Per- and polyfluorinated alkyl substances (PFAS) in Pennsylvania surface waters: A statewide assessment, associated sources, and land-use relations.

The objectives of this study are to identify per- and polyfluoroalkyl substances (PFAS) in Pennsylvania surface waters, corresponding associations with potential sources of PFAS contamination (PSOC) and other parameters, and compare raw surface water concentrations to human and ecological benchmarks. Surface water samples from 161 streams were collected in September 2019 and were analyzed for 33 target PFAS and water chemistry. Land use and physical attributes in upstream catchments and geospatial counts of PSOC in local catchments are summarized. The hydrologic yield of the sum of 33 PFAS (∑PFAS) for each stream was computed by normalizing each site's load by the drainage area of the upstream catchment. Utilizing conditional inference tree analysis, the percentage of development (>7.58 %) was identified as a primary driver of the ∑PFAS hydrologic yields. When percentage of development was removed from analysis, ∑PFAS yields were closely related to surface water chemistry associated with landscape alteration (e.g., development or agricultural cropland), such as concentrations of total nitrogen, chloride, and ammonia, but also to count of water pollution control facilities (agricultural, industrial, stormwater, and/or municipal waste pollution abatement facilities). In oil and gas development regions, ∑PFAS yields were associated with combined sewage outfalls. Sites surrounded by ≥2 electronic manufacturing facilities had elevated ∑PFAS yields (median = 241 ng/s/km2). Study results are critical to guide future research, regulatory policy, best practices that will mitigate PFAS contamination, and the communication of human health and ecological risks associated with PFAS exposure from surface waters.

An analysis of stone management over the decade before the COVID-19 pandemic in Germany, France and England.

OBJECTIVES: To understand the implications that the rising upper urinary tract (UUT) stone prevalence in Europe and the increasing burden places on patients and healthcare providers (HCPs), we investigated the evolution of diagnoses and procedures in Germany, France and England over the decade before the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We identified International Classification of Diseases (ICD)-10 codes related to UUT stones diagnosis and extracted procedure volumes for extracorporeal shockwave lithotripsy (ESWL), ureteroscopy (URS), percutaneous nephrolithotomy and open surgery using national procedure codes from the German Institute for the Hospital Remuneration System, the French Technical Agency of Hospitalisation Information and NHS England Hospital Episode Statistics. We analysed procedures vs hospital diagnoses from 2010 to 2019 and reported results per 100 000 inhabitants. RESULTS: Between 2010 and 2019, ICD-10 N20 codes for calculus of kidney and ureter increased by 8%, 26% and 15% in Germany, France, and England respectively; whereas procedures increased by 3%, 38% and 18%. Of the patients diagnosed with stones, the percentage that received treatment (of any type) differed between countries. In 2019, in Germany 83% of patients diagnosed with stones received treatment, in France 88%, and in England 56%. These figures were relatively stable over the 10-year study period. Over the past decade, the dominant procedure shifted from ESWL to URS, and the average length of stay for URS decreased. Day case procedures increased in France and England (by 68% and 23%), no data were available in Germany. CONCLUSION: This analysis highlights an increase in stone diagnoses and procedures, and a shift of surgical management. This development may be due to clinical advantages and advanced technology. The continued stone prevalence rise affects patients, hospitals, and HCPs.

Multiresidue extraction of current-use pesticides from complex solid matrices using energized dispersive guided extraction with analysis by gas and liquid chromatography tandem mass spectroscopy.

The development of sample processing techniques that recover a broad suite of pesticides from solid matrices, while mitigating coextracted matrix interferences, and reducing processing time is beneficial for high throughput analyses. The objective of this study was to evaluate the effectiveness of an automated extraction system for pesticide analyses in solid environmental samples. An Energized Dispersive Guided Extraction (EDGE) system was used to evaluate two different extraction solvents in optimizing the extraction of 210 pesticides and pesticide transformation products. A graphitized carbon cleanup step was implemented, and three elution solvents were evaluated separately for analyte recoveries. Recoveries between 70 and 130% were achieved for 167 compounds in a test soil using acetonitrile as an extraction solvent and carbon cleanup with acetonitrile and dichloromethane elutions. Nine field samples (soil, sediment, and biosolids) were extracted using the newly developed method and were compared with a previously validated pressurized liquid extraction (PLE) method using an Accelerated Solvent Extraction (ASE) system. Concentrations obtained from the two methods were comparable (linear R2 > 0.999), suggesting similar performance between the EDGE and PLE extractions in complex matrices. The new method provided slightly better sensitivities in comparison to the PLE method, ranging from 0.09 to 2.56 ng g-1. The method presented here significantly reduces extraction setup and runtimes while also minimizing the volume of carcinogenic solvents (e.g., dichloromethane) used in the laboratory and presents a sensitive multiresidue method for a wide range of pesticides in solid matrices.

