Examining the barriers of influenza vaccine hesitancy in persons with dementia: a literature review.

BACKGROUND/AIMS: Despite the proven benefits of vaccine prevention and the continuous development of this important public health measure, vaccine hesitancy is among the top ten threats to global health according to the World Health Organization in 2019. Those who contract the influenza virus will typically develop a mild illness. However, for populations at a higher risk, including those diagnosed with dementia, influenza is proven to be more detrimental. Persons with dementia (PWD) face a serious threat to influenza on an annual basis, and vaccine hesitancy may further potentiate this risk. The purpose of this paper is to explore and understand the barriers PWD face in receiving the influenza vaccine. METHODS: A literature review was conducted to examine the barriers that prevent PWD from seeking out the annual influenza vaccine. A thematic analysis provided an understanding of the overarching relationships found among the influences between the identified themes. RESULTS: Three main influences were identified: (1) intra-personal, (2) inter-personal, and (3) extra-personal, with each influence containing several subsequent sub-themes. DISCUSSION/CONCLUSION: The literature review found that there is a lack of research involving this high-risk population and the barriers they face, especially within the extra-personal influences. Further research is required to understand how each barrier relates and connects with each other. Understanding this connection will aid public health organizations in decreasing the threat of vaccine hesitancy, thus decreasing the incidents of preventable deaths.

Living well with dementia: The role volunteer-based social recreational programs in promoting social connectedness of people with dementia and their caregivers.

Objectives: This evaluation study was designed to examine the factors that contribute the promotion of social connectedness among people with dementia and their caregivers through social recreational programs; develop an understanding of volunteer's impact on program success; and identify the barriers and facilitators to improve the volunteer-based programs to promote social connectedness.Method: A qualitative descriptive research design was used to explore the study participants' lived experiences of social recreational programs from Alzheimer's Society of Durham Region (ASDR) in Ontario, Canada. A final sample of 31 participants was recruited including people with dementia, informal caregivers, and community volunteers. Qualitative data was collected through face-to-face semi-structured interviews. Emerging themes were derived from the qualitative descriptive data using thematic analysis.Results: The qualitative interviews highlighted the impact of social recreational programs on people with dementia, caregivers and volunteers in the promotion of social connectedness, as well as the examination of barriers and facilitators to identify opportunities for the future improvement of ASDR programs that would benefit the dementia populations. The study findings revealed that the project 'Living Well with Dementia' has been able to successfully foster social connectedness through its volunteer-led social recreational programs by promoting the physical and mental well-being of people with dementia and their caregivers.Conclusion: Our study findings underscored the critical roles of volunteers who contributed to the success of community-based programs. Future research is needed to identify the opportunities to address current gaps in services and to strengthen the social recreational programs using evidence-based practices and client-centered approaches.Supplemental data for this article can be accessed online at http://doi.org/10.1080/13607863.2021.1950614.

Dementia care in Ontario, Canada: evidence of more timely diagnosis among persons with dementia receiving care at home compared with residential facilities.

OBJECTIVE: Home care (HC) has been promoted as an efficient alternative to residential care (RC). However, little is known about the individuals who receive HC. This study compared the cognitive and functional statuses of persons with dementia receiving HC or RC at the time of diagnosis with dementia. It was hypothesized that persons with dementia receiving RC would have declined further, both cognitively and functionally. STUDY DESIGN: Population-based secondary data analysis. METHODS: Data from the Canadian Institute for Health Information's Continuing Care Reporting System and the Home Care Reporting System, 2009-2011, were used. Respective populations of 39,604 and 21,153 persons with dementia who received either RC or HC were included. Cognitive and functional statuses were measured using a cognitive performance scale (CPS) and an activities of daily living (ADL) scale, respectively. RESULTS: The mean CPS score was higher for the RC group (3.2 vs 2.5). The proportion of individuals diagnosed when impairment was moderate to very severe (CPS ≥ 4) was higher in the RC group (32.0% vs 13.3%). The mean ADL score was also higher for the RC group (3.5 vs 1.6). The proportion of individuals diagnosed when they required extensive assistance or were totally dependent (ADL ≥ 3) was markedly higher in the RC group (72.3% vs 27.3%). All findings were statistically significant (P < 0.0001). Multivariable analysis suggested that RC clients were nearly four times more likely than HC clients to be diagnosed at a later stage (odds ratio = 3.74, 95% confidence interval 3.54-3.95). CONCLUSIONS: Persons with dementia in RC facilities in Ontario are diagnosed when their cognitive and functional statuses have declined more than those of their HC counterparts.

