Mapping the distribution of health equity research and practice across a university: a network analysis.

Introduction: Health equity research spans various disciplines, crossing formal organizational and departmental barriers and forming invisible communities. This study aimed to map the nomination network of scholars at the University of Rochester Medical Center who were active in racial and ethnic health equity research, education, and social/administrative activities, to identify the predictors of peer recognition. Methods: We conducted a snowball survey of faculty members with experience and/or interest in racial and ethnic health equity, nominating peers with relevant expertise. Results: Data from a total of 121 individuals (64% doing research on extent and outcomes of racial/ethnic disparities and racism, 48% research on interventions, 55% education, and 50% social/administrative activities) were gathered in six rounds of survey. The overlap between expertise categories was small with coincidence observed between education and social/administrative activities (kappa: 0.27; p < 0.001). Respondents were more likely to nominate someone if both were involved in research (OR: 3.1), if both were involved in education (OR: 1.7), and if both were affiliated with the same department (OR: 3.7). Being involved in health equity research significantly predicted the centrality of an individual in the nomination network, and the most central actors were involved in multiple expertise categories. Conclusions: Compared with equity researchers, those involved in racial equity social/administrative activities were less likely to be recognized by peers as equity experts.

Assessment of Mouse Liver Histopathology Following Exposure to HFPO-DA With Emphasis on Understanding Mechanisms of Hepatocellular Death.

Ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate (HFPO-DA) is a short chain member of per- and polyfluoroalkyl substances (PFAS). To better understand the relevance of histopathological effects seen in livers of mice exposed to HFPO-DA for human health risk assessment, histopathological effects were summarized from hematoxylin and eosin (H&E)-stained sections in several repeat-dose toxicity studies in mice. Findings across studies revealed histopathological changes consistent with peroxisomal proliferation, whereas two reports of steatosis could not be confirmed in the published figures. In addition, mechanisms of hepatocellular death were assessed in H&E sections as well as with the apoptotic marker cleaved caspase-3 (CCasp3) in newly cut sections from archived liver blocks from select studies. A comparison of serially CCasp3 immunolabeled and H&E-stained sections revealed that mechanisms of hepatocellular death cannot be clearly discerned in H&E-stained liver sections alone as several examples of putatively necrotic cells were positive for CCasp3. Published whole genome transcriptomic data were also reevaluated for enrichment of various forms of hepatocellular death in response to HFPO-DA, which revealed enrichment of apoptosis and autophagy, but not ferroptosis, pyroptosis, or necroptosis. These morphological and molecular findings are consistent with transcriptomic evidence for peroxisome proliferator-activated receptor alpha (PPARα) signaling in HFPO-DA exposed mice.

Assessment of the mode of action underlying development of liver lesions in mice following oral exposure to HFPO-DA and relevance to humans.

HFPO-DA (ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoate) is a short-chain polyfluorinated alkyl substance (PFAS) used in the manufacture of some types of fluorinated polymers. Like many PFAS, toxicity studies with HFPO-DA indicate the liver is the primary target of toxicity in rodents following oral exposure. Due to the structural diversity of PFAS, the mode of action (MOA) can differ between PFAS for the same target tissue. There is significant evidence for involvement of peroxisome proliferator-activated receptor alpha (PPARα) activation based on molecular and histopathological responses in the liver following HFPO-DA exposure, but other MOAs have also been hypothesized based on limited evidence. The MOA underlying the liver effects in mice exposed to HFPO-DA was assessed in the context of the Key Events (KEs) outlined in the MOA framework for PPARα activator-induced rodent hepatocarcinogenesis. The first 3 KEs (ie, PPARα activation, alteration of cell growth pathways, and perturbation of cell growth/survival) are supported by several lines of evidence from both in vitro and in vivo data available for HFPO-DA. In contrast, alternate MOAs, including cytotoxicity, PPARγ and mitochondrial dysfunction are generally not supported by the scientific literature. HFPO-DA-mediated liver effects in mice are not expected in humans as only KE 1, PPARα activation, is shared across species. PPARα-mediated gene expression in humans produces only a subset (ie, lipid modulating effects) of the responses observed in rodents. As such, the adverse effects observed in rodent livers should not be used as the basis of toxicity values for HFPO-DA for purposes of human health risk assessment.

