Adults with Down syndrome: a comprehensive approach to manage complexity.

BACKGROUND: Down syndrome (DS) is characterised by premature ageing that affects selected organ systems, and persons with this condition can present patterns of co-morbidities and deficits often observed in the older population without DS. However, information on the characteristics of adult persons with DS is limited. The objective of the study is to describe characteristics of adults with DS collected with a standardised, comprehensive assessment instrument. METHODS: Cross-sectional study. Four hundred thirty adults with DS (age range 18/75 years) from three countries (Italy, n = 95; USA, n = 175; and Canada, n = 160). A standardised assessment instrument (interRAI intellectual disability) was used to assess sample characteristics. RESULTS: Mean age ranged from 35.2 (standard deviation 12.0) years in the US sample to 48.8 (standard deviation 9.0) years in the Canadian sample. Most participants in the Italian and US sample were living in private homes, while more than half of those in the Canadian sample were institutionalised. Prevalences of geriatric conditions, including cognitive deficits, disability in the common activities of daily living, symptoms of withdrawal or anhedonia, aggressive behaviour, communication problems, falls and hearing problems were high in the study sample. Gastrointestinal symptoms, skin and dental problems and obesity were also frequently observed. CONCLUSIONS: Adults with DS present with a high level of complexity, which may suggest the need for an approach based on a comprehensive assessment and management that can provide adequate care. Further research is needed to understand better the effectiveness of such an approach in the DS population.

Diagnosis and inflammatory response of patients with candiduria.

Candiduria is common in hospitalised patients, but the clinical relevance is still unclear. This study was done to further our knowledge on detection of and host responses to candiduria. Urines and clinical data from 136 patients in whom presence of yeast was diagnosed by microscopic urinalysis were collected. Diagnosis by standard urine culture methods on blood and MacConkey agar as well as on fungal culture medium (Sabouraud dextrose agar) was compared. Inflammatory parameters (IL-6 and IL-17, Ig) were quantified in the urine and compared with levels in control patients without candiduria. Standard urine culture methods detected only 37% of Candida spp. in urine. Sensitivity was especially low (23%) for C. glabrata and was independent of fungal burden. Candida specific IgG but not IgA was significantly elevated when compared with control patients (P < 0.0001 and 0.07 respectively). In addition, urine levels of IL-6 and IL-17 were significantly higher in candiduric patients when compared with control patients (P < 0.001). Multivariate analysis documented an independent association between an increased IgG (odds ratio (OR) 136.0, 95% confidence interval (CI) 25.7-719.2; P < 0.0001), an increased IL-17 (OR 17.4, 95% CI 5.3-57.0; P < 0.0001) and an increased IL-6 level (OR 4.9, 95% CI 1.9-12.4; P = 0.001) and candiduria. In summary, our data indicate that clinical studies on candiduria should include fungal urine culture and that inflammatory parameters may be helpful to identify patients with clinically relevant candiduria.

Cryptococcus neoformans variants generated by phenotypic switching differ in virulence through effects on macrophage activation.

Macrophages have a central role in the pathogenesis of cryptococcosis since they are an important line of defense, serve as a site for fungal replication, and also can contribute to tissue damage. The objective of this study was to investigate the interaction of macrophages with cells from smooth-colony variants (SM) and mucoid-colony variants (MC) arising from phenotypic switching of Cryptococcus neoformans. Alveolar macrophages (AMs) isolated from SM- and MC-infected mice exhibited differences in gene and surface expression of PD-L1, PD-L2, and major histocompatibility class II (MHC-II). PD-L1 and PD-L2 are the ligands for PD1 and are differentially regulated in Th1- and Th2-type cells. In addition, macrophage activation in SM- and MC-infected mice was characterized as alternatively activated. Flow cytometric and cytokine analysis demonstrated that MC infection was associated with the emergence of Th17 cells and higher levels of interleukin-17 (IL-17) in lung tissue, which were reduced by AM depletion. In conclusion, our results indicate that macrophages play a significant role in maintaining damage-promoting inflammation in the lung during MC infection, which ultimately results in death.

Validating the Mental Health Assessment Protocols (MHAPs) in the Resident Assessment Instrument Mental Health (RAI-MH).

