Nurses' perspectives on whether medical aid in dying should be accessible to incompetent patients with dementia: findings from a survey conducted in Quebec, Canada.

We conducted a survey in a random sample of 514 Quebec nurses caring for the elderly to assess their attitudes towards extending medical aid in dying to incompetent patients and to explore associated factors. Attitudes were measured using clinical vignettes featuring a hypothetical patient with Alzheimer disease. Vignettes varied according to the stage of the disease (advanced or terminal) and the presence or absence of a written request. Of the 291 respondents, 83.5% agreed with the current legislation that allows physicians to administer aid in dying to competent patients who are at the end of life and suffer unbearably. A similar proportion (83%, p = 0.871) were in favor of extending medical aid in dying to incompetent patients who are at the terminal stage of Alzheimer disease, show signs of distress, and have made a written request before losing capacity.

[Development of indicators to promote measures for the prevention and rehabilitation of functional decline in older people]. / Développement d'indicateurs pour valoriser des actions de prévention et de réadaptation de la perte d'autonomie des personnes âgées.

BACKGROUND: In Europe and Asia, long-term care funding is disability-based. This introduces a perverse effect by inappropriately adding value to functional decline among beneficiaries. To support the efforts in prevention and rehabilitation made by personnel in long-term care services, indicators have to be developed to promote functional improvement of beneficiaries. As people receiving those services are already experiencing a functional decline process, it is essential to know the natural magnitude of functional decline in order to assess deviation from this expected decline. The objective of the study was to estimate the natural decrease of autonomy in beneficiaries of home care services and nursing homes. METHODS: Two databases were used: for home-dwelling people, 1235 subjects over 75 years old who participated in the PRISMA study; for institutions, 1330 residents over 65 years old of a nursing home in Sherbrooke (QC, Canada). These subjects were assessed several times over many years with the Functional Autonomy Measurement System (SMAF). Growth analyses were used to estimate the annual decrease in the SMAF score according to age, gender and the initial autonomy status. RESULTS: At home, only age was significantly associated with the slope of functional decline. The average annual decrease of subjects 75-84 years old was 2.4 points on the SMAF score (out of 87); for those aged over 85, the annual loss was 3.8 points. In institutions, gender and the initial autonomy profile were associated with the annual decrease. For men, the annual decrease varied between 0.7 for the most disabled subjects to 5.2 for the most autonomous. For women, those values varied from 0.2 to 6.6, respectively. CONCLUSION: A decrease in the SMAF score less than these expected values should be associated with a bonus to support personnel training, prevention activities, rehabilitation and activities aimed at supporting the autonomy of the beneficiaries. Such a strategy requires the implementation of a precise and reliable assessment instrument like the SMAF and also the availability of a longitudinal database where data for each beneficiary could be linked over time.

[Comparing ethics committees from France and Quebec with respect to incapacity to consent to research]. / Comparaison des comités d'éthique de France et du Québec en regard de l'incapacité à consentir à la recherche.

BACKGROUND: French and Quebec legislation allow the inclusion of decisionally-incompetent subjects in research, provided certain conditions are met. In both jurisdictions, ethics committees are charged with ensuring that research protocols meet these conditions. We investigated committee members' knowledge and opinions regarding substitute consent for research purposes. METHODS: Two consecutive postal surveys were conducted among all members of ethics committees from France and Quebec. Knowledge and opinions about proxy consent were measured with clinical vignettes describing hypothetical situations involving incapable adults. For each vignette, respondents were asked to either identify the person legally authorized to consent or choose the substitute decision-maker whom they considered best suited to do so. RESULTS: Knowledge of the legislation governing substitute consent was poor in both samples, especially in situations involving an incompetent person who did not have a legal representative. Knowledge was worse among French ethics committee members (p<0.001). In hypothetical clinical studies that involved no risk to the subject's health, 59% of respondents favored consent from a close relative. As the risk increased, the proportion gradually decreased to 14.2%, while the proportion against soliciting the cognitively impaired older adult tended to increase (from 5.8 to 31.2%). These trends were observed in both samples. CONCLUSION: These findings underscore the need to better educate ethics committee members about legislation regarding prospective subjects who lack decisional capacity. Such efforts could improve both knowledge of and compliance with legal provisions that enable or restrict the participation of cognitively-impaired patients in research projects. Moreover, study findings provide some support for enlarging the category of persons who are authorized to consent to low-risk research on behalf of incapacitated adults who lack legal representation.

