Nitrate and nitrite contamination in drinking water and cancer risk: A systematic review with meta-analysis

BACKGROUND: Pollution of water sources, largely from wide-scale agricultural fertilizer use has resulted in nitrate and nitrite contamination of drinking water. The effects on human health of raised nitrate and nitrite levels in drinking water are currently unclear. OBJECTIVES: We conducted a systematic review of peer-reviewed literature on the association of nitrate and nitrite in drinking water with human health with a specific focus on cancer. METHODS: We searched eight databases from 1 January 1990 until 28 February 2021. Meta-analyses were conducted when studies had the same exposure metric and outcome. RESULTS: Of 9835 studies identified in the literature search, we found 111 studies reporting health outcomes, 60 of which reported cancer outcomes (38 case-control studies; 12 cohort studies; 10 other study designs). Most studies were set in the USA (24), Europe (20) and Taiwan (14), with only 3 studies from low and middle-income countries. Nitrate exposure in water (59 studies) was more commonly investigated than nitrite exposure (4 studies). Colorectal (15 studies) and gastric (13 studies) cancers were the most reported. In meta-analyses (4 studies) we identified a positive association of nitrate exposure with gastric cancer, OR = 1.91 (95%CI = 1.09-3.33) per 10 mg/L increment in nitrate ion. We found no association of nitrate exposure with colorectal cancer (10 studies; OR = 1.02 [95%CI = 0.96-1.08]) or cancers at any other site. CONCLUSIONS: We identified an association of nitrate in drinking water with gastric cancer but with no other cancer site. There is currently a paucity of robust studies from settings with high levels nitrate pollution in drinking water. Research into this area will be valuable to ascertain the true health burden of nitrate contamination of water and the need for public policies to protect human health

What concentration of tranexamic acid is needed to inhibit fibrinolysis? A systematic review of pharmacodynamics studies.

: Intravenous tranexamic acid (TXA) reduces death because of bleeding in patients with trauma and postpartum haemorrhage. However, in some settings intravenous injection is not feasible. To find different routes of administration, we first need to determine the minimal concentration of TXA in the blood that is required to inhibit fibrinolysis.We conducted a systematic review of in-vitro and in-vivo pharmacodynamics studies. We searched MEDLINE, EMBASE, OviSP, and ISI Web of Science from database inception to November 2017 for all in-vitro (including simulated clotting models) or in-vivo studies reporting the relationship between the TXA concentration in blood or plasma and any reliable measure of fibrinolysis.We found 21 studies of which 20 were in vitro and one was in vivo. Most in-vitro studies stimulated fibrinolysis with tissue plasminogen activator and measured fibrinolysis using viscoelastic, optical density, or immunological assays. TXA concentrations between 10 and 15 mg/l resulted in substantial inhibition of fibrinolysis, although concentrations between 5 and 10 mg/l were partly inhibitory.TXA concentrations of 10-15 mg/l may be suitable targets for pharmacokinetic studies, although TXA concentrations above 5 mg/l may also be effective

Air pollution and child health impacts of decarbonization in 16 global cities: Modelling study.

Most research on the air pollution-related health effects of decarbonization has focused on adults. We assess the potential health benefits that could be achieved in children and young people in a global sample of 16 cities through global decarbonization actions. We modelled annual average concentrations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) at 1x1 km resolution in the cities using a general circulation/atmospheric chemistry model assuming removal of all global combustion-related emissions from land transport, industries, domestic energy use and power generation. We modelled the impact on childhood asthma incidence and adverse birth outcomes (low birthweight, pre-term births) using published exposure-response relationships. Removal of combustion emissions was estimated to decrease annual average PM2.5 by between 2.9 μg/m3 (8.4%) in Freetown and 45.4 μg/m3 (63.7%) in Dhaka. For NO2, the range was from 0.3 ppb (7.9%) in Freetown to 18.8 ppb (92.3%) in Mexico City. Estimated reductions in asthma incidence ranged from close to zero in Freetown, Tamale and Harare to 149 cases per 100,000 population in Los Angeles. For pre-term birth, modelled impacts ranged from a reduction of 135 per 100,000 births in Dar es Salaam to 2,818 per 100,000 births in Bhubaneswar and, for low birthweight, from 75 per 100,000 births in Dar es Salaam to 2,951 per 100,000 births in Dhaka. The large variations chiefly reflect differences in the magnitudes of air pollution reductions and estimated underlying disease rates. Across the 16 cities, the reduction in childhood asthma incidence represents more than one-fifth of the current burden, and an almost 10% reduction in pre-term and low birthweight births. Decarbonization actions that remove combustion-related emissions contributing to ambient PM2.5 and NO2 would likely lead to substantial but geographically-varied reductions in childhood asthma and adverse birth outcomes, though there are uncertainties in causality and the precision of estimates

