Essential and Toxic Elements in Infant Cereal in Brazil: Exposure Risk Assessment.

Infant cereals, one of the first solid foods introduced to infants, have been reported to pose risks to human health because they contain toxic elements and an excess of essential elements. The objective of this study was to assess the cancer and non-cancer risk of exposure to essential and toxic elements in infant cereal in Brazil. In our analyses, we included data from 18 samples of infant cereals made from different raw materials and estimated the incremental lifetime cancer risks and non-cancer hazard quotients (HQs) for their consumption. Rice cereal is particularly concerning because it is immensely popular and usually contains high levels of inorganic arsenic. In addition to arsenic, we assessed aluminum, boron, barium, cadmium, chromium, copper, lead, manganese, nickel, selenium, silver, strontium, and zinc. The cancer risk was highest for rice cereal, which was also found to have an HQ > 1 for most of the tested elements. Inorganic As was the element associated with the highest cancer risk in infant cereal. All of the infant cereals included in this research contained at least one element with an HQ > 1. The essential and non-essential elements that presented HQ > 1 more frequently were zinc and cadmium, respectively. The cancer and non-cancer risks could potentially be decreased by reducing the amount of toxic and essential elements (when in excess), and public policies could have a positive influence on risk management in this complex scenario.

Exposure to Inorganic Arsenic in Rice in Brazil: A Human Health Risk Assessment.

In certain populations, rice is the main source of exposure to inorganic arsenic (iAs), which is associated with cancer and non-cancer effects. Although rice is a staple food in Brazil, there have been few studies about the health risks for the Brazilian population. The objective of this study was to assess the risks of exposure to iAs from white rice and brown rice in Brazil, in terms of the carcinogenic and non-carcinogenic effects, and to propose measures to mitigate those risks. The incremental lifetime cancer risk (ILCR) and hazard quotient (HQ) were calculated in a probabilistic framework. The mean ILCR was 1.5 × 10-4 for white rice and 6.0 × 10-6 for brown rice. The HQ for white and brown rice was under 1. The ILCR for white and brown rice was high, even though the iAs concentration in rice is below the maximum contaminant level. The risk for brown rice consumption was lower, which was not expected. Various mitigation measures discussed in this report are estimated to reduce the risk from rice consumption by 5-67%. With the support of public policies, measures to reduce these risks for the Brazilian population would have a positive impact on public health.

Real-Time In Vitro Assessment of Aerosol Delivery During Mechanical Ventilation.

Background: A new real-time method for assessing factors determining aerosol delivery is described. Methods: A breath-enhanced jet nebulizer operated in a ventilator/heated humidifier system was tested during bolus and continuous infusion aerosol delivery. 99mTc (technetium)/saline was either injected (3 or 6 mL) or infused over time into the nebulizer. A shielded gamma ratemeter was oriented to count radioaerosol accumulating on an inhaled mass (IM) filter at the airway opening of a test lung. Radioactivity measured at 2-10-minute intervals was expressed as % nebulizer charge (bolus) or % syringe activity per minute infused. All circuit parts were measured and imaged by gamma camera to determine mass balance. Results: Ratemeter activity quantitatively reflected immediate changes in IM: 3 and 6 mL bolus IM% = 16.1 and 18.8% in 6 and 14 minutes, respectively; infusion IM% = 0.64 + 0.13 (run time, min), R2 0.999. Effect of nebulizer priming and system anomalies were readily detected in real time. Mass balance (basis = dose infused in 90 minutes): IM 39.2%, breath-enhanced jet nebulizer residual 35.5%, circuit parts including humidifier 23.4%, and total recovery 98.1%. Visual analysis of circuit component images identified sites of increased deposition. Conclusion: Real-time ratemeter measurement with gamma camera imaging provides operational feedback during in vitro testing procedures and yields a detailed analysis of the parameters influencing drug delivery during mechanical ventilation. This method of analysis facilitates assessment of device function and influence of circuit parameters on drug delivery.

Oil palm cultivation can be expanded while sparing biodiversity in India.