[Management of thyroid dysfunction by primary care physicians of the Province of Quebec: a transversal study]. / Etude transversale sur l'approche thérapeutique des patients avec troubles thyroïdiens par les omnipraticiens du Québec.

OBJECTIVES: This study aims to evaluate clinical practice of primary care physicians regarding common thyroid disorders. MATERIALS AND METHODS: A sample of 210 primary care physicians was randomly selected in three Quebec's administrative regions. Four clinical vignettes (V1 to V4) were presented by mail: two cases of subclinical hypothyroidism (women of 25 years - V1 - and 70 - V2 - years of age) for which physicians had to choose to either treat or not with thyroid replacement and two cases of hyperthyroidism (women of 30 - V3 - and 66 - V4- years of age) for which they had to choose a course of action (observation, treatment or referral to a specialist). V1 and V2 where followed by four sub-questions presenting supportive elements that could influence the decision to treat (presence of antithyroid antibodies, accumulation of symptoms, LDL cholesterol and thyreostimulin levels). RESULTS: The overall response rate was 22%. Forty-two percent of respondents would have treated V1 outright and 49% would have treated V2. The therapeutic approach in the face of these two vignettes, independently of the presence or absence of supportive clinical or biochemical elements, did not vary according to geographic practice area. However, one region was significantly more conservative for V4. The number of years in practice or assistance to continuous medical education activities did not affect management of vignettes. CONCLUSION: This study outlines the importance of clinical practice guidelines and tools to facilitate their application in clinical management of thyroid disorders.

Knowledge of the legislation governing proxy consent to treatment and research.

OBJECTIVE: To assess the knowledge of four groups of individuals regarding who is legally authorised to consent to health care or research involving older patients. DESIGN: A provincewide postal survey. SETTING: Province of Quebec, Canada. PARTICIPANTS: Three hundred older adults, 434 informal caregivers of cognitively impaired individuals, 98 researchers in aging and 136 members of research ethics boards (REBs). MEASUREMENTS: Knowledge was assessed through a pretested postal questionnaire comprising five vignettes that describe hypothetical situations involving an older adult who requires medical care or is solicited for research. The respondent had to identify the person who is legally authorised to provide consent. RESULTS: Nearly 80% of all respondents provided the correct answer when the hypothetical scenario depicted a person who was competent to consent or incompetent but legally represented. Knowledge was worse (from 2% among older adults to 44% among REB members) for the scenario describing a research situation that involved an incompetent adult without a legal guardian. CONCLUSION: The observed lack of knowledge raises doubts about the ability of current legislation to truly protect the rights of older adults with diminished decision making capacity. It points to the need for educational programmes aimed at increasing public awareness of the legislation put in place for those requiring special protection.

Impact of motor, cognitive, and perceptual disorders on ability to perform activities of daily living after stroke.

BACKGROUND AND PURPOSE: Using confirmatory factor analysis, this study evaluates the relative impact of motor, cognitive, and perceptual deficits on functional autonomy with 100 elderly (aged 55 to 79 years) victims of stroke. METHODS: Two different approaches were used for measuring functional autonomy: the Functional Autonomy Measurement System (Système de Mesure de l'Autonomie Fonctionnelle [SMAF]) and the Assessment of Motor and Process Skills (AMPS). RESULTS: The results of the confirmatory factor analysis show that motor, cognitive, and perceptual factors all make a significant contribution to the variation in functional autonomy and confirm the accuracy of the model (93% of the variance is explained when the SMAF is used to measure functional autonomy, and 64% of the variance is explained when the AMPS is used). CONCLUSIONS: The factors that make the greatest contribution in explaining the variance in functional autonomy are, in order of importance, the motor factor, the perceptual factor, and the cognitive factor.