For persons with mental illness and addictions, comprehensive assessment of their strengths, preferences and needs is central to person-centred care planning. In this study, the validity of the Mental Health Assessment Protocols (MHAPs) embedded in the Resident Assessment Instrument Mental Health instrument (the mandated assessment system for Ontario adult inpatient psychiatry) is examined, and triggering rates are compared in inpatient and community-based mental health settings. The sample is based on adults admitted to a psychiatric facility (n = 963) and to community mental health programmes (n = 1505) participating in the study. An international panel of mental health experts further evaluated study results. Among the 27 MHAPs, all but one had sensitivity rates above 80%, and the specificity was over 80% for 74% of the MHAPs. The expert panel found that the MHAPs worked well and could be used to support mental health care. The present study found that the MHAPs are valid measures, though more complex triggering algorithms capable of differentiating individuals based on outcomes were suggested to enhance their clinical relevance to care planning. Further, the use of compatible instrumentation in community-based mental health settings was promoted to enhance continuity of care.

A review of evidence on the reliability and validity of Minimum Data Set data.

This paper reviews the reliability and validity of the Minimum Data Set (MDS) assessment, which is being used increasingly in Canadian nursing homes and continuing care facilities. The central issues that surround the development and implementation of a standardized assessment such as the MDS are presented, including implications for health care managers in how to approach data quality concerns. With other sectors such as home care and inpatient psychiatry using MDS for national reporting, these issues have importance in and beyond residential care management.

Measurement of staphylococcal enterotoxin B in serum and culture supernatant with a capture enzyme-linked immunosorbent assay.

Staphylococcal enterotoxin B (SEB) is a select agent because it is a potent mitogen that elicits life-threatening polyclonal T-cell proliferation and cytokine production at very low concentrations. Efforts are in progress to develop therapeutic reagents and vaccines that neutralize or prevent the devastating effects of this toxin. Because of its rapid binding to in vivo receptors, this toxin is difficult to detect in serum. This rapid binding also constitutes a major challenge for the development of effective therapeutic reagents that can neutralize the effects of the toxin in vivo. We have developed a highly sensitive capture enzyme-linked immunosorbent assay that detects SEB in body fluids at very low levels. With this assay, the peak levels of SEB in serum and renal clearance can be measured in mice. After either oral ingestion or nasal inhalation of SEB by mice, this assay documents the transcytosis of SEB across the mucosal membranes into serum within 2 h. Furthermore, this assay was used to compare the SEB levels in different murine models for SEB-induced lethal shock and demonstrated that the coadministration of toxin-enhancing chemicals, such as D-galactosamine and lipopolysaccharide, can alter the peak serum SEB levels. Hence, this assay is a potentially useful tool for the study of the pharmacokinetics of SEB and the effects of potential therapeutic reagents on serum SEB levels.

Lactic acidosis after treatment with linezolid.

Linezolid is currently indicated to treat vancomycin-resistant Enterococcus faecium infections, nosocomial pneumonia caused by Staphylococcus aureus or Streptococcus pneumoniae, complicated and uncomplicated skin and skin structure infections, and community-acquired pneumonia. We report a case of linezolid-induced lactic acidosis during treatment of vancomycin-resistant enterococcal bacteremia after mitral valve replacement and permanent pacemaker implantation. We also review the current literature describing other cases of linezolid-associated hyperlactatemia.

Biofilm formation by and antifungal susceptibility of Candida isolates from urine.

Biofilm formation (BF) in the setting of candiduria has not been well studied. We determined BF and MIC to antifungals in Candida spp. isolates grown from urine samples of patients and performed a retrospective chart review to examine the correlation with risk factors. A total of 67 Candida spp. isolates were grown from urine samples from 55 patients. The species distribution was C. albicans (54%), C. glabrata (36%), and C. tropicalis (10%). BF varied greatly among individual Candida isolates but was stable in sequential isolates during chronic infection. BF also depended on the growth medium and especially in C. albicans was significantly enhanced in artificial urine (AU) compared to RPMI medium. In nine of the C. albicans strains BF was 4- to 10-fold higher in AU, whereas in three of the C. albicans strains and two of the C. glabrata strains higher BF was measured in RPMI medium than in AU. Determination of the MICs showed that planktonic cells of all strains were susceptible to amphotericin B (AMB) and caspofungin (CASPO) and that three of the C. glabrata strains and two of the C. albicans strains were resistant to fluconazole (FLU). In contrast, all biofilm-associated adherent cells were resistant to CASPO and FLU. The biofilms of 14 strains (28%) were sensitive to AMB (MIC(50) of <1 mug/ml). Correlation between degree of BF and MIC of AMB was not seen in RPMI grown biofilms but was present when grown in AU. A retrospective chart review demonstrated no correlation of known risk factors of candiduria with BF in AU or RPMI. We conclude that BF is a stable characteristic of Candida strains that varies greatly among clinical strains and is dependent on the growth medium. Resistance to AMB is associated with higher BF in AU, which may represent the more physiologic medium to test BF. Future studies should address whether in vitro BF can predict treatment failure in vivo.