Colon cancer care and survival: income and insurance are more predictive in the USA, community primary care physician supply more so in Canada.

BACKGROUND: Our research group advanced a health insurance theory to explain Canada's cancer care advantages over America. The late Barbara Starfield theorized that Canada's greater primary care-orientation also plays a critically protective role. We tested the resultant Starfield-Gorey theory by examining the effects of poverty, health insurance and physician supplies, primary care and specialists, on colon cancer care in Ontario and California. METHODS: We analyzed registry data for people with non-metastasized colon cancer from Ontario (n = 2,060) and California (n = 4,574) diagnosed between 1996 and 2000 and followed to 2010. We obtained census tract-based socioeconomic data from population censuses and data on county-level physician supplies from national repositories: primary care physicians, gastroenterologists and other specialists. High poverty neighborhoods were oversampled and the criterion was 10 year survival. Hypotheses were explored with standardized rate ratios (RR) and tested with logistic regression models. RESULTS: Significant inverse associations of poverty (RR = 0.79) and inadequate health insurance (RR = 0.80) with survival were observed in the California, while they were non-significant or non-existent in Ontario. The direct associations of primary care physician (RRs of 1.32 versus 1.11) and gastroenterologist (RRs of 1.56 versus 1.15) supplies with survival were both stronger in Ontario than California. The supply of primary care physicians took precedence. Probably mediated through the initial course of treatment, it largely explained the Canadian advantage. CONCLUSIONS: Poverty and health insurance were more predictive in the USA, community physician supplies more so in Canada. Canada's primary care protections were greatest among the most socioeconomically vulnerable. The protective effects of Canadian health care prior to enactment of the Affordable Care Act (ACA) clearly suggested the following. Notwithstanding the importance of insuring all, strengthening America's system of primary care will probably be the best way to ensure that the ACA's full benefits are realized. Finally, Canada's strong primary care system ought to be maintained.

Multiplicative disadvantage of being an unmarried and inadequately insured woman living in poverty with colon cancer: historical cohort exploration in California.

BACKGROUND: Many Americans diagnosed with colon cancer do not receive indicated chemotherapy. Certain unmarried women may be particularly disadvantaged. A 3-way interaction of the multiplicative disadvantages of being an unmarried and inadequately insured woman living in poverty was explored. METHODS: California registry data were analyzed for 2,319 women diagnosed with stage II to IV colon cancer between 1996 and 2000 and followed until 2014. Socioeconomic data from the 2000 census classified neighborhoods as high poverty (≥30% of households poor), middle (5-29%) or low poverty (<5% poor). Primary health insurance was private, Medicare, Medicaid or none. Comparisons of chemotherapy rates used standardized rate ratios (RR). We respectively used logistic and Cox regression models to assess chemotherapy and survival. RESULTS: A statistically significant 3-way marital status by health insurance by poverty interaction effect on chemotherapy receipt was observed. Chemotherapy rates did not differ between unmarried (39.0%) and married (39.7%) women who lived in lower poverty neighborhoods and were privately insured. But unmarried women (27.3%) were 26% less likely to receive chemotherapy than were married women (37.1%, RR = 0.74, 95% CI 0.58, 0.95) who lived in high poverty neighborhoods and were publicly insured or uninsured. When this interaction and the main effects of health insurance, poverty and chemotherapy were accounted for, survival did not differ by marital status. CONCLUSIONS: The multiplicative barrier to colon cancer care that results from being inadequately insured and living in poverty is worse for unmarried than married women. Poverty is more prevalent among unmarried women and they have fewer assets so they are probably less able to absorb the indirect and direct, but uncovered, costs of colon cancer care. There seem to be structural inequities related to the institutions of marriage, work and health care that particularly disadvantage unmarried women that policy makers ought to be cognizant of as future reforms of the American health care system are considered.

