Associations between toxicity-weighted concentrations and dementia risk: Results from the Cardiovascular Health Cognition Study.

BACKGROUND: Air pollution is a modifiable risk factor for dementia. Yet, studies on specific sources of air pollution (i.e., toxic chemical emissions from industrial facilities) and dementia risk are scarce. We examined associations between toxicity-weighted concentrations of industrial pollution and dementia outcomes among a large, multi-site cohort of older adults. METHODS: Participants (n = 2770) were ≥ 65 years old (Mean = 75.3, SD = 5.1 years) from the Cardiovascular Health Cognition Study (1992-1999). Toxicity-weighted concentrations were estimated using the Risk Screening Environmental Indicator (RSEI) model which incorporates total reported chemical emissions with toxicity, fate, and transport models. Estimates were aggregated to participants' baseline census tract, averaged across 1988-1992, and log2-transformed. Dementia status was clinically adjudicated in 1998-1999 and categorized by subtype (Alzheimer's, vascular, mixed). We assessed whether RSEI-estimated toxicity-weighted concentrations were associated with 1) odds of prevalent dementia and 2) incident dementia risk by subtype. RESULTS: After adjusting for individual and census-tract level covariates, a doubling in toxicity-weighted concentrations was associated with 9 % higher odds of prevalent dementia (OR = 1.09, 95 % CI: 1.00, 1.19). In discrete-time survival models, each doubling in toxicity-weighted concentrations was associated with a 16 % greater hazard of vascular dementia (HR = 1.16, 95 % CI: 1.01, 1.34) but was not significantly associated with all-cause, Alzheimer's disease, or mixed dementia (p's > 0.05). DISCUSSION: Living in regions with higher toxicity-weighted concentrations was associated with higher odds of prevalent dementia and a higher risk of incident vascular dementia in this large, community-based cohort of older adults. These findings support the need for additional studies to examine whether toxic chemical emissions from industrial and federal facilities may be a modifiable target for dementia prevention.

Cardiorespiratory fitness is associated with hippocampal resting state connectivity in women newly diagnosed with breast cancer.

Background: Breast cancer and its treatment are associated with aberrant patterns of resting state functional connectivity (rsFC) between the hippocampus and several areas of the brain, which may account for poorer cognitive outcomes in patients. Higher cardiorespiratory fitness (CRF) has been associated with enhanced rsFC and cognitive performance; however, these associations have not been well studied in breast cancer. We examined the relationship between CRF, rsFC of the hippocampus, and cognitive performance among women newly diagnosed with breast cancer. Methods: Thirty-four postmenopausal women newly diagnosed with Stage 0-IIIa breast cancer (Mage = 63.59 ± 5.73) were enrolled in a 6-month randomized controlled trial of aerobic exercise vs. usual care. During baseline assessments, participants completed functional brain imaging, a submaximal CRF test, and cognitive testing. Whole-brain, seed-based analyses were used to examine the relationship between CRF and hippocampal rsFC, with age, years of education, and framewise displacement included as covariates. Cognition was measured with a battery of validated neurocognitive measures, reduced to seven composite factors. Results: Higher CRF was positively associated with greater rsFC of the hippocampus to a cluster within the dorsomedial and dorsolateral frontal cortex (z-max = 4.37, p = 0.003, cluster extent = 1,020 voxels). Connectivity within cluster peaks was not significantly related to cognitive factors (all ps > 0.05). Discussion: CRF was positively associated with hippocampal rsFC to frontal cortex structures, comprising a network of regions commonly suppressed in breast cancer. Future longitudinal research is needed to explore whether baseline rsFC predicts long-term cognitive resilience in breast cancer.

Impact of the Dog-Human Bond on Canine Social Evaluation: Attachment Predicts Preference toward Prosocial Actors.

Scholars have argued that social evaluation, the capacity to evaluate different potential social partners, is an important capacity not just for humans but for all cooperative species. Recent work has explored whether domesticated dogs share a human-like ability to evaluate others based on prosocial and antisocial actions toward third parties. To date, this work has shown mixed results, suggesting that individual differences may play a role in dogs' capacity to evaluate others. In the present study, we test whether attachment-an individual difference that affects human social evaluation performance-can explain the mixed pattern of social evaluation results observed in dogs. We first tested dogs on a social evaluation task in which an experimenter either helped or refused to help the dog's owner open a container. We then assessed dogs' attachment strength using a subset of the C-BARQ. We found that attachment was a statistically significant predictor of dogs' preference toward the prosocial actor but was not a predictor in antisocial or control conditions. This finding provides early evidence that attachment may drive positivity biases in dogs and that attachment might explain mixed results within canine social evaluation literature.

