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Increased contributions from wastewater discharges and algal activity in drinking water supplies can lead to elevated levels of dissolved organic nitrogen (DON), which can increase the likelihood for the formation of emerging nitrogenous disinfection by-products (N-DBPs) of health concern. Dissolved organic matter (DOM) isolated from five waters, using a newly developed DOM isolation method specific to DON fractionation, produced thirty-four isolates of suitable mass. Each isolate was treated with free chlorine or chloramines under formation potential conditions. The DBP yields were determined for three halogenated DBPs (trichloromethane, dichloroacetonitrile, and trichloronitromethane) and one non-halogenated DBP (N-nitrosodimethylamine [NDMA]). Halogenated DBP yields were greater during the application of free chlorine, however chloramination produced significant levels of halogenated N-DBPs for some isolates. NDMA was only observed to form from selected nitrogen-enriched isolates (DOC/DON ratio , 20 mg/mg), especially those isolated from treated wastewater. Other results indicated that nitrogen-enriched DOM resulted in increased yields of the other N-DBPs studied. [ABSTRACT FROM AUTHOR]

Previous research has established that patients with irritable bowel syndrome (IBS) frequently have comorbid psychiatric disorders. This study sought to establish if the timing of the onset of psychiatric disorders indicated that IBS was more likely to be caused by or more likely to cause psychological difficulties. Participants were 188 treatment-seeking IBS patients who were assessed for psychiatric diagnoses using a semistructured clinical interview. Timing of the onset of any lifetime psychiatric disorders was noted in an attempt to determine if psychiatric disorders were more likely to precede or follow the onset of IBS symptoms. Those participants that met criteria for an Axis I disorder sometime during their life were significantly more likely to develop an Axis I disorder before the onset of IBS symptoms. Anxiety disorders were the most likely disorder to develop before IBS. These results support the theory that psychiatric symptoms, especially anxiety, play a role in the development of IBS. [ABSTRACT FROM AUTHOR]

Aims: Stress echocardiography is widely used to assess patients with chest pain. The clinical value of a positive or negative test result to inform on likely longer-term outcomes when applied in real-world practice across a healthcare system has not been previously reported., Methods and Results: Five thousand five hundred and three patients recruited across 32 UK NHS hospitals between 2018 and 2022, participating in the EVAREST/BSE-NSTEP prospective cohort study, with data on medical outcomes up to 2023 available from NHS England were included in the analysis. Stress echocardiography results were related to outcomes, including death, procedures, hospital admissions, and relevant cardiovascular diagnoses, based on Kaplan-Meier analysis and Cox proportional hazard ratios (HRs). Median follow-up was 829 days (interquartile range 224-1434). A positive stress echocardiogram was associated with a greater risk of myocardial infarction [HR 2.71, 95% confidence interval (CI) 1.73-4.24, P < 0.001] and a composite endpoint of cardiac-related mortality and myocardial infarction (HR 2.03, 95% CI 1.41-2.93, P < 0.001). Hazard ratios increased with ischaemic burden. A negative stress echocardiogram identified an event-free 'warranty period' of at least 5 years in patients with no prior history of coronary artery disease and 4 years for those with disease., Conclusion: In real-world practice, the degree of myocardial ischaemia recorded by clinicians at stress echocardiography correctly categorizes risk of future events over the next 5 years. Reporting a stress echocardiogram as negative correctly identifies patients with no greater than a background risk of cardiovascular events over a similar time period., Competing Interests: Conflict of interest: A.K. has received an educational grant from Lantheus Medical Imaging and honoraria from Bracco and Tom-Tec-Phillips. K.W. is a member of the British Cardiovascular Society Guidelines and Practice Committee (unpaid role). R.Se. has received honoraria from Bracco, Lantheus Medical Imaging, and GE Healthcare. P.L. is a shareholder and founder of Ultromics Ltd and has received personal consultancy fees from Ultromics Ltd. P.L. is an inventor on patients in the field of echocardiography. All other authors have no conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Hypertensive pregnancy disorders are associated with adverse cardiac remodeling, which can fail to reverse in the postpartum period in some women. The Physician-Optimized Postpartum Hypertension Treatment trial demonstrated that improved blood pressure control while the cardiovascular system recovers postpartum associates with persistently reduced blood pressure. We now report the effect on cardiac remodeling., Methods: In this prospective, randomized, open-label, blinded end point trial, in a single UK hospital, 220 women were randomly assigned 1:1 to self-monitoring