Effects on child and adolescent health of climate change mitigation policies: A systematic review of modelling studies

There is a growing body of modelling evidence that demonstrates the potential for immediate and substantial benefits to adult health from greenhouse gas mitigation actions, but the effects on the health of younger age groups is largely unknown. We conducted a systematic review to identify the available published evidence of the modelled effects on child and adolescent health (≤18 years of age) of greenhouse gas mitigation. We searched six databases of peer-reviewed studies published between January 1, 1990 and July 27, 2022, screened 27,282 original papers and included 23 eligible papers. All included studies were set in high- and middle-income countries; and all studies modelled the effects of interventions that could mitigate greenhouse gas emissions and improve air quality. Most of the available evidence suggests positive benefits for child and adolescent respiratory health from greenhouse gas mitigation actions that simultaneously reduce air pollution (specifically PM2.5 and nitrogen dioxide). We found scant evidence on child and adolescent health from regions more vulnerable to climate change, or on mitigation interventions that could affect exposures other than air pollution

Comparison of built environment adaptations to heat exposure and mortality during hot weather, West Midlands region, UK.

There is growing recognition of the need to improve protection against the adverse health effects of hot weather in the context of climate change. We quantify the impact of the Urban Heat Island (UHI) and selected adaptation measures made to dwellings on temperature exposure and mortality in the West Midlands region of the UK. We used 1) building physics models to assess indoor temperatures, initially in the existing housing stock and then following adaptation measures (energy efficiency building fabric upgrades and/or window shutters), of representative dwelling archetypes using data from the English Housing Survey (EHS), and 2) modelled UHI effect on outdoor temperatures. The ages of residents were combined with evidence on the heat-mortality relationship to estimate mortality risk and to quantify population-level changes in risk following adaptations to reduce summertime heat exposure. Results indicate that the UHI effect accounts for an estimated 21% of mortality. External shutters may reduce heat-related mortality by 30-60% depending on weather conditions, while shutters in conjunction with energy-efficient retrofitting may reduce risk by up to 52%. The use of shutters appears to be one of the most effective measures providing protection against heat-related mortality during periods of high summer temperatures, although their effectiveness may be limited under extreme temperatures. Energy efficiency adaptations to the dwellings and measures to increase green space in the urban environment to combat the UHI effect appear to be less beneficial for reducing heat-related mortality

Simultaneous absence of dopamine D1 and D2 receptor-mediated signaling is lethal in mice

Dopamine (DA) controls a wide variety of physiological functions in the central nervous system as well as in the neuroendocrine and gastrointestinal systems. DA signaling is mediated by five cloned receptors named D1-D5. Knockout mouse models for the five receptors have been generated, and, albeit impaired for some important DA-mediated functions, they are viable and can reproduce. D1 and D2 receptors are the most abundant and widely expressed DA receptors. Cooperative/synergistic effects mediated by these receptors have been suggested, in particular, in the control of motor behaviors. To analyze the extent of such interrelationship, we have generated double D1/D2 receptor mutants. Interestingly, in contrast to single knockouts, we found that concurrent ablation of the D1 and D2 receptors is lethal during the second or third week after birth. This dramatic phenotype is likely to be related to altered feeding behavior and dysfunction of the gastrointestinal system, especially because major anatomical changes were not identified in the brain. Similarly, in the absence of functional D1, heterozygous D2 mutants (D1r -/-;D2r +/-) showed severe growth retardation and did not survive their postweaning period. The analysis of motor behavior in D1r/D2r compound mutants showed that loss of D2-mediated functions reduces motor abilities, whereas the effect of D1r ablation on locomotion strongly depends on the experimental paradigms used. These studies highlight the interrelationship between D1 and D2 receptor-mediated control of motor activity, food intake, and gastrointestinal functions, which has been elusive in the single-gene ablation studies

Mapping the evidence of novel plant-based foods: a systematic review of nutritional, health, and environmental impacts in high-income countries.

