Leaving emergency departments without completing treatment among First Nations and non-First Nations patients in Alberta: a mixed-methods study.

BACKGROUND: Our previous research showed that, in Alberta, Canada, a higher proportion of visits to emergency departments and urgent care centres by First Nations patients ended in the patient leaving without being seen or against medical advice, compared with visits by non-First Nations patients. We sought to analyze whether these differences persisted after controlling for patient demographic and visit characteristics, and to explore reasons for leaving care. METHODS: We conducted a mixed-methods study, including a population-based retrospective cohort study for the period of April 2012 to March 2017 using provincial administrative data. We used multivariable logistic regression models to control for demographics, visit characteristics, and facility types. We evaluated models for subgroups of visits with pre-selected illnesses. We also conducted qualitative, in-person sharing circles, a focus group, and 1-on-1 telephone interviews with health directors, emergency care providers, and First Nations patients from 2019 to 2022, during which we reviewed the quantitative results of the cohort study and asked participants to comment on them. We descriptively categorized qualitative data related to reasons that First Nations patients leave care. RESULTS: Our quantitative analysis included 11 686 287 emergency department visits, of which 1 099 424 (9.4%) were by First Nations patients. Visits by First Nations patients were more likely to end with them leaving without being seen or against medical advice than those by non-First Nations patients (odds ratio 1.96, 95% confidence interval 1.94-1.98). Factors such as diagnosis, visit acuity, geography, or patient demographics other than First Nations status did not explain this finding. First Nations status was associated with greater odds of leaving without being seen or against medical advice in 9 of 10 disease categories or specific diagnoses. In our qualitative analysis, 64 participants discussed First Nations patients' experiences of racism, stereotyping, communication issues, transportation barriers, long waits, and being made to wait longer than others as reasons for leaving. INTERPRETATION: Emergency department visits by First Nations patients were more likely to end with them leaving without being seen or against medical advice than those by non-First Nations patients. As leaving early may delay needed care or interfere with continuity of care, providers and departments should work with local First Nations to develop and adopt strategies to retain First Nations patients in care.

Barriers and supports for uptake of human papillomavirus vaccination in Indigenous people globally: A systematic review.

Despite the availability of effective and safe human papillomavirus (HPV) vaccines that reduce the incidence and impact of cervical cancer and other cancers, HPV vaccine coverage rates remain persistently low and the cervical cancer burden disproportionately high among Indigenous people globally. This study aimed to systematically identify, appraise, and summarize the literature on documented barriers and supports to HPV vaccination in Indigenous populations internationally. Forty-three studies were included and an inductive, qualitative, thematic synthesis was applied. We report on 10 barrier themes and 7 support themes to vaccine uptake, and provide a quantitative summary of metrics. Focusing on Indigenous perspectives reported in the literature, we propose recommendations on community-research collaboration, culturally safe intergenerational and gender-equitable community HPV vaccine education, as well as multi-level transparency to ensure informed consent is secured in the context of reciprocal relationships. Although the voices of key informant groups (e.g., HPV-vaccine eligible youth and community Elders) are underrepresented in the literature, the identification of barriers and supports to HPV vaccination in a global Indigenous context might help inform researchers and health policy makers who aim to improve HPV vaccine uptake in Indigenous populations.

Cross-Canada Variability in Blood Donor SARS-CoV-2 Seroprevalence by Social Determinants of Health.

We compared the seroprevalence of SARS-CoV-2 anti-nucleocapsid antibodies in blood donors across Canadian regions in 2021. The seroprevalence was the highest in Alberta and the Prairies, and it was so low in Atlantic Canada that few correlates were observed. Being male and of young age were predictive of seropositivity. Racialization was associated with higher seroprevalence in British Columbia and Ontario but not in Alberta and the Prairies. Living in a materially deprived neighborhood predicted higher seroprevalence, but it was more linear across quintiles in Alberta and the Prairies, whereas in British Columbia and Ontario, the most affluent 60% were similarly low and the most deprived 40% similarly elevated. Living in a more socially deprived neighborhood (more single individuals and one parent families) was associated with lower seroprevalence in British Columbia and Ontario but not in Alberta and the Prairies. These data show striking variability in SARS-CoV-2 seroprevalence across regions by social determinants of health. IMPORTANCE Canadian blood donors are a healthy adult population that shows clear disparities associated with racialization and material deprivation. This underscores the pervasiveness of the socioeconomic gradient on SARS-CoV-2 infections in Canada. We identify regional differences in the relationship between SARS-CoV-2 seroprevalence and social determinants of health. Cross-Canada studies, such as ours, are rare because health information is under provincial jurisdiction and is not available in sufficient detail in national data sets, whereas other national seroprevalence studies have insufficient sample sizes for regional comparisons. Ours is the largest seroprevalence study in Canada. An important strength of our study is the interpretation input from a public health team that represented multiple Canadian provinces. Our blood donor seroprevalence study has informed Canadian public health policy at national and provincial levels since the start of the SARS-CoV-2 pandemic.

