination Survey participants (7%, p=0.30). Predonation psychiatric disorders were more common in unrelated than related donors (p=0.05). Postdonation predictors of depressive symptoms included nonwhite race OR=2.00, p=0.020), younger age at donation (OR=1.33 per 10 years, p=0.002), longer recovery time from donation (OR=1.74, p=0.0009), greater financial burden (OR=1.32, p=0.013) and feeling morally obligated to donate (OR=1.23, p=0.003). While cross-sectional prevalence of depression is comparable to population normative data, some factors identifiable around time of donation, including longer recovery, financial stressors, younger age and moral obligation to donate may identify donors more likely to develop future depression, providing an opportunity for intervention.

Health-related quality of life in kidney donors from the last five decades: results from the RELIVE study.

Live donation benefits recipients, but the long-term consequences for donors remain uncertain. Renal and Lung Living Donors Evaluation Study surveyed kidney donors (N = 2455; 61% women; mean age 58, aged 24-94; mean time from donation 17 years, range 5-48 years) using the Short Form-36 Health Survey (SF-36). The 95% confidence intervals for White and African-American donors included or exceeded SF-36 norms. Over 80% of donors reported average or above average health for their age and sex (p < 0.0001). Donors' age-sex adjusted physical component summary (PCS) scores declined by half a point each decade after donation (p = 0.0027); there was no decline in mental component summary (MCS) scores. White donors' PCS scores were three points higher (p = 0.0004) than non-Whites'; this difference remained constant over time. Nine percent of donors had impaired health (PCS or MCS score >1 SD below norm). Obesity, history of psychiatric difficulties and non-White race were risk factors for impaired physical health; history of psychiatric difficulties was a risk factor for impaired mental health. Education, older donation age and a first-degree relation to the recipient were protective factors. One percent reported that donation affected their health very negatively. Enhanced predonation evaluation and counseling may be warranted, along with ongoing monitoring for overweight donors.

Demographic, metabolic, and blood pressure characteristics of living kidney donors spanning five decades.

While cautious criteria for selection of living kidney donors are credited for favorable outcomes, recent practice changes may include acceptance of less than ideal donors. To characterize trends in donor acceptance, the Renal and Lung Living Donors Evaluation (RELIVE) Study evaluated 8,951 kidney donors who donated between 1963 and 2007 at three major U.S. transplant centers. Over the study interval, there was an increase in the percentage of donors >40 years old from 38% to 51%; donors >60 years varied between 1% and 4%. The proportion of donors with obesity increased from 8% to 26% and with glucose intolerance from 9% to 25%. The percentage of hypertensive donors was consistent (5-8%). Accepted donors ≥60 years old were more likely to have obesity, glucose intolerance, and/or hypertension compared to younger donors (p<0.0001). Our results demonstrate important trends in acceptance of older and more obese donors. The fraction of older donors accepted with glucose intolerance or hypertension remains small and for the majority includes mild elevations in glucose or blood pressure that were previously classified as within normal limits.

Living donor age and kidney transplant outcomes.

We assessed the relationship between living donor (LD) age and kidney survival in 1063 adults transplanted between 1980 and 2007. Increasing LD age was associated with lower kidney function (GFR) before and after transplantation and loss of GFR beyond 1 year. Increasing LD age was also associated with low-moderate proteinuria posttransplant (151-1500 mg/day, p < 0.0001). By univariate analysis, reduced graft survival related to lower GFR at 1 year [HR = 0.925 (0.906-0.944), p < 0.0001], proteinuria [HR = 1.481 (1.333-1.646), p < 0.0001] and increasing LD age [HR = 1.271 (1.219-1.326), p = 0.001]. The impact of LD age on graft survival was noted particularly >4 years posttransplant and was modified by recipient age. Thus, compared to a kidney graft that was within 5 years of the recipient age, younger kidneys had a survival advantage [HR = 0.600 (0.380-0.949), p = 0.029] while older kidneys had a survival disadvantage [HR = 2.217 (1.507-3.261), p < 0.0001]. However, this effect was seen only in recipients <50 years old. By multivariate analysis, the relationship between LD age and graft survival was independent of GFR but related to proteinuria. In conclusion, LD age is an important determinant of long-term graft survival, particularly in younger recipients. Older kidneys with reduced survival are identifiable by the development of proteinuria posttransplant.