India is the world's largest consumer and importer of palm oil. In an aggressive push towards self-sufficiency in vegetable oils, the Indian government is prioritizing the rapid expansion of domestic oil palm plantations to meet an expected doubling in palm oil consumption in the next 15 years. Yet the current expansion of oil palm in India is occurring at the expense of biodiversity-rich landscapes. Using a spatially explicit model, we show that at the national scale India appears to have viable options to satisfy its projected national demand for palm oil without compromising either its biodiversity or its food security. At finer spatial scales, India's oil palm expansion needs to incorporate region-specific contingencies and account for trade-offs between biodiversity conservation, climate change, agricultural inputs and economic and social security. The policy decisions that India takes with respect to oil palm can substantially reduce future pressures to convert forests to oil palm plantations in the tropics globally.

Transforming our relationship with the social determinants of health: a scoping review of social justice interventions in Canadian Medical Schools.

This article was migrated. The article was marked as recommended. Background/Purpose: Physicians are in a powerful position to improve the health status of communities through mitigating disparities rooted in social inequities. However, it is uncertain whether medical schools are preparing future physicians with the skills needed to care for diverse populations. The current scoping review aimed to describe how Canadian medical schools teach social justice, comparing pedagogical strategies. Methods: A search was performed using OVID to identify published studies of implemented and evaluated social justice-based interventions within Canadian medical school curricula. Results: Six studies were included. Common themes included increased content knowledge, greater understanding of SDoH, acknowledgement of power and privilege imbalances, identification of physicians' roles as advocates, emphasis on the importance of interdisciplinary care, and increased capacity for self-reflection and personal growth. Experiential interventions were associated with greater personal transformation, but had limited accessibility. Conclusion: Despite the widespread recognition of physicians' roles as health advocates, there is a lack of consensus about an effective strategy for teaching social justice in medical education in Canada. While additional research focusing on the relative merits of didactic versus experiential learning is needed, these preliminary results suggest that experiential learning emphasizing self-reflection and personal growth may be optimal when approaching transformative learning.

Saiga horn user characteristics, motivations, and purchasing behaviour in Singapore.

Unsustainable wildlife trade is a pervasive issue affecting wildlife globally. To address this issue, a plethora of demand reduction efforts have been carried out. These necessitate consumer research which provides crucial knowledge for designing and evaluating targeted interventions. We implemented a rigorous consumer survey on saiga (Saiga tatarica) horn use in Singapore, where usage is legal and widely sold. Saiga are Critically Endangered antelopes from Central Asia with horns (often marketed as ling yang) used in traditional Chinese medicine (TCM). Few past studies have assessed saiga horn consumers. This work is the most extensive consumer research to date specifically characterising saiga horn consumers and usage. We conducted 2294 in-person surveys on saiga horn use with Chinese Singaporeans, employing neutral questioning approaches. We found 19% of individuals reported saiga horn as a product they choose most often for themselves and/or others when treating fever and/or heatiness (a TCM state of illness), indicating a minimum estimate of high-frequency usage, not including possible low-frequency users. Overall saiga users were most characterised as middle-aged Buddhists and Taoists. However, saiga users were found in a range of demographic groups. Women preferred saiga shavings (the more traditional form), while men preferred saiga cooling water (the more modern form). About 53% of individuals who used saiga horn themselves also bought it for someone else. Buyers for others were most likely to be female middle-aged Buddhists or Taoists. Key motivating reasons for usage were "it works" and "someone recommended it to me." The top two reported recommenders were family and TCM shopkeepers. Saiga users were more likely than non-saiga users to perceive saiga as a common species in the wild. This research holds significance for interventions targeting saiga horn consumption within Singapore and throughout Asia, by identifying potential target audiences, product types, non-desirable alternatives, and motivations for use.

Social factors in frequent callers: a description of isolation, poverty and quality of life in those calling emergency medical services frequently.

