Trends in diagnosis, referral, red flag onset, patient profiles and natural outcome of de novo cardiac amyloidosis and their multidisciplinary implications.

BACKGROUND: Cardiac amyloidosis (CA) is often overlooked or misdiagnosed. Effects of growing disease awareness, diagnostic ameliorations and novel treatment options on CA diagnosis and management are scarcely reported. OBJECTIVE: To report trends in diagnosis, referral routes, clinical presentation, early onset diagnostic red flags and outcome in de novo CA subjects. METHODS: An unselected cohort of 139 de novo CA patients over an 8-year period in a tertiary referral hospital was recruited. RESULTS: Transthyretin (ATTR, 82%, n = 114) was the most common CA form; Light-chain (AL, 15%, n = 21) and secondary (AA, 3%, n = 4) are less prevalent. Increased awareness over time led to a marked ATTR diagnostic surge, steep non-invasive diagnostic approach increment and increased nuclear medicine and external cardiologist referrals (all p < 0.001). A total of 41% (n = 57/139) of patients were referred by non-cardiology specialist disciplines. Specific referral to rule out CA (24-36%) and diagnostic time lag from symptom onset (9 ± 12 to 8 ± 14 months), however, did not improve (all p > 0.050). Multiple early red flag events preceded CA diagnose several years in ATTR: Left ventricular hypertrophy (LVH, 60%, 4.9 ± 4.3 y), heart failure (54%, 2.5 ± 3.5 y), atrial fibrillation (47%, 5.9 ± 6.7 y), bilateral carpal tunnel syndrome (43%, 9.5 ± 5.7 y) and spinal stenosis (40%, 7.4 ± 6.5 y). LVH ≥ 12 mm was absent in 11% ATTR (n = 13/114) and 5% AL (n = 1/21) patients. Hypertension was common in both ATTR (n = 70/114, 62%) and AL (n = 10/21, 48%). 56% (n = 78/139) of CA presented with heart failure. Cumulative 1 and 5-year mortality of 10%/66%, 40%/52% and 75%/75% for ATTR, AL, and AA, respectively, remains high. CONCLUSIONS: Although CA diagnostic uptake and referral improve, specialist-specific disease and diagnostic red flag ignorance result in non-timely diagnosis and unfavourable outcome.

Alzheimer's disease and driving: review of the literature and consensus guideline from Belgian dementia experts and the Belgian road safety institute endorsed by the Belgian Medical Association.

Alzheimer's disease (AD) is a highly prevalent condition and its prevalence is expected to further increase due to the aging of the general population. It is obvious that the diagnosis of AD has implications for driving. Finally, driving discussions are also emotionally charged because driving is associated with independence and personal identity. However, it is not clear how to implement this in clinical practice and the Belgian law on driving is rather vague in its referral to neurodegenerative brain diseases in general nor does it provide clear-cut instructions for dementia or AD compared to for example driving for patients with epilepsy and as such does not prove to be very helpful. The present article reviews what is known from both literature and existing guidelines and proposes a consensus recommendation tailored to the Belgian situation agreed by both AD experts and the Belgian Road Safety Institute endorsed by the Belgian Medical Association. It is concluded that the decision about driving fitness should be considered as a dynamic process where the driving fitness is assessed and discussed early after diagnosis and closely monitored by the treating physician. The diagnosis of AD on itself definitely does not imply the immediate and full revocation of a driving license nor does it implicate a necessary referral for a formal on-road driving assessment. There is no evidence to recommend a reduced exposure or a mandatory co-pilot. A MMSE-based framework to trichotomise AD patients as safe, indeterminate or unsafe is presented. The final decision on driving fitness can only be made after careful history taking and clinical examination, neuropsychological, functional and behavioral evaluation and, only for selected cases, a formal assessment of driving performance.

Feasibility of implementing a practice guideline for fall prevention on geriatric wards: a multicentre study.

