Novel portable platform for molecular detection of toxigenic Clostridium difficile in faeces: a diagnostic accuracy study.

BACKGROUND: A novel portable platform for nucleic acid amplification enables rapid detection of diarrhoea causing toxigenic Clostridium difficile directly from faeces, even in resource-limited settings. We evaluated the accuracy and precision of the new commercial molecular test system. METHODS: One thousand one hundred and sixty faecal samples from patients suspected of having Clostridium difficile infection (CDI) were analysed using the Orion GenRead C. difficile test system (Orion Diagnostica Oy, Espoo, Finland) and comparative methods in three teaching hospital laboratories in Finland and France. The precision of the Orion GenRead C. difficile test system was evaluated in a reproducibility study with a set of blind-coded samples. The test system is based on a new isothermal amplification technology (Strand Invasion Based Amplification, SIBA®) and detection of the tcdB gene of C. difficile. We calculated the sensitivity, specificity, and the overall agreement according to Clinical and Laboratory Standards Institute recommendations. FINDINGS: The overall agreement of the Orion GenRead C. difficile test when compared to the comparative methods in routine use in the participating laboratories was between 96.7% and 98.8%. In the reproducibility study; the total percent agreement between three laboratories was 99.8%. INTERPRETATION: The identification of toxigenic C. difficile from faeces with the light-weight portable Orion GenRead test system was highly sensitive and specific, and the results were reproducible in the participating laboratories. This platform could enable fast and accurate molecular pathogen detection even in resource-limited or point-of-care settings.

An international study of the quality of national-level guidelines on driving with medical illness.

BACKGROUND: Medical illnesses are associated with a modest increase in crash risk, although many individuals with acute or chronic conditions may remain safe to drive, or pose only temporary risks. Despite the extensive use of national guidelines about driving with medical illness, the quality of these guidelines has not been formally appraised. AIM: To systematically evaluate the quality of selected national guidelines about driving with medical illness. DESIGN: A literature search of bibliographic databases and Internet resources was conducted to identify the guidelines, each of which was formally appraised. METHODS: Eighteen physicians or researchers from Canada, Australia, Ireland, USA and UK appraised nine national guidelines, applying the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. RESULTS: Relative strengths were found in AGREE II scores for the domains of scope and purpose, stakeholder involvement and clarity of presentation. However, all guidelines were given low ratings on rigour of development, applicability and documentation of editorial independence. Overall quality ratings ranged from 2.25 to 5.00 out of 7.00, with modifications recommended for 7 of the guidelines. Intra-class coefficients demonstrated fair to excellent appraiser agreement (0.57-0.79). CONCLUSIONS: This study represents the first systematic evaluation of national-level guidelines for determining medical fitness to drive. There is substantive variability in the quality of these guidelines, and rigour of development was a relative weakness. There is a need for rigorous, empirically derived guidance for physicians and licensing authorities when assessing driving in the medically ill.

Effective normative samples for the detection of cognitive impairment in older adults.

The inclusion of individuals with incipient dementia in normative data contaminates the distinction between normal and pathological aging. Conventional and Robust (excluding persons with incipient dementia) norms were created using data from the Canadian Study of Health and Aging (CSHA). Robust norms were not significantly better at distinguishing between normal and pathological aging. Norms reflecting the relationship between age and the prevalence of dementia revealed a probability of dementia of less than 35%. The results of the norming procedure serve to illustrate the validity of our current measures and methods for identifying cognitive impairment. CSHA Conventional norms are adequate for the identification of cognitive impairment.

Neuropsychological prediction of attrition due to death.

In aging research, attrition bias produces underestimates of cognitive decline and limits the interpretation of cognitive change. Using data from the Canadian Study of Health and Aging, we identified neuropsychological predictors of death among not cognitively impaired (NCI) and cognitively impaired, not-demented (CIND) persons. For those with NCI, two neuropsychological measures significantly predicted attrition, over and above age, in the short term, while age was the best long-term predictor. The absence of neuropsychological predictors for the CIND group may reflect the group's etiological heterogeneity. In future research, the use of a more homogeneous subset of CIND may yield additional predictors.