A structural equation modelling approach to understanding the determinants of childhood vaccination in Nigeria, Uganda and Guinea.

Vaccines have contributed to reductions in morbidity and mortality from preventable diseases globally, but low demand for vaccination threatens to reverse these gains. Explorations of the determinants of vaccination uptake may rely on proxy variables to describe complex phenomena and construct models without reference to underlying theories of vaccine demand. This study aimed to use the results of a formative qualitative study (described elsewhere) to construct and test a model to explain the determinants of vaccination uptake. Using the results of a survey among more than 3,000 primary caregivers of young children in Nigeria, Uganda and Guinea, factor analysis produced six explanatory factors. We then estimated the effects of each of these factors on uptake of immunization using a structural equation model. The results showed that the probability that a child is fully vaccinated increases if a caregiver has support from others to vaccinate them (B = 0.33, ß = 0.21, p<0.001) and if caregivers had poor experiences with the healthcare system (B = 0.09, ß = 0.09, p = 0.007). Conversely, the probability of full vaccination decreases if the caregiver's husband exerts control over her decision-making ability (B = -0.29, ß = -0.20, p<0.001), or if the caregiver perceives vaccines to be of low importance (B = -0.37, ß = -0.27, p<0.001). Belief in religious protection (B = -0.07, ß = -0.05, p = 0.118) and a belief that vaccines are harmful (B = -0.12, ß = -0.04, p = 0.320) did not have an observed effect on vaccination status. This research suggests that interventions may benefit from that including entire families and communities in their design.

Applying a social-ecological model to understand factors impacting demand for childhood vaccinations in Nigeria, Uganda, and Guinea.

Vaccines have reduced child mortality across the world, but low levels of demand for vaccination threatens to undermine progress. Existing frameworks to understand demand tend to prioritise primary caregivers' decision-making processes. We aimed to build a wider understanding of vaccine demand by applying an adapted socio-ecological model to analyse 158 interviews with primary caregivers and fathers of young children, and community influencers in Nigeria, Uganda, and Guinea. We found that several factors come together to inform a primary caregiver's demand for vaccination, including their familial and social relationships, their interactions with government and healthcare institutions, and the wider social and cultural norms in their communities. The study suggests that interventions targeted at families and communities instead of individuals could be effective. The results could be used to ensure that vaccine demand frameworks used by researchers and intervention designers are comprehensive and consider a wider range of influences on the primary caregiver.

Antibacterial Drug Residues in Small Ruminant Edible Tissues and Milk: A Literature Review of Commonly Used Medications in Small Ruminants.

This review provides a summary of extracted data from the published literature that contains drug residue depletion data for edible tissues and milk following treatment of sheep and goats. Out of 20,234 records obtained during the initial search, data from 177 records were included in this review. The data is separated by antibiotic class for ease of comparison between studies. Extracted data includes the active ingredient, dosing information, animal health status, analytical method and limits of detection, tolerance and maximum residue limit information, and time frames relative to residue absence or detection. This information is useful for understanding drug residue depletion profiles following extra-label use and for estimating withdrawal intervals, in order to protect the human food chain.

Comparison of florfenicol depletion in dairy goat milk using ultra-performance liquid chromatography with tandem mass spectrometry and a commercial on-farm test.