BACKGROUND: About 40% of all adverse events in hospital are falls, but only about one in three Belgian hospitals have a fall prevention policy in place. The implementation of a national practice guideline is urgently needed. OBJECTIVE AND DESIGN: This multicentre study aimed to determine the feasibility of a previously developed guideline. SETTING, PARTICIPANTS AND METHOD: Seventeen geriatric wards, selected at random out of 40 Belgian hospitals who agreed to take part in the study, evaluated the fall prevention guideline. After the one-month test period, 49 healthcare workers completed a questionnaire on the feasibility of the guideline. RESULTS: At the end of the study, 512 geriatric patients had been assessed using the practice guideline. The average time spent per patient on case finding, multifactorial assessment and initiating a treatment plan was 5.1, 76.1 and 30.6 min, respectively. For most risk assessments and risk modifications, several disciplines considered themselves as being responsible and capable. The majority (more than 69%) of the respondents judged the practice guideline as useful, but only a small majority (62.3%) believed that the guideline could be successfully integrated into their daily practice over a longer period of time. Barriers for implementation included a large time investment (81.1%), lack of communication between the different disciplines (35.8%), lack of motivation of the patient (34.0%), lack of multidisciplinary teamwork (28.3%), and lack of interest from the hospital management (15.4%). CONCLUSION: Overall, the guideline was found useful, and for each risk factor (except for visual impairment), at least one discipline felt responsible and capable. Towards future implementation of the guideline, following steps should be considered: division of the risk-factor assessment duties and interventions among different healthcare workers; patient education; appointment of a fall prevention coordinator; development of a fall prevention policy with support from the management of the hospital.

Translating fall incidence data into fall-preventive measures in geriatric wards--a survey in Belgian hospitals.

BACKGROUND: Fall incidents and their negative outcomes represent a considerable problem in hospitals, especially in geriatric wards, and require implementation of strategies to prevent these undesirable events. For this reason, the College of Geriatrics, a body funded by the Belgian Government to set up quality improvement initiatives in geriatric wards, selected 'Fall prevention in Belgian hospitals' as a quality project for the year 2006. OBJECTIVES: Before developing and implementing a practice guideline specifically adapted to the clinical context in Belgian geriatric wards, this study was set up to gain insight into fall prevention measures currently implemented in geriatric wards of Belgian hospitals. METHODS: In this study, we used a cross-sectional survey design. The study involved 113 hospitals with a geriatric department. Participants were geriatricians, head nurses, medical directors, care coordinators and occupational therapists. Measurements were carried out using a survey questionnaire (response rate: 56.6%). RESULTS: Less than one third (32.8%) of Belgian geriatric wards had a formal fall prevention policy. However, more than 90.0% systematically registered falls, but less than a quarter used these data to improve preventive measures. Although the majority used screening (78.1%), comprehensive assessment (92.2%), and preventive strategies (98.4%) when patients are admitted, only about 10% used a standard plan to direct these efforts. Furthermore, 93.8% acknowledged using physical restraints as a fall prevention strategy. CONCLUSION: Given the high rates and complexity of falls in geriatric wards, hospitals need to further implement evidence-based assessment and standard intervention care plans to maintain uniformity and quality of care.

Reaction times and performance variability in normal aging, mild cognitive impairment, and Alzheimer's disease.

This study evaluated whether reaction times (RT) and performance variability are potential markers for the early detection of Alzheimer's disease (AD). Cognitively healthy elderly (n = 218), persons with amnestic MCI (a-MCI) (n = 29) and patients with AD (n = 50) were examined with RT tasks with increasing complexity, subdividing RT into a decision and a movement component. Persons with cognitive deterioration demonstrated more intra-individual variability and more slowing than cognitively healthy elderly. The slowing in AD affects both the cognitive and the motor component, while performance variability mainly affects the cognitive component of the RT. Although in a-MCI not all differences reached statistical significance, primarily the cognitive component of the RT is affected in a-MCI. Intra-individual variability and RT of the complex tasks are the best predictors for a-MCI and AD status, respectively. We conclude that performance variability can be regarded as a useful preclinical marker for AD.

Heat shock proteins and chemokine/cytokine secretion profile in ageing and inflammation.