Glomerular volume and renal histology in obese and non-obese living kidney donors.

The link between obesity and renal disease is unclear, and there is no consensus as to whether obese individuals are at increased risk for kidney disease after living kidney donation if they otherwise meet acceptance criteria. We retrospectively studied time-zero (implantation) biopsies in 49 obese (body mass index (BMI) > or = 30 kg/m2) and 41 non-obese (BMI < 30 kg/m2) renal donors that met acceptance criteria. We found that our obese donor population had higher systolic blood pressure (P < 0.001 vs non-obese) and higher absolute iothalamate clearance (P = 0.001 vs non-obese) before donation. The obese donors had larger glomerular planar surface area compared to non-obese controls (P = 0.017), and this parameter correlated with patient weight and urinary microalbumin excretion. Detailed examination of the biopsies revealed that although most histologic findings were similar between groups, the obese donors had more tubular dilation (P = 0.01), but less tubular vacuolization (P = 0.02) than the non-obese controls. There was also a trend toward more arterial hyalinosis in the obese patients than controls (P = 0.08). From these data, our studies detected subtle differences in donor organs obtained from obese compared to non-obese individuals. Further studies should be carried out to quantify the long-term impact of these findings.

Renal artery stenosis and a functioning hilar paraganglioma: a rare cause of renovascular hypertension--a case report.

Surgically correctable causes of hypertension are uncommon. Simultaneous occurrence of 2 such causes in the same individual is extremely rare. The authors describe a 25-year-old woman with congenital erythrocytosis, renal artery stenosis, and a paraganglioma. The possible mechanisms of renal artery stenosis in the presence of a catecholamine-secreting tumor are discussed.

Posttransplantation hypertension related to calcineurin inhibitors.

Calcineurin inhibitors are a mainstay of transplant immunosuppression and commonly induce hypertension. They are highly lipid soluble and penetrate vascular smooth muscle cell membranes readily. Changes in vascular tone are universally observed during administration of these agents, particularly within the kidney, leading to diminished glomerular filtration and enhanced sodium retention. Disturbances of endothelial function are prevalent in many tissues, including stimulation of endothelin and impaired nitric oxide synthesis. Multiple additional pathways produce increased vasoconstriction, leading to an increase in arterial pressure. Clinical manifestations include disturbances in circadian blood pressure patterns, left ventricular hypertrophy, and acceleration of atherosclerotic and renal injury. Rapid increases in pressure occasionally produce accelerated hypertension and microangiopathic tissue damage. Principles of therapy require recognition of hazards of changing arterial pressures during calcineurin use and preferential use of vasodilating drugs, particularly dihydropyridine calcium channel blocking agents. Attention must be paid to interactions between antihypertensive agents and calcineurin inhibitor blood levels.

Hypertension after liver transplantation: a predictive role for pretreatment hemodynamics and effects of isradipine on the systemic and renal circulations.

Hypertension developing after liver transplantation during immunosuppression with cyclosporine A reflects an unusual hemodynamic transition from peripheral vasodilation to systemic and renal vasoconstriction. Although dihydropyridine calcium channel blockers are often administered for their efficacy in promoting vasodilation, some liver transplant recipients report marked symptomatic intolerance to these agents. In the present study we examined systemic and renal responses to isradipine using systemic (thoracic bioimpedance) and renal hemodynamic measurements in 15 liver transplant recipients studied at the time of initial diagnosis of posttransplant hypertension and after 3 months of treatment. Circadian blood pressure patterns were examined by overnight ambulatory blood pressure monitoring before and during antihypertensive therapy. During isradipine administration, blood pressure decreased from 151 +/- 3/91 +/- 2 to 130 +/-3/81 +/- 2 mm Hg (P < .01) without change in renal blood flow (406 +/- 43 to 425 +/- 52 mL/min/1.73m2, P = NS) or renal vascular resistance index (25,674 +/-3312 to 20,520 +/- 2311 dynes x sec x cm(-5)/m2, P = NS). Pre-treatment differences in systemic vascular tone persisted during treatment and predicted the tendency for symptomatic tachycardia and flushing, predominantly in those with hyperdynamic circulations. Twice daily dosing of isradipine was associated with partial and significant restoration of the nocturnal decrease in blood pressure (systolic blood pressure decreased 5.5%, normal 13%), usually absent early after transplantation. Our results demonstrate the ability of hemodynamic measurements to predict the symptomatic response to antihypertensive therapy in the posttransplant setting.