Factors associated with long-term institutionalization of older people with dementia: data from the Canadian Study of Health and Aging.

BACKGROUND: In Canada, half the people with dementia live in institutions. Factors associated with institutionalization should be identified with the goal of implementing strategies not only to permit those with dementia to stay in their homes as long as is feasible but also to ensure that steps are taken for timely institutionalization when appropriate. METHODS: Informal caregivers of 326 individuals with dementia living in the community were identified and interviewed as part of the Canadian Study of Health and Aging (CSHA). These subjects were contacted again 2.5 and 5 years after the baseline interview to collect information on the status of their care recipients. Survival analyses using clinical data for the individuals with dementia and data from the interviews with their informal caregivers were carried out using Cox proportional hazard modeling to estimate the hazard ratio (HR). RESULTS: Over the 5-year period, 166 individuals with dementia (50.9%) were institutionalized and the median time to admission was 41 months. From the multivariate analysis, the factors significantly associated with institutionalization were: type of dementia (Alzheimer's disease: HR = 1.83), severity of disability (mild: 1.51; moderate: 2.34; total impairment: 4.02), caregiver's age over 60 (1.83), caregiver not a spouse or child (1.55), and severe caregiver burden (1.71). Caregiver's burden was associated with the care-receiver's behavioral disturbance (partial r =.55) and the caregiver's depressive mood (r =.55). CONCLUSIONS: Screening caregivers for burden and depression and designing interventions to decrease the consequences of behavioral disturbance on caregivers would be relevant avenues to explore to decrease institutionalization of people with dementia.

Transcription-independent RNA polymerase II dephosphorylation by the FCP1 carboxy-terminal domain phosphatase in Xenopus laevis early embryos.

The phosphorylation of the RNA polymerase II (RNAP II) carboxy-terminal domain (CTD) plays a key role in mRNA metabolism. The relative ratio of hyperphosphorylated RNAP II to hypophosphorylated RNAP II is determined by a dynamic equilibrium between CTD kinases and CTD phosphatase(s). The CTD is heavily phosphorylated in meiotic Xenopus laevis oocytes. In this report we show that the CTD undergoes fast and massive dephosphorylation upon fertilization. A cDNA was cloned and shown to code for a full-length xFCP1, the Xenopus orthologue of the FCP1 CTD phosphatases in humans and Saccharomyces cerevisiae. Two critical residues in the catalytic site were identified. CTD phosphatase activity was observed in extracts prepared from Xenopus eggs and cells and was shown to be entirely attributable to xFCP1. The CTD dephosphorylation triggered by fertilization was reproduced upon calcium activation of cytostatic factor-arrested egg extracts. Using immunodepleted extracts, we showed that this dephosphorylation is due to xFCP1. Although transcription does not occur at this stage, phosphorylation appears as a highly dynamic process involving the antagonist action of Xp42 mitogen-activated protein kinase and FCP1 phosphatase. This is the first report that free RNAP II is a substrate for FCP1 in vivo, independent from a transcription cycle.

The incidence of vascular dementia in Canada: a comparison with Europe and East Asia.

Vascular dementia (VaD) is the second commonest subtype of dementia after Alzheimer's disease (AD). However, its incidence has been studied much less extensively than that of AD. This article reviews the incidence data for VaD reported in the international literature. Results from 10 incidence studies are compared to those of the Canadian Study of Health and Aging using age-standardized incidence ratios (SIR). SIRs vary from 0.42 to 2.68, indicating that geographical variation is still present after taking into account the countries' differential age distributions. It is still unclear if these differences are due to genetic and/or environmental factors since a large part reflects methodological differences between studies.

Imputation of missing dates of death or institutionalization for time-to-event analyses in the Canadian Study of Health and Aging.

Data from the Canadian Study of Health and Aging (CSHA) allow investigators to study patterns and predictors of mortality and institutional placement in a well characterized, population-based cohort of elderly Canadians. However, it is impossible to study the timing of these events if the date of occurrence is missing. This technical article describes a procedure for imputing missing dates of death or institutionalization. The first step consists in identifying and correcting dates that are inconsistent with other available dates on which we know the event has or has not occurred. A missing date for an event is then replaced by the middle of a range of plausible dates for its occurrence. This constitutes a valuable addition to the CSHA data since it precludes the loss of information that results from discarding subjects with missing occurrence dates in time-to-event analyses.