Budget impact analysis of transurethral water vapor therapy for treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia in the Spanish national healthcare system.

BACKGROUND: Several surgical treatments are available for managing lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH). Water vapor thermal therapy (WVTT) is a new minimally invasive therapy. This study estimates the budget impact of introducing WVTT for LUTS/BPH into the Spanish health care system. METHODS: A model simulated the evolution of men over 45 years of age with moderate-severe LUTS/BPH after surgical treatment, over a 4-year time horizon, from the Spanish public health care service´s perspective. The technologies in scope included those most used in Spain: WVTT, transurethral resection (TURP), photoselective laser vapourization (PVP) and holmium laser enucleation (HoLEP). Transition probabilities, adverse events and costs were identified from the scientific literature and validated by a panel of experts. Sensitivity analyses were performed by varying the most uncertain parameters. RESULTS: Per intervention, WVTT resulted in savings of €3,317, €1,933 and €2,661 compared to TURP, PVP and HoLEP. Over a 4-year time horizon, when performed in 10% of the cohort of 109,603 Spanish males with LUTS/BPH, WVTT saved €28,770,125 against the scenario without WVTT availability. CONCLUSIONS: WVTT could reduce the cost of managing LUTS/BPH, increase the quality of health care and reduce the length of procedure and hospital stay.

Transurethral water vapor therapy for treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: a cost-minimization and budget impact analysis from an Italian healthcare perspective.

BACKGROUND: The aim of this study was to compare the costs and budget impact of adopting water vapor thermal therapy with the Rezum™ System, for treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) to transurethral resection of the prostate (TURP), from an Italian hospital healthcare perspective. METHODS: A Markov model (4-year time horizon, 3-month cycle length), developed to support a submission to the National Institute of Health and Care Excellence (NICE) in England, was adapted to an Italian payer perspective. A cost minimization analysis was conducted, assuming equal efficacy between both therapies. Net difference in costs per patient was reported, considering procedure, adverse events and retreatment costs. Probabilistic and deterministic sensitivity analyses considered the uncertainty of the results. Population data and market share distribution assumptions were applied to a cohort of Italian patients treated in one year to report the budget and capacity impact of increased use of Rezum. RESULTS: Over 4 years, the costs per patient with Rezum were €2072 compared to €2836 with TURP, resulting in net savings of €764. Sensitivity analyses showed that this conclusion was robust. Replacing 10% of TURP procedures with Rezum generates cost-savings of € 7,139,549 over 4 years and saves 4671 theatre hours and 26,856 bed days in one year. Replacing 30% of BPH surgical procedures with Rezum generates cost-savings to € 21,418,647 over 4 years, saves 14,012 theatre hours and 80,567 bed-days in one year. CONCLUSIONS: This analysis demonstrates that Rezum is highly likely to be cost-saving compared to TURP from an Italian hospital healthcare perspective.

Comparing imidacloprid, clothianidin, and azoxystrobin runoff from lettuce fields using a soil drench or treated seeds in the Salinas Valley, California.