Lack of access to chemotherapy for colon cancer: multiplicative disadvantage of being extremely poor, inadequately insured and African American.

BACKGROUND: Despite evidence of chemotherapy's ability to cure or comfort those with colon cancer, nearly half of such Americans do not receive it. African Americans (AA) seem particularly disadvantaged. An ethnicity by poverty by health insurance interaction was hypothesized such that the multiplicative disadvantage of being extremely poor and inadequately insured is worse for AAs than for non-Hispanic white Americans (NHWA). METHODS: California registry data were analyzed for 459 AAs and 3,001 NHWAs diagnosed with stage II to IV colon cancer between 1996 and 2000 and followed until 2011. Socioeconomic data from the 2000 census categorized neighborhoods: extremely poor (≥ 30% of households poor), middle (5-29% poor) and low poverty (< 5% poor). Participants were randomly selected from these poverty strata. Primary health insurers were Medicaid, Medicare, private or none. Chemotherapy rates were age and stage-adjusted and comparisons used standardized rate ratios (RR). Logistic and Cox regressions, respectively, modeled chemotherapy receipt and long term survival. RESULTS: A significant 3-way ethnicity by poverty by health insurance interaction effect on chemotherapy receipt was observed. Among those who did not live in extremely poor neighborhoods and were adequately insured privately or by Medicare, chemotherapy rates did not differ significantly between AAs (37.7%) and NHWAs (39.5%). Among those who lived in extremely poor neighborhoods and were inadequately insured by Medicaid or uninsured, AAs (14.6%) were nearly 60% less likely to receive chemotherapy than were NHWAs (25.5%, RR = 0.41). When the 3-way interaction effect as well as the main effects of poverty, health insurance and chemotherapy was accounted for, survival rates of AAs and NHWAs were the same. CONCLUSIONS: The multiplicative barrier to colon cancer care that results from being extremely poor and inadequately insured is worse for AAs than it is for NHWAs. AAs are more prevalently poor, inadequately insured, and have fewer assets so they are probably less able to absorb the indirect and direct, but uncovered, costs of colon cancer care. Policy makers ought to be cognizant of these factors as they implement the Affordable Care Act and consider future health care reforms.

Prevalence and correlates of potentially undetected dementia among residents of institutional care facilities in Ontario, Canada, 2009-2011.

OBJECTIVES: This study aims to determine the prevalence of potentially undetected dementia among institutional care facility residents in Ontario, Canada, and to identify factors associated with undetection. METHODS: We utilized a population-based secondary data analysis approach, pertaining to data from the Canadian Institute for Health Information's Continuing Care Reporting System, 2009-2011. Potentially undetected dementia was defined as having severely impaired cognitive function and requiring extensive assistance on activity of daily living (ADL) but no records of dementia diagnoses. Cognitive function was measured by the Cognitive Performance Scale (CPS), 0 (intact) to 6 (very severe impairment), and ADL by a hierarchy scale, 0 (independent) to 6 (total dependence). RESULTS: Of the 242,957 residents who had no records of dementia diagnoses, 11.6% (n = 28,078) had a CPS score ≥4 (severe impairment or higher) and ADL score ≥3 (required extensive assistance or more). Data from 11,614 demented residents with corresponding CPS and ADL scores were used for comparison. Residents without dementia diagnosis were younger (77 vs. 84 years), more likely to have never married (20% vs. 6%), and have longer admission (4 vs. 2.8 years). The most significant factors for no diagnoses were never married (adjusted odds ratio = 2.1, 95% confidence interval [CI] = 1.91-2.29), admitted to hospital-based facilities (adjusted odds ratio = 1.58, 95% CI = 1.48-1.69), presence of schizophrenia (adjusted odds ratio = 1.43, 95% CI = 1.22-1.69), depression (adjusted odds ratio = 1.23, 95% CI = 1.16-1.29), and diabetes mellitus (adjusted odds ratio = 1.32, 95% CI = 1.26-1.40). CONCLUSIONS: A large number of residents who had poor cognitive function and inadequate ADL ability did not have dementia diagnoses on record. Social and comorbid conditions were contributing factors to potentially undetected dementia.