First Nations emergency care in Alberta: descriptive results of a retrospective cohort study.

BACKGROUND: Worse health outcomes are consistently reported for First Nations people in Canada. Social, political and economic inequities as well as inequities in health care are major contributing factors to these health disparities. Emergency care is an important health services resource for First Nations people. First Nations partners, academic researchers, and health authority staff are collaborating to examine emergency care visit characteristics for First Nations and non-First Nations people in the province of Alberta. METHODS: We conducted a population-based retrospective cohort study examining all Alberta emergency care visits from April 1, 2012 to March 31, 2017 by linking administrative data. Patient demographics and emergency care visit characteristics for status First Nations persons in Alberta, and non-First Nations persons, are reported. Frequencies and percentages (%) describe patients and visits by categorical variables (e.g., Canadian Triage and Acuity Scale). Means, medians, standard deviations and interquartile ranges describe continuous variables (e.g., age). RESULTS: The dataset contains 11,686,288 emergency care visits by 3,024,491 unique persons. First Nations people make up 4% of the provincial population and 9.4% of provincial emergency visits. The population rate of emergency visits is nearly 3 times higher for First Nations persons than non-First Nations persons. First Nations women utilize emergency care more than non-First Nations women (54.2% of First Nations visits are by women compared to 50.9% of non-First Nations visits). More First Nations visits end in leaving without completing treatment (6.7% v. 3.6%). CONCLUSIONS: Further research is needed on the impact of First Nations identity on emergency care drivers and outcomes, and on emergency care for First Nations women.

Antibiotic dispensation rates among participants in community-driven health research projects in Arctic Canada.

BACKGROUND: Community-driven projects that aim to address public concerns about health risks from H. pylori infection in Indigenous Arctic communities (estimated H. pylori prevalence = 64%) show frequent failure of treatment to eliminate the bacterium. Among project participants, treatment effectiveness is reduced by antibiotic resistance of infecting H. pylori strains, which in turn, is associated with frequent exposure to antibiotics used to treat other infections. This analysis compares antibiotic dispensation rates in Canadian Arctic communities to rates in urban and rural populations in Alberta, a southern Canadian province. METHODS: Project staff collected antibiotic exposure histories for 297 participants enrolled during 2007-2012 in Aklavik, Tuktoyaktuk, and Fort McPherson in the Northwest Territories, and Old Crow, Yukon. Medical chart reviews collected data on systemic antibiotic dispensations for the 5-year period before enrolment for each participant. Antibiotic dispensation data for urban Edmonton, Alberta (average population ~ 860,000) and rural northern Alberta (average population ~ 450,000) during 2010-2013 were obtained from the Alberta Government Interactive Health Data Application. RESULTS: Antibiotic dispensation rates, estimated as dispensations/person-years (95% confidence interval) were: in Arctic communities, 0.89 (0.84, 0.94); in Edmonton, 0.55 (0.55, 0.56); in rural northern Alberta, 0.63 (0.62, 0.63). Antibiotic dispensation rates were higher in women and older age groups in all regions. In all regions, the highest dispensation rates occurred for ß-lactam and macrolide antibiotic classes. CONCLUSIONS: These results show more frequent antibiotic dispensation in Arctic communities relative to an urban and rural southern Canadian population.

Burden of disease from Helicobacter pylori infection in western Canadian Arctic communities.