Neonicotinoid insecticide use has increased over the last decade, including as agricultural seed treatments (application of chemical in a coating to the seed prior to planting). In California, multiple crops, including lettuce, can be grown using neonicotinoid treated seeds or receive a direct neonicotinoid soil application (drenching) at planting. Using research plots, this study compared pesticide runoff in four treatments: (1) imidacloprid seed treatment; (2) clothianidin seed treatment; (3) imidacloprid drench and an azoxystrobin seed treatment; and (4) a control with no pesticidal treatment. Neonicotinoid and azoxystrobin concentrations were measured in surface water runoff during six irrigations events in the 2020 growing seasons. Results showed runoff concentrations up to 1308 (±1200) ng L-1 for imidacloprid drench treatment, 431 (±100) ng L-1 for clothianidin seed treatment, 135 (±60) ng L-1 for imidacloprid seed treatment, and 13 (±10) ng L-1 for azoxystrobin seed treatment (treatments averaged). The percent of applied mass in runoff over the entire sampling period varied by compound; the imidacloprid seed treatment and drench were similar (0.015 and 0.019%, respectively) to the clothianidin seed treatment (0.036%) while the azoxystrobin seed treatment was much higher (15%). Although the proportion of imidacloprid in runoff was similar for imidacloprid treatments, the mass applied during soil drench was > 4x the amount applied from the imidacloprid seed treatment. Surface soils were collected before planting and at the end of the trial. The neonicotinoids were detected in soil throughout the study and average maximum concentrations were 9-13 ng g-1; azoxystrobin was detected in only two soils at concentrations up to 0.57 ng g-1. These results elucidate the comparative mass runoff resulting from planting treated seed and soil drench applications and highlight the value of additional work to characterize off-site transport from the many commodities that may be utilizing treated seeds.

Delphi study to identify consensus on patient selection for hydrogel rectal spacer use during radiation therapy for prostate cancer in the UK.

OBJECTIVES: To identify consensus on patient prioritisation for rectal hydrogel spacer use during radiation therapy for the treatment of prostate cancer in the UK. DESIGN: Delphi study consisting of two rounds of online questionnaires, two virtual advisory board meetings and a final online questionnaire. SETTING: Radical radiation therapy for localised and locally advanced prostate cancer in the UK. PARTICIPANTS: Six leading clinical oncologists and one urologist from across the UK. INTERVENTIONS: Rectal hydrogel spacer. PRIMARY AND SECONDARY OUTCOME MEASURES: None reported. RESULTS: The panel reached consensus on the importance of minimising toxicity for treatments with curative intent and that even low-grade toxicity-related adverse events can significantly impact quality of life. There was agreement that despite meeting rectal dose constraints, too many patients experience rectal toxicity and that rectal hydrogel spacers in eligible patients significantly reduces toxicity-related adverse events. However, as a consequence of funding limitations, patients need to be prioritised for spacer use. A higher benefit of spacers can be expected in patients on anticoagulation and in patients with diabetes or inflammatory bowel disease, but consensus could not be reached regarding patient groups expected to benefit less. While radiation therapy regimen is not a main factor determining prioritisation, higher benefit is expected in ultrahypofractionated regimens. CONCLUSION: There is a strong and general agreement that all patients with prostate cancer undergoing radical radiation therapy have the potential to benefit from hydrogel spacers. Currently, not all patients who could potentially benefit can access hydrogel spacers, and access is unequal. Implementation of the consensus recommendations would likely help prioritise and equalise access to rectal spacers for patients in the UK.

The Efficacy and Safety of Laser and Electrosurgical Transurethral Procedures for the Treatment of BPO in High-Risk Patients: A Systematic Review.

Objective: To compare efficacy and safety outcomes of GreenLight, Holmium and Thulium laser  techniques with standard monopolar and bipolar transurethral resection of the prostate (TURP) in high-risk patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO). Methods: We conducted a systematic literature review of studies in patients undergoing BPO surgeries who may be considered high-risk for standard TURP, with higher risk defined as follows: large prostates (≥80 mL) and/or taking antithrombotic agents and/or urinary retention and/or age >80 years and/or significant comorbidity.  Outcomes summarised included bleeding complications, re-intervention rates, hospital length of stay, and standard measures of disease and symptom severity for all available timepoints. Results: A total of 276 studies of 32,722 patients reported relevant data. Studies were heterogeneous in methodology, population and outcomes reported. IPSS reduction, Qmax improvement and PVR were similar across all interventions. Mean values at baseline and after 12 months across interventions were 13.2-29 falling to 2.3-10.8 for IPSS, 0-19 mL/s increasing to 7.5-34.1 mL/s for Qmax and 41.4-954 mL falling to 5.1-138.3 mL for PVR. Laser treatments show some advantages compared with monopolar and bipolar TURP for some adverse events and safety parameters such as bleeding complications. Duration of hospital stay, reinterventions and recatheterisations were lower with GreenLight, HoLEP, Thulium lasers, and bipolar enucleation than TURP. Conclusions: Laser therapies are effective and well-tolerated treatment options in high-risk patients with BPO compared with monopolar or bipolar TURP. The advantageous safety profile of laser treatments means that patients with a higher bleeding risk should be offered laser surgery preferentially to mTURP or bTURP.