Impact of the global economic crisis on the health of unemployed autoworkers.

A phenomenological investigation was undertaken to examine the effects of the 2008-09 global economic recession on the health of unemployed blue-collar autoworkers in the Canadian province of Ontario between September and November 2009. A total of 22 men and 12 women took part. Participants completed a quantitative demographic and financial questionnaire. The qualitative aspect of the study consisted of a phenomenological component comprising semi-structured focus group sessions lasting 2 to 2.5 hours. The number of years employed ranged from 2 to 31.7 with a mean of 15 +/- 8. Participants reported high levels of stress, anxiety, and depression; increased physical pain and discomfort; changes in weight and sexual function; and financial hardships, including inability to purchase prescribed medications. The authors conclude that unemployment associated with the global recession has negative health effects on autoworkers in Ontario.

A scoping review to inform the development of dementia care competencies.

Health professionals and care partners of persons living with dementia have expressed that learning needs related to dementia care are a priority. There are currently a variety of training programs available in Ontario (Canada) to address aspects of dementia care, but no commonly accepted description of the core knowledge, skills, and abilities, (i.e., competencies) that should underpin dementia-related training and education in the province. The aim of this study was to review current evidence to inform the later development of competency statements describing the knowledge, skills and actions required for dementia care among care providers ranging from laypersons to health professionals. We also sought to validate existing dementia care principles and align new concepts to provide a useful organizing framework for future competency development. We distinguished between micro-, meso- and macro-level concepts to clarify the competencies required by individuals situated in different locations across the healthcare system, linking competency development in dementia care to broader system transformation. This review precedes the co-development of a holistic competency framework to guide approaches to dementia care training in Ontario.

Effects of being uninsured or underinsured and living in extremely poor neighborhoods on colon cancer care and survival in California: historical cohort analysis, 1996-2011.

BACKGROUND: We examined the mediating effects of health insurance on poverty-colon cancer care and survival relationships and the moderating effects of poverty on health insurance-colon cancer care and survival relationships among women and men in California. METHODS: We analyzed registry data for 3,291 women and 3,009 men diagnosed with colon cancer between 1996 and 2000 and followed until 2011 on lymph node investigation, stage at diagnosis, surgery, chemotherapy, wait times and survival. We obtained socioeconomic data for individual residences from the 2000 census to categorize the following neighborhoods: high poverty (30% or more poor), middle poverty (5-29% poor) and low poverty (less than 5% poor). Primary health insurers were Medicaid, Medicare, private or none. RESULTS: Evidence of mediation was observed for women, but not for men. For women, the apparent effect of poverty disappeared in the presence of payer, and the effects of all forms of health insurance seemed strengthened. All were advantaged on 6-year survival compared to the uninsured: Medicaid (RR = 1.83), Medicare (RR = 1.92) and private (RR = 1.83). Evidence of moderation was also only observed for women. The effects of all forms of health insurance were stronger for women in low poverty neighborhoods: Medicaid (RR = 2.90), Medicare (RR = 2.91) and private (RR = 2.60). For men, only main effects of poverty and payers were observed, the advantaging effect of private insurance being largest. Across colon cancer care processes, Medicare seemed most instrumental for women, private payers for men. CONCLUSIONS: Health insurance substantially mediates the quality of colon cancer care and poverty seems to make the effects of being uninsured or underinsured even worse, especially among women in the United States. These findings are consistent with the theory that more facilitative social and economic capital is available in more affluent neighborhoods, where women with colon cancer may be better able to absorb the indirect and direct, but uncovered, costs of care.

Effects of socioeconomic status on colon cancer treatment accessibility and survival in Toronto, Ontario, and San Francisco, California, 1996-2006.