Florfenicol is a broad-spectrum antibiotic commonly prescribed in an extra-label manner for treating meat and dairy goats. Scientific data in support of a milk withdrawal interval recommendation is limited to plasma pharmacokinetic data and minimal milk residue data that is limited to cattle. Therefore, a rapid residue detection test (RRDT) could be a useful resource to determine if milk samples are free of drug residues and acceptable for sale. This study compared a commercially available RRDT (Charm® FLT strips) to detect florfenicol residues in fresh milk samples from healthy adult dairy breed goats treated with florfenicol (40 mg/kg subcutaneously twice 4 days apart) with quantitative analysis of florfenicol concentrations using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS). In addition, storage claims for testing bovine milk using the RRDT were assessed using stored goat milk samples. Milk samples were collected every 12 h for a minimum of 26 days. Commercial RRDT strips remained positive in individual goats ranging from 528 to 792 h (22-33 days) after the second dose, whereas, UPLC-MS/MS indicated the last detectable florfenicol concentration in milk samples ranged from 504 to 720 h (21-30 days) after the second dose. Results from stored milk samples from treated goats indicate that samples can be stored for up to 5 days in the refrigerator and 60 days in the freezer after milking prior to being tested with a low risk of false-negative test results due to drug degradation. Elevated somatic cell counts and bacterial colony were noted in some of the milk samples in this study, but further study is required to understand the impact of these quality factors on RRDT results.

A web-based interactive physiologically based pharmacokinetic (iPBPK) model for meloxicam in broiler chickens and laying hens.

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) commonly used in food-producing animals, including chickens in an extralabel manner. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model for meloxicam in broiler chickens and laying hens to facilitate withdrawal interval (WDI) estimations. The model structure for broiler chickens contained six compartments including plasma, muscle, liver, kidney, fat and rest of body, while an additional compartment of ovary was included for laying hens. The model adequately simulated available pharmacokinetic data of meloxicam in plasma of broiler chickens as well as tissue and egg data of laying hens. The model was converted to a web-based interface and used to predict WDIs following extralabel administrations. The results showed that the estimated WDIs were 50, 44, 11, 3, 3, 22 and 4 days for liver, kidney, muscle, fat, ovary, yolk and white, respectively in laying hens after 14 repeated oral administrations of meloxicam (1 mg/kg) at 24-h intervals. This model provides a useful and flexible tool for risk assessment and management of residues for meat and eggs from chickens treated with meloxicam and will serve as a basis for extrapolation to other NSAID drugs and other poultry species to aid animal-derived food safety assessment.

Residue depletion profiles and withdrawal interval estimations of meloxicam in eggs and ovarian follicles following intravenous (Meloxicam solution for injection) and oral (Meloxidyl®) administration in domestic chickens (Gallus domesticus).

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) commonly prescribed in an extralabel manner for treating chickens in urbanized settings. The objectives of this study were to determine meloxicam depletion profiles in eggs and ovarian follicles and to estimate associated withdrawal intervals (WDI) in laying hens following a single intravenous or repeated oral administration. The observed peak concentration of meloxicam in ovarian follicles were consistently higher than in egg yolk and egg white samples. Terminal half-lives were 31-h, 113-h and 12-h in ovarian follicles, egg yolk and egg white samples, respectively, for repeated oral administrations at 1 mg/kg for 20 doses at 12-h intervals. The terminal half-life following a single intravenous administration at 1 mg/kg was 50-h for ovarian follicles. Meloxicam WDI estimations using ovarian follicle and egg yolk concentration data following 20 doses at 12-h intervals were 36 and 12 days, respectively. Meloxicam WDI estimation using egg yolk concentration data following 8 doses at 24-h intervals was 12 days. These results improve our understanding on the residue depletion of meloxicam from chickens' reproductive tracts and egg products and provide WDIs to help ensure food safety for humans consuming eggs from treated laying hens.

Pharmacokinetic Parameters and Estimating Extra-Label Tissue Withdrawal Intervals Using Three Approaches and Various Matrices for Domestic Laying Chickens Following Meloxicam Administration.