Evaluation of ELISA for the analysis of imidacloprid in biological matrices: Cross-reactivities, matrix interferences, and comparison to LC-MS/MS.

Imidacloprid is among the most used pesticides worldwide and there are toxicity concerns for nontarget organisms. Accurate and sensitive methods are necessary to quantitate imidacloprid concentrations in biological matrices to better understand their fate and effects. Here we evaluated an enzyme-linked immunosorbent assay (ELISA) kit for the analysis of imidacloprid in biological samples. Following the dosing of Japanese quail (Coturnix japonica) with imidacloprid-treated wheat seeds, plasma, liver, and fecal matter samples were analyzed by ELISA and compared to previous analyses that employed liquid chromatography-tandem mass spectrometry (LC-MS/MS). Imidacloprid metabolites-5-OH-imidacloprid, imidacloprid-olefin, imidacloprid-urea, desnitro-imidacloprid, and 6-chloronicotinic acid-were tested for their cross-reactivity to antibodies within the commercial imidacloprid ELISA kit. The two major metabolites, 5-OH-imidacloprid and imidacloprid-olefin, showed cross-reactivities of 0.93-26 %. ELISA and LC-MS/MS results were positively correlated but there was poor agreement in concentrations: plasma and fecal matter imidacloprid concentrations were higher by ELISA, whereas liver imidacloprid concentrations were higher by LC-MS/MS. Matrix interferences observed in analyses were minimized by the application of matrix-matched calibration curves. ELISA provided an effective screening tool for imidacloprid in these biological matrices, but the presence of cross-reactants confounded results. Confirmation of ELISA results by more selective techniques (e.g., LC-MS/MS) is suggested for complex samples.

SpaceOAR hydrogel spacer injection prior to stereotactic body radiation therapy for men with localized prostate cancer: A systematic review.

BACKGROUND: Conventionally fractionated radiotherapy is a common treatment for men with localized prostate cancer. A growing consensus suggests that stereotactic body radiation therapy (SBRT) is similarly effective but less costly and more convenient for patients. The SpaceOAR hydrogel rectal spacer placed between the prostate and rectum reduces radiation-induced rectal injury in patients receiving conventionally fractionated radiotherapy, but spacer efficacy with SBRT is unclear. The purpose of this research was to assess the clinical utility of the hydrogel rectal spacer in men receiving SBRT for prostate cancer. METHODS: We performed systematic searches of Medline, Embase, and the Cochrane Central Register of Controlled Trials for studies in men who received the SpaceOAR hydrogel spacer prior to SBRT (≥5.0 Gy fractions) for treatment of localized prostate center. Rectal irradiation results were compared to controls without spacer implant; all other outcomes were reported descriptively owing to lack of comparative data incuding perirectal separation distance, rectal irradiation on a dosimetric curve, gastrointestinal (GI) toxicity, and freedom from biochemical failure. GI toxicity was reported as the risk of a grade 2 or 3+ bowel complication in early (≤3 months) and late (>3 months) follow-up. RESULTS: In 11 studies with 780 patients, SBRT protocols ranged from 7 to 10 Gy per fraction with total dose ranging from 19 to 45 Gy. Perirectal distance achieved with the rectal spacer ranged from 9.6 to 14.5 mm (median 10.8 mm). Compared to controls receiving no spacer, SpaceOAR placement reduced the radiation delivered to the rectum by 29% to 56% across a dosimetric profile curve. In early follow-up, grade 2 GI complications were reported in 7.0% of patients and no early grade 3+ GI complications were reported. In late follow-up, the corresponding rates were 2.3% for grade 2 and 0.3% for grade 3 GI toxicity. Over 16 months median follow-up, freedom from biochemical failure ranged from 96.4% to 100% (pooled mean 97.4%). CONCLUSIONS: SpaceOAR hydrogel spacer placed between the prostate and rectum prior to SBRT is a promising preventative strategy that increases the distance between the prostate and rectum, reduces rectal radiation exposure, and may lower the risk of clinically important GI complications.

SpaceOAR Hydrogel Spacer for Reducing Radiation Toxicity During Radiotherapy for Prostate Cancer. A Systematic Review.