A hemodynamic approach to resistant hypertension.

Resistant hypertension affects a minority of treated hypertensive patients, yet the resulting target organ damage causes disproportionate morbidity and increased risk of cardiovascular events. The clinical features and efforts to adjust drug treatment in a resistant hypertensive patient are described. As demonstrated, serial hemodynamic measurements using thoracic bioimpedance may provide a rationale for selection of effective combination antihypertensive therapy. (c)2000 by CHF, Inc.

Cyclosporin-induced hypertension: incidence, pathogenesis and management.

Blood pressure increases soon after administration of immunosuppressive regimens using cyclosporin. Characteristic vascular changes lead to systemic and renal vasoconstriction. Changes in blood pressure are commonly associated with disturbed circadian regulation and may promote the rapid development of target organ injury, including intracranial haemorrhage, left ventricular hypertrophy and microangiopathic haemolysis. The mechanisms underlying this disorder are complex and include altered vascular endothelial function. Vasodilators such as prostacyclin and nitric oxide are suppressed, whereas vasoconstrictors, including endothelin, are increased. Changes in the kidney include vasoconstriction, reduced glomerular filtration and sodium retention. Effective therapy depends upon rigorous blood pressure control by administration of vasodilating agents, with attention to potential interactions with cyclosporin.

Late hypertension after liver transplantation: a comparison of cyclosporine and tacrolimus (FK 506).

Hypertension frequently develops early after liver transplantation when cyclosporine-based immunosuppression is used. However, initial experience with tacrolimus has suggested that its use leads to a lower early incidence of hypertension. In this study, the blood pressure status of patients treated with cyclosporine (n = 131) and those treated with tacrolimus (n = 28) was compared 24 months after liver transplantation. At this time interval, the prevalence of hypertension in the cyclosporine and tacrolimus groups were 82% and 64%, respectively (P < .05). For those patients who were hypertensive by 24 months, onset was delayed in the tacrolimus group compared with the cyclosporine group: 40% versus 71% and 73% versus 93% at 1 and 12 months, respectively (P < .05). Within the cyclosporine group, patients with hypertension were heavier than those with normal blood pressure, 84.7 +/- 1.8 versus 73.4 +/- 4.0 kg, respectively (P < .05). Within the tacrolimus group, hypertensive patients had lower glomerular filtration rates and higher renal vascular resistances compared with normotensive patients, 74 +/- 12 versus 47 +/- 6 mL/min and 15,711 +/- 2,445 versus 28,830 +/- 4,310 dyne/s/cm5/m2, respectively (P < .05). There were no within-group differences for age, gender, pretransplant history of hypertension, family history of hypertension, graft function, or daily doses of prednisone, cyclosporine, or tacrolimus. These results indicate that, compared with cyclosporine, the onset of hypertension after liver transplantation is delayed and less prevalent with tacrolimus. Additionally, hypertension is associated with increased body weight in cyclosporine-treated patients and with more severe renal dysfunction in patients receiving tacrolimus. The relationships of these findings to the development of posttransplant hypertension requires further study.

Hypertension in women: current understanding of gender differences.

High blood pressure is a major individual and public-health issue because of its wide prevalence and associated complications. More women than men have hypertension, but until recently, women have been relatively underrepresented in clinical trials. Gender differences in the physiology, genetics, and treatment benefit of hypertension have been noted in several studies that have included women. These findings have raised concerns about the generalizability of the results of previous investigations to women. The currently available information regarding gender differences and similarities and the results of hypertension treatment trials in women are reviewed herein. These studies suggest that, although gender differences exist, women benefit significantly when they receive therapy to normalize blood pressure.

Evolution of cardiovascular risk after liver transplantation: a comparison of cyclosporine A and tacrolimus (FK506).