Meloxicam is commonly prescribed for treating chickens in backyard or small commercial operations despite a paucity of scientific data establishing tissue withdrawal interval recommendations following extra-label drug use (ELDU). Historically, ELDU withdrawal intervals (WDIs) following meloxicam administration to chickens have been based on the time when meloxicam concentrations fall below detectable concentrations in plasma and egg samples. To date, no studies have addressed tissue residues. ELDU WDIs are commonly calculated using terminal elimination half-lives derived from pharmacokinetic studies. This study estimated pharmacokinetic parameters for laying hens following meloxicam administration and compared ELDU WDIs calculated using tissue terminal elimination half-lives vs. those calculated using FDA tolerance and EMA's maximum regulatory limit statistical methods, respectively. In addition, ELDU WDIs were calculated using plasma meloxicam concentrations from live birds to determine if plasma data could be used as a proxy for estimating tissue WDIs. Healthy domestic hens were administered meloxicam at 1 mg/kg intravenous (IV) once, 1 mg/kg orally (PO) once daily for eight doses or 1 mg/kg PO twice daily for 20 doses. Analytical method validation was performed and meloxicam concentrations were quantified using high-performance liquid chromatography. In general, the terminal elimination technique resulted in the longest ELDU WDIs, followed by the FDA tolerance and then EMA's maximum residue limit methods. The longest ELDU WDIs were 72, 96, and 384 (or 120 excluding fat) h for the IV, PO once daily for eight doses, and PO twice daily for 20 doses, respectively. Plasma data are a possible dataset for estimating a baseline for tissue ELDU WDI estimations when tissue data are not available for chickens treated with meloxicam. Finally, pharmacokinetic parameters were similar in laying hens to those published for other avian species.

Large-Scale Data Mining of Rapid Residue Detection Assay Data From HTML and PDF Documents: Improving Data Access and Visualization for Veterinarians.

Extra-label drug use in food animal medicine is authorized by the US Animal Medicinal Drug Use Clarification Act (AMDUCA), and estimated withdrawal intervals are based on published scientific pharmacokinetic data. Occasionally there is a paucity of scientific data on which to base a withdrawal interval or a large number of animals being treated, driving the need to test for drug residues. Rapid assay commercial farm-side tests are essential for monitoring drug residues in animal products to protect human health. Active ingredients, sensitivity, matrices, and species that have been evaluated for commercial rapid assay tests are typically reported on manufacturers' websites or in PDF documents that are available to consumers but may require a special access request. Additionally, this information is not always correlated with FDA-approved tolerances. Furthermore, parameter changes for these tests can be very challenging to regularly identify, especially those listed on websites or in documents that are not publicly available. Therefore, artificial intelligence plays a critical role in efficiently extracting the data and ensure current information. Extracting tables from PDF and HTML documents has been investigated both by academia and commercial tool builders. Research in text mining of such documents has become a widespread yet challenging arena in implementing natural language programming. However, techniques of extracting tables are still in their infancy and being investigated and improved by researchers. In this study, we developed and evaluated a data-mining method for automatically extracting rapid assay data from electronic documents. Our automatic electronic data extraction method includes a software package module, a developed pattern recognition tool, and a data mining engine. Assay details were provided by several commercial entities that produce these rapid drug residue assay tests. During this study, we developed a real-time conversion system and method for reflowing contents in these files for accessibility practice and research data mining. Embedded information was extracted using an AI technology for text extraction and text mining to convert to structured formats. These data were then made available to veterinarians and producers via an online interface, allowing interactive searching and also presenting the commercial test assay parameters in reference to FDA-approved tolerances.

Differences in adolescent cerebral perfusion as a function of obesity: Results from the FLEX-Brain study.

OBJECTIVE: Children and adolescents have greater resting cerebral blood flow (rCBF) during periods of rapid brain growth. Overweight and obesity have a global impact on brain cerebrovascular health in adults, but whether these effects are discernable in adolescents with overweight and obesity remains unknown. This study examined differences in rCBF between adolescents with a healthy weight (HW) and adolescents with overweight or obesity (OW). METHODS: The current study focused on analyzing data from 58 participants (mean age = 15.43 [SD 1.37] years). Participants were classified into OW (n = 38) and HW groups (n = 20) according to the Centers for Disease Control and Prevention's guidelines for children. Voxelwise t tests between the HW and OW groups were conducted to test for regional group differences in rCBF, controlling for age and sex. Mean rCBF was extracted from a gray matter mask to compare global rCBF between the HW and OW groups. RESULTS: The HW group had greater rCBF compared with the OW group in five clusters, with peaks in the cerebellum, precentral gyrus, and supplementary motor area. No clusters survived correction for the OW > HW contrast. Global rCBF did not significantly differ between the groups (p = 0.09). CONCLUSIONS: These results suggest that overweight and obesity in adolescence are associated with discernable reductions in blood flow to specific brain regions rather than having a global impact on rCBF.

