Creation of a Clinical Demonstration Unit: Embedding Academic Research into Point of Care in a Geriatric Unit.

Given that there are limited evidence-informed non-pharmacological interventions to treat behavioural and psychological symptoms of dementia, a specialized psychiatric hospital partnered with an academic university to create a clinical demonstration unit (CDU) - a learning health systems (LHS) model to advance dementia care. In this paper, we identify five key enablers that led to the successful creation of the CDU, its achievements and challenges encountered. The paper provides learnings for other healthcare providers who are considering initiating an LHS model within their setting to advance patient care.

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.

Association of diagnostic delay with impairment severity among institutional care facility residents diagnosed with dementia in Ontario, Canada.

AIM: To compare the levels of cognitive function at the time of diagnosis among institutional care facility residents with dementia, who were diagnosed either before or after admission to a facility in Ontario, Canada. METHODS: The study utilized a population-based secondary data analysis approach, using data from the Canadian Institute for Health Information's Continuing Care Reporting System from 2009 to 2011. Cognitive function within 30 days of diagnosis was measured by a seven-point cognitive performance scale (CPS) - 0 (intact) to 6 (very severe impairment). RESULTS: Data were extracted from 39633 institutional care facility residents who had a diagnosis of dementia on record. The average CPS score was higher for residents whose diagnosis was made after admission to a facility than for residents whose diagnosis was made before admission (3.1 vs 2.9, P=0.009). The proportion of diagnosis at CPS ≥ 4 (moderately severe to very severe impairment) was also higher in the diagnosis after admission group (29.7% vs 24.6%, P=0.001). Multivariable analysis showed that diagnoses made after admission were more likely to be at a severe stage of cognitive decline (CPS ≥ 4) than diagnoses made before admission (adjusted odds ratio 1.49, P=0.001). A similar result was also noted when comparison was made between mild and moderate-to-severe stages of cognitive decline. After admission diagnoses were more likely to be at moderate-to-severe stages of cognitive decline (CPS ≥ 3) than before admission diagnoses (adjusted odds ratio 1.70, P=0.001). CONCLUSION: Our findings suggest that dementia diagnoses after admission to institutional care facilities are more likely to be made at poorer stages of cognitive function decline.

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.

Quality-of-life outcomes among Alzheimer's disease family caregivers following community-based intervention.

This study sought to determine how community-based interventions such as adult day programs and caregiver support groups affected the quality of life (QOL) of caregivers of Alzheimer's disease clients. The authors hypothesized that using community-based interventions would increase the QOL of caregivers of Alzheimer's disease clients. They conducted a pilot study employing a cross-sectional comparative design involving 62 caregivers in the Durham region, Ontario, Canada. Individuals were recruited at five adult day programs and at six caregiver support groups, involving primary data collection consisting of a self-report questionnaire and a 13-item QOL scale. The authors' findings show that caregivers of Alzheimer's disease clients who used community-based interventions enjoyed similar levels of QOL as caregivers of non-Alzheimer's disease clients. These findings suggest that community-based interventions may be beneficial and should target the multiple needs of caregivers, including their knowledge of community resources and coping strategies.

Gram-negative and gram-positive antibacterial properties of the whole plant extract of willow herb (Epilobium angustifolium).

The emergence of new pathogens and the increase in the number of multidrug-resistant strains in well-established pathogens during the past decade represent a growing public health concern globally. With the current lack of research and development of new antibiotics by large pharmaceutical companies due to poor financial returns, new alternatives need to be explored including natural herbal or plant-based extracts with reported antibacterial properties. Willow herb (Epilobium angustifolium) preparations have been used in traditional aboriginal and folk medicine preparations externally as an antiphlogistic to treat prostate and gastrointestinal disorders and as an antiseptic to treat infected wounds. The authors hypothesized that a whole plant extract of willow herb would exhibit antimicrobial properties on a variety of both Gram-positive and gram-negative bacteria in culture. The authors found that, in comparison to growth controls, willow herb extract significantly inhibited the growth of Micrococcus luteus (p < .01), Staphylococcus aureus (p < .05), Escherichia coli (p < .001), and Pseudomonas aeruginosa (p < .001). They also found that willow herb extract inhibited the growth of bacteria in culture more effectively than vancomycin (p < .05) or tetracycline (p < .004). These results provide preliminary support for the traditional folkloric claim that the plant willow herb possesses antibacterial properties against a variety of gram-positive and gram-negative bacteria. Given that whole plant extract was utilized for this study, further investigations are warranted to determine which specific part of the plant (i.e., leaves, stem, roots, and flowers) possess the antibacterial properties.