Cardiac tamponade and septic shock caused by viral infection in a previously healthy woman.

A previously healthy woman was admitted to hospital after 'flu-like' symptoms for 5 days followed by acute intense abdominal and lower back pain. On admission she was found to be in severe shock and was transferred to the ICU. Echocardiography revealed cardiac tamponade, and pericardiocentesis was performed immediately. Thereafter her cardiovascular state improved, but she developed hypotension with low systemic vascular resistance and required vasoactive treatment for 4 days. Nine days after admission the patient was transferred to the ward, after which she recovered rapidly and completely. The cause of her illness was extensively screened. No underlying disease was found, and all bacterial cultures remained negative. Acute virus infection was confirmed by diagnostic elevations of antibody titers to Influenza A and adenovirus. Adenovirus was also isolated from her bronchoalveolar lavage fluid.

Caregiver physical and mental health predicts reactions to caregiving.

Self-reported health and reactions to providing care to older adults with cognitive or physical impairments were examined. Health status was examined on a single occasion in 177 persons (aged 63-94 years) referred to programs within a comprehensive set of geriatric care services and the 133 family members involved in their care (ages 31-96 years). The five-scale Caregiver Reaction Assessment (CRA) was administered to the family members. Reliability analyses revealed that the CRA had good internal consistency. Being older was related to experiencing greater health problems in the caregiver role. Greater health problems from providing care were reported by caregivers in worse physical health and also when the care recipient had more physical pain. Caregivers who reported fewer health problems attributed to caregiving reported better mental health and less depressive symptomatology. Caregivers with health problems may be at increased risk of suffering from stress from caregiving.

Awareness of financial skills in dementia.

The present study examined the relations among levels of cognitive functioning, executive dysfunction, and awareness of financial management capabilities among a sample of 42 community-dwelling persons with dementia. Financial tasks on the Measure of Awareness of Financial Skills (MAFS) were dichotomized as simple or complex based on Piaget's operational levels of childhood cognitive development. Severity of global cognitive impairment and executive dysfunction were significantly related to awareness of financial abilities as measured by informant-participant discrepancy scores on the MAFS. For persons with mild and moderate/severe dementia, and persons with and without executive dysfunction, proportions of awareness within simple and complex financial task categories were tabulated. Significantly less awareness of financial abilities occurred on complex compared with simple tasks. Individuals with mild dementia were significantly less aware of abilities on complex items, whereas persons with moderate/severe dementia were less aware of abilities, regardless of task complexity. Similar patterns of awareness were observed for individuals with and without executive dysfunction. These findings support literature suggesting that deficits associated with dementia first occur for complex cognitive tasks involving inductive reasoning or decision-making in novel situations, and identify where loss of function in the financial domain may first be expected.

Measuring awareness of financial skills: reliability and validity of a new measure.

This paper examines the psychometric properties of a three-part (participant, informant, and performance) Measure for assessing Awareness of Financial Skills (MAFS). The MAFS was administered to 10 seniors with dementia and 25 well-functioning seniors, and their informants. Measures of cognitive functioning, social desirability, neuroticism, and perceived control were administered to each participant to allow for an assessment of validity. Internal consistency estimates for the participant and informant questionnaires were found to be 0.92 and 0.97, respectively. Convergent validity analysis indicated that performance on this measure was related to level of cognitive functioning, with higher level of unawareness associated with decreased cognitive ability. Discriminant validity analysis showed that performance on this measure was not related to social desirability or neuroticism. This study provides evidence that the MAFS is a reliable and valid tool for assessing awareness of financial skills in older adults.

Correcting the 3MS for bias does not improve accuracy when screening for cognitive impairment or dementia.