We have used a multiplex bead array assay to detect simultaneously 25 different circulating cytokines in 35 control subjects (young versus old) and 29 patients (young versus old) with acute infection. Intracellular PBMC levels of heat shock proteins (Hsp) were determined using flow cytometry. Levels of MIG and IL-6 were higher in the elderly normal subjects and patients, respectively, compared to their young counterparts. Hsp32, Hsp70 and Hsp90 were higher in elderly compared to young normal subjects. This difference disappeared for patients with inflammation who had increased levels of Hsp32, Hsp70 and Hsp90 compared to normal subjects. Most striking, a different pattern of association between cytokines and Hsp was noticed in healthy elderly subjects compared to the other groups of participants. It is concluded that age-related stress, possibly oxidative, which can down-regulate cytokine production with a concomitant up-regulation of Hsp production, could be involved in this differential pattern of association.

The influence of galantamine on reaction time, attention processes, and performance variability in elderly Alzheimer patients.

OBJECTIVE: To examine the effect of galantamine in elderly patients with mild to moderate Alzheimer disease (AD) on reaction time (RT), selective (SA) and alternating attention (AA), errors, and on interindividual and intraindividual variability. METHODS: Forty-one outpatients with AD were included in an open-label prospective trial and evaluated at baseline and after 8 and 22 weeks of treatment using a RT test that allows differentiation between the decision and movement time components of the total RT. The various tasks of the RT test allowed calculation of SA and AA. Standard AD evaluation tests were performed at baseline and after 22 weeks. RESULTS: After 8 and 22 weeks of treatment, an improvement of decision time and RT at all complexity levels was noted. For movement time, improvements were less pronounced and not present at both follow-up moments or at all complexity levels. Selective attention, but not AA, improved significantly after 22 weeks. A decrease in the number of errors was noted. At several complexity levels, both at 8 and 22 weeks, the interindividual and intraindividual variability decreased. Changes in Mini Mental State Evaluation score were correlated with those in SA. CONCLUSIONS: Our study provides arguments that galantamine treatment improves various parameters of the RT, attention, and interindividual and intraindividual variability in elderly AD patients. Because the study is not a controlled trial, further investigation is needed.

Prevalence of patients with do-not-resuscitate status on acute geriatric wards in Flanders, Belgium.

BACKGROUND: Elderly hospitalized patients have low survival rates after cardiopulmonary resuscitation, especially in the long term. This study aims to investigate the prevalence of patients with do-not-resuscitate (DNR) status on acute geriatric wards and the characteristics of the preceding decision-making process. METHODS: On all 94 geriatric wards in Flanders, Belgium (2002), the geriatrician who performed the bulk of clinical work was asked to fill in a retrospective structured mail questionnaire. RESULTS: The response rate was 72.3%. A DNR status was attributed to 20.3% of patients. A significant higher prevalence of patients with DNR status was found on wards with a geriatrician who had been active in patient care for 15 years or less and on wards with a DNR policy. Mostly, DNR status was attributed when the patient's condition declined (34.0%) or became critical (29.0%). Geriatricians consulted at least one person in 81.0% of the cases: (head) nurses in 72.2%, next of kin in 61.9%, the patient's general practitioner in 22.6%, and the patient him- or herself in 15.7%. Reasons stated to make a DNR decision were the prognosis (68.1%) and the physical condition of the patient (62.2%). Age was mentioned in only 21.1% of the cases, always in combination with other reasons. CONCLUSIONS: One fifth of patients on acute geriatric wards in Flanders have DNR status. The decision to attribute DNR status is most often made late in the course of the disease. (Head) nurses and the patient's next of kin are often consulted, the patient and his or her general practitioner rarely.

Nurses' involvement in 'do not resuscitate' decisions on acute elder care wards.