Apolipoprotein E and Health in Older Men: The Concord Health and Ageing in Men Project.

APOE genotype has been associated with various age-related outcomes including Alzheimer's disease, frailty, and mortality. In this study, the relationship between health, particularly cognitive function, and APOE was investigated in older men from the Concord Health and Ageing in Men Project (n = 1,616; age 76.9 ± 5.5 years [range 70-97 years]; Australia). Baseline characteristics and survival up to 12 years were determined. Frailty was measured using Cardiovascular Health study (CHS) criteria and Rockwood frailty index, and cognition using Mini-Mental State Examination (MMSE) and Addenbrookes Cognitive Examination. APOE ε4 was less common in the oldest men and those born in Mediterranean countries. APOE ε2 was beneficially associated with cholesterol, creatinine, gamma-glutamyl transaminase, glucose, and HDL cholesterol while APOE ε4 was adversely associated with cholesterol and albumin. APOE ε4 was associated with a clinical diagnosis of Alzheimer's disease when adjusted for age and region of birth (ε4 homozygotes Odds ratio (OR) 7.0; ε4 heterozygotes OR 2.4, p < .05), and APOE ε2 had a small positive association with cognition. On multivariate regression, overall cognitive function in the entire cohort was associated with age, country of birth, education, and frailty (all p < .001). APOE was not associated with frailty or survival. In conclusion, age and region of birth influenced distribution of APOE genotype in older men. Although APOE ε4 was associated with Alzheimer's disease, overall cognitive function in the cohort was associated more strongly with frailty than APOE genotype.

Assessment of the Mode of Action Underlying the Effects of GenX in Mouse Liver and Implications for Assessing Human Health Risks.

GenX is an alternative to environmentally persistent long-chain perfluoroalkyl and polyfluoroalkyl substances. Mice exposed to GenX exhibit liver hypertrophy, elevated peroxisomal enzyme activity, and other apical endpoints consistent with peroxisome proliferators. To investigate the potential role of peroxisome proliferator-activated receptor alpha (PPARα) activation in mice, and other molecular signals potentially related to observed liver changes, RNA sequencing was conducted on paraffin-embedded liver sections from a 90-day subchronic toxicity study of GenX conducted in mice. Differentially expressed genes were identified for each treatment group, and gene set enrichment analysis was conducted using gene sets that represent biological processes and known canonical pathways. Peroxisome signaling and fatty acid metabolism were among the most significantly enriched gene sets in both sexes at 0.5 and 5 mg/kg GenX; no pathways were enriched at 0.1 mg/kg. Gene sets specific to the PPARα subtype were significantly enriched. These findings were phenotypically anchored to histopathological changes in the same tissue blocks: hypertrophy, mitoses, and apoptosis. In vitro PPARα transactivation assays indicated that GenX activates mouse PPARα. These results indicate that the liver changes observed in GenX-treated mice occur via a mode of action (MOA) involving PPARα, an important finding for human health risk assessment as this MOA has limited relevance to humans.

Identifying and Addressing Barriers to Osteoporosis Treatment Associated with Improved Outcomes: An Observational Cohort Study.