with research physician-optimized antihypertensive titration or usual postnatal care from a primary care physician and midwife. Participants were 18 years of age or older, with preeclampsia or gestational hypertension, requiring antihypertensives on hospital discharge postnatally. Prespecified secondary cardiac imaging outcomes were recorded by echocardiography around delivery, and again at blood pressure primary outcome assessment, around 9 months postpartum, when cardiovascular magnetic resonance was also performed., Results: A total of 187 women (101 intervention; 86 usual care) underwent echocardiography at baseline and follow-up, at a mean 258±14.6 days postpartum, of which 174 (93 intervention; 81 usual care) also had cardiovascular magnetic resonance at follow-up. Relative wall thickness by echocardiography was 0.06 (95% CI, 0.07-0.05; P <0.001) lower in the intervention group between baseline and follow-up, and cardiovascular magnetic resonance at follow-up demonstrated a lower left ventricular mass (-6.37 g/m 2 ; 95% CI, -7.99 to -4.74; P <0.001), end-diastolic volume (-3.87 mL/m 2 ; 95% CI, -6.77 to -0.98; P =0.009), and end-systolic volume (-3.25 mL/m 2 ; 95% CI, 4.87 to -1.63; P <0.001) and higher left and right ventricular ejection fraction by 2.6% (95% CI, 1.3-3.9; P <0.001) and 2.8% (95% CI, 1.4-4.1; P <0.001), respectively. Echocardiography-assessed left ventricular diastolic function demonstrated a mean difference in average E/E' of 0.52 (95% CI, -0.97 to -0.07; P =0.024) and a reduction in left atrial volumes of -4.33 mL/m 2 (95% CI, -5.52 to -3.21; P <0.001) between baseline and follow-up when adjusted for baseline differences in measures., Conclusions: Short-term postnatal optimization of blood pressure control after hypertensive pregnancy, through self-monitoring and physician-guided antihypertensive titration, associates with long-term changes in cardiovascular structure and function, in a pattern associated with more favorable cardiovascular outcomes., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04273854., Competing Interests: Disclosures L.M. and P.L. are supported by the National Institute for Health and Care Research Oxford Biomedical Research Centre. L.M. is a part-time employee of EMIS Group plc. P.L. is a founder and shareholder of a health care imaging company and a named inventor on patents related to cardiovascular imaging. R.M. has received blood pressure monitors for research from Omron and has worked with Omron and Sensyne on telemonitoring interventions for which licensing and consultancy fees have been paid to the University of Oxford. C.R. has received consultancy fees from Sensyne Health for work on telemonitoring products. J.K. is an executive committee member of the British Society of Cardiac Imaging and Cardiac Computed Tomography. The other authors report no conflicts.

Background: Stress echocardiography (SE) is one of the most commonly used diagnostic imaging tests for coronary artery disease (CAD) but requires clinicians to visually assess scans to identify patients who may benefit from invasive investigation and treatment. EchoGo Pro provides an automated interpretation of SE based on artificial intelligence (AI) image analysis. In reader studies, use of EchoGo Pro when making clinical decisions improves diagnostic accuracy and confidence. Prospective evaluation in real world practice is now important to understand the impact of EchoGo Pro on the patient pathway and outcome., Methods: PROTEUS is a randomized, multicenter, 2-armed, noninferiority study aiming to recruit 2,500 participants from National Health Service (NHS) hospitals in the UK referred to SE clinics for investigation of suspected CAD. All participants will undergo a stress echocardiogram protocol as per local hospital policy. Participants will be randomized 1:1 to a control group, representing current practice, or an intervention group, in which clinicians will receive an AI image analysis report (EchoGo Pro, Ultromics Ltd, Oxford, UK) to use during image interpretation, indicating the likelihood of severe CAD. The primary outcome will be appropriateness of clinician decision to refer for coronary angiography. Secondary outcomes will assess other health impacts including appropriate use of other clinical management approaches, impact on variability in decision making, patient and clinician qualitative experience and a health economic analysis., Discussion: This will be the first study to assess the impact of introducing an AI medical diagnostic aid into the standard care pathway of patients with suspected CAD being investigated with SE., Trial Registration: Clinicaltrials.gov registration number NCT05028179, registered on 31 August 2021; ISRCTN: ISRCTN15113915; IRAS ref: 293515; REC ref: 21/NW/0199., Competing Interests: Declaration of Competing Interest GW, RS, WH, TD, ES, MB, OH, LT, JL, RU are all employees of Ultromics Ltd GW, RS, WH, BT, JL hold share options for Ultromics Ltd PL and RU are founders and shareholders of Ultromics Ltd and have patents in the field of AI and imaging. SEP provides consultancy to Circle Cardiovascular Imaging, Inc, Calgary, Alberta, Canada. All other authors