Neural effects of placebo analgesia in fibromyalgia patients and healthy individuals.

ABSTRACT: Placebo analgesia is hypothesized to involve top-down engagement of prefrontal regions that access endogenous pain inhibiting opioid pathways. Fibromyalgia (FM) patients have neuroanatomical and neurochemical alterations in pathways relevant to placebo analgesia. Thus, it remains unclear whether placebo analgesic mechanisms would differ in FM patients compared to healthy controls (HCs). Here, using placebo-analgesia-inducing paradigms that included verbal suggestions and conditioning manipulations, we examined whether behavioral and neural placebo analgesic responses differed between 32 FM patients and 46 age- and sex-matched HCs. Participants underwent a manipulation scan, where noxious high and low heat were paired with the control and placebo cream, respectively, and a placebo experimental scan with equal noxious heat temperatures. Before the experimental scan, each participant received saline or naloxone, an opioid receptor antagonist. Across all participants, the placebo condition decreased pain intensity and unpleasantness ratings, decreased activity within the right insula and bilateral secondary somatosensory cortex, and modulated the neurologic pain signature. There were no differences between HCs and FM patients in pain intensity ratings or neural responses during the placebo condition. Despite the perceptual and neural effects of the placebo manipulation, prefrontal circuitry was not activated during the expectation period and the placebo analgesia was unaltered by naloxone, suggesting placebo effects were driven more by conditioning than expectation. Together, these findings suggest that placebo analgesia can occur in both HCs and chronic pain FM patients, without the involvement of opioidergic prefrontal modulatory networks.

Default mode network changes in fibromyalgia patients are largely dependent on current clinical pain.

Differences in fMRI resting-state connectivity of the default mode network (DMN) seen in chronic pain patients are often interpreted as brain reorganization due to the chronic pain condition. Nevertheless, patients' pain at the time of fMRI might influence the DMN because pain, like cognitive stimuli, engages attentional mechanisms and cognitive engagement is known to alter DMN activity. Here, we aimed to dissociate the influence of chronic pain condition (trait) from the influence of current pain experience (state) on DMN connectivity in patients with fibromyalgia (FM). We performed resting-state fMRI scans to test DMN connectivity in FM patients and matched healthy controls in two separate cohorts: (1) in a cohort not experiencing pain during scanning (27 FM patients and 27 controls), (2) in a cohort with current clinical pain during scanning (16 FM patients and 16 controls). In FM patients without pain during scanning, the connectivity of the DMN did not differ significantly from controls. By contrast, FM patients with current clinical pain during the scan had significantly increased DMN connectivity to bilateral anterior insula (INS) similar to previous studies. Regression analysis showed a positive relationship between DMN-midINS connectivity and current pain. We therefore suggest that transient DMN disruptions due to current clinical pain during scanning (current pain state) may be a substantial contributor to DMN connectivity disruptions observed in chronic pain patients.

Clinical Pharmacist-Led Impact on Inappropriate Albumin Use and Costs in the Critically Ill.

Background:Optimal albumin use in the intensive care unit (ICU) remains challenging with inappropriate use approaching 50%. No published reports have described clinical pharmacist impact aimed at mitigating inappropriate albumin use in the ICU. Objective: To evaluate the clinical and economic impact of a clinical pharmacist-led intervention strategy targeting inappropriate albumin in the ICU. Methods: A retrospective cohort study evaluated all adult (≥18 years) ICU patients administered albumin at an academic medical center over a 2-year period. Institutional guidelines were developed with clinical pharmacists targeting inappropriate albumin use. The primary end point was to compare inappropriate use of albumin administered before and after pharmacist intervention implementation. Secondary analyses compared the overall albumin use between study periods. In-hospital mortality, length of stay, and albumin-related costs between study periods were also compared. Results: A total of 4419 patients were identified, with 2448 (55.4%) critically ill patients included. The pharmacist-led strategy resulted in a 50.9% reduction of inappropriate albumin use (P < 0.001). The rate of inappropriate albumin use was 44.3 ± 10.5 and 5.5 ± 2.9 g per patient-day in the preimplementation and postimplementation periods, respectively (P < 0.001). Costs associated with overall and inappropriate albumin use in the ICU decreased by 34.8% and 87.1%, respectively. Total annual cost-savings was $355 393 in the ICUs. No differences in clinical outcomes were found. Conclusion and Relevance: Clinical pharmacist-led interventions reduced overall and inappropriate albumin use and costs without negatively affecting clinical outcomes.