OBJECTIVE: To evaluate the association between SpaceOAR and radiation dosing, toxicity and quality-of-life vs no spacer across all radiotherapy modalities for prostate cancer. METHODS: A systematic search of the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase was performed from database inception through May 2020. Two reviewers independently screened titles/abstracts and full papers. Data extraction was performed, and quality assessed by 1 reviewer and checked by a second, using a third reviewer as required. The synthesis was narrative. RESULTS: 19 studies (3,622 patients) were included (only 1 randomized controlled trial, in image-guided intensity-modulated radiotherapy (IG-IMRT), 18 comparatives non-randomized controlled trials in external-beam radiotherapy (EBRT), brachytherapy, and combinations thereof). No hypofractionation studies were found. Regardless of radiotherapy type, SpaceOAR significantly reduced rectal radiation dose (eg, V40 average difference -6.1% in high dose-rate brachytherapy plus IG-IMRT to -9.1% in IG-IMRT) and reduced gastrointestinal and genitourinary toxicities (eg, late gastrointestinal toxicity 1% vs 6% (P = .01), late genitourinary toxicity of 15% vs 32% (P < .001) in stereotactic body radiotherapy). Improvements were observed in most Expanded Prostate Cancer Index Composite quality-of-life domains (eg, bowel function score decrease at 3 and 6 months: Average change of zero vs -6.25 and -3.57 respectively in low dose-rate brachytherapy plus EBRT). CONCLUSION: The randomized controlled trial in IG-IMRT demonstrated that SpaceOAR reduces rectal radiation dose and late gastrointestinal and genitourinary toxicities, with urinary, bowel, and sexual quality-of-life improvement. These advantages were verified in observational studies in various radiotherapy types. Further research is required in hypofractionation.

The Quality of Life and Economic Burden of Erectile Dysfunction.

Erectile dysfunction (ED) is a common disorder in adult males that results in withdrawal from sexual intimacy, psychosocial problems (ie, poor self-esteem, depression, anxiety), decreased work productivity, and reduction in quality of life for both the men suffering from ED and their female partners. A pragmatic literature review was undertaken using PUBMED to identify original research studies published over the past 20 years that assessed the impact of ED on a male's quality of life, the impact of ED on a female partner's quality of life, or the economic impact of ED on employers. Twenty studies were selected for inclusion. This review showed that men with ED have a poorer quality of life than men without ED (n=9 studies). Results from a global burden of illness study showed that men with ED report substantially lower SF-36 Mental and Physical Component Summary scores and SF-6D scores compared to men without ED (p<0.001). Similarly, the partner is also negatively impacted by ED due to relationship difficulties and decreased sexual satisfaction (n=8 studies). Results from the Female Experience of Men's Attitudes to Life Events and Sexuality study showed that females were significantly less satisfied and engaged in sexual activity less frequently after their partner developed ED (p<0.001). ED also poses a substantial economic burden on employers (n=3 studies). An observational study in men aged 40-70 showed that men with ED had significantly higher rates of absenteeism (2x) and work productivity impairment compared to men without ED (p<0.001). Overall, this contemporary review demonstrated that ED imposes a substantial quality of life burden on men and their female partners as well as a significant economic burden on their employers. These findings underscore the need for more education and awareness of the burden of ED and greater access to appropriate ED treatments to help alleviate this burden.

Widespread Use of the Nitrification Inhibitor Nitrapyrin: Assessing Benefits and Costs to Agriculture, Ecosystems, and Environmental Health.

Agricultural production and associated applications of nitrogen (N) fertilizers have increased dramatically in the last century, and current projections to 2050 show that demands will continue to increase as the human population grows. Applied in both organic and inorganic fertilizer forms, N is an essential nutrient in crop productivity. Increased fertilizer applications, however, create the potential for more N loss before plant uptake. One strategy for minimizing N loss is the use of enhanced efficiency fertilizers, fortified with a nitrification inhibitor, such as nitrapyrin. In soils and water, nitrapyrin inhibits the activity of ammonia monooxygenase, a microbial enzyme that catalyzes the first step of nitrification from ammonium to nitrite. Potential benefits of using nitrification inhibitors range from reduced nitrate leaching and nitrous oxide emissions to increased crop yield. The extent of these benefits, however, depends on environmental conditions and management practices. Thus, such benefits are not always realized. Additionally, nitrapyrin has been shown to transport off-field, and it is unknown what effects environmental nitrapyrin could have on nontarget organisms and the ecological nitrogen cycle. Here, we review the agronomic and environmental benefits and costs of nitrapyrin use and present a series of research questions and considerations to be addressed with future nitrification inhibitor research.