declare that they have no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Stress echocardiography is widely used to detect coronary artery disease, but little evidence on downstream hospital costs in real-world practice is available. We examined how stress echocardiography accuracy and downstream hospital costs vary across NHS hospitals and identified key factors that affect costs to help inform future clinical planning and guidelines., Methods: Data on 7636 patients recruited from 31 NHS hospitals within the UK between 2014 and 2020 as part of EVAREST/BSE-NSTEP clinical study, were used. Data included all diagnostic tests, procedures, and hospital admissions for 12 months after a stress echocardiogram and were costed using the NHS national unit costs. A decision tree was built to illustrate the clinical pathway and estimate average downstream hospital costs. Multi-level regression analysis was performed to identify variation in accuracy and costs at both patient, procedural, and hospital level. Linear regression and extrapolation were used to estimate annual hospital cost-savings associated with increasing predictive accuracy at hospital and national level., Results: Stress echocardiography accuracy varied with patient, hospital and operator characteristics. Hypertension, presence of wall motion abnormalities and higher number of hospital cardiology outpatient attendances annually reduced accuracy, adjusted odds ratio of 0.78 (95% CI 0.65 to 0.93), 0.27 (95% CI 0.15 to 0.48), 0.99 (95% CI 0.98 to 0.99) respectively, whereas a prior myocardial infarction, angiotensin receptor blocker medication, and greater operator experience increased accuracy, adjusted odds ratio of 1.77 (95% CI 1.34 to 2.33), 1.64 (95% CI 1.22 to 2.22), and 1.06 (95% CI 1.02 to 1.09) respectively. Average downstream costs were £646 per patient (SD 1796) with significant variation across hospitals. The average downstream costs between the 31 hospitals varied from £384-1730 per patient. False positive and false negative tests were associated with average downstream costs of £1446 (SD £601) and £4192 (SD 3332) respectively, driven by increased non-elective hospital admissions, adjusted odds ratio 2.48 (95% CI 1.08 to 5.66), 21.06 (95% CI 10.41 to 42.59) respectively. We estimated that an increase in accuracy by 1 percentage point could save the NHS in the UK £3.2 million annually., Conclusion: This study provides real-world evidence of downstream costs associated with stress echocardiography practice in the UK and estimates how improvements in accuracy could impact healthcare expenditure in the NHS. A real-world downstream costing approach could be adopted more widely in evaluation of imaging tests and interventions to reflect actual value for money and support realistic planning., (© 2023. The Author(s).)

N‑nitrosodimethylamine (NDMA) was detected in the source water of some Chinese drinking water treatment plants (DWTPs), which decreased in concentration along the treatment train. Volatilization, photolysis, and/or biodegradation were suspected of being capable of attenuating NDMA. In this study, the contribution of these mechanisms to NDMA removal was investigated by a field study in a conventional DWTP with aerated bio-pretreatment, as well as in laboratory-based experiments. The effluent of each unit process (i.e., aerated bio-pretreatment tank, horizontal sedimentation tank, sand filter) of this DWTP was sampled in the winter and summer, and the concentration of NDMA, its formation potential, and other water quality parameters were measured. NDMA removal by volatilization and biodegradation was simulated in batch experiments, and that by photolysis was calculated with parameters reported in the literature. The sampling results indicated that the aerated biofilm reactor of this DWTP removed 48% of the NDMA in August and 22% in December. According to modeling results, it could be well explained by photolysis (NDMA removal of 51% in summer and 25% in winter) and biotreatment (NDMA removal of 0.2-12% in summer and 0.1-6.1% in winter), with little contribution from aeration (NDMA removal of 0.8%). The sampling results indicated that the sedimentation tank removed 19% of NDMA in August and 9.2% in December. According to modeling results, it could be well explained by photolysis (NDMA removal of 16% in August and 9.4% in December), but little by volatilization. Thus, photolysis was shown to be the most important process for NDMA removal in this DWTP. Further investigation is needed to better understand NDMA removal during biotreatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In order to better understand the occurrence of disinfection byproducts (DBPs) in tap water and their real impacts on consumers, this study made a one-year long survey of the temporal variations of a series of DBPs before and after a point-of-use (POU) treatment facility installed in a building serving for ∼300 people. Water samples were collected every week at a fixed location and time for 1 year, and frequent samplings were carried out every 6 h a day for 1 month at selected seasons, which ultimately amounted to 322 samples. The results show that the concentrations