Attitudes and Perceptions Toward Authorized Deception: A Pilot Comparison of Healthy Controls and Fibromyalgia Patients.

OBJECTIVE: Little is known about the perceptions and attitudes of participants who volunteer in studies involving authorized deception. Thus, this cross-sectional pilot study measured, for the first time, the perceptions about participation in an authorized-deception placebo analgesia study in chronic pain patients with fibromyalgia and assessed whether their perceptions differed from healthy controls. METHODS: An anonymous survey with questions about trust in research and willingness to participate in future research involving deception was mailed to participants in both groups after completion of the parent study. Statistical analyses were performed using the Mann-Whitney U and chi-square tests (31 controls and 16 fibromyalgia patients were included in the analyses). RESULTS: The majority of participants expressed little or no concern about the deception, still trusted the scientific process, and found the debriefing procedure helpful and worthwhile. Group differences were found in willingness to 1) participate in the parent study had the deceptive element been disclosed in advance (controls = definitely, fibromyalgia patients = probably, U = 341.5, P = 0.01) and 2) participate in future studies (controls = definitely, fibromyalgia patients = probably, U = 373, P < 0.001). CONCLUSIONS: Despite slightly less favorable responses of fibromyalgia patients and the relatively small size of the study, these findings suggest that attitudes and perceptions about participating in an authorized placebo study remain positive in both healthy and chronic pain populations.

Consensus Recommendations for Optimizing Electronic Health Records for Nutrition Care.

Provision of nutrition care is vital to the health and well-being of any patient who enters the health care system, whether in the ambulatory, inpatient, or long-term care setting. Interdisciplinary professionals-nurses, physicians, advanced practice providers, pharmacists, and dietitians-identify and treat nutrition problems or clinical conditions in each of these health care settings. The documentation of nutrition care in a structured format from screening and assessment to discharge allows communication of the nutrition treatment plans. The goal of this document is to provide recommendations to clinicians for working with an organization's Information Systems department to create tools for documentation of nutrition care in the electronic health record. These recommendations can also serve as guidance for health care organizations choosing and implementing health care software.

Consensus Recommendations for Optimizing Electronic Health Records for Nutrition Care.

Provision of nutrition care is vital to the health and well-being of any patient who enters the health care system, whether in the ambulatory, inpatient, or long-term care setting. Interdisciplinary professionals-nurses, physicians, advanced practice providers, pharmacists, and dietitians-identify and treat nutrition problems or clinical conditions in each of these health care settings. The documentation of nutrition care in a structured format from screening and assessment to discharge allows communication of the nutrition treatment plans. The goal of this document is to provide recommendations to clinicians for working with an organization's Information Systems department to create tools for documentation of nutrition care in the electronic health record. These recommendations can also serve as guidance for health care organizations choosing and implementing health care software.

Pharmacist Outlooks on Prescribing Hormonal Contraception Following Statewide Scope of Practice Expansion.

In an effort to increase access to contraception, the pharmacist scope of practice is being expanded to allow prescribing. While this is being accomplished in the United States by a variety of models, legislation that allows pharmacists to prescribe hormonal contraception under a statewide protocol is the most common. This study was designed to explore the outlooks of pharmacists regarding prescribing contraception in the period following the first state legislation and prior to statewide protocol development and availability. A qualitative study of community pharmacists in California using structured phone interviews explored their opinions regarding access to contraception in pharmacies and outlooks regarding prescribing. Data were analyzed using an inductive approach to identify themes. Among the thirty participants, the majority worked in a chain pharmacy. Themes were identified in five overarching domains: Pharmacist barriers, system barriers, patient issues, safety concerns, and pharmacist role. Most were unfamiliar with the new law, yet were interested in expanding access for patient benefit despite foreseeing challenges with implementing the service in community pharmacies. Barriers will need to be addressed and requisite training disseminated widely to facilitate successful implementation and thus improve access on a broad scale. Further research following protocol implementation is needed to understand service implementation, as well as patient utilization and satisfaction.