We investigated the effects of correcting for demographic biases on the sensitivity and specificity of the Modified Mini Mental Status Exam (3MS) using a sample of English-speaking older adults (N=8901) from the Canadian Studies of Health and Aging. The sensitivity and specificity of the original 3MS were compared to the 3MS regression-adjusted for the influence of demographic variables and then to 3MS percentiles based on published normative data with age and education corrected cutoff scores. According to receiver operating characteristic curve analyses, the regression-adjusted 3MS was no more accurate than the original 3MS when screening for dementia, and it was less accurate when screening for cognitive impairment. The use of 3MS percentiles based on normative data with age and education corrected cut-off points were less accurate than the original 3MS when screening for both cognitive impairment and when screening for dementia.

Subjects with allergic rhinitis show signs of more severely impaired paranasal sinus functioning during viral colds than nonallergic subjects.

BACKGROUND: Viral cold is thought to be the major contributing factor in the pathogenesis of sinusitis, as it causes ostiomeatal obstruction. The aim was to evaluate whether paranasal sinus functioning during viral colds is similar in subjects with and without allergic rhinitis. METHODS: Forty-eight volunteers were examined during an early (2-4 days) natural cold and again 3 weeks later. The examinations included computed tomography (CT) scans, nasal mucosal biopsies, and viral and bacterial specimens. Subjects with positive skin prick tests and persistent or intermittent rhinitis were considered to have allergic immunoglobulin E (IgE)-mediated rhinitis. In addition, specific IgE antibodies to staphylococcal enterotoxin B (SEB) were measured. RESULTS: Nine subjects (19%) had allergic rhinitis. The allergic subjects were significantly more often IgE sensitized to SEB than the nonallergic subjects (33%vs 3%, P = 0.02). Viral etiology of the cold was identified in 32 (67%) subjects. The subjects with allergic rhinitis had significantly higher CT scores compared with nonallergic subjects during the colds (median (range) scores 16 (6-22) vs 6 (0-17), P = 0.004). In both groups, the median scores declined markedly during convalescence, but the difference remained significant (P = 0.009). Among the allergic subjects, those who were IgE sensitized to SEB tended to have the highest CT scores [median (range) 16 (16-22)]. Total serum IgE and the nasal subepithelial eosinophil counts correlated with the CT scores during the cold (rs = 0.38, P = 0.008 and rs = 0.46, P = 0.001, respectively). CONCLUSIONS: Subjects with allergic IgE-mediated rhinitis had more severe paranasal sinus changes in CT scans than nonallergic subjects during viral colds. These changes indicate impaired sinus functioning and may increase the risk of bacterial sinusitis.

Cognitive decline in high-functioning older adults: reserve or ascertainment bias?

The detection of mild cognitive impairment and dementia in high-functioning older adults can be difficult. It has also been observed that high-functioning persons show a lower prevalence of dementia than low-functioning persons. Three alternative explanations for this observation have been proposed in the literature: brain reserve capacity (BRC), cognitive reserve, and ascertainment bias. With data from a prospective, population-based study of incident dementia, the Canadian Study of Health and Aging (CSHA), we classified participants as being high- (HF) or low-functioning (LF) in three ways: educational and occupational attainment, and estimated premorbid IQ. We observed that fewer HF older adults were diagnosed with dementia after five years, which is in accordance with both the BRC and cognitive reserve models. Contrary to expectations, no difference on rate of memory deterioration was observed between those HF and LF persons who exhibited mild cognitive impairment at CSHA-1. However, HF persons who subsequently were diagnosed with dementia (CSHA-2) showed more rapid decline on five of the six memory measures over time than did LF persons diagnosed with dementia at CSHA-2. When performance on measures of memory functioning at CSHA-1 was examined for highly educated older adults, significantly more of those with dementia at CSHA-2 (n = 59) had scores falling within or below the average range in comparison to normative standards than those who continued to show no cognitive impairment (n = 145). Our findings suggest that the lower incidence of dementia for HF persons may be primarily the result of ascertainment bias, not underlying differences in brain or cognitive reserve.

Lymphocyte and mast cell counts are increased in the nasal mucosa in symptomatic natural colds.