Vascular dementia : incidence and risk factors in the Canadian study of health and aging.

BACKGROUND AND PURPOSE: Very few population-based studies have systematically examined incident vascular dementia (VaD). From the Canadian Study of Health and Aging cohort, incidence rates of VaD were determined and risk factors analyzed. METHODS: This was a cohort incidence study that followed 8623 subjects presumed to be free of dementia over a 5-year period. The risk factors were examined with a nested prospective case-control study. Exposure was determined by means of a risk factor questionnaire administered to the subject or a proxy at the beginning of the study. RESULTS: On the basis of 38 476 person-years at risk, the annual incidence rate was estimated to be 2.52 per thousand undemented Canadians (95% CI 2. 02 to 3.02). Including an estimation of the probability of VaD among the decedents, this figure rose to 3.79. For the risk factors study, 105 incident cases of VaD according to the NINCDS-AIREN criteria were compared with 802 control subjects. Significant risk factors were: age (OR=1.05), residing in a rural area (2.03), living in an institution (2.33), diabetes (2.15), depression (2.41), apolipoprotein E epsilon4 (2.34), hypertension for women (2.05), heart problems for men (2.52), taking aspirin (2.33), and occupational exposure to pesticides or fertilizers (2.05). Protective factors were eating shellfish (0.46) and regular exercise for women (0.46). There was no relation with sex, education, or alcohol. CONCLUSIONS: The study confirmed some previously reported risk factors but also suggested new ones. It raised concerns about the prescription of aspirin and perhaps other factors related to rural life.

Heat-induced relocalization of protein kinase CK2. Implication of CK2 in the context of cellular stress.

Among various other roles described so far, protein kinase CK2 has been involved in cell cycle, proliferation, and development. Here, we show that in response to specific stresses (heat shock or UV irradiation), a pool of the cellular CK2 content relocalizes in a particular nuclear fraction, increasing the activity of the kinase there. Electron microscopic analysis shows that upon heat shock, CK2alpha and CK2beta subunits are both detected in similar speckle structures occurring in the interchromatin space but are differentially targeted inside the nucleolus. This CK2 relocalization process takes place in a time- and dose-dependent manner and is reversible upon recovery at 37 degrees C. Altogether, this work suggests CK2 be involved in the response to physiological stress in higher eukaryotic cells.

Regulated phosphorylation of the RNA polymerase II C-terminal domain (CTD).

The largest subunit of RNA polymerase II has an intriguing feature in its carboxyl-terminal domain (CTD) that consists of multiple repeats of an evolutionary conserved motif of seven amino acids. CTD phosphorylation plays a pivotal role in controlling mRNA synthesis and maturation. In exponentially growing cells, the phosphate turnover on the CTD is fast; it is blocked by common inhibitors of transcription, such as 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole and actinomycin D. Transcription-independent changes in CTD phosphorylation are observed at critical developmental stages, such as meiosis and early development.

Transcription-independent phosphorylation of the RNA polymerase II C-terminal domain (CTD) involves ERK kinases (MEK1/2).

The largest subunit of the mammalian RNA polymerase II possesses a C-terminal domain (CTD) consisting of 52 repeats of the consensus sequence, Tyr(1)-Ser(2)-Pro(3)-Thr(4)-Ser(5)-Pro(6)-Ser(7). Phosphorylation of the CTD is known to play a key role in gene expression. We now show that treatments such as osmotic and oxidative shocks or serum stimulation generate a new type of phosphorylated subunit, the IIm form. This IIm form might be generated in vivo by ERK-type MAP kinase phosphorylation as: (i) ERK1/2 are major CTD kinases found in cell extracts; (ii) the immunoreactivity of the IIm form against a panel of monoclonal antibodies indicates that the CTD is exclusively phosphorylated on Ser-5 in the repeats, like RNA polymerase II phosphorylated in vitro by an ERK1/2; and (iii) the IIm form does not appear when ERK activation is prevented by treating cells with low concentrations of highly specific inhibitors of MEK1/2. Since the IIm subunit is not affected by inhibition of transcription and is not bound to chromatin, it does not participate in transcription.