BACKGROUND: Frequent users of emergency medical services (EMS) comprise a disproportionate percentage of emergency department (ED) visits. EDs are becoming increasingly overwhelmed and a portion of use by frequent callers of EMS is potentially avoidable. Social factors contribute to frequent use however few studies have examined their prevalence. This study aims to describe social isolation/loneliness, poverty, and quality of life in a sample of frequent callers of EMS in the Hamilton region, a southern Ontario mid-sized Canadian city. STUDY DESIGN: Cross-sectional quantitative study. METHODS: We surveyed people who called EMS five or more times within 12 months. A mailed self-administered survey with validated tools, and focused on four major measures: demographic information, social isolation, poverty, and quality of life. RESULTS: Sixty-seven frequent EMS callers revealed that 37-49% were lonely, 14% had gone hungry in the preceding month, and 43% had difficulties making ends meet at the end of the month. For quality of life, 78% had mobility problems, 55% had difficulty with self-care, 78% had difficulty with usual activities, 87% experienced pain/discomfort, and 67% had anxiety/depression. Overall quality adjusted life years value was 0.53 on a scale of 0 to 1. The response rate was 41.1%. CONCLUSIONS: Loneliness in our participants was more common than Hamilton and Canadian rates. Frequent EMS callers had higher rates of poverty and food insecurity than average Ontario citizens, which may also act as a barrier to accessing preventative health services. Lower quality of life may indicate chronic illness, and users who cannot access ambulatory care services consistently may call EMS more frequently. Frequent callers of EMS had high rates of social loneliness and poverty, and low quality of life, indicating a need for health service optimization for this vulnerable population.

Addressing Health Equity Through Action on the Social Determinants of Health: A Global Review of Policy Outcome Evaluation Methods.

BACKGROUND: Epidemiological evidence on the social determinants of health inequity is well-advanced, but considerably less attention has been given to evaluating the impact of public policies addressing those social determinants. Methodological challenges to produce evidence on policy outcomes present a significant barrier to mobilising policy actions for health equities. This review aims to examine methodological approaches to policy evaluation of health equity outcomes and identify promising approaches for future research. METHODS: We conducted a systematic narrative review of literature critically evaluating policy impact on health equity, synthesizing information on the methodological approaches used. We searched and screened records from five electronic databases, using pre-defined protocols resulting in a total of 50 studies included for review. We coded the studies according to (1) type of policy analysed; (2) research design; (3) analytical techniques; (4) health outcomes; and (5) equity dimensions evaluated. RESULTS: We found a growing number of a wide range of policies being evaluated for health equity outcomes using a variety of research designs. The majority of studies employed an observational research design, most of which were cross-sectional, however, other approaches included experimental designs, simulation modelling, and meta-analysis. Regression techniques dominated the analytical approaches, although a number of novel techniques were used which may offer advantages over traditional regression analysis for the study of distributional impacts of policy. Few studies made intra-national or cross-national comparisons or collected primary data. Despite longstanding challenges of attribution in policy outcome evaluation, the majority of the studies attributed change in physical or mental health outcomes to the policy being evaluated. CONCLUSION: Our review provides an overview of methodological approaches to health equity policy outcome evaluation, demonstrating what is most commonplace and opportunities from novel approaches. We found the number of studies evaluating the impacts of public policies on health equity are on the rise, but this area of policy evaluation still requires more attention given growing inequities.

Assessment of Health Effects of Exogenous Urea: Summary and Key Findings.

PURPOSE OF REVIEW: Urea has been utilized as a reductant in diesel fuels to lower emission of nitrogen oxides, igniting interest in probable human health hazards associated with exposure to exogenous urea. Here, we summarize and update key findings on potential health effects of exogenous urea, including carcinogenicity. RECENT FINDINGS: No definitive target organs for oral exposure were identified; however, results in animal studies suggest that the liver and kidney could be potential target organs of urea toxicity. The available human-subject literature suggests that the impact on lung function is minimal. Based on the literature on exogenous urea, we concluded that there was inadequate information to assess the carcinogenic potential of urea, or perform a quantitative assessment to derive reference values. Given the limited information on exogenous urea, additional research to address gaps for exogenous urea should include long-term cancer bioassays, two-generation reproductive toxicity studies, and mode-of-action investigations.

Leveraging human genetic and adverse outcome pathway (AOP) data to inform susceptibility in human health risk assessment.