of DBPs were higher in the summer than other seasons, with the lowest DBP levels being observed in spring. Within one week, higher levels of haloacetic acids (HAAs) were identified on weekdays than those on weekends. Diurnally, trihalomethanes, HAAs, and haloacetaldehydes were found to be higher at noon but lower in the evening. Consistent with other studies, the variations of most DBPs were somewhat positively related to the changes of temperature and organic matter, but negatively related to the quantity of free chlorine. With the use of a POU facility, which equips with two activated carbon cartridges and a boiler in sequence, most of DBPs were dramatically reduced, leading to 62-100% lower cytotoxicity for the measured DBPs. The study hence provides a real-water evidence about the DBP occurrences in a typical distribution system endpoint and the efficiency of a typical POU on mitigating DBP risks., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: N-nitroso compounds (NOC) formed endogenously after nitrate/nitrite ingestion and disinfection by-products (DBPs) are suspected colorectal carcinogens, but epidemiologic evidence of these associations is limited., Objectives: We investigated the relationship between drinking water exposures and incident colorectal cancers in a cohort of postmenopausal women., Methods: Using historical nitrate-nitrogen (NO 3 -N) measurements and estimates of total trihalomethanes (TTHM), the sum of 5 or 6 haloacetic acids (HAAs), and individual DBPs in public water supplies (PWS), we computed average exposures and years of exposure above one-half the U.S. maximum contaminant level (>1/2-MCL; >5 mg/L NO 3 -N and >40 μg/L TTHM). Nitrate/nitrite intakes from dietary sources were estimated using a food frequency questionnaire. We estimated hazard ratios (HR) and 95% confidence intervals (CI) from Cox regression models. We assessed NO 3 -N interactions with DBPs and with factors influencing endogenous NOC formation., Results: We identified 624 colon and 158 rectal cancers (1986-2010) among 15,910 women reporting PWS use >10 years. Ingestion of NO 3 -N from drinking water was not associated with risk. Colon cancer risks were non-significantly associated with the average TTHM levels >17.7 μg/L (HR Q5vsQ1  = 1.13, CI = 0.89-1.44; p trend  = 0.11) and were elevated for any duration of exposure >1/2-MCL. Rectal cancer risks were associated with the highest TTHM levels (HR Q5vsQ1  = 1.71, CI = 1.00-2.92; p trend  = 0.22) but not with years >1/2-MCL. Bromodichloromethane (HR Q4vsQ1  = 1.89, CI = 1.17-3.00; p trend  = 0.09) and trichloroacetic acid (HR Q4vsQ1  = 1.92, CI = 1.20-3.09; p trend  = 0.18) levels were also associated with risk of rectal cancer. We found no evidence of interaction between TTHM and NO 3 -N on the risk of either cancer. Dietary analyses yielded a positive colon cancer association with red meat, but not with processed meat intake or estimated nitrate/nitrite from specific dietary sources., Conclusions: Our results suggest that exposure to TTHM in drinking water is associated with increased risk of rectal cancer. Positive findings for individual THMs and HAAs for both colon and rectal cancers require replication in other studies. We found no associations for nitrate overall or in subgroups with presumed higher NOC exposure., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Nitrate and nitrite are precursors of N-nitroso compounds (NOC), probable human carcinogens that cause pancreatic tumors in animals. Disinfection by-products (DBP) exposures have also been linked with digestive system cancers, but few studies have evaluated relationships with pancreatic cancer. We investigated the association of pancreatic cancer with these drinking water contaminants and dietary nitrate/nitrite in a cohort of postmenopausal women in Iowa (1986-2011). We used historical monitoring and treatment data to estimate levels of long-term average nitrate and total trihalomethanes (TTHM; the sum of the most prevalent DBP class) and the duration exceeding one-half the maximum contaminant level (>½ MCL; 5 mg/L nitrate-nitrogen, 40 µg/L TTHM) among participants on public water supplies (PWS) >10 years. We estimated dietary nitrate and nitrite intakes using a food frequency questionnaire. We computed hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression and evaluated nitrate interactions with smoking and vitamin C intake. We identified 313 cases among 34,242 women, including 152 with >10 years PWS use (N = 15,710). Multivariable models of average nitrate showed no association with pancreatic cancer (HR p95 vs . Q1  = 1.16, 95% CI: 0.51-2.64). Associations with average TTHM levels were also null (HR Q4 vs . Q1  = 0.70, 95% CI:0.42-1.18). We observed no trend with increasing years of exposure to either contaminant at levels >½ MCL. Positive associations were suggested in the highest dietary nitrite intake from processed meat (HR p95 vs . Q1  = 1.66, 95% CI 1.00-2.75;p trend  = 0.05). We found no interactions of nitrate with known modifiers of endogenous NOC formation. Our results suggest that nitrite intake from processed meat may be a risk factor for pancreatic cancer., (2017 UICC.)