CONTEXT: Shifting from current dietary patterns to diets rich in plant-based (PB) foods and lower in animal-based foods (ABFs) is generally regarded as a suitable strategy to improve nutritional health and reduce environmental impacts. Despite the recent growth in supply of and demand for novel plant-based foods (NPBFs), a comprehensive overview is lacking. OBJECTIVES: This review provides a synthesis of available evidence, highlights challenges, and informs public health and environmental strategies for purposeful political decision-making by systematically searching, analyzing, and summarizing the available literature. DATA SOURCES: Five peer-reviewed databases and grey literature sources were rigorously searched for publications. DATA EXTRACTION: Study characteristics meeting the inclusion criteria regarding NPBF nutrient composition and health and environmental outcomes in high-income countries were extracted. DATA ANALYSIS: Fifty-seven peer-reviewed and 36 grey literature sources were identified; these were published in 2016-2022. NPBFs typically have substantially lower environmental impacts than ABFs, but the nutritional contents are complex and vary considerably across brands, product type, and main primary ingredient. In the limited evidence on the health impacts, shifts from ABFs to PB meats were associated with positive health outcomes. However, results were mixed for PB drinks, with links to micronutrient deficiencies. CONCLUSION: If carefully selected, certain NPBFs have the potential to be healthier and nutrient-rich alternatives to ABFs and typically have smaller environmental footprints. More disaggregated categorization of various types of NPBFs would be a helpful step in guiding consumers and key stakeholders to make informed decisions. To enable informed policymaking on the inclusion of NPBFs in dietary transitions as part of a wider net-zero and health strategy, future priorities should include nutritional food standards, labelling, and subdivisions or categorizations of NPBFs, as well as short- and long-term health studies evaluating dietary shifts from ABFs to NPBFs and standardized environmental impact assessments, ideally from independent funders

Changes in upper airways microbiota in ventilator-associated pneumonia

Background: The role of upper airways microbiota and its association with ventilator-associated pneumonia (VAP) development in mechanically ventilated (MV) patients is unclear. Taking advantage of data collected in a prospective study aimed to assess the composition and over-time variation of upper airway microbiota in patients MV for non-pulmonary reasons, we describe upper airway microbiota characteristics among VAP and NO-VAP patients. Methods: Exploratory analysis of data collected in a prospective observational study on patients intubated for non-pulmonary conditions. Microbiota analysis (trough 16S-rRNA gene profiling) was performed on endotracheal aspirates (at intubation, T0, and after 72 h, T3) of patients with VAP (cases cohort) and a subgroup of NO-VAP patients (control cohort, matched according to total intubation time). Results: Samples from 13 VAP patients and 22 NO-VAP matched controls were analyzed. At intubation (T0), patients with VAP revealed a significantly lower microbial complexity of the microbiota of the upper airways compared to NO-VAP controls (alpha diversity index of 84 ± 37 and 160 ± 102, in VAP and NO_VAP group, respectively, p-value < 0.012). Furthermore, an overall decrease in microbial diversity was observed in both groups at T3 as compared to T0. At T3, a loss of some genera (Prevotella 7, Fusobacterium, Neisseria, Escherichia-Shigella and Haemophilus) was found in VAP patients. In contrast, eight genera belonging to the Bacteroidetes, Firmicutes and Fusobacteria phyla was predominant in this group. However, it is unclear whether VAP caused dysbiosis or dysbiosis caused VAP. Conclusions: In a small sample size of intubated patients, microbial diversity at intubation was less in patients with VAP compared to patients without VAP

The WOMAN Trial: Clinical and Contextual Factors Surrounding the Deaths of 483 Women Following Post-Partum Hemorrhage in Developing Countries