Estimation of susceptibility differences in human health risk assessment (HHRA) has been challenged by a lack of available susceptibility and variability data after exposure to a specific environmental chemical or pharmaceutical. With the increasingly large number of available data sources that contain polymorphism and other genetic data, human genetic variability that informs susceptibility can be better incorporated into HHRA. A recent policy, the 2016 The Frank R. Lautenberg Chemical Safety for the twenty-first Century Act, requires the US Environmental Protection Agency to evaluate new and existing toxic chemicals with explicit consideration of susceptible populations of all types (life stage, exposure, genetic, etc.). We propose using the adverse outcome pathway (AOP) construct to organize, identify, and characterize human genetic susceptibility in HHRA. We explore how publicly available human genetic datasets can be used to gain mechanistic understanding of molecular events and characterize human susceptibility for an adverse outcome. We present a computational method that implements publicly available human genetic data to prioritize AOPs with potential for human genetic variability. We describe the application of this approach across multiple described AOPs for health outcomes of interest, and by focusing on a single molecular initiating event. This contributes to a long-term goal to improve estimates of human susceptibility for use in HHRA for single and multiple chemicals.

Shortening the decade-long gap between adult and paediatric drug formulations: a new framework based on the HIV experience in low- and middle-income countries.

INTRODUCTION: Despite the coordinated efforts by several stakeholders to speed up access to HIV treatment for children, development of optimal paediatric formulations still lags 8 to 10 years behind that of adults, due mainly to lack of market incentives and technical complexities in manufacturing. The small and fragmented paediatric market also hinders launch and uptake of new formulations. Moreover, the problems affecting HIV similarly affect other disease areas where development and introduction of optimal paediatric formulations is even slower. Therefore, accelerating processes for developing and commercializing optimal paediatric drug formulations for HIV and other disease areas is urgently needed. DISCUSSION: The Global Accelerator for Paediatric Formulations (GAP-f) is an innovative collaborative model that will accelerate availability of optimized treatment options for infectious diseases, such as HIV, tuberculosis and viral hepatitis, affecting children in low- and middle-income countries (LMICs). It builds on the HIV experience and existing efforts in paediatric drug development, formalizing collaboration between normative bodies, research networks, regulatory agencies, industry, supply and procurement organizations and funding bodies. Upstream, the GAP-f will coordinate technical support to companies to design and study optimal paediatric formulations, harmonize efforts with regulators and incentivize manufacturers to conduct formulation development. Downstream, the GAP-f will reinforce coordinated procurement and communication with suppliers. The GAP-f will be implemented in a three-stage process: (1) development of a strategic framework and promotion of key regulatory efficiencies; (2) testing of feasibility and results, building on the work of existing platforms such as the Paediatric HIV Treatment Initiative (PHTI) including innovative approaches to incentivize generic development and (3) launch as a fully functioning structure. CONCLUSIONS: GAP-f is a key partnership example enhancing North-South and international cooperation on and access to science and technology and capacity building, responding to Sustainable Development Goal (SDG) 17.6 (technology) and 17.9. (capacity-building). By promoting access to the most needed paediatric formulations for HIV and high-burden infectious diseases in low-and middle-income countries, GAP-f will support achievement of SDG 3.2 (infant mortality), 3.3 (end of AIDS and combat other communicable diseases) and 3.8 (access to essential medicines), and be an essential component of meeting the global Start Free, Stay Free, AIDS Free super-fast-track targets.

Understanding the acceptability and adherence to paediatric antiretroviral treatment in the new formulation of pellets (LPV/r): the protocol of a realist evaluation.

BACKGROUND: Improving access to paediatric HIV treatment requires both large-scale treatment programmes and medication that is adapted to infants and children's needs. The WHO recommends lopinavir/ritonavir as first-line antiretroviral therapy for all HIV-infected children younger than 3 years. There is currently little evidence on the acceptability of, and adherence to, a formulation of this combination treatment if given in the form of pellets. This protocol presents how we will carry a realist evaluation to assess the factors that contribute to the acceptability and adherence to the new pellets formulation in 3 hospitals in Kenya. METHODS: We structured the protocol along the realist evaluation cycle following 4 steps: (1) the initial programme theory, (2) the study design, (3) the data collection methods and (4) the data analysis plan. Theories of behavioural sciences were reviewed for frames that could provide insights into how using such new formulations may contribute to better acceptability and adherence. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of the Institute of Tropical Medicine, the Ethical Committee of the University Hospital Antwerp and the Kenyatta National Hospital/University of Nairobi Ethics and Research Committee. We aim to disseminate the findings through international conferences and peer-reviewed journals and to share them with Drugs for Neglected Diseases initiative's (DNDi) programme managers and with the Kenyan healthcare providers. DISCUSSION: In developing this study, we encountered some challenges. First, methods to measure the acceptability of any formulation and adherence to it are not standardised. The second challenge is common in realist evaluation and relates to how to choose from different potentially interesting theoretical frameworks. We identified relevant and empirically tested theories from behavioural science that may be helpful in our study. We will test them in 3 settings by exploring the multilevel factors that influence acceptability and adherence of this new paediatric Antiretroviral (ARV) formulation.