OBJECTIVES: We examined the differential effects of socioeconomic status on colon cancer care and survival in Toronto, Ontario, Canada, and San Francisco, California. METHODS: We analyzed registry data for colon cancer patients from Ontario (n = 930) and California (n = 1014), diagnosed between 1996 and 2000 and followed until 2006, on stage, surgery, adjuvant chemotherapy, and survival. We obtained socioeconomic data for individuals' residences from population censuses. RESULTS: Income was directly associated with lymph node evaluation, chemotherapy, and survival in San Francisco but not in Toronto. High-income persons had better survival rates in San Francisco than in Toronto. After adjustment for stage, survival was better for low-income residents of Toronto than for those of San Francisco. Middle- to low-income patients were more likely to receive indicated chemotherapy in Toronto than in San Francisco. CONCLUSIONS: Socioeconomic factors appear to mediate colon cancer care in urban areas of the United States but not in Canada. Improvements are needed in screening, diagnostic investigations, and treatment access among low-income Americans.

Associations of physician supplies with colon cancer care in Ontario and California, 1996 to 2006.

BACKGROUND: This study examined the differential effects of physician supplies on colon cancer care in Ontario and California. The associations of physician supplies with colon cancer stage at diagnosis, receipt of surgery and adjuvant chemotherapy, and 5-year survival were observed within each country and compared between-country. METHODS: Random samples of Ontario and California cancer registries provided 2,461 and 2,200 colon cancer cases that were diagnosed between 1996 and 2000, and followed until 2006. Both registries included data on the stage of disease at the time of diagnosis, receipt of cancer-directed surgery, receipt of adjuvant chemotherapy, and survival. Census tract-level data on low-income prevalence were, respectively, taken from 2001 and 2000 Canadian and United States population censuses. County-level primary care physician and gastroenterologist densities were computed for the same years. RESULTS: Significant income-adjusted, gastroenterologist density threshold effects (2.0 or more vs. less than 2.0 per 100,000 inhabitants) were observed for early diagnosis (OR = 1.57) and 5-year survival (OR = 1.63) in Ontario, but not in California. Significant incremental threshold effects of primary care physician densities on chemotherapy receipt (8.0 and 9.0 or more per 10,000 inhabitants, respective ORs of 1.79 and 2.37) were also only observed in Ontario. CONCLUSIONS: These colon cancer care findings support the theory that while personal economic resources are more predictive in America, community-level resources such as physician supplies are more predictive of health care access and effectiveness in Canada.

Increased racial differences on breast cancer care and survival in America: historical evidence consistent with a health insurance hypothesis, 1975-2001.

PURPOSE: This study examined whether race/ethnicity had differential effects on breast cancer care and survival across age strata and cohorts within stages of disease. METHODS: The Detroit Cancer Registry provided 25,997 breast cancer cases. African American and non-Hispanic white, older Medicare-eligible and younger non-eligible women were compared. Successive historical cohorts (1975-1980 and 1990-1995) were, respectively, followed until 1986 and 2001. RESULTS: African American disadvantages on survival and treatments increased significantly, particularly among younger women who were much more likely to be uninsured. Within node positive disease all treatment disadvantages among younger African American women disappeared with socioeconomic adjustment. CONCLUSIONS: Growth of this racial divide implicates social, rather than biological, forces. Its elimination will require high quality health care for all.

Is There an Association between Physical Activity and Sleep in Community-Dwelling Persons with Dementia: An Exploratory Study Using Self-Reported Measures?

Sleep disturbances are common in persons with dementia (PWD). While pharmacotherapy is widely used, non-pharmacological interventions are beginning to surface as first-line management strategies. This study sought to investigate if physical activity was associated with more favourable sleep patterns in PWD, and to compare the sleep quantity and quality between active and inactive PWD. We conducted an exploratory study to tackle these research questions. Self-reported telephone questionnaires were administered to 40 caregivers of PWD, who answered questions as proxies on behalf of their care recipient. Just over half (55%) of our participants met the criteria for being active. Walking was the most popular form of physical activity for both active and inactive PWD. Active PWD also preferred exercise classes and gardening, whereas inactive PWD favoured chair exercises. Compared to their inactive counterparts, active PWD were more likely to experience appropriate sleep quantity (p = 0.00). The active group also reported significantly better overall sleep quality (p = 0.003). Together, our findings suggest that physical activity may be associated with improved sleep in PWD. Future studies are warranted to investigate whether physical activity can be promoted as a safe and effective means to improve quality-of-life in this population.