Accuracy assessment of prediction in patient outcomes.

In order to provide effective health care to patients, clinicians must rely on their ability to accurately diagnose disease and to prognosticate the outcomes. Prognostic studies have received considerable attention in health science and medicine in relation to patient outcomes. However, little effort has been spent on evaluating prognostic accuracy. The purpose of this paper is to present a comprehensive review of the methods for assessing prognostic accuracy in patient outcome prediction. The strengths and limitations of these approaches are critically appraised. We argue that we need to consider incorporating accuracy assessment for predicting patient outcomes both in clinical practice and in research.

Who will teach the nurses of the future?

The authors predict that if the number of nursing faculty does not increase, nursing education in Canada will face a severe human resources crisis within the next decade, and certain schools of nursing will not have the critical mass of faculty to deliver their undergraduate and graduate programs. Various factors contributing to the shortage of faculty are highlighted, including the aging of the professoriate; superior salaries and benefits available in non-academic settings; and excessive academic workloads. Resolving and effectively managing the nursing faculty crisis needs to be regarded as a national health-care priority. The authors provide recommendations for addressing the problem.

A comparison of studies on the quality of life of primary caregivers of stroke survivors: a systematic review of the literature.

BACKGROUND AND PURPOSE: Few studies have been conducted on the quality of life (QOL) of primary caregivers of stroke survivors (with and without aphasia), with little consistency in the methods of evaluation. The purpose of this systematic review of the literature was to determine the appropriateness of study designs and instruments used to assess QOL in caregivers of stroke survivors. METHOD: A comprehensive literature review was conducted to identify peer-reviewed articles of caregiver's QOL where CINAHL, MEDLINE, and PsycINFO databases were searched. RESULTS: Nine studies that met the inclusion criteria used different QOL instruments and study designs. None of the instruments were specific to caregivers of stroke survivors. CONCLUSION: Future studies are warranted to assess the quality of life of caregivers of stroke survivors with and without aphasia.

The dose-dependent effects of chronic iron overload on the production of oxygen free radicals and vitamin E concentrations in the liver of a murine model.

Genetic disorders of iron metabolism such as primary and secondary hemochromatosis affect thousands of individuals worldwide and are major causes of liver dysfunction, morbidity, and mortality. Although the exact mechanism of hepatic injury associated with these genetic disorders is not fully understood, the propagation of excess concentrations of iron-catalyzed oxygen free radicals (OFRs) may play a role. The authors hypothesized that chronic iron burden would result in dose-dependent (a) increases in hepatic iron stores, (b) increases in hepatic OFR-mediated hepatic cellular injury as quantified by the cytotoxic aldehydes malondialdehyde (MDA) and hexanal, and (c) decreases in protective antioxidant reserve status as quantified by plasma vitamin E (alpha-tocopherol) levels in a murine model. Twenty B(6)D(2)F1 male mice were randomized to the (a) saline control (0.05 mL intraperiotoneal [i.p.]/mouse/day, n = 5), (b) 100 mg total iron burden (n = 5), (c) 200 mg total iron burden (n = 5), or (d) 400 mg total iron burden (n = 5) group. Iron burden was achieved by daily injections of iron dextran (Imferon, 0.05 mL i.p./mouse/day). In comparison to control mice and in support of the hypothesis, the authors observed significant dose-dependent increases in total hepatic iron burden (p < .001) with corresponding increases in MDA and hexanal concentrations (p < .001) and decreases in the protective plasma antioxidant vitamin E (p < .001). These findings suggest that iron-catalyzed OFR-mediated damage may play a role in damaging the liver in chronic states of iron burden.