BACKGROUND: Indigenous communities across the circumpolar north have elevated H. pylori (Hp) prevalence and stomach cancer incidence. We aimed to describe the Hp-associated disease burden among western Canadian Arctic participants in community-driven projects that address concerns about health risks from Hp infection. METHODS: During 2008-2013, participants underwent Hp screening by urea breath test and gastroscopy with gastric biopsies. We estimated Hp prevalence and prevalence by Hp status of endoscopic and histopathologic diagnoses. RESULTS: Among 878 participants with Hp status data, Hp prevalence was: 62% overall; 66% in 740 Indigenous participants; 22% in 77 non-Indigenous participants (61 participants did not disclose ethnicity); 45% at 0-14 years old, 69% at 15-34 years old, and 61% at 35-96 years old. Among 309 participants examined endoscopically, visible mucosal lesions were more frequent in the stomach than the duodenum: the gastric to duodenal ratio was 2 for inflammation, 8 for erosions, and 3 for ulcers. Pathological examination in 308 participants with gastric biopsies revealed normal gastric mucosa in 1 of 224 Hp-positive participants and 77% (65/84) of Hp-negative participants with sharp contrasts in the prevalence of abnormalities between Hp-positive and Hp-negative participants, respectively: moderate-severe active gastritis in 50 and 0%; moderate-severe chronic gastritis in 91 and 1%; atrophic gastritis in 43 and 0%; intestinal metaplasia in 17 and 5%. CONCLUSIONS: The observed pattern of disease is consistent with increased risk of stomach cancer and reflects substantial inequity in the Hp-associated disease burden in western Arctic Canadian hamlets relative to most North American settings. This research adds to evidence that demonstrates the need for interventions aimed at reducing health risks from Hp infection in Indigenous Arctic communities.

Gastric Cancer in Northern Canadian Populations: A Focus on Cardia and Non-Cardia Subsites.

In northern Canada where there is a high prevalence of Helicobacter pylori infection, there is a paucity of information on gastric cancer by the topographical subsites cardia (CGC) and non-cardia (NCGC). Here we describe the incidence of CGC and NCGC, separately, among northern Canadian populations. We used data from the Cancer Incidence in Five Continents Volumes X (CI5X) and XI (CI5XI) to obtain CGC and NCGC incidence for Canada and for Yukon (YT), a northern Canadian territory. Using these data with those provided by the Government of the Northwest Territories (NT), we estimated standardized incidence ratios comparing northern populations to Canada as a whole. We also estimated age-standardized incidence rates to permit comparisons across populations globally. NT and YT populations were disproportionately impacted by gastric cancer, particularly NCGC. This was especially true for Indigenous populations: NCGC incidence rates among NT Indigenous men were 2.7 times the rates among all men in Canada, while rates among NT Indigenous women were 3.1 times the rates among all women in Canada. Similarly, age-standardized rates of NCGC among Indigenous NT residents were comparable to global regions where there is a high burden of NCGC. This study has, for the first time, quantified the incidence of CGC and NCGC for the NT and YT, providing new insights into the burden of these cancers among northern Canadian populations.

Barriers, supports, and effective interventions for uptake of human papillomavirus- and other vaccines within global and Canadian Indigenous peoples: a systematic review protocol.

BACKGROUND: Despite the existence of human papilloma virus (HPV) vaccines with demonstrated safety and effectiveness and funded HPV vaccination programs, coverage rates are persistently lower and cervical cancer burden higher among Canadian Indigenous peoples. Barriers and supports to HPV vaccination in Indigenous peoples have not been systematically documented, nor have interventions to increase uptake in this population. This protocol aims to appraise the literature in Canadian and global Indigenous peoples, relating to documented barriers and supports to vaccination and interventions to increase acceptability/uptake or reduce hesitancy of vaccination. Although HPV vaccination is the primary focus, we anticipate only a small number of relevant studies to emerge from the search and will, therefore, employ a broad search strategy to capture literature related to both HPV vaccination and vaccination in general in global Indigenous peoples. METHODS: Eligible studies will include global Indigenous peoples and discuss barriers or supports and/or interventions to improve uptake or to reduce hesitancy, for the HPV vaccine and/or other vaccines. Primary outcomes are documented barriers or supports or interventions. All study designs meeting inclusion criteria will be considered, without restricting by language, location, or data type. We will use an a priori search strategy, comprised of key words and controlled vocabulary terms, developed in consultation with an academic librarian, and reviewed by a second academic librarian using the PRESS checklist. We will search several electronic databases from date of inception, without restrictions. A pre-defined group of global Indigenous websites will be reviewed for relevant gray literature. Bibliographic searches will be conducted for all included studies to identify relevant reviews. Data analysis will include an inductive, qualitative, thematic synthesis and a quantitative analysis of measured barriers and supports, as well as a descriptive synthesis and quantitative summary of measures for interventions. DISCUSSION: To our knowledge, this study will contribute the first systematic review of documented barriers, supports, and interventions for vaccination in general and for HPV vaccination. The results of this study are expected to inform future research, policies, programs, and community-driven initiatives to enhance acceptability and uptake of HPV vaccination among Indigenous peoples. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Registration Number: CRD42017048844.