Association of the Placement of a Perirectal Hydrogel Spacer With the Clinical Outcomes of Men Receiving Radiotherapy for Prostate Cancer: A Systematic Review and Meta-analysis.

Importance: Perirectal spacers are intended to lower the risk of rectal toxic effects associated with prostate radiotherapy. A quantitative synthesis of typical clinical results with specific perirectal spacers is limited. Objective: To evaluate the association between perirectal hydrogel spacer placement and clinical outcomes of men receiving radiotherapy for prostate cancer. Data Sources: A systematic search was performed of the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for articles published through September 2019. Study Selection: Studies comparing men who received a hydrogel spacer vs men who did not receive a spacer (controls) prior to prostate radiotherapy. Data Extraction and Synthesis: Via random-effects meta-analysis, group comparisons were reported using the weighted mean difference for continuous measures and the risk ratio for binary measures. Main Outcomes and Measures: Procedural results, the percentage volume of rectum receiving at least 70 Gy radiation (v70), early (≤3 months) and late (>3 months) rectal toxic effects, and early and late changes in bowel-related quality of life on the Expanded Prostate Cancer Index Composite (minimal clinically important difference, 4 points). Results: The review included 7 studies (1 randomized clinical trial and 6 cohort studies) involving 1011 men (486 who received a hydrogel spacer and 525 controls), with a median duration of patient follow-up of 26 months (range, 3-63 months). The success rate of hydrogel spacer placement was 97.0% (95% CI, 94.4%-98.8% [5 studies]), and the weighted mean perirectal separation distance was 11.2 mm (95% CI, 10.1-12.3 mm [5 studies]). Procedural complications were mild and transient, occurring in 0% to 10% of patients within the studies. The hydrogel spacer group received 66% less v70 rectal irradiation compared with controls (3.5% vs 10.4%; mean difference, -6.5%; 95% CI, -10.5% to -2.5%; P = .001 [6 studies]). The risk of grade 2 or higher rectal toxic effects was comparable between groups in early follow-up (4.5% in hydrogel spacer group vs 4.1% in control group; risk ratio, 0.82; 95% CI, 0.52-1.28; P = .38 [6 studies]) but was 77% lower in the hydrogel spacer group in late follow-up (1.5% vs 5.7%; risk ratio, 0.23; 95% CI, 0.06-0.99; P = .05 [4 studies]). Changes in bowel-related quality of life were comparable between groups in early follow-up (mean difference, 0.2; 95% CI, -3.1 to 3.4; P = .92 [2 studies]) but were greater in the hydrogel spacer group in late follow-up (mean difference, 5.4; 95% CI, 2.8-8.0; P < .001 [2 studies]). Conclusions and Relevance: For men receiving prostate radiotherapy, injection of a hydrogel spacer was safe, provided prostate-rectum separation sufficient to reduce v70 rectal irradiation, and was associated with fewer rectal toxic effects and higher bowel-related quality of life in late follow-up.

Fate and transport of nitrapyrin in agroecosystems: Occurrence in agricultural soils, subsurface drains, and receiving streams in the Midwestern US.

Nitrapyrin is a nitrification inhibitor that is co-applied with nitrogen fertilizer in agroecosystems. There is limited information on the fate of nitrapyrin after it is applied to agricultural soils. Over the course of one year (March 2016 to June 2017), 192 water samples from seven streams across Iowa and Illinois were analyzed for nitrapyrin, its metabolite 6­chloropicolinic acid (6­CPA), and three widely used herbicides acetochlor, atrazine, and metolachlor. Additional environmental samples were collected and analyzed in spring 2017: 63 water samples from eight subsurface drains in Illinois, and 33 soil samples from a field in Iowa that received direct application of nitrapyrin. Nitrapyrin was detected in all seven streams (56% detection) with concentrations ranging from less than LOD to 1200 ng/L; 6­CPA was detected in six of the seven streams (13% detection) with concentrations ranging from less than LOD to 13 ng/L. Nitrapyrin was detected in 10% of the subsurface drain samples with concentrations ranging from less than LOD to 12 ng/L; 6­CPA was detected in six of the eight subsurface drains and in 33% of drain samples with concentrations ranging from less than LOD to 6 ng/L. Nitrapyrin was detected in 67% of the soil samples collected, and concentrations ranged from less than LOD to 42 ng/g. Generally, all three herbicides were detected more frequently and at higher concentrations than nitrapyrin in the streams, subsurface drains, and soils. The environmental fate of nitrapyrin after application is dominated by sorption to soil and off-field transport via leaching and overland flow.