Palliative chemotherapy among people living in poverty with metastasised colon cancer: facilitation by primary care and health insurance.

BACKGROUND: Many Americans with metastasised colon cancer do not receive indicated palliative chemotherapy. We examined the effects of health insurance and physician supplies on such chemotherapy in California. METHODS: We analysed registry data for 1199 people with metastasised colon cancer diagnosed between 1996 and 2000 and followed for 1 year. We obtained data on health insurance, census tract-based socioeconomic status and county-level physician supplies. Poor neighbourhoods were oversampled and the criterion was receipt of chemotherapy. Effects were described with rate ratios (RR) and tested with logistic regression models. RESULTS: Palliative chemotherapy was received by less than half of the participants (45%). Facilitating effects of primary care (RR=1.23) and health insurance (RR=1.14) as well as an impeding effect of specialised care (RR=0.86) were observed. Primary care physician (PCP) supply took precedence. Adjusting for poverty, PCP supply was the only significant and strong predictor of chemotherapy (OR=1.62, 95% CI 1.02 to 2.56). The threshold for this primary care advantage was realised in communities with 8.5 or more PCPs per 10 000 inhabitants. Only 10% of participants lived in such well-supplied communities. CONCLUSIONS: This study's observations of facilitating effects of primary care and health insurance on palliative chemotherapy for metastasised colon cancer clearly suggested a way to maximise Affordable Care Act (ACA) protections. Strengthening America's system of primary care will probably be the best way to ensure that the ACA's full benefits are realised. Such would go a long way towards facilitating access to palliative care.

Palliative Care Integration Project (PCIP) quality improvement strategy evaluation.

This study evaluated the effectiveness of implementation of common assessment tools, collaborative care plans, and symptom management guidelines for cancer patients as a strategy to improve the quality, coordination, and integration of palliative care service across organizations and health care sectors. A pre-post design to measure the impact on symptom management, caregiver burden and satisfaction with care delivery, and service utilization was used. Two cohorts of eligible patients and caregivers completed Edmonton Symptom Assessment Scales, Caregiver Reaction Assessment and FAMCARE Scales and chart audits were conducted. Administrative data from each participating site were examined for utilization trends. Audits of 53 charts preimplementation and 63 postimplementation showed an increase in documentation of pain from 24.5% to 74.6% (P<0.001) of charts. Administrative data showed a decrease in the percentage of patients with at least one emergency room visit from 94.3% to 84.8% (P<0.001), in the percentage of patients with at least one admission to the acute care hospital (P<0.001), and deaths in acute care 43.1%-35.7% (P=0.133). There was minimal change in the intensity of symptoms (P=0.591), and no change in the burden on the caregiver (P=0.086) or caregiver satisfaction with care (P=0.942). This study showed that implementation of common assessment tools, collaborative care plans, and symptom management guidelines across health sectors can result in some increased documentation of symptoms and efficiencies in care. Future projects should consider imbedding a continuous quality improvement methodology and longer timelines into their projects to improve outcomes.

Cancer survival in Ontario, 1986-2003: evidence of equitable advances across most diverse urban and rural places.

OBJECTIVES: This study examined whether place and socio-economic status had differential effects on the survival of women diagnosed with breast cancer in Ontario during the 1980s and the 1990s. METHODS: The Ontario Cancer Registry provided 29,934 primary malignant breast cancer cases. Successive historical cohorts (1986-1988 and 1995-1997) were, respectively, followed until 1994 and 2003. Diverse places were compared: the greater metropolitan Toronto area, other cities, ranging in size from 50,000 to a million people, smaller towns and villages, and rural and remote areas. Socio-economic data for each woman's residence at the time of diagnosis were taken from population censuses. RESULTS: Very small cities (6%) with populations between 50,000 and 100,000 were the only places where breast cancer survival had advanced less compared to the province as a whole. Income gradients began to appear, however, in larger cities. Urban residents in the lowest income areas were significantly disadvantaged compared to the highest income areas during the 1990s, but not during the 1980s. CONCLUSION: This historical analysis of breast cancer survival evidenced remarkably equitable advances across nearly all of Ontario's diverse places. The most likely explanation for such substantial equity seems to be Canada's universally accessible, single-payer, health care system.