AIM: This paper reports the involvement of nurses in 'do not resuscitate' decision-making on acute elder care wards and their adherence to such decisions in the case of an actual cardiopulmonary arrest. BACKGROUND: Previous literature showed that nurses are involved in half or less than half of 'do not resuscitate' decisions in hospitals, but their involvement in this decision-making on acute elder care wards in particular has not been investigated. METHOD: A questionnaire was sent in 2002 to the head nurses of all acute elder care wards in Flanders, Belgium (n = 94). They were asked whether nurses had been involved in the last 'do not resuscitate' decision-making process on their ward and whether nurses 'never', 'rarely', 'sometimes', 'often' or 'always' started resuscitation in case of cardiopulmonary arrest of patients with 'do not resuscitate' status and of those without. RESULTS: The response rate was 86.2% (n = 81). In 74.7% of the last 'do not resuscitate' decisions on acute elder care wards in Flanders, a nurse was involved in the decision-making process. For patients with 'do not resuscitate' status, 54.3% of respondents reported that cardiopulmonary resuscitation was 'never' started on their ward, 'rarely' on 39.5% and 'sometimes' on 6.2%. For patients without 'do not resuscitate' status, nurses started cardiopulmonary resuscitation 'rarely' or 'sometimes' on 22.2% of all wards, and 'often' or 'always' on 77.8%. CONCLUSION: To make appropriate 'do not resuscitate' decisions and to avoid rash decision-making in cases of actual cardiopulmonary arrest, nurses should be involved early in 'do not resuscitate' decision-making. If institutional 'do not resuscitate' guidelines were to stress more clearly the important role of nurses in all kinds of end-of-life decisions, this might improve the 'do not resuscitate' decision-making process.

Basal and infection-induced levels of heat shock proteins in human aging.

Heat shock proteins (Hsp) are ubiquitously expressed proteins, which are highly inducible by a variety of stressful stimuli. As organisms age, various denatured proteins such as proteins modified by oxidation have been detected. Such abnormal proteins might serve as stress signals for the induction of Hsp, which plays indispensable roles in protecting proteins from denaturation. Although it is well known that the heat shock induced expression of Hsp decreases with age, little attention has been given to the unstimulated, basal levels of Hsp. Therefore, a study was performed to examine the expression pattern of various Hsp with aging, under normal physiological conditions in human peripheral blood cells. The basal levels of Hsp32, Hsp70 and Hsp90 increased significantly with age in controls but not patients. Moreover, the levels of Hsp32, Hsp70, Hsp90, but not Hsp27 correlated positively among each other, indicating both common and different regulatory mechanisms. Higher levels of Hsp32, Hsp70 and Hsp90 were noticed in patients with inflammation, a commonly occurring natural stimulant of Hsp production, compared to control subjects. The production of Hsp appeared to be related to the circulating levels of C-reactive protein and cytokines.

Attentional processes discriminate between patients with mild Alzheimer's disease and cognitively healthy elderly.

BACKGROUND: It is generally accepted that Alzheimer's disease (AD) is mainly characterized by memory disorders. Although recent studies also point to an important role of attention deficits early in the disease, this notion has not yet emerged in clinical practice. Our aim was to assess whether attention, quantified by reaction times, can discriminate between patients with mild AD and controls and therefore contribute to clinical diagnosis. METHODS: In a cross-sectional study, 33 patients with mild AD were matched with cognitively healthy elderly controls for age, gender, educational level and depressive mood. Selective attention (SA), alternating attention (AA) and error-rates were measured by a modified reaction time test. RESULTS: Significant differences between both groups were found for all measures. Logistic regression showed that SA (corrected for individual processing speed) and error-rates could correctly classify subjects with an overall hit ratio of 81%. When attention measures were not corrected for individual processing speed, the overall hit ratio improved to 97%. CONCLUSION: SA and AA deteriorate in patients with mild AD and these measures can be used to discriminate between patients and matched controls, independently of depressive mood.

Heat shock protein 32 in human peripheral blood mononuclear cells: effect of aging and inflammation.

The purpose of the present study was to assess the influence of age and acute infection on the production of Hsp32 in human peripheral blood cells, using flow cytometry. Thirty-five controls and 31 patients with acute infection participated. We found that the age and inflammatory status correlated positively with Hsp32 levels in both heat shocked (HS) and non-HS monocytes and lymphocytes. In addition, the HS response of Hsp32 was different in these peripheral blood cells; whereas HS exerted an up-regulation in the levels of Hsp32 in monocytes, a significant decrease in Hsp32 levels was noticed for lymphocytes. We found significant relationships between circulating C-reactive protein as well as interleukin-6 and the levels of Hsp32 in cells. We conclude that Hsp32 is up-regulated in the elderly as well as in individuals with inflammation, and that the HS response of Hsp32 is different in monocytes as compared to lymphocytes.