Background: N-nitroso compounds formed endogenously after nitrate/nitrite ingestion are animal renal carcinogens. Previous epidemiologic studies of drinking water nitrate did not evaluate other potentially toxic water contaminants, including the suspected renal carcinogen chloroform., Methods: In a cohort of postmenopausal women in Iowa (1986-2010), we used historical measurements to estimate long-term average concentrations of nitrate-nitrogen (NO3-N) and disinfection by-products (DBP) in public water supplies. For NO3-N and the regulated DBP (total trihalomethanes [THM] and the sum of five haloacetic acids [HAA5]), we estimated the number of years of exposure above one-half the current maximum contaminant level (>½-MCL NO3-N; >5 mg/L). Dietary intakes were assessed via food frequency questionnaire. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox models, and evaluated interactions with factors influencing N-nitroso compound formation., Results: We identified 125 incident kidney cancers among 15,577 women reporting using water from public supplies >10 years. In multivariable models, risk was higher in the 95th percentile of average NO3-N (HRp95vsQ1 = 2.3; CI: 1.2, 4.3; Ptrend = 0.33) and for any years of exposure >½-MCL; adjustment for total THM did not materially change these associations. There were no independent relationships with total THM, individual THMs chloroform and bromodichloromethane, or with haloacetic acids. Dietary analyses yielded associations with high nitrite intake from processed meats but not nitrate or nitrite overall. We found no interactions., Conclusions: Relatively high nitrate levels in public water supplies were associated with increased risk of renal cancer. Our results also suggest that nitrite from processed meat is a renal cancer risk factor.

This study systematically evaluates the capabilities of five types of household water treatment (HWT) methods (including boiler heating, microwave irradiation, pouring, stirring, and shaking) on the removals of four regulated trihalomethanes (THM 4 ) and three iodinated halomethanes (IHMs) under a variety of conditions simulative of residential uses. Overall, the results clearly showed promising capabilities of all five HWT methods in controlling volatile disinfection by-products (DBPs), and heating with a boiler was the most effective approach among all methods due to the synergistic effects of water turbulence and bubbling phenomena. A contemporary boiler equipped with an automatic switch-off function reduced on average 92% of seven halomethanes (HM 7 ) at favourable conditions. The removal increased significantly with increasing initial concentrations and the rates correlated well with the logarithmic Henry's law constants and molecular weights of compounds, with triiodomethane being the most refractory species. Meanwhile, the importance of water handling habits was revealed, including power input, operation time, volume, heating/cooling speed, cooling method, and capping conditions. The findings hence explored the potentials of HWTs on DBP control and pointed out a potential limit to DBP epidemiology studies that do not consider water handling habits., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: We examined the association between exposure during pregnancy to trihalomethanes, the most common water disinfection by-products, and birth outcomes in a European cohort study (Health Impacts of Long-Term Exposure to Disinfection By-Products in Drinking Water). We took into account exposure through different water uses, measures of water toxicity, and genetic susceptibility., Methods: We enrolled 14,005 mothers (2002-2010) and their children from France, Greece, Lithuania, Spain, and the UK. Information on lifestyle- and water-related activities was recorded. We ascertained residential concentrations of trihalomethanes through regulatory records and ad hoc sampling campaigns and estimated route-specific trihalomethane uptake by trimester and for whole pregnancy. We examined single nucleotide polymorphisms and copy number variants in disinfection by-product metabolizing genes in nested case-control studies., Results: Average levels of trihalomethanes ranged from around 10 μg/L to above the regulatory limits in the EU of 100 μg/L between centers. There was no association between birth weight and total trihalomethane exposure during pregnancy (β = 2.2 g in birth weight per 10 μg/L of trihalomethane, 95% confidence interval = 3.3, 7.6). Birth weight was not associated with exposure through different routes or with specific trihalomethane species. Exposure to trihalomethanes was not associated with low birth weight (odds ratio [OR] per 10 μg/L = 1.02, 95% confidence interval = 0.95, 1.10), small-for-gestational age (OR = 0.99, 0.94, 1.03) and preterm births (OR = 0.98, 0.9, 1.05). We found no gene-environment interactions for mother or child polymorphisms in relation to preterm birth or small-for-gestational age., Conclusions: In this large European study, we found no association between birth outcomes and trihalomethane exposures during pregnancy in the total population or in potentially genetically susceptible subgroups. (See video abstract at http://links.lww.com/EDE/B104.).