Correlates of care quality in long-term care facilities: a multilevel analysis.

Hierarchical modeling was employed to explore correlates of the quality of care provided in long-term care facilities. For this purpose, a multilevel analysis offers two advantages over traditional analytical approaches. First, it accounts for the correlated nature of data recorded on multiple residents from the same facility. Second, it enables the investigators to study the influence of both resident and facility characteristics on care quality. The analysis was performed on data from 301 residents randomly sampled from 88 facilities located in the Province of Quebec, Canada. Results revealed that the presence of cognitive deficits was the strongest correlate of the quality of care provided to a resident. However, this relationship was found to vary significantly across facilities. Four facility-level variables were found to influence the relationship between cognitive functioning and care quality: the number of external collaborators the facility has, the type of training the facility manager has, the size of the facility, and the age distribution of its clientele. From these results, we suggest means to improve the quality of care provided to cognitively impaired older adults living in long-term care facilities.

Quality of care in unlicensed homes for the aged in the eastern townships of Quebec.

BACKGROUND: The recent proliferation of unlicensed homes for the aged in Quebec, coupled with the increased needs of the population they serve, has raised concerns about the quality of case these homes provide. The authors compared the quality of care in unlicensed homes with that in licensed long-term care facilities in a region of Quebec. METHODS: The study involved 301 impaired people aged 65 and over in 88 residential care facilities (52 unlicensed, 36 licensed) in the Eastern Townships of Quebec. Study participants were chosen according to a 2-stage sampling scheme: stratified sampling of the primary units (facilities) and random sampling of the secondary units (residents). Quality of care was measured using the QUALCARE scale, a multidimensional instrument that uses a 5-point scale to assess 6 dimensions of care: environmental, physical, medical management, psychosocial, human rights and financial. A mean score of more than 2 was considered indicative of inadequate care. RESULTS: Overall, the quality of care was similar in the unlicensed and licensed facilities (mean global score 1.61 [standard error of the mean (SEM) 0.06] and 1.47 [SEM 0.09] respectively). Examination of dimension-specific quality-of-care scores revealed that the unlicensed homes performed worse than the licensed facilities in 2 areas of care: physical care (mean score 1.80 [SEM 0.08] v. 1.51 [SEM 0.09] respectively, p = 0.017) and medical management (1.37 [SEM 0.06] v. 1.14 [SEM 0.05], p = 0.004). The dimension-specific scores also revealed that both types of homes lacked appropriate attention to the psychosocial aspect of care. Overall, 25% of the facilities provided inadequate care to at least one resident. This situation was especially prevalent among homes with fewer than 40 residents, where up to 20% of the residents received inadequate care. INTERPRETATION: Most of the unlicensed homes for the aged that were studied delivered care of relatively good quality. However, some clearly provided inadequate care.

The transcriptional inhibitors, actinomycin D and alpha-amanitin, activate the HIV-1 promoter and favor phosphorylation of the RNA polymerase II C-terminal domain.

Actinomycin D and alpha-amanitin are commonly used to inhibit transcription. Unexpectedly, however, the transcription of the human immunodeficiency virus (HIV-1) long terminal repeats (LTR) is shown to be activated at the level of elongation, in human and murine cells exposed to these drugs, whereas the Rous sarcoma virus LTR, the human cytomegalovirus immediate early gene (CMV), and the HSP70 promoters are repressed. Activation of the HIV LTR is independent of the NFkappaB and TAR sequences and coincides with an enhanced average phosphorylation of the C-terminal domain (CTD) from the largest subunit of RNA polymerase II. Both the HIV-1 LTR activation and the bulk CTD phosphorylation enhancement are prevented by several CTD kinase inhibitors, including 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole. The efficacies of the various compounds to block CTD phosphorylation and transcription in vivo correlate with their capacities to inhibit the CDK9/PITALRE kinase in vitro. Hence, the positive transcription elongation factor, P-TEFb, is likely to contribute to the average CTD phosphorylation in vivo and to the activation of the HIV-1 LTR induced by actinomycin D.