Caregiver strain and caregiver burden of primary caregivers of stroke survivors with and without aphasia.

Little is known about how the burden and strain of caring for stroke patients with or without aphasia affects primary caregivers. This article (a) critically examines the literature on the burden and strain of care experienced by caregivers of stroke patients and (b) examines the relationship between aphasia and caregiver burden and strain. Two literature reviews of three databases were conducted. Fourteen articles (12 quantitative articles, 1 mixed-design article, and 1 qualitative article) were found to comply with the study criteria for the first literature search. A second literature search focused on the effects of stroke survivors' aphasia on caregiving; none of the articles retrieved met the inclusion criteria. This article suggests that there is a lack of research in this area and that several key initiatives are needed, including the development of an instrument with psychometric properties appropriate for assessing the burden and strain on caregivers of stroke patients. Implications for future nursing practice and research are highlighted.

Dose-dependent effects of chronic iron burden on heart aldehyde and acyloin production in mice.

Iron's chemical structure and its ability to initiate one-electron reactions are properties that cause it to play a major role in the production and metabolism of oxygen free radicals in biological systems. Oxygen free radicals are conjectured to cause cardiac failure in individuals afflicted with disorders of iron overload. We report on the use of both acyloins and aldehydes as markers of oxidative stress in a murine model of chronic iron-overload cardiomyopathy. Twenty mice were randomized to four treatment groups: (1) control (0.2 mL normal saline ip/mouse/d); (2) 100 mg iron (0.05 mL iron dextran/mouse/d); (3) 200 mg iron (0.1 mL iron dexxtran/mouse/d); (4) 400 mg iron (0.2 mL iron dextran/mouse/d). Significant dose-dependent increases in both total heart aldehyde and total heart acyloin concentrations were found. Furthermore, a significant positive correlation existed between the dose of iron administered and each quantified aldehyde and acyloin found in the heart.

Ebselen decreases oxygen free radical production and iron concentrations in the hearts of chronically iron-overloaded mice.

Chronic iron overload is a major cause of cardiac failure throughout the world, but its pathogenesis remains to be clarified. It is conjectured that the toxicity of iron is due to its ability to catalyze the formation of oxygen free radicals (OFR), which can damage cellular membranes, proteins, and DNA. The authors report on the cardioprotective effects of the glutathione peroxidase (GPx) mimic ebselen on iron concentrations in the heart and GPx activity, and on the production of the cytotoxic aldehydes hexanal, 4-hydroxyl-2-nonenal (HNE), and malondialdehyde (MDA). Fifteen B6D2F1 mice were randomized to 1 of 3 treatment groups for a total of 20 treatments: 1) control (0.1 mL normal saline i.p. per mouse, per day); 2) iron-only (10 mg iron dextran i.p. per mouse, per day); 3) iron plus ebselen (25 mg/kg p.o. per mouse, per day). In comparison to iron-only treated mice, the authors' findings show that supplementation with ebselen can decrease both cytotoxic aldehyde and iron concentrations in heart tissue. Additionally, mice supplemented with ebselen had an increase in GPx activity level in comparison to iron-only treated mice. To the authors' knowledge, this is the first study to examine the cardioprotective effects of ebselen against OFR damage in a model of chronic iron overload. These findings suggest that ebselen may have significance in the management of disorders of iron overload.

Milk whey protein decreases oxygen free radical production in a murine model of chronic iron-overload cardiomyopathy.