OBJECTIVE: To identify and address patient-reported barriers in osteoporosis care after a fracture. METHODS: A longitudinal cohort of fragility fracture patients over 50 years of age was seen in a provincewide fracture liaison service. Followup interviews were done at 6 months for osteoporosis care indicators. Univariate statistics were used to describe baseline characteristics, osteoporosis-related outcomes, and reasons cited for not achieving them. Two phases of this program were compared (Phase I: education and communication, and Phase II: risk assessment education and communication). Phase II was further divided into those who fully participated and those who declined. RESULTS: Phase I (n = 3997) had lower testing and treatment rates than Phase II (n = 1363). Rates were highest in those confirmed as having participated in Phase II (n = 569). Phase II nonparticipants (n = 794) had results as in Phase I. In Phase I, the main patient-reported barriers for not visiting their physician or not having a bone mineral density (BMD) test were patient- and physician-oriented (e.g., being instructed by their physician to not have the BMD test). In Phase II, BMD testing was part of the program, thus the main barriers were around treatment choices. Phase II eligible nonparticipants experienced many of the same barriers as Phase I patients, with lower BMD testing rates (54.9% and 65.4%, respectively). CONCLUSION: Evaluating and addressing barriers to guideline implementation reduced those barriers and was associated with higher downstream treatment rates. Monitoring barriers in a program like this provides useful insights for program changes and research interventions.

Participation in Hospital in the Home for patients in inner metropolitan Sydney: implications for access and equity.

Objective The aim of this study was to identify whether the Hospital in the Home (HITH) program was taken up equitably by eligible patients in relation to their age, sex, country of birth, place of residence and primary diagnosis. Methods This study presents results of a descriptive analysis of the administrative records of 3552 people with specific conditions who met the study criteria of potential eligibility to HITH and resided within the health district boundary. Results Systematic differences were found for participation in HITH and in-patient care according to sex, language spoken at home and socioeconomic status based on place of residence. This suggests that people from higher socioeconomic backgrounds who speak English at home were more likely to participate in and benefit from HITH. Tailored interventions were identified as a potential way to reduce the gap in access to quality health care for women and people who speak a language other than English at home. If HITH is the optimum treatment available, then these differences could be considered potentially avoidable and unfair. Conclusion Data analysis through an equity lens can effectively identify who is accessing health services and who is missing out. Further analysis is required to understand patient and system barriers to accessing HITH. What is known about the topic? Advances in medical and surgical treatments and pharmaceuticals reduce the need for in-patient hospitalisation. For some conditions, home-based treatment is safer, cheaper and preferable to the patient and carers, particularly some older people who may experience deteriorating cognitive and physical functioning related to hospitalisation. It is well known that health and access to health care is not equally distributed in society. What does this paper add? This study represents the first effort to quantitatively evaluate differences in patterns of participation in HITH related to socioeconomic and language characteristics. There are underutilised opportunities for improved participation in HITH by identifying who is not accessing programs at a comparable rate and therefore not benefitting from optimal health services. By exploring why this may be occurring at an individual and system level, we can be more informed to address these reasons and achieve better health and social outcomes. What are the implications for practitioners? It is important to consider both consumer and service provider views in shaping current and future service models. Comprehensive assessment of support needs to participate in HITH for patients and carers, as well as communicating potential benefits in ways patients understand, can improve participation and satisfaction, reduce health costs and improve health outcomes.

Preclinical assessment of antiviral combination therapy in a genetically humanized mouse model for hepatitis delta virus infection.

Chronic delta hepatitis, caused by hepatitis delta virus (HDV), is the most severe form of viral hepatitis, affecting at least 20 million hepatitis B virus (HBV)-infected patients worldwide. HDV/HBV co- or superinfections are major drivers for hepatocarcinogenesis. Antiviral treatments exist only for HBV and can only suppress but not cure infection. Development of more effective therapies has been impeded by the scarcity of suitable small-animal models. We created a transgenic (tg) mouse model for HDV expressing the functional receptor for HBV and HDV, the human sodium taurocholate cotransporting peptide NTCP. Both HBV and HDV entered hepatocytes in these mice in a glycoprotein-dependent manner, but one or more postentry blocks prevented HBV replication. In contrast, HDV persistently infected hNTCP tg mice coexpressing the HBV envelope, consistent with HDV dependency on the HBV surface antigen (HBsAg) for packaging and spread. In immunocompromised mice lacking functional B, T, and natural killer cells, viremia lasted at least 80 days but resolved within 14 days in immunocompetent animals, demonstrating that lymphocytes are critical for controlling HDV infection. Although acute HDV infection did not cause overt liver damage in this model, cell-intrinsic and cellular innate immune responses were induced. We further demonstrated that single and dual treatment with myrcludex B and lonafarnib efficiently suppressed viremia but failed to cure HDV infection at the doses tested. This small-animal model with inheritable susceptibility to HDV opens opportunities for studying viral pathogenesis and immune responses and for testing novel HDV therapeutics.