Lipid peroxidation and protein modification in a mouse model of chronic iron overload.

Iron-storage diseases are believed to cause organ damage through generation of reactive oxygen species. Using a murine model of iron overload, we found that hepatic iron stores increased logarithmically during 3 weeks of chronic intraperitoneal administration of iron dextran, while hepatic glutathione peroxidase activity declined linearly by approximately 50% during the same period. Plasma concentrations of aliphatic aldehydes increased by 2- to 3-fold, and plasma malondialdehyde (MDA) by 6-fold. Modification of total liver protein by products of lipid peroxidation, including MDA-lysine, 4-hydroxynonenal-lysine, and N(epsilon)-(carboxymethyl)lysine (CML), increased by approximately 3-fold, while levels of the protein oxidation marker, methionine sulfoxide (MetSO), were unchanged. Skin collagen was resistant to modification until the third week, when 2- to 3-fold increases in both CML and MetSO were observed. Our results document that iron overload increases lipid peroxidation, with concomitant increases in reactive aldehydes in plasma and chemical modification of tissue proteins. CML was a sensitive indicator of hepatocellular oxidative stress, compared to MetSO, while extensive modification of extracellular skin collagen was not observed until the late stages of iron overload and oxidative stress. These observations provide direct evidence for the contribution of reactive oxygen species, lipid peroxidation, and reactive carbonyl intermediates to the pathogenesis of iron-overload diseases.

Decreasing effects of iron toxicosis on selenium and glutathione peroxidase activity.

Heart failure due to chronic iron overload is a leading cause of cardiovascular mortality in the second and third decades of life worldwide, but its mechanism is not known. Deficiencies of selenium have been shown to result in damage to the myocardium and to the development of various cardiomyopathies. In the current investigation, the dose-dependent effects of chronic iron toxicosis on heart tissue concentrations of selenium and the protective antioxidant enzyme glutathione peroxidase (GPx) were investigated in a murine model of iron-overload cardiomyopathy (n = 20). Significant dose-dependent decreases in heart tissue selenium concentrations (r = -0.95, p < 0.001) and selenium-dependent GPx activity (r = -0.93, p < 0.001) were observed in chronically iron-loaded mice in comparison with placebo controls. These results suggest that dietary supplementation with selenium may be beneficial in the clinical management of disorders of iron metabolism.

A case-control study examining the effects of active versus sedentary lifestyles on measures of body iron burden and oxidative stress in postmenopausal women.

Approximately half of the Canadian adults have sedentary lifestyles that increase their risk of developing cardiovascular disease (CVD). Women are 10 times more likely to die from CVD than from any other disease. Their risk almost doubles with the onset of menopause, which may result in increased body iron burden and oxidative stress in sedentary women. Body iron burden may catalyze the production of cytotoxic oxygen species in vivo. We hypothesized that postmenopausal women who engage in moderate forms of aerobic exercise for at least 30 min three or more times per week would have significantly (i) lower levels of body iron burden, (ii) increased glutathione peroxidase (GPx) activity, and (iii) decreased oxidative stress in comparison to sedentary controls. An age-matched, case-control study was employed to examine the effects of active (N = 25) versus sedentary (N = 25) lifestyles in women aged 55-65 years on measures of body iron burden as quantified by total serum iron, transferrin saturation, and serum ferritin levels; GPx activity; and oxidative stress as quantified by 4-hydroxynonenal, malondialdehyde, and hexanal. Measures of body iron burden were significantly elevated in sedentary women in comparison to active women (p < .001). Red cell GPx activity was higher in active women compared to sedentary women (p < .001). Measures of oxidative stress were significantly higher in sedentary versus active women (p < .001). These findings suggest that aerobic forms of exercise may mitigate the risk of developing CVD in postmenopausal women by improving antioxidant capacity and decreasing body iron burden.