BACKGROUND: Chronic iron overload is a major cause of organ failure worldwide, but its pathogenesis remains to be elucidated. OBJECTIVES: To examine in an experimental murine model of iron-overload cardiomyopathy the relation between milk whey protein and, first, the production of reactive oxygen free radical species and, second, antioxidant reserve status. METHODS: B6D2F1 mice were randomly assigned to four treatment groups (n=8 per treatment group): placebo control; iron only; whey only; and iron with whey. Reactive oxygen free radical species in the heart were quantified by the cytotoxic aldehydes malondialdehyde (MDA), 4-hydroxy-nonenal (HNE) and hexanal, while antioxidant reserve status was quantified by glutathione (GSH) and glutathione peroxidase (GPx) activity in the heart tissue. RESULTS: Significantly decreased concentrations (pmol/100 mg wet weight tissue) of MDA (2468+/-261), HNE (912+/-38) and hexanal (5385+/-927) were observed in the heart tissue of the group receiving iron with whey, in comparison with the iron-only treatment group (MDA 9307+/-387, HNE 1416+/-157, hexanal 14,874+/-2955; P<0.001). Significantly increased GPx (141+/-38 IU/L) and GSH (521+/-136 IU/L) activity were observed in mice receiving iron with whey, in comparison with mice receiving iron only (GPx 100+/-10 IU/L, GSH 446+/-33 IU/L; P<0.001). CONCLUSION: Mice receiving iron treatments with whey supplementation had significantly lower concentrations of cytotoxic aldehydes and significantly higher cardiac levels of GPx and GSH activity than did iron-only treated mice. Additional basic research is warranted to examine the exact mechanisms by which milk whey protein protects the heart.

Amlodipine decreases iron uptake and oxygen free radical production in the heart of chronically iron overloaded mice.

Hereditary hemochromatosis is a disorder of iron metabolism, which is currently the most prevalent autosomal recessive disorder in the world, with an expression of the homozygous form occurring in approximately 1 in 200 individuals of European descent. Approximately one third of patients with hemochromatosis die of iron-induced cardiac complications. Although the exact mechanism is not known, it is believed that the toxicity of excess iron in biological systems is due to its ability to catalyze the generation of harmful reactive oxygen free radical species (ROS), which can damage proteins, lipids, and DNA. There is preliminary evidence to suggest that non-transferrin-bound iron uptake in the myocardium may occur through voltage-dependent L-type calcium channels, and that calcium channel blockers (CCBs) may possess antioxidant properties. Accordingly, the authors hypothesized that the administration of amlodipine besylate would (1) decrease iron uptake in the myocardium and (2) decrease oxygen free radical production as measured by cytotoxic aldehyde-derived peroxidation products in a murine model of iron overload cardiomyopathy. The findings show that the CCB amlodipine is partially effective in limiting iron uptake in the heart and significantly inhibits the production of ROS in chronically iron-loaded mice. These are important preliminary findings because they suggest that CCBs may have significance in the clinical management of genetic disorders of iron metabolism.

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.

Erythropoiesis: Comparison of Cytotoxic Aldehyde Generation in Beta-Thalassemia Patients Chelated with Deferoxamine or Deferiprone (L1) Versus NO Chelation.

The mechanism of iron-induced organ failure in iron overload disorders is not known, but it is conjectured that excess iron-catalyzed free radical generation contributes to organ damage. We hypothesized that free radical generation, quantified by the presence of 20 separate cytotoxic aldehydes in plasma, would be significantly increased in non-chelated beta-thalassemia major patients, in comparison to those chelated with either deferiprone (L1) or deferoxamine (desferal). We also report on red cell glutathione peroxidase activity in these patient groups, an enzyme involved in averting the damaging effects of free radicals. Ten patients were chelated with nightly subcutaneous infusions of desferal and 10 received the experimental oral chelator L1. Body iron burden was assessed by serum ferritin and hepatic iron concentrations. In comparison to non-chelated controls, significant decreases of 62% and 64% in total cytotoxic aldehyde concentrations were observed in patients chelated with desferal and L1, respectively (p < 0.001). Significantly lower red cell glutathione peroxidase activity was also observed in non-chelated controls, in comparison to those chelated with either desferal or L1 (p < 0.001). This is the first report on the concentrations of cytotoxic aldehydes in non-chelated beta-thalassemia major patients, and the first to report on the effects of L1 against cytotoxic aldehyde formation in plasma of patients with iron-overload.