Cancer incidence and mortality among the Métis population of Alberta, Canada.

BACKGROUND: Cancer has been identified as a major cause of morbidity and mortality in Canada over the last decade. However, there is a paucity of information about cancer patterns in Aboriginal people, particularly for Métis. This study aims to explore cancer incidence and mortality burden among Métis and to compare disease estimates with non-Métis population. METHODS: This population-based descriptive epidemiological study used cancer incidence and mortality data from 2007 to 2012 obtained from Alberta Health Care Insurance Plan (AHCIP) - Central Stakeholder Registry - and Alberta Cancer Registry (ACR). To identify cancer cases in Métis, the ACR was linked with the Métis Nation of Alberta (MNA) Identification Registry. In Métis and non-Métis people, age-standardized cancer incidence and mortality rates were estimated and subsequently compared between both groups. RESULTS: A higher incidence of bronchus/lung cancer was found among Métis men compared with their non-Métis counterparts (RR=1.69, CI 1.28-2.09; p=0.01). No other statistically significant differences in cancer incidence or mortality were found between Métis and non-Métis people living in Alberta over the course of the 6 years studied. CONCLUSIONS: Overall incidence and mortality associated with cancer were not higher among Métis people compared with non-Métis people. However, special efforts should be considered to decrease the higher incidence of bronchus/lung cancer in Métis men. Further development and maintenance of new and existing institutional collaborations are necessary to continue cancer research and health status surveillance in Métis population.

Obesity and the Incidence of Upper Gastrointestinal Cancers: An Ecological Approach to Examine Differences across Age and Sex.

BACKGROUND: Esophageal and gastric cancers differ in their epidemiology but have several risk factors in common. The aim of this study was to assess age and sex differences in the burden of esophageal and gastric cancers in the context of the global obesity epidemic. METHODS: Data from 50 countries were obtained from Cancer Incidence in Five Continents Volume X and GLOBOCAN 2012. Age-specific and age-standardized incidence rates of esophageal adenocarcinoma and squamous cell carcinoma (ESCC), as well as cardia (CGC) and noncardia (NCGC) gastric cancer, were estimated. Countries were grouped and analyzed according to their obesity prevalence. RESULTS: A gradient across quartiles of obesity prevalence was found for esophageal adenocarcinoma, with the highest incidence rates in high prevalence countries (ASR 3.0 vs. 0.8 per 100,000 in highest vs. lowest obesity quartiles, males). In contrast, for ESCC as well as for CGC and NCGC the reverse was true, with the highest rates observed in countries with the lowest obesity prevalence (ESCC, 2.2 vs. 11.5; CGC, 2.8 vs. 7.8; NCGC, 3.9 vs. 17.4 in highest vs. lowest obesity quartiles, males). Although for esophageal adenocarcinoma, sex and age differences in incidence were most pronounced in countries with a high prevalence of obesity, these differences were much smaller for the other cancer sites assessed. CONCLUSIONS: Variation in obesity prevalence may partly explain age and sex differences in the incidence of esophageal adenocarcinomas. IMPACT: Ecologic studies can help assess relationships between risk factors and cancer, and generate new hypotheses that may be pursued through more directed research.

Cancer incidence in indigenous people in Australia, New Zealand, Canada, and the USA: a comparative population-based study.