Heat shock of HeLa cells inactivates a nuclear protein phosphatase specific for dephosphorylation of the C-terminal domain of RNA polymerase II.

Reversible phosphorylation of the C-terminal domain (CTD) of the largest RNA polymerase II (RNAP II) subunit plays a key role in gene expression. Stresses such as heat shock result in marked changes in CTD phosphorylation as well as in major alterations in gene expression. CTD kinases and CTD phosphatase(s) contribute in mediating differential CTD phosphory-lation. We now report that heat shock of HeLa cells at temperatures as mild as 41 degreesC results in a decrease in CTD phosphatase activity in cell extracts. The obser-vation that this CTD phosphatase interacts with the RAP74 subunit of the general transcription factor TFIIF suggests that it corresponds to the previously charac-terized major CTD phosphatase. This conclusion is also supported by the finding that the distribution of the 150 kDa subunit of CTD phosphatase in cells is altered by heat shock. Although CTD phosphatase is found predominantly in low salt extracts in unstressed cells, immunofluorescence microscopy indicates that its intracellular localization is nuclear. The decrease in CTD phosphatase activity correlates with a decrease in amount of 150 kDa phosphatase subunit in the extracts. During heat shock, CTD phosphatase switches to an insoluble form which remains aggregated to the nuclear matrix fraction. In contrast, heat shock did not result in a redistribution of RAP74, indicating that not all nuclear proteins aggregate under these conditions. Accordingly, the heat-inactivation of both the CTD phosphatase and the TFIIH-associated CTD kinase might contribute to the selective synthesis of heat-shock mRNAs.

Profile of residents in unlicensed homes for the aged in the eastern townships of Quebec.

BACKGROUND: The number of unlicensed homes for the aged in Quebec has increased rapidly over the last decade. Because these homes are not linked in any formal way to the Quebec Ministry of Health and Social Services, little is known about their residents. The objective of this study was to describe the sociodemographic characteristics and disability profile of elderly residents in unlicensed homes for the aged. Comparisons were made to a sample of residents drawn from licensed long-term facilities. METHODS: The target population was restricted to residents aged 65 years and over in facilities in the Eastern Townships of Quebec who had some difficulties with at least 2 activities of daily living. This population included 94% of elderly people in licensed facilities and 64% of those in unlicensed homes. The study population comprised 301 impaired people in 88 residential care facilities (36 licensed, 52 unlicensed). They were selected using a 2-stage sampling scheme: stratified sampling of the primary units (homes) and simple random sampling of the secondary units (residents). Facility managers were interviewed to collect descriptive information about themselves and their facilities. Residents were assessed with regard to their cognitive abilities (using the Modified Mini-Mental State [3MS] Examination) and their functional autonomy (using the Functional Autonomy Measurement System [Système de mesure de láutonomie fonctionnelle (SMAF)]. RESULTS: Although residents without impairment were excluded from the study, the unlicensed facilities were found to house people who were, on average, less cognitively and physically impaired than their counterparts in the licensed facilities (p < 0.001). Nonetheless, a substantial proportion of the residents in the unlicensed homes had severe cognitive disabilities (38.5% had 3MS score of less than 60) and functional disabilities (17.0% had an SMAF score of more than 40). The corresponding figures for residents in the licensed facilities with these scores were 65.3% and 66.7%. Of the managers of the unlicensed facilities 31.9% had no training and 58.8% had no previous experience in caring for the elderly people. The staff-resident ratio was lower among the unlicensed homes than among the licensed facilities (mean 0.05 [standard error of the mean (SEM) 0.01] v. 0.39 [SEM 0.03], p < 0.001). In addition, only 26.0% of the unlicensed homes employed qualified staff, as compared with 63.0% of the licensed facilities (p < 0.001). INTERPRETATION: This study provides evidence that many residents of unlicensed homes have considerable care needs. These homes appear ill-equipped to address their needs, which raises doubts about their ability to deliver high-quality care.