Residential age care and domiciliary oral health services: Reach-OHT-The development of a metropolitan oral health programme in Sydney, Australia.

OBJECTIVE: To describe an oral health care programme for older people in Residential Aged Care Facilities (RACFs) to improve access to care and support facilities. INTRODUCTION: Different models of residential care have been proposed, but few have been comprehensive (providing on-site health promotion and service delivery) or sustainable. METHODS: A partnership model of oral health care, with dental services plus oral health education, was integrated into the community outreach services of a metropolitan hospital department of aged care. The programme provided annual oral health education and training to staff, and on-site dental care to 10 (RACFs). RESULTS: None of the RACFs had received organised education or on-site dental service care prior to the programme. At the completion of the third year of the programme, 607 residents (75% of the total bed capacity for the 10 RACFs) had received an annual oral health assessment, and 271 (46.5%) had received on-site dental care. More than 120 nursing and allied health staff had received education and training in oral health support to residents. Oral cleanliness, the proportion not experiencing dental pain and referral for additional care decreased significantly over the period, but dental caries experience and periodontal conditions remained a concern. CONCLUSIONS: Sustainable domiciliary oral health services and oral health education are feasible and practical using a partnership model within the Australian health system. Adaptability, continuity and the use of oral health therapists/dental hygienists in the coordination and management of the programme further contribute to viability.

Aortic anatomic severity grade correlates with resource utilization.

BACKGROUND: Potential cost effectiveness of endovascular aneurysm repair (EVAR) compared with open aortic repair (OAR) is offset by the use of intraoperative adjuncts (components) or late reinterventions. Anatomic severity grade (ASG) can be used preoperatively to assess abdominal aortic aneurysms, and provide a quantitative measure of anatomic complexity. The hypothesis of this study is that ASG is directly related to the use of intraoperative adjuncts and cost of aortic repair. METHODS: Patients who undergo elective OAR and EVAR for abdominal aortic aneurysms were identified over a consecutive 3-year period. ASG scores were calculated manually using three-dimensional reconstruction software by two blinded reviewers. Statistical analysis of cost data was performed using a log transformation. Regression analyses, with a continuous or dichotomous outcome, used a generalized estimating equations approach with the sandwich estimator, being robust with respect to deviations from model assumptions. RESULTS: One hundred forty patients were identified for analysis, n = 33 OAR and n = 107 EVAR. The mean total cost (± standard deviation) for OAR was per thousand (k) $38.3 ± 49.3, length of stay (LOS) 13.5 ± 14.2 days, ASG score 18.13 ± 3.78; for EVAR, mean total cost was k $24.7 ± 13.0 (P = .016), LOS 3.0 ± 4.4 days (P = .012), ASG score 15.9 ± 4.13 (P = .010). In patients who underwent EVAR, 25.2% required intraoperative adjuncts, and analysis of this group revealed a mean total cost of k $31.5 ± 15.9, ASG score 18.48 ± 3.72, and LOS 3.9 ± 4.5, which were significantly greater compared with cases without adjunctive procedures. An ASG score of ≥15 correlated with an increased propensity for requirement of intraoperative adjuncts; odds ratio, 5.75 (95% confidence interval, 1.82-18.19). ASG >15 was also associated with chronic kidney disease, end stage renal disease, hypertension, female sex, increased cost, and use of adjunctive procedures. CONCLUSIONS: Complex aneurysm anatomy correlates with increased total cost and need for adjunctive procedures during EVAR. Preoperative assessment with ASG scores can delineate patients at greater risk for increased resource use. Patient comorbid factors are associated with anatomic complexity defined according to ASG. A critical examination of the relationship between anatomic complexity and finances is required within the context of aggressive endovascular treatment strategies and shifts toward value-based reimbursement.