Background: Nitrate is a drinking water contaminant arising from agricultural sources, and it is a precursor in the endogenous formation of N-nitroso compounds (NOC), which are possible bladder carcinogens., Objectives: We investigated the ingestion of nitrate and nitrite from drinking water and diet and bladder cancer risk in women., Methods: We identified incident bladder cancers among a cohort of 34,708 postmenopausal women in Iowa (1986-2010). Dietary nitrate and nitrite intakes were estimated from a baseline food frequency questionnaire. Drinking water source and duration were assessed in a 1989 follow-up. For women using public water supplies (PWS) > 10 years (n = 15,577), we estimated average nitrate (NO3-N) and total trihalomethane (TTHM) levels and the number of years exceeding one-half the maximum contaminant level (NO3-N: 5 mg/L, TTHM: 40 μg/mL) from historical monitoring data. We computed hazard ratios (HRs) and 95% confidence intervals (CIs), and assessed nitrate interactions with TTHM and with modifiers of NOC formation (smoking, vitamin C)., Results: We identified 258 bladder cancer cases, including 130 among women > 10 years at their PWS. In multivariable-adjusted models, we observed nonsignificant associations among women in the highest versus lowest quartile of average drinking water nitrate concentration (HR = 1.48; 95% CI: 0.92, 2.40; ptrend = 0.11), and we found significant associations among those exposed ≥ 4 years to drinking water with > 5 mg/L NO3-N (HR = 1.62; 95% CI: 1.06, 2.47; ptrend = 0.03) compared with women having 0 years of comparable exposure. TTHM adjustment had little influence on associations, and we observed no modification by vitamin C intake. Relative to a common reference group of never smokers with the lowest nitrate exposures, associations were strongest for current smokers with the highest nitrate exposures (HR = 3.67; 95% CI: 1.43, 9.38 for average water NO3-N and HR = 3.48; 95% CI: 1.20, 10.06 and ≥ 4 years > 5 mg/L, respectively). Dietary nitrate and nitrite intakes were not associated with bladder cancer., Conclusions: Long-term ingestion of elevated nitrate in drinking water was associated with an increased risk of bladder cancer among postmenopausal women. Citation: Jones RR, Weyer PJ, DellaValle CT, Inoue-Choi M, Anderson KE, Cantor KP, Krasner S, Robien K, Beane Freeman LE, Silverman DT, Ward MH. 2016. Nitrate from drinking water and diet and bladder cancer among postmenopausal women in Iowa. Environ Health Perspect 124:1751-1758; http://dx.doi.org/10.1289/EHP191., Competing Interests: This study was approved by the institutional review boards of the University of Minnesota and the University of Iowa. We thank J. Kantamneni of the Center for Health Effects of Environmental Contamination at the University of Iowa for providing us with the public water supply data, and we also thank C.-P. Hong of the University of Minnesota and M. Butcher at Information Management Services for their programming support on this study. The authors declare they have no actual or potential competing financial interests.