INTRODUCTION: Indigenous people have disproportionally worse health and lower life expectancy than their non-indigenous counterparts in high-income countries. Cancer data for indigenous people are scarce and incidence has not previously been collectively reported in Australia, New Zealand, Canada, and the USA. We aimed to investigate and compare, for the first time, the cancer burden in indigenous populations in these countries. METHODS: We derived incidence data from population-based cancer registries in three states of Australia (Queensland, Western Australia, and the Northern Territory), New Zealand, the province of Alberta in Canada, and the Contract Health Service Delivery Areas of the USA. Summary rates for First Nations and Inuit in Alberta, Canada, were provided directly by Alberta Health Services. We compared age-standardised rates by registry, sex, cancer site, and ethnicity for all incident cancer cases, excluding non-melanoma skin cancers, diagnosed between 2002 and 2006. Standardised rate ratios (SRRs) and 95% CIs were computed to compare the indigenous and non-indigenous populations of each jurisdiction, except for the Alaska Native population, which was compared with the white population from the USA. FINDINGS: We included 24 815 cases of cancer in indigenous people and 5 685 264 in non-indigenous people from all jurisdictions, not including Alberta, Canada. The overall cancer burden in indigenous populations was substantially lower in the USA except in Alaska, similar or slightly lower in Australia and Canada, and higher in New Zealand compared with their non-indigenous counterparts. Among the most commonly occurring cancers in indigenous men were lung, prostate, and colorectal cancer. In most jurisdictions, breast cancer was the most common cancer in women followed by lung and colorectal cancer. The incidence of lung cancer was higher in indigenous men in all Australian regions, in Alberta, and in US Alaska Natives than in their non-indigenous counterparts. For breast cancer, rates in women were lower in all indigenous populations except in New Zealand (SRR 1·23, CI 95% 1·16-1·32) and Alaska (1·14, 1·01-1·30). Incidence of cervical cancer was higher in indigenous women than in non-indigenous women in most jurisdictions, although the difference was not always statistically significant. INTERPRETATION: There are clear differences in the scale and profile of cancer in indigenous and non-indigenous populations in Australia, New Zealand, Canada, and the USA. Our findings highlight the need for much-improved, targeted programmes of screening, vaccination, and smoking cessation, among other prevention strategies. Governments and researchers need to work in partnership with indigenous communities to improve cancer surveillance in all jurisdictions and facilitate access to cancer data. FUNDING: International Agency for Research on Cancer-Australia Fellowship.

Challenges in conducting community-driven research created by differing ways of talking and thinking about science: a researcher's perspective.

Increasingly, health scientists are becoming aware that research collaborations that include community partnerships can be an effective way to broaden the scope and enhance the impact of research aimed at improving public health. Such collaborations extend the reach of academic scientists by integrating a variety of perspectives and thus strengthening the applicability of the research. Communication challenges can arise, however, when attempting to address specific research questions in these collaborations. In particular, inconsistencies can exist between scientists and community members in the use and interpretation of words and other language features, particularly when conducting research with a biomedical component. Additional challenges arise from differing perceptions of the investigative process. There may be divergent perceptions about how research questions should and can be answered, and in expectations about requirements of research institutions and research timelines. From these differences, misunderstandings can occur about how the results will ultimately impact the community. These communication issues are particularly challenging when scientists and community members are from different ethnic and linguistic backgrounds that may widen the gap between ways of talking and thinking about science, further complicating the interactions and exchanges that are essential for effective joint research efforts. Community-driven research that aims to describe the burden of disease associated with Helicobacter pylori infection is currently underway in northern Aboriginal communities located in the Yukon and Northwest Territories, Canada, with the goal of identifying effective public health strategies for reducing health risks from this infection. This research links community representatives, faculty from various disciplines at the University of Alberta, as well as territorial health care practitioners and officials. This highly collaborative work will be used to illustrate, from a researcher's perspective, some of the challenges of conducting public health research in teams comprising members with varying backgrounds. The consequences of these challenges will be outlined, and potential solutions will be offered.

Challenges created by data dissemination and access restrictions when attempting to address community concerns: individual privacy versus public wellbeing.

BACKGROUND: Population health data are vital for the identification of public health problems and the development of public health strategies. Challenges arise when attempts are made to disseminate or access anonymised data that are deemed to be potentially identifiable. In these situations, there is debate about whether the protection of an individual's privacy outweighs potentially beneficial public health initiatives developed using potentially identifiable information. While these issues have an impact at planning and policy levels, they pose a particular dilemma when attempting to examine and address community concerns about a specific health problem. METHODS: Research currently underway in northern Canadian communities on the frequency of Helicobacter pylori infection and associated diseases, such as stomach cancer, is used in this article to illustrate the challenges that data controls create on the ability of researchers and health officials to address community concerns. RESULTS: Barriers are faced by public health professionals and researchers when endeavouring to address community concerns; specifically, provincial cancer surveillance departments and community-driven participatory research groups face challenges related to data release or access that inhibit their ability to effectively address community enquiries. The resulting consequences include a limited ability to address misinformation or to alleviate concerns when dealing with health problems in small communities. CONCLUSIONS: The development of communication tools and building of trusting relationships are essential components of a successful investigation into community health concerns. It may also be important to consider that public wellbeing may outweigh the value of individual privacy in these situations. As such, a re-evaluation of data disclosure policies that are applicable in these circumstances should be considered.