Liver biomarker and in vitro assessment confirm the hepatic origin of aminotransferase elevations lacking histopathological correlate in beagle dogs treated with GABAA receptor antagonist NP260.

NP260 was designed as a first-in-class selective antagonist of α4-subtype GABAA receptors that had promising efficacy in animal models of pain, epilepsy, psychosis, and anxiety. However, development of NP260 was complicated following a 28-day safety study in dogs in which pronounced elevations of serum aminotransferase levels were observed, although there was no accompanying histopathological indication of hepatocellular injury. To further investigate the liver effects of NP260, we assayed stored serum samples from the 28-day dog study for liver specific miRNA (miR-122) as well as enzymatic biomarkers glutamate dehydrogenase and sorbitol dehydrogenase, which indicate liver necrosis. Cytotoxicity assessments were conducted in hepatocytes derived from dog, rat, and human liver samples to address the species specificity of the liver response to NP260. All biomarkers, except ALT, returned toward baseline by Day 29 despite continued drug treatment, suggesting adaptation to the initial injury. In vitro analysis of the toxicity potential of NP260 to primary hepatocytes indicated a relative sensitivity of dog>human>rat, which may explain, in part, why the liver effects were not evident in the rodent safety studies. Taken together, the data indicate that a diagnostic biomarker approach, coupled with sensitive in vitro screening strategies, may facilitate interpretation of toxicity potential when an adaptive event masks the underlying toxicity.

Community influences on intimate partner violence in India: Women's education, attitudes towards mistreatment and standards of living.

Intimate partner violence (IPV) directed towards women is a serious public health problem. Women's education may offer protection against IPV, but uncertainty exists over how it might reduce risk for IPV at the community and individual levels. The objectives of this study are to: (1) disentangle community from individual-level influences of women's education on risk for IPV; (2) quantify the moderating influence of communities on individual-level associations between women's education and IPV; (3) determine if women's attitudes towards mistreatment and living standards at the community and individual levels account for the protective influence of women's education; and (4) determine if the protective influence of education against IPV is muted among women living in communities exhibiting attitudes more accepting of mistreatment. Study information came from 68,466 married female participants in the National Family Health Survey conducted throughout India in 1998-1999. Multilevel logistic regression was used to address the study objectives. IPV showed substantial clustering at both the state (10.2%) and community levels (11.5%). At the individual level, there was a strong non-linear association between women's education and IPV, partially accounted for by household living standards. The strength of association between women's education and IPV varied from one community to the next with evidence that the acceptance of mistreatment at the community level mutes the protective influence of higher education. Furthermore, women's attitudes towards mistreatment and their standards of living accounted for community-level associations between women's education and IPV. Place of residence accounted for substantial variation in risk of IPV and also modified individual-level associations between IPV and women's education. At the community level, women's education appeared to exert much of its protective influence by altering population attitudes towards the acceptability of mistreatment. However, there was no residual association between women's education and IPV at the community level once living standards are taken into account. While women's education provides strong, independent leverage for reducing the risk of IPV, planners must keep in mind important community factors that modify its protective influence.

The role of pathology in the identification of drug-induced hepatic toxicity.

Pathologists play a central role in the recognition and prevention of drug-induced toxicity. Pathologists engaged in clinical practice must identify a pattern of histological lesions that are interpreted in concert with a variety of clinical data to determine the probability of drug-induced toxicity versus background disease processes and the most likely drug, often of many, to have caused the specific injury. Toxicological pathologists, working in concert with other scientists, have the responsibility of preventing drug-induced toxicity in humans by identifying potentially toxic drugs and keeping them from the marketplace. In this process of drug development, a broad array of in vivo testing using a number of animal species and in vitro assays are used. Technological advances require pathologists to integrate molecular-based mechanistic data effectively with traditional morphological evaluation to develop a more detailed grasp of the pathogenesis of drug-induced injury. All pathologists have the responsibility to effectively and accurately communicate their findings and interpretations to the appropriate audiences.