N-Nitrosamines (NAs) in drinking water have attracted considerable attention in recent years due to their high carcinogenicity, frequent occurrence, and their potential regulation. During the past three years, we have collected about 164 water samples of finished water, tap water, and source water from 23 provinces, 44 cities from large cities to small towns, and 155 sampling points all over China. The occurrence of NAs in the finished and tap water was much higher in China than that in the U.S. Nine NAs were measured and NDMA had the highest concentration. The occurrence of NDMA was in 33% of the finished waters of water treatment plants and in 41% of the tap waters. The average NDMA concentration in finished and tap waters was 11 and 13 ng/L, respectively. Formation potentials (FPs) of source waters were examined with an average NDMA FP of 66 ng/L. Large variations in NA occurrence were observed geographically in China and temporally in different seasons. The Yangtze River Delta area, one sub-area in East China, had the highest concentrations of NAs, where the average NDMA concentrations in the finished and tap water were 27 and 28.5 ng/L, respectively, and the average NDMA FP in the source water was 204 ng/L. NA control may be achieved by applying breakpoint free chlorination and/or advanced treatment of ozone - granular activated carbon process to remove the NA precursors before disinfection., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOC), potential human carcinogens. We evaluated the association of nitrate and nitrite ingestion with postmenopausal ovarian cancer risk in the Iowa Women's Health Study. Among 28,555 postmenopausal women, we identified 315 incident epithelial ovarian cancers from 1986 to 2010. Dietary nitrate and nitrite intakes were assessed at baseline using food frequency questionnaire data. Drinking water source at home was obtained in a 1989 follow-up survey. Nitrate-nitrogen (NO3 -N) and total trihalomethane (TTHM) levels for Iowa public water utilities were linked to residences and average levels were computed based on each woman's duration at the residence. We computed multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards regression. We tested interactions of nitrate with TTHMs and dietary factors known to influence NOC formation. Ovarian cancer risk was 2.03 times higher (CI = 1.22-3.38, ptrend  = 0.003) in the highest quartile (≥2.98 mg/L) compared with the lowest quartile (≤0.47 mg/L; reference) of NO3 -N in public water, regardless of TTHM levels. Risk among private well users was also elevated (HR = 1.53, CI = 0.93-2.54) compared with the same reference group. Associations were stronger when vitamin C intake was

Background & Aims: Patient-reported outcomes (PROs) are used to gauge the benefit of treatments for functional gastrointestinal disorders, including irritable bowel syndrome (IBS). Commonly used end points derived from scales of symptom severity differ in their structure, format, and the extent to which they are based on established psychometric fundamentals. We evaluated the overlap between 2 measures of IBS symptom severity, documented their association with different symptoms (pain, bloating, altered defecation), and identified psychological factors that might bias PRO ratings, by affecting how patients interpret IBS symptom severity., Methods: Ninety-eight patients diagnosed with IBS, based on Rome III criteria, completed the multicomponent IBS Symptom Severity Scale and the single-item, UCLA Symptom Severity Scale. Data were collected on pain, bloating, and bowel habits, as well as somatization, sensitivity to arousal symptoms (anxiety sensitivity), and a negative thinking style called pain catastrophizing., Results: The 2 global scales were correlated with one another (r = 0.56); each scale was associated most strongly with variation in abdominal pain. Data were consistent with a model in which pain catastrophizing and somatization influenced 1 or more of patients' judgments of pain, bloating, and/or bowel habits, which then affected the PROs., Conclusions: Depending on their structure and format, PROs can have different levels of sensitivity to core IBS symptoms and be influenced by psychological and somatic complaints that are beyond the aim of therapy and labeling claim. PROs that rely on patients' perspectives to index symptom severity can be improved by consideration of psychometric principles that influence self-report., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Over 200 treatment-seeking irritable bowel syndrome (IBS) patients completed 4 weeks of daily prospective measures of stress and gastrointestinal symptoms as well as retrospective measures of stress (life events over 12 months, hassles over 1 month). We also obtained the stress measures on 66 nonill controls. Irritable bowel syndrome patients report more frequent hassles than controls and a greater stress impact than controls. Using structural equation modeling, we found that the data were consistent with a model of robust autocorrelation effects of both week-to-week gastrointestinal (GI) symptom indices (r=.84) and stress indices (r=.73), as well as strong concurrent effects of stress on IBS symptoms (r=.90) and vice versa (r=.41). The data also were consistent with a model where there were effects of stress in Week t upon GI symptoms in Week t+1 and t+2, but they were mediated through the concurrent week effects and/or autocorrelation effects. There were no statistically significant independent pathways from stress in Week t to GI symptoms in Week t+1 or t+2. Thus, there is more support for a reciprocal relation between stress and symptoms than there is for a causal relation.

We randomized, at two sites, 210 patients with Rome II diagnosed irritable bowel syndrome (IBS), of at least moderate severity, to one of three conditions: group-based cognitive therapy (CT; n=120), psychoeducational support groups (n=46) as an active control, or intensive symptom and daily stress monitoring (n=44). One hundred eighty-eight participants completed the initial treatment. Those in symptom monitoring were then crossed over to CT. For an intent to treat analysis on a composite GI symptom measure derived from daily symptom diaries, both CT and the psychoeducational support groups were significantly more improved than those in the intensive symptom monitoring condition, but the CT and psychoeducational support group did not differ. Among treatment completers on the same composite measure of GI symptoms, again, both CT and psychoeducational support groups were statistically superior to symptom monitoring but did not differ on the symptom composite, or on any other measure. On individual IBS symptoms, both CT and psychoeducational support were statistically superior to symptom monitoring on reductions in abdominal pain and tenderness and for flatulence. Patient global ratings at the end of treatment showed the two active conditions statistically superior to symptom monitoring on change in Bowel Regularity, with CT superior to symptom monitoring on reduction in overall pain and in improvement in sense of well-being. Three-month follow-up data on 175 patients revealed maintenance of significant improvement or continued significant improvement on all IBS symptoms, including the McGill Pain Questionnaire. Group CT and psychoeducational support groups continued not to differ on any measure. We thus conclude that group CT is not superior to an attention placebo control condition.