Knowledge of the virus-induced immune response is important in understanding the pathophysiology of respiratory virus infections. Data on the cellular immune response is still limited and based mainly on experimental studies. Natural colds may differ in their pathophysiology from experimentally induced ones. To evaluate the inflammatory cell responses in the upper respiratory tract during natural colds we counted the number of lymphocytes, mast cells and macrophages in the nasal mucosa. Nasal biopsies were taken from 22 adult volunteers during the acute (2-4 days of symptoms) and convalescent phases (day 21) of the cold, and the numbers of cells were counted with immunohistochemical methods. Viral aetiology was identified in 14 (64%) subjects by using viral isolation, antigen detection and rhino-polymerase chain reaction assays. The number of T lymphocytes was increased in the nasal epithelium and that of T and B lymphocytes and mast cells in the subepithelial layer in the acute phase compared to the convalescent phase. Intraepithelial T lymphocyte counts were significantly higher in the subjects who had a proven viral infection or a finding of pathogenic bacteria in the nasopharynx compared to the subjects without such findings (P = 0.005 and P = 0.04, respectively). Contrary to the earlier experimental studies, we found that viruses cause accumulation of T and B lymphocytes and mast cells during the first days of a symptomatic naturally acquired respiratory infection.

The common cold in patients with a history of recurrent sinusitis: increased symptoms and radiologic sinusitislike findings.

BACKGROUND: We evaluated whether the symptoms and signs and radiologic findings during a common cold are similar in patients who have and have not suffered from recurrent sinusitis. METHODS: We recruited 2 series of volunteer cases from February 1, 1996, to December 31, 1996. Twenty-three adults who claimed to have suffered from recurrent sinusitis and 25 who had never had sinusitis were examined during the period of a self-diagnosed cold of 48 to 96 hours' duration and again after 21 days. Symptom scores were recorded, nasoendoscopy and computed tomography scans were performed, and viral and bacterial specimens were taken. RESULTS: The patients with a history of sinusitis had significantly higher symptom scores than the control patients (P=.04) and had radiologic sinusitislike changes more often (65% [15] vs 36% [9]; difference 29% [95% confidence interval, 2%-56%]; P=.04). The viral etiology of the common cold (verified in 67% of the episodes) was similar in both groups. Pathogenic bacteria were isolated from the middle meatus in 24% (6) of the control patients and only 9% (2) of the sinusitis-prone patients (P=.15). On the basis of the symptomatology, radiologic findings, and bacterial cultures only 2 patients in the sinusitis-prone group should have been treated with antimicrobials. CONCLUSIONS: Some patients are susceptible to both sinusitislike symptoms and radiologic findings during viral common colds. This may cause them to consult their physicians earlier and more often during viral colds, which may result in unnecessary antibiotic treatments. Nasopharyngeal bacteriological cultures may prove to be useful in ruling out bacterial sinusitis.

Cognitive impairment, no dementia: concepts and issues.

This article reviews the concept of mild cognitive impairment in groups of people whose cognitive impairment does not warrant a diagnosis of dementia (cognitive impairment, no dementia; CIND). Problems with the application of existing sets of criteria to the Canadian Study of Health and Aging (CSHA) data sets are addressed and a procedure for identifying a subgroup presumed "at risk" for developing dementia is presented. Application of an informant's report of changes in cognitive functioning and neuropsychologists' ratings of mild to severe deficits in any of eight cognitive domains results in approximately half of the CIND cases being identified as "at risk." The rationale for the collection of specific information related to CIND in CSHA-2 is provided. A minority of people identified with CIND at CSHA-2 showed only memory impairment, and most demonstrated cognitive loss over the preceding five-year interval. This article provides a conceptual basis for procedures to identify people with cognitive impairment most likely to decline to dementia.

Pro- and retrospective memory in late adulthood.