Circulating acute phase mediators and skeletal muscle performance in hospitalized geriatric patients.

BACKGROUND: There is growing evidence for the significant involvement of inflammatory processes in the development of muscle wasting in old age. Therefore, any disease accompanied by inflammation can be threatening to the muscle function in geriatric patients. METHODS: Sixty-three hospitalized geriatric patients (42 female, 21 male; mean age 84.2 +/- 5.7 years) were monitored weekly for muscle function (grip strength, fatigue resistance, shoulder extension strength, and hip extension strength) and for concentration of circulating C-reactive protein (CRP), fibrinogen, interleukin 6 (IL-6), and tumor necrosis factor-alpha alpha (TNF-alpha). RESULTS: On the basis of circulating CRP and fibrinogen concentrations, 42 patients were categorized on admission as inflammatory and 21 as noninflammatory. Inflammatory patients presented significantly weaker grip strength, shoulder extension strength, and a worse fatigue resistance than did noninflammatory patients. These muscle functions were negatively correlated with the concentrations of circulating CRP and IL-6, but not with fibrinogen or TNF-alpha. In noninflammatory patients, the fatigue resistance improved significantly during the first week of hospitalization. In patients admitted with inflammation, no improvement of muscle function was observed. Patients who remained inflammatory for 2 weeks or more presented a significant worsening of fatigue resistance. CONCLUSIONS: Geriatric hospitalized patients presenting with inflammation show significantly worse muscle functions, which do not improve during hospitalization despite adequate treatment of the primary disease. Reduced strength and fatigue resistance are significantly related to the concentration of circulating CRP and IL-6. Standard treatment of the underlying illness and classic physical therapy are not sufficient to normalize the skeletal muscle strength and fatigue resistance in these hospitalized patients.

Do-not-resuscitate policy on acute geriatric wards in Flanders, Belgium.

OBJECTIVES: To describe the historical development and status of a do-not-resuscitate (DNR) policy on acute geriatric wards in Flanders, Belgium, and to compare it with the international situation. DESIGN: Structured mail questionnaires. SETTING: All 94 acute geriatric wards in hospitals in Flanders in 2002 (the year Belgium voted a law on euthanasia). PARTICIPANTS: Head geriatricians. MEASUREMENTS: A questionnaire was mailed about the existence, development, and implementation of the DNR policy (guidelines and order forms), with a request to return copies of existing DNR guidelines and DNR order forms. RESULTS: The response was 76.6%, with hospital characteristics not significantly different for responders and nonresponders. Development of DNR policy began in 1985, with a step-up in 1997 and 2001. In 2002, a DNR policy was available in 86.1% of geriatric wards, predominantly with institutional DNR guidelines and individual, patient-specific DNR order forms. Geriatric wards in private hospitals implemented their policy later (P=.01) and more often had order forms (P=.04) than those in public hospitals. The policy was initiated and developed predominantly from an institutional perspective by the hospital. The forms were not standardized and generally lacked room to document patient involvement in the decision making process. CONCLUSION: Implementation of institutional DNR guidelines and individual DNR order forms on geriatric wards in Flanders lagged behind that of other countries and was still incomplete in 2002. DNR policies varied in content and scope and were predominantly an expression of institutional defensive attitudes rather than a tool to promote patient involvement in DNR and other end-of-life decisions.

The six-minute walk test in community dwelling elderly: influence of health status.