Using a sample of over 125 patients with irritable bowel syndrome (IBS) who were treated with cognitive therapy administered in small groups, we sought to predict end of treatment and 3-month follow-up improvement in two changes indices of gastrointestinal (GI) symptoms (Pain/Discomfort Index which assessed change in abdominal pain, abdominal tenderness and bloating and Bowel Regularity Index which assessed change in diarrhea and constipation). We also sought to predict scores on IBS specific quality of life (QOL) and overall level of psychological distress using the Global Severity Index (GSI) of the Brief Symptom Inventory (BSI). Significant, but modest, levels of prediction were found for prediction of improvement in GI symptoms (4-15% of variance). Stronger significant prediction was obtained for the QOL and global psychological distress measure with R(2)'s ranging from 0.36 to 0.50. A wide variety of demographic, GI symptom, psychological status and psychiatric status variables entered the final prediction equations.

Objective: High rates of early abuse and psychopathology are commonly reported among treatment-seeking patients with irritable bowel syndrome (IBS). The purpose of this study is to further explore the relations among IBS, early abuse, Axes I and II psychopathology, and other medically unexplained disorders., Methods: One hundred and ninety-six IBS patients seeking nondrug treatment for their symptoms were characterized in terms of their gastrointestinal (GI) status, psychiatric status (Axis I and Axis II), early abuse status, and the presence of other functional disorders. Patients were divided into two groups based on early abuse status., Results and Conclusion: No significant differences emerged between abused and nonabused groups on either the presence of Axis II disorders or other functional health conditions, although there were high levels of both in the IBS population. Patients with a history of abuse were significantly more likely to meet criteria for an Axis I disorder, especially substance abuse disorders, dysthymia, and generalized anxiety disorder., (Copyright 2004 Elsevier Inc.)

The formation and speciation of disinfection byproducts (DBPs) resulting from chlorination of nanofilter permeates obtained from various source water locations and membrane types are examined. Specific ultraviolet absorbance and bromide utilization are shown to decrease following nanofiltration. Both dissolved organic carbon (DOC) concentration and ultraviolet absorbance at 254 nm were found to correlate strongly with trihalomethane (THM), haloacetic acid (HAA), and total organic halide (TOX) concentrations in chlorinated nanofilter permeates, suggesting that they can be employed as surrogates for DBPs in nanofiltered waters. Because smooth curves were obtained for individual THM and HAA species as well as bromine and chlorine incorporation into THMs and HAAs as a function of Br-/DOC molar ratio, it is likely that mole fractions of these DBPs are more strongly influenced by chlorination conditions, Br-, and DOC concentrations than NOM source and membrane type. Mole fractions of mono-, di-, and trihalogenated HAAs were found to be independent of Br-/DOC. Even at a very low Br-/DOC of 2.9microM/mM, the mixed bromochloro- and tribromoacetic acids constituted 20% of total HAAs on a molar basis. This increased to approximately 50% as Br-/DOC increased to approximately 25microM/mM or more, proving that a large fraction of HAAs may not be covered under existing federal regulations. Total THM and HAA9 concentrations decreased in permeate waters with increasing Br-/DOC suggesting that nanofilter permeates are limited with respect to DBP precursors.

Three Oscillatoria strains and one Anabaena species were isolated from three different water supply systems in California that experienced earthy-musty taste and odor problems in their drinking water. Unialgal cultures, free of actinomycetes, were purged using the Grob closed-loop stripping analysis method, and the resulting methylene chloride extracts were analyzed on a gas chromatograph/mass spectrometer. Geosmin was produced by Oscillatoria simplicissima and Anabaena scheremetievi, and 2-methylisoborneol was produced by O. curviceps and O. tenuis. These compounds are the two major causes of earthy-musty tastes and odors in water. In three instances, the major odorant found in culture was previously identified in the water or sediment sample from which the respective organism was isolated. O. curviceps was implicated in a taste and odor episode involving 2-methylisoborneol in a major reservoir. Geosmin and 2-methylisoborneol were easily detected with culture samples of only 4 to 25 ml.