Uptake of Three Antibiotics and an Antiepileptic Drug by Wheat Crops Spray Irrigated with Wastewater Treatment Plant Effluent.

With rising demands on water supplies necessitating water reuse, wastewater treatment plant (WWTP) effluent is often used to irrigate agricultural lands. Emerging contaminants, like pharmaceuticals and personal care products (PPCPs), are frequently found in effluent due to limited removal during WWTP processes. Concern has arisen about the environmental fate of PPCPs, especially regarding plant uptake. The aim of this study was to analyze uptake of sulfamethoxazole, trimethoprim, ofloxacin, and carbamazepine in wheat ( L.) plants that were spray-irrigated with WWTP effluent. Wheat was collected before and during harvest, and plants were divided into grain and straw. Subsamples were rinsed with methanol to remove compounds adhering to surfaces. All plant tissues underwent liquid-solid extraction, solid-phase extraction cleanup, and liquid chromatography-tandem mass spectrometry analysis. Residues of each compound were present on most plant surfaces. Ofloxacin was found throughout the plant, with higher concentrations in the straw (10.2 ± 7.05 ng g) and lower concentrations in the grain (2.28 ± 0.89 ng g). Trimethoprim was found only on grain or straw surfaces, whereas carbamazepine and sulfamethoxazole were concentrated within the grain (1.88 ± 2.11 and 0.64 ± 0.37 ng g, respectively). These findings demonstrate that PPCPs can be taken up into wheat plants and adhere to plant surfaces when WWTP effluent is spray-irrigated. The presence of PPCPs within and on the surfaces of plants used as food sources raises the question of potential health risks for humans and animals.

Dose comparison of conivaptan (Vaprisol®) in patients with euvolemic or hypervolemic hyponatremia--efficacy, safety, and pharmacokinetics.

PURPOSE: This study aimed to evaluate the efficacy, safety, and pharmacokinetics of 20 and 40 mg/day conivaptan (Vaprisol®) in patients with hypervolemic or euvolemic hyponatremia. METHODS: Hyponatremic patients - serum sodium (sNa) ≤130 mEq/L - received either 20 or 40 mg/day of conivaptan for 4 days, following an initial 20 mg loading dose. Efficacy was evaluated by the magnitude and extent of change in sNa. Safety was evaluated by the incidence of adverse events, changes in vital signs and laboratory parameters, rate of sNa correction, and frequency of infusion-site reactions. Pharmacokinetic parameters were also measured. RESULTS: A total of 37 patients received 20 mg/day and 214 patients received 40 mg/day conivaptan. Baseline-adjusted sNa-area under the concentration-time curve increased by an average of 753.8±499.9 mEq·hr/L (20 mg/day) and 689.2±417.3 mEq·hr/L (40 mg/day) over the course of the 4-day treatment period. The majority of patients in both treatment groups achieved a 4 mEq/L increase in sNa over baseline in ~24 hours (82.5%). Average increase in sNa after 4 days was ~10 mEq/L, varying with dosage level and baseline volume status. Treatment success (normal sNa or increase of ≥6 mEq/L) was attained by 70.3% of patients in the 20 mg/day group and 72.0% in the 40 mg/day group. CONCLUSION: Both 20 and 40 mg/day doses of conivaptan are efficacious in increasing sNa over 4 days of treatment with no observed increase in the frequency of adverse events or specific infusion-site reactions using the higher dose. The pharmacokinetic parameters of both doses were similar to what has been reported previously, exhibiting greater-than-dose-proportional plasma concentrations.

An integrated safety analysis of intravenous ibuprofen (Caldolor(®)) in adults.