Conformational analysis of the effects of methylmercury on nerve growth factor and brain derived neurotrophic factor.

Methylmercury is a neurotoxicant that is detrimental to the development and physiology of the nervous system. One possible mechanism for methylmercury's toxicity stems from its ability to interfere with the signaling of the neurotrophins nerve growth factor and brain derived neurotrophic factor. In this study, we examine the effect of methylmercury to determine if it interferes with neurotrophin conformation in a manner similar to Hg(2+), or if it occurs via an alternate mechanism. Our findings indicate that although MeHg inhibits neurotrophin signaling, its toxic effects are not mediated via an induced conformational change, as seen with other metal ions, including Hg(2+).

The nerve growth factor precursor proNGF exhibits neurotrophic activity but is less active than mature nerve growth factor.

Nerve growth factor (NGF) promotes neuronal survival and differentiation and stimulates neurite outgrowth. NGF is synthesized as a precursor, proNGF, which undergoes post-translational processing to generate mature beta-NGF. It has been assumed that, in vivo, NGF is largely processed into the mature form and that mature NGF accounts for the biological activity. However, we recently showed that proNGF is abundant in CNS tissues whereas mature NGF is undetectable, suggesting that proNGF has biological functions beyond its role as a precursor. To determine whether proNGF exhibits biological activity, we mutagenized the precursor-processing site and expressed unprocessed, cleavage-resistant proNGF protein in insect cells. Survival and neurite outgrowth assays on murine superior cervical ganglion neurons and PC12 cells indicated that proNGF exhibits neurotrophic activity similar to mature 2.5S NGF, but is approximately fivefold less active. ProNGF binds to the high-affinity receptor, TrkA, as determined by cross-linking to PC12 cells, and is also slightly less active than mature NGF in promoting phosphorylation of TrkA and its downstream signaling effectors, Erk1/2, in PC12 and NIH3T3-TrkA cells. These data, coupled with our previous report that proNGF is the major form of NGF in the CNS, suggest that proNGF could be responsible for much of the biological activity normally attributed to mature NGF in vivo.

Differential activity of the nerve growth factor (NGF) antagonist PD90780 [7-(benzolylamino)-4,9-dihydro-4-methyl-9-oxo-pyrazolo[5,1-b]quinazoline-2-carboxylic acid] suggests altered NGF-p75NTR interactions in the presence of TrkA.

The neurotrophin nerve growth factor (NGF) binds to two receptor types: the tyrosine kinase receptor TrkA and the common neurotrophin receptor p75(NTR). Although many of the biological effects of NGF (such as neuronal growth and survival) are associated with TrkA activation, p75(NTR) also contributes to these activities by enhancing the action of TrkA when receptors are coexpressed. The NGF antagonist PD90780 [7-(benzolylamino)-4,9-dihydro-4-methyl-9-oxo-pyrazolo[5,1-b]quinazoline-2-carboxylic acid] interacts with NGF, preventing its binding to p75(NTR). In this study, the actions of this compound are further explored, and it is found that PD90780 is not able to inhibit the binding of either brain-derived neurotrophic factor or neurotrophin-3 to p75(NTR), consistent with the direct interactions of the antagonist with NGF. In addition, we demonstrate that the ability of PD90780 to inhibit NGF-p75(NTR) interactions is lower when receptors are coexpressed, compared with when p75(NTR) is the only neurotrophin receptor expressed. These results suggest that the interaction between NGF and the p75(NTR) receptor is altered when TrkA is coexpressed. This alteration can be exploited in the development of antagonists that will selectively inhibit the pro-apoptotic actions of p75(NTR) when expressed in the absence of TrkA, although having less effect on the pro-survival effects of p75(NTR) mediated by enhanced TrkA activation.