The etiology of maternal mortality is postpartum hemorrhage in approximately 8.0% of cases in developed countries and 19.7% in developing countries. As a leading cause of maternal death, its prevention and early treatment are a priority. As part of the WOMANTrial, a randomized trial of tranexamic acid to treat postpartum hemorrhage, information on the causes ofmaternal death was recorded. The aim of this study was to review the circumstances of maternal death inmore than 20,000 women in 21 countries. The WOMAN Trial demonstrated that tranexamic acid reduced maternal death in women with postpartum hemorrhage. The study took place between 2010 and 2016 in 193 hospitals in 21 countries and recruited 20,060 women who were 16 years or older and were diagnosed with postpartumhemorrhage following vaginal or cesarean deliveries. In cases ofmaternal death, obstetricians were asked to record the cause of death and provide a brief narrative of the circumstances surrounding the death. Of the 20,060 women recruited for the trial, 12,343 were from Africa, 6030 from Asia, and 1049 from Europe. A total of 483 deathswere recorded, with case fatality rates of 3.0%(n = 375) in Africa and 1.7%(n = 105) in Asia; there were no deaths in the European cohort. Narratives were obtained for 52% of the recorded deaths. The odds of maternal death were 5 times higher in cases involving stillbirths versus live births (odds ratio = 5.26, 95%confidence interval = 4.34 6.39). The risk of death was also associated with more than 1000 mL of blood loss, a systolic blood pressure of <90 mm Hg, and hemodynamic instability. Among the 483 deaths, 13.3% were women who died within 3 hours of delivery and 59.8% who died between 3 and 24 hours after delivery. Women who gave birth outside of a participating hospital were 3 times more likely to die than those who gave birth at a participating hospital (odds ratio = 3.12, 95% confidence interval = 2.55 3.81). Based on the narratives, women who gave birth elsewhere were often in critical condition upon their arrival at a participating hospital. Bleeding was the most common cause of death for 346 women (72%). Bleeding was the cause of death for 91% of women who died within 3 hours of delivery and 83% of those who died within 24 hours of delivery. The primary cause of bleeding was uterine atony (53.2%). On average, women who died lost 2.1 L of blood (SD = 0.9 L, median = 2 L, interquartile range = 1.5 2.5 L) versus 1.2 L of blood for women who lived (SD = 0.6 L, median = 1 L, interquartile range = 0.8 1.5 L). More women who died received blood transfusions than those who lived (92.1% vs 53.8%). The narratives noted that blood was often unavailable for transfusion because of blood shortages or the family's inability to purchase blood. In this study, blood loss was observed to be the leading cause of death in women fromAfrica and Asia. Achieving mortality rates in developing countries similar to those in developed countries will require attention to issues such as late presentation due to births outside of hospitals and the lack of blood for transfusion

The impact of home energy efficiency interventions and winter fuel payments on winter- and cold-related mortality and morbidity in England: a natural equipment mixed-methods study

Background England, and the UK more generally, has a large burden of winter- and cold-related mortality/morbidity in comparison with nearby countries in continental Europe. Improving the energy efficiency of the housing stock may help to reduce this, as well as being important for climate change and energy security objectives. Objectives To evaluate the impact of home energy efficiency (HEE) interventions on winter- and cold-related mortality/morbidity, including assessing the impact of winter fuel payments (WFPs) and fuel costs. Design A mixed-methods study – an epidemiological time-series analysis, an analysis of data on HEE interventions, the development and application of modelling methods including a multicriteria decision analysis and an in-depth interview study of householders. Setting England, UK. Participants The population of England. In-depth interviews were conducted with 12 households (2–4 participants each) and 41 individuals in three geographical regions. Interventions HEE interventions. Main outcome measures Mortality, morbidity and intervention-related changes to the home indoor environment. Data sources The Homes Energy Efficiency Database, mortality and hospital admissions data and weather (temperature) data. Results There has been a progressive decline in cold-related deaths since the mid-1970s. Since the introduction of WFPs, the gradient of association between winter cold and mortality [2.00%, 95% confidence interval (CI) 1.74% to 2.28%] per degree Celsius fall in temperature is somewhat weaker (i.e. that the population is less vulnerable to cold) than in earlier years (2.37%, 95% CI 0.22% to 2.53%). There is also evidence that years with above-average fuel costs were associated with higher vulnerability to outdoor cold. HEE measures installed in England in 2002–10 have had a relatively modest impact in improving the indoor environment. The gains in winter temperatures (around +0.09 °C on a day with maximum outdoor temperature of 5 °C) are associated with an estimated annual reduction of ≈280 cold-related deaths in England (an eventual maximum annual impact of 4000 life-years gained), but these impacts may be appreciably smaller than those of changes in indoor air quality. Modelling studies indicate the potential importance of the medium- and longer-term impacts that HEE measures have on health, which are not observable in short-term studies. They also suggest that HEE improvements of similar annualised cost to current WFPs would achieve greater improvements in health while reducing (rather than increasing) carbon dioxide emissions. In-depth interviews suggest four distinct householder framings of HEE measures (as home improvement, home maintenance, subsidised public goods and contributions to sustainability), which do not dovetail with current ‘consumerist’ national policy and may have implications for the uptake of HEE measures. Limitations The quantification of intervention impacts in this national study is reliant on various indirect/model-based assessments. Conclusions Larger-scale changes are required to the housing stock in England if the full potential benefits for improving health and for reaching increasingly important climate change mitigation targets are to be realised. Future work Studies based on data linkage at individual dwelling level to examine health impacts. There is a need for empirical assessment of HEE interventions on indoor air quality. Funding This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 6, No. 11. See the NIHR Journals Library website for further project information. </jats:sec