Intravenous (IV) nonsteroidal anti-inflammatory drugs such as IV ibuprofen are increasingly used as a component of multimodal pain management in the inpatient and outpatient settings. The safety of IV ibuprofen as assessed in ten sponsored clinical studies is presented in this analysis. Overall, 1,752 adult patients have been included in safety and efficacy trials over 11 years; 1,220 of these patients have received IV ibuprofen and 532 received either placebo or comparator medication. The incidence of adverse events (AEs), serious AEs, and changes in vital signs and clinically significant laboratory parameters have been summarized and compared to patients receiving placebo or active comparator drug. Overall, IV ibuprofen has been well tolerated by hospitalized and outpatient patients when administered both prior to surgery and postoperatively as well as for nonsurgical pain or fever. The overall incidence of AEs is lower in patients receiving IV ibuprofen as compared to those receiving placebo in this integrated analysis. Specific analysis of hematological and renal effects showed no increased risk for patients receiving IV ibuprofen. A subset analysis of elderly patients suggests that no dose adjustment is needed in this higher risk population. This integrated safety analysis demonstrates that IV ibuprofen can be safely administered prior to surgery and continued in the postoperative period as a component of multimodal pain management.

Vadose Zone Transport of Natural and Synthetic Estrogen Hormones at Penn State's "Living Filter" Wastewater Irrigation Site.

The increase in endocrine-disrupting compounds in the environment has generated research focused on the behavior of these compounds in natural soil and water ecosystems. To understand how estrogens behave in the soil environment as a result of 25+ yr of wastewater irrigation, soils from Penn State's "Living Filter" wastewater irrigation site were extracted and analyzed for two natural estrogens (17ß-estradiol and estrone) and one synthetic estrogen (17α-ethynylestradiol). Soil estrogen concentrations were compared for two independent variables: type of land cover and sampling time. Soils were sampled from cropped and forested land areas, and soils were sampled 2 d and 3 wk after a single 12-h effluent irrigation event. A nonirrigated control site was sampled to provide natural background data. For 17ß-estradiol, the nonirrigated mean concentration was 0.68 ± 0.11 ng cm, and the irrigated values, including samples from both land areas and time frames, ranged from 0.99 ± 0.11 to 1.82 ± 0.69 ng cm. For estrone, the nonirrigated mean concentration was 2.36 ± 0.22 ng cm, and the irrigated values, including samples from both land areas collected and time frames, ranged from 2.18 ± 0.20 to 6.24 ± 3.14 ng cm. The 17α-ethynylestradiol nonirrigated mean concentration was 0.47 ± 0.40 ng cm. The irrigated values, including samples from both land areas and time frames, ranged from 0.25 ± 0.06 to 1.37 ± 0.39 ng cm. This study found that time of sampling, land cover, and irrigation can affect estrogen concentrations in soils, resulting in levels that exceed natural background and require improvements in management practices.

Vkappa polymorphisms in NOD mice are spread throughout the entire immunoglobulin kappa locus and are shared by other autoimmune strains.

The diversity of immunoglobulin (Ig) and T cell receptor (TCR) genes available to form the lymphocyte repertoire has the capacity to produce a broad array of both protective and harmful specificities. In type 1 diabetes (T1D), the presence of antibodies to insulin and other islet antigens predicts disease development in both mice and humans, and demonstrate that immune tolerance is lost early in the disease process. Anti-insulin T cells isolated from T1D-prone non-obese diabetic (NOD) mice use polymorphic TCRalpha chains, suggesting that the available T cell repertoire is altered in these autoimmune mice. To probe whether insulin-binding B cells also possess polymorphic V genes, Ig light chains were isolated and sequenced from NOD mice that harbor an Ig heavy chain transgene. Three insulin-binding Vkappa genes were identified, all of which were polymorphic to the closest germline sequence matches present in the GenBank database. Additional analysis of over 300 light chain sequences from multiple sources, including germline DNA, shows that polymorphisms are spread throughout the entire NOD Igkappa locus, as these polymorphic sequences represent 43 distinct Vkappa genes which belong to 14 Vkappa families. Database searches reveal that a majority of polymorphic Vkappa genes identified in NOD are identical to Vkappa genes isolated from SLE-prone NZBxNZW F1 or MRL strains of mice, suggesting that a shared Igkappa haplotype may be present. Predicted amino acid changes preferentially occur in CDR, and thus could alter antigen recognition by the germline B cell repertoire of autoimmune versus non-autoimmune mouse strains.