An analysis of volumes, prices and pricing trends of the pediatric antiretroviral market in developing countries from 2004 to 2012.

BACKGROUND: The pediatric antiretroviral (ARV) market is poorly described in the literature, resulting in gaps in understanding treatment access. We analyzed the pediatric ARV market from 2004 to 2012 and assessed pricing trends and associated factors. METHODS: Data on donor funded procurements of pediatric ARV formulations reported to the Global Price Reporting Mechanism database from 2004 to 2012 were analyzed. Outcomes of interest were the volume and mean price per patient-year ARV formulation based on WHO ARV dosing recommendations for a 10 kg child. Factors associated with the price of formulations were assessed using linear regression; potential predictors included: country income classification, geographical region, market segment (originator versus generic ARVs), and number of manufacturers per formulation. All analyses were adjusted for type of formulations (single, dual or triple fixed-dose combinations (FDCs)) RESULTS: Data from 111 countries from 2004 to 2012 were included, with procurement of 33 formulations at a total value of USD 204 million. Use of dual and triple FDC formulations increased substantially over time, but with limited changes in price. Upon multivariate analysis, prices of originator formulations were found to be on average 72 % higher than generics (p < 0.001). A 10 % increase in procurement volume was associated with a 1 % decrease (p < 0.001) in both originator and generic prices. The entry of one additional manufacturer producing a formulation was associated with a decrease in prices of 2 % (p < 0.001) and 8 % (p < 0.001) for originator and generic formulations, respectively. The mean generic ARV price did not differ by country income level. Prices of originator ARVs were 48 % (p < 0.001) and 14 % (p < 0.001) higher in upper-middle income and lower-middle income countries compared to low income countries respectively, with the exception of South Africa, which had lower prices despite being an upper-middle income country. CONCLUSIONS: The donor funded pediatric ARV market as represented by the GPRM database is small, and lacks price competition. It is dominated by generic drugs due to the lower prices offered and the practicality of FDC formulations. This market requires continued donor support and the current initiatives to protect it are important to ensure market viability, especially if new formulations are to be introduced in the future.

Systematic review of differential inorganic arsenic exposure in minority, low-income, and indigenous populations in the United States.

Inorganic arsenic (iAs) is a human carcinogen and associated with cardiovascular, respiratory, and skin diseases. Natural and anthropogenic sources contribute to low concentrations of iAs in water, food, soil, and air. Differential exposure to environmental hazards in minority, indigenous, and low income populations is considered an environmental justice (EJ) concern, yet it is unclear if higher iAs exposure occurs in these populations. A systematic review was conducted to evaluate evidence for differential iAs exposure in the United States (US). The peer-reviewed literature was searched for studies that (1) estimated iAs exposure based on environmental concentrations of iAs in water, food, soil, or iAs biomarkers and (2) examined iAs exposure in minority, indigenous, and low income US populations. Five studies were identified that estimated exposures and provided demographic information about EJ populations. These studies reported arsenic concentrations in water, soil, or food to estimate exposure, with varied evidence of differential exposure. Additionally, six studies were identified that suggested potential arsenic exposure from environmental sources including soil, rice, private well-water, and fish, but did not report data stratified by demographic information. Evidence across these 11 studies was qualitatively integrated to draw conclusions about differential iAs exposure. The total body of evidence is limited by lack of individual exposure measures, lack of iAs concentration data, and insufficient comparative demographic data. Based upon these data gaps, there is inadequate evidence to conclude whether differential exposure to iAs is an EJ concern in the US.

Will oil palm's homecoming spell doom for Africa's great apes?