BACKGROUND: The 6 minutes walk test (6MWT) is a useful assessment instrument for the exercise capacity of elderly persons. The impact of the health status on the 6MWT-distance in elderly, however, remains unclear, reducing its value in clinical settings. The objective of this study was to investigate to what extent the 6MWT-distance in community dwelling elderly is determined by health conditions. METHODS: One hundred and fifty-six community dwelling elderly people (53 male, 103 female) were assessed for health status and performed the 6MWT. After clinical evaluation, electrocardiography and laboratory examination participants were categorized into a stratified six-level classification system according to their health status, going from A (completely healthy) to D (signs of active disease at the moment of examination). RESULTS: The mean 6MWT-distance was 603 m (SD = 178). The 6MWT-distance decreased significantly with increasing age (ANOVA p = 0.0001) and with worsening health status (ANCOVA, corrected for age p < 0.001).A multiple linear regression model with health status, age and gender as independent variables explained 31% of the 6MWT-distance variability. Anthropometrical measures (stature, weight and BMI) did not significantly improve the prediction model. A significant relationship between 6MWT-distance and stature was only present in category A (completely healthy). CONCLUSIONS: Significant differences in 6MWT-distance are observed according to health status in community-dwelling elderly persons. The proposed health categorizing system for elderly people is able to distinguish persons with lower physical exercise capacity and can be useful when advising physical trainers for seniors.

The influence of celecoxib on muscle fatigue resistance and mobility in elderly patients with inflammation.

BACKGROUND: Acute inflammation has a negative effect on the muscular system in elderly patients, compromising the outcome of the underlying disease. OBJECTIVE: The aim of this study was to evaluate the effect of cyclooxygenase-2 (COX-2) inhibition on muscle performance and mobility in hospitalized elderly patients with acute inflammation of infectious origin. METHODS: In this single-blind, controlled trial, consecutively hospitalized elderly patients (age > or = 70 years) with inflammation (C-reactive protein [CRP] levels > or =10 mg/L) due to acute infection were randomly assigned to receive 2 weeks of treatment with the COX-2-selective inhibitor celecoxib, acetaminophen, or no supplementary medication (control). The following variables were assessed at baseline and at 1 and 2 weeks' follow-up: muscle fatigue resistance (primary outcome measure); grip strength and mobility (secondary outcome measures); and levels of the acute-phase markers CRP, interleukin (IL)-1beta, IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta (TGF-beta) as explanatory variables. RESULTS: Forty-three consecutively hospitalized elderly patients (31 women, 12 men; mean [SD] age, 84 [6] years) were enrolled. Fourteen patients received celecoxib, 14 received acetaminophen, and 15 received no supplementary medication. The change in fatigue resistance was significantly different between groups (P = 0.021, Kruskal-Wallis chi-square test), with significantly greater improvement in patients receiving celecoxib compared with the acetaminophen and control groups (63% increase from baseline; P < 0.05). There were no significant between-group differences in changes in grip strength, mobility, IL-1beta, IL-6, TNF-alpha, or TGF-beta. The changes in levels of IL-10 differed significantly between groups (P = 0.020, Kruskal-Wallis chi-square test), with greater improvement in the celecoxib group compared with the acetaminophen group (P = 0.032). CONCLUSION: The results of this study suggest that COX-2-selective inhibition has a beneficial effect on muscle fatigue resistance in hospitalized elderly patients with acute inflammation of infectious origin. However, until further trials are conducted, the use of COX-2-selective inhibitors for this indication is not recommended.

The induction of heat shock protein 70 in peripheral mononuclear blood cells in elderly patients: a role for inflammatory markers.

The induction of heat shock proteins (Hsp) is the response to a plethora of stress signals including hyperthermia, physical stress, and various disease states. Although changes in Hsp expression are associated with certain diseases, the question as to whether this is an adaptation to a particular pathophysiologic state or a reflection of the suboptimal cellular environment associated with the disease remains open. In this study we have investigated the effects of inflammatory mediators on the induction of Hsp 70 in human peripheral mononuclear blood cells using flow cytometry. We demonstrate that without heat shock, the levels of the inflammatory mediators are positively related to Hsp 70 production in monocytes. On the contrary, negative correlations were found between heat induced Hsp 70 production and interleukin-6 (IL-6), as well as various markers of inflammation. These observations are in agreement with the antagonistic effects between heat stress and the inflammatory mediators on the activation of Hsp promoter.