The development of atherosclerotic cardiovascular complications is a common and serious problem for the long-term survivors of organ transplantation. Cyclosporine A plus steroid-based immuno-suppression regimens in these patients are associated with the development of hypertension, hyperlipidemia, obesity, and diabetes mellitus. Whether the new immunosuppressive agent tacrolimus (FK506) confers any advantage in terms of these cardiovascular risk factors has been less well studied. We compared serial changes in blood pressure, lipids, body weight, and glucose levels during the first 12 months after liver transplantation in patients using either cyclosporine A (n = 39) or tacrolimus (n = 24)-based immunosuppression. By 12 months, the prevalence of hypertension, hypercholesterolemia, and obesity was increased in the cyclosporine A group compared to tacrolimus: 82% versus 33%, 33% versus 0%, and 46% versus 29%, respectively (all p < .05). Triglyceride and total cholesterol levels were 196 +/- 23 versus 125 +/- 13 mg/dL and 225 +/- 9 versus 159 +/- 7 mg/dL for the cyclosporine A versus tacrolimus groups, respectively (p < .05). Cumulative posttransplant steroid dose was not related to the observed lipid changes in either group, although the increase in triglycerides was positively correlated to weight gain and diuretic use in the cyclosporine A group. The incidence of diabetes mellitus was not increased from baseline in either group. These results indicate that tacrolimus, compared to cyclosporine A, is associated with a less adverse cardiovascular risk profile in the first year after liver transplantation. Whether these differences persist and become clinically relevant to a liver transplant recipient population that is increasingly older and has more preexisting cardiovascular disease remains to be determined.

Role of steroid dose in hypertension early after liver transplantation with tacrolimus (FK506) and cyclosporine.

Transplant immunosuppression using either cyclosporine (CsA) or tacrolimus (FK506) leads to renal vasoconstriction and nephrotoxicity. Despite producing similar effects within the kidney and blood vessels, clinical hypertension occurs less frequently with tacrolimus during the first year after transplantation, compared with CsA. To examine the role of steroid dose in early posttransplant hypertension, we measured blood pressure and kidney function in liver transplant recipients treated with tacrolimus and either high-dose (TAC-HI-P, n = 19) or low-dose (TAC-LO-P,n = 20) prednisone, compared with CsA-treated recipients (n = 29) receiving prednisone doses similar to the TAC-HI-P group. At 1 month, hypertension occurred more often with CsA (72%) than with TAC-HI-P (42%, P < 0.05) or TAC-LO-P (30%, P < 0.05). By 4 months after transplantation, hypertension developed in nearly twice as many TAC-HI-P (63%) as TAC-LO-P patients (32%, P < 0.05), with no difference between TAC-HI-P and CsA (86%, NS). Daily prednisone dose at 1 month closely paralleled cumulative steroid dose in the first month in the TAC-HI-P and TAC-LO-P groups. Fourteen of 19 TAC-HI-P patients (74%) required bolus steroids for treatment of rejection within the first month, compared with 3/20 (15%) TAC-LO-P and 10/29 (34%) CsA recipients. Glomerular filtration rate fell from pretransplant levels at 1 month and 4 months to the same degree in CsA, TAC-HI-P, and TAC-LO-P patients. These results demonstrate a central role for steroid dose in the rate of onset of hypertension early after liver transplantation using tacrolimus immunosuppression. Both daily dose and cumulative dosage, including bolus treatment for rejection, may impact on the development of hypertension. Since prevalence rates rise to levels comparable to CsA by 24 months regardless of steroid dose, hypertension after liver transplant may be mediated by different mechanisms at different stages of the posttransplant course.

Nurse management of posttransplant hypertension in liver transplant patients.

Hypertension develops soon after organ transplantation using cyclosporine- or FK506-based immunosuppression. Sustained rises in blood pressure require intervention to reduce the risk of intracranial bleeding and other cardiovascular complications. Antihypertensive treatment is complicated by reduced renal function and potential interference with absorption and/or metabolism of cyclosporine or FK506. To manage early and long-term hypertension related to immunosuppression with cyclosporine or FK506 and prednisone following orthotopic liver transplantation, a comprehensive nurse-managed hypertension clinic was developed. Blood pressure, heart rate, and antihypertensive and immunosuppressive regimens were evaluated according to a standard protocol at 1, 4, 12, 24, and 36 months after orthotopic liver transplantation. Data indicate that posttransplantation hypertension develops within the first months after orthotopic liver transplantation and persists indefinitely. If comprehensively managed by the hypertension nurse-clinician, the percentage of controlled hypertension patients can increase over time.