Expansion of oil palm plantations has led to extensive wildlife habitat conversion in Southeast Asia [1]. This expansion is driven by a global demand for palm oil for products ranging from foods to detergents [2], and more recently for biofuels [3]. The negative impacts of oil palm development on biodiversity [1, 4, 5], and on orangutans (Pongo spp.) in particular, have been well documented [6, 7] and publicized [8, 9]. Although the oil palm is of African origin, Africa's production historically lags behind that of Southeast Asia. Recently, significant investments have been made that will likely drive the expansion of Africa's oil palm industry [10]. There is concern that this will lead to biodiversity losses similar to those in Southeast Asia. Here, we analyze the potential impact of oil palm development on Africa's great apes. Current great ape distribution in Africa substantially overlaps with current oil palm concessions (by 58.7%) and areas suitable for oil palm production (by 42.3%). More importantly, 39.9% of the distribution of great ape species on unprotected lands overlaps with suitable oil palm areas. There is an urgent need to develop guidelines for the expansion of oil palm in Africa to minimize the negative effects on apes and other wildlife. There is also a need for research to support land use decisions to reconcile economic development, great ape conservation, and avoiding carbon emissions.

Proceedings from the 2013 American Association of Oral and Maxillofacial Surgeons Research Summit.

The American Association of Oral and Maxillofacial Surgeons, the Oral and Maxillofacial Surgery Foundation, and the International Association of Oral and Maxillofacial Surgeons sponsored the fifth research summit, which convened on May 2 and 3 in Rosemont, Illinois. The Research Summits are convened biennially to facilitate the discussion and collaboration of oral and maxillofacial surgeons with clinical and basic science researchers in fields affecting the specialty. The goal is to advance the field of oral and maxillofacial surgery through exposure and education in topics that ultimately benefit the oral and maxillofacial surgical patient. This edition of the research summit included the topics of robotic surgery and antiresorptive-related osteonecrosis of the jaws (ARONJ). Most importantly, this research summit saw the development of research interest groups (RIGs) in the fields of anesthesia, maxillofacial oncology and reconstructive surgery, obstructive sleep apnea and orthognathic surgery, temporomandibular joint surgery, and trauma. These RIGs developed specific research goals with a plan to continue working on potential projects at the AAOMS Clinical Trials Course on May 7 to 9, 2013 at the University of Michigan in Ann Arbor. The summit program was developed by the AAOMS Committee on Research Planning and Technology Assessment. The charge of the committee is to encourage and promote research within the specialty and to encourage interdisciplinary collaboration. The research summit serves as a platform for oral and maxillofacial surgeons to lead the goal of advancement of research relevant to the specialty. This article provides an overview of the presentations that were made in the sessions on robotic surgery and ARONJ. The research summit keynote address and two additional presentations on patient registries are summarized and updates from the RIGs that were formed at the 2013 research summit are highlighted.

Cost and cost-effectiveness of switching from d4T or AZT to a TDF-based first-line regimen in a resource-limited setting in rural Lesotho.

BACKGROUND: Latest World Health Organization guidelines recommend shifting away from Stavudine (d4T)-based regimens due to severe side effects. However, widespread replacement of d4T by Tenofovir (TDF) or Zidovudine (AZT) is hampered by cost concerns. METHODS: We established the cost-effectiveness of alternative first-line regimens using primary utilization, cost, and outcome data from a program in a rural district in Lesotho. We calculated cost per patient-year, incremental costs, and incremental cost-effectiveness ratios per life year, and per Quality Adjusted Life Year gained. Uncertainty was assessed using multiway and probabilistic sensitivity analyses. RESULTS: Our study included 1260 patients representing 1635 patient-years on antiretroviral therapy (ART). Six hundred eight patients were on TDF, 290 were on AZT, and 362 were on d4T. Patients on d4T experienced more toxicities; toxicities with the biggest impact on quality of life were moderate neuropathy and severe lipodystrophy. The cost per patient-year ranged from US $266 on d4T to US $353 on TDF. Inpatient care and essential drug costs were higher for patients on d4T than on AZT or TDF. Incremental cost-effectiveness ratio results suggest that AZT-based ART is weakly dominated by a combination of d4T- and TDF-based ART. DISCUSSION: This is one of the first analyses to investigate the cost-effectiveness of TDF using primary data in a resource-poor setting. Although TDF-based first-line ART is more costly than d4T, it is also more effective. Political pressure should be exerted to encourage further price reductions and additional generic manufacturing for TDF and partner drugs such as Efavirenz. This should be met by a commitment from donors and implementers to ensure that supply is met by a clear demand.