Everyday tasks, such as getting groceries en route from work, involve two distinct components, one prospective (i.e., remembering the plan) and the other retrospective (i.e., remembering the grocery list). The present investigation examined the size of the age-related performance declines in these components, as well as the relationship between these components and age-related differences in processing resources. The subjects were 133 community-dwelling adults between 65 and 95 years of age. They completed a large battery of tests, including tests of pro- and retrospective memory as well as tests for indexing processing resources. The results showed similar age-related declines in pro- and retrospective memory. There was only a weak relationship between pro- and retrospective memory, and the age-related decline in processing resources was related more strongly to retro- than prospective memory.

Predicting caregiver burden and depression in Alzheimer's disease.

OBJECTIVES: The purpose of this study was to investigate the predictors of caregiver burden and depression, including objective stressors and mediation forces influencing caregiving outcomes. METHODS: This investigation is based on the 1994 Canadian Study of Health and Aging (CSHA) database. Participants were 613 individuals with dementia, living in either the community or an institution, and their informal caregivers. Participants for the CSHA were identified by screening a large random sample of elderly persons across Canada. Structural equation models representing four alternative pathways from caregiving stressors (e.g., functional limitations, disturbing behaviors, patient residence, assistance given to caregiver) to caregiver burden and depression were compared. RESULTS: The data provided the best fit to a model whereby the effects on the caregiver's well-being are mediated by appraisals of burden. A higher frequency of disturbing behavior, caring for a community-dwelling patient, and low informal support were related to higher burden, which in turn led to more depressive symptomatology. Caregivers of patients exhibiting more disturbing behaviors and functional limitations received less help from family and friends, whereas those whose care recipients resided in an institution received more informal support. DISCUSSION: Our findings add to the preexisting literature because we tested alternative models of caregiver burden using an unusually large sample size of participants and after overcoming methodological limitations of past research. Results highlight the importance of the effective management of disturbing behaviors, the provision of formal services for caregivers with highly impaired patients and no informal support, and the improvement of coping skills in burdened caregivers.

Cognitive impairment with no dementia (CIND): longitudinal studies, the findings, and the issues.

Identification of persons at risk for developing dementia is of increasing importance as the proportion of persons over the age of 65 years grows globally. This review examines the neuropsychological literature specifically addressing the concept of impaired cognitive functioning of insufficient magnitude to warrant a diagnosis of dementia and its meaning with respect to the development of dementia. Although the most obvious finding in the literature is that persons with impaired cognitive functioning have varied outcomes, it is clear that a significant proportion of persons with mild cognitive impairment progress to dementia over a 1- to 2-year interval and approximately 50% progress to dementia by 5 years. The best and most commonly identified predictors of decline to dementia include age and lower baseline performance on neuropsychological measures (e.g., measures of memory). In discussing these findings, issues related to sample definition, sample selection, and methodology are identified and recommendations for future research are provided.

A comparison of alternative approaches to the scoring of clock drawing.

Although a number of scoring procedures for clock drawing have emerged in the literature, no systematic comparison of the psychometric properties of various approaches has yet been conducted on a large sample of persons over 64 years of age diagnosed with dementia or deemed cognitively intact. The present study examined the reliability and validity of five scoring approaches (Doyon, Bouchard, Morin, Bourgeois, & Cote, 1991; Shulman, Shedletsky, & Silver, 1986; Tuokko, Hadjistavropoulos, Miller, & Beattie, 1992; Watson, Arfken, & Birge, 1993; Wolf-Klein, Silverstone, Levy, Brod, & Breuer, 1989) among the 493 participants of the Canadian Study of Health and Aging who completed clock drawing and who had a final diagnosis assigned at the conclusion of a comprehensive clinical examination. Inter- and intra-rater reliabilities were highest for the Tuokko et al. method. The Tuokko and Shulman scoring procedures had the highest sensitivities and relatively low specificities. The Wolf-Klein procedure had relatively low sensitivities and high specificities. Estimated areas under receiver operating curves were relatively high for all scoring methods. However, the area under the curve for the Watson procedure was significantly lower than the other procedures. All claims to the utility of clock drawing for differentiating between normal persons over 64 years of age and those with dementia appear validated.