Phagocytic efficacy of macrophage-like cells as a function of cell cycle and Fcgamma receptors (FcgammaR) and complement receptor (CR)3 expression.

Previous studies have shown that the efficiency of phagocytosis is a function of cell cycle and that phagocytosis promotes cell cycle progression. Because phagocytosis is dependent on cellular receptors we hypothesized that Fcgamma receptors (FcgammaR) and complement receptors (CR) expression varied with cell cycle. Consequently, we used centrifugal elutriation of macrophage-like cells, fluorescence activated cell sorting analysis and receptor staining to investigate expression of FcgammaR and CR as a function of cell cycle. We confirmed that FcgammaR expression on macrophage-like cells increased as the cells progressed from G1 to G2 phases. Moreover, CR3 expression varied as a function of cell cycle in a manner similar to FcgammaR. Correlation of receptor expression with cell size showed that FcgammaR and CR3 expression on macrophages was determined largely by cell size enlargement during the cell cycle. The efficacy of both Fc- and complement-mediated phagocytosis of live Cryptococcus neoformans (Cn) showed a biphasic pattern with the efficacy of phagocytosis decreasing when the cells approached the G1-S interface, which paralleled the changes in receptor surface expression when cells exited G1 phase. Live Cn cells were significantly more resistant to phagocytosis than dead cells at all stages of macrophage-like cell cycle. In contrast to live cells, the efficacy of phagocytosis of dead Cn decreased as surface receptor expression increased. Hence, the efficacy of phagocytosis in this system as function of cell cycle is not related to phagocytic receptor expression.

Phenotypic switching in a Cryptococcus neoformans variety gattii strain is associated with changes in virulence and promotes dissemination to the central nervous system.

This is the first report of a Cryptococcus neoformans var. gattii strain (serotype B) that switches reversibly between its parent mucoid (NP1-MC) colony morphology and a smooth (NP1-SM) colony morphology. Similar to C. neoformans var. grubii and C. neoformans var. neoformans strains, the switch is associated with changes in the polysaccharide capsule and virulence in animal models. In murine infection models, NP1-MC is significantly more virulent than NP1-SM (P < 0.021). In contrast to the serotype A and D strains, the serotype B strain switches in vivo reversibly between both colony morphologies. The polysaccharide of NP1-MC exhibits a thicker capsule, and thus NP1-MC exhibits enhanced intracellular survival in macrophages. Consistent with this finding, switching to the mucoid variant is observed in pulmonary infection with NP1-SM. In contrast, the thin polysaccharide capsule of NP1-SM permits better crossing of the blood-brain barrier. In this regard, only smooth colonies were grown from brain homogenates of NP1-MC-infected mice. Our findings have important implications for the pathogenesis of cryptococcosis and suggest that phenotypic switching affects host-pathogen interactions in the local microenvironment. This altered interaction then selects for specific colony variants to arise in a pathogen population.

Phenotypic switching in Cryptococcus neoformans.

Phenotypic switching has been described in serotype A and D strains of Cryptococcus neoformans. It occurs in vivo during chronic infection and is associated with differential gene expression and changes in virulence. The switch involves changes in the polysaccharide capsule and cell wall that affect the yeast's ability to resist phagocytosis. In addition, the phenotypic switch variants elicit qualitatively different inflammatory responses in the host. In animal models of chronic cryptococosis, the immune response of the host ultimately determines which of the switch variants are selected and maintained. The importance of phenotypic switching is further underscored by several findings that are relevant in the setting of human disease. These include the ability of the mucoid colony variant of RC-2 (RC-2 MC) but not the smooth variant (RC-2 SM) to promote increased intracerebral pressure in a rat model of cryptococcal meningitis. Furthermore, chemotherapeutic and immunological antifungal interventions can promote the selection of the RC-2 MC variant during chronic murine infection.

Molecular epidemiology of clinical Cryptococcus neoformans strains from India.

Little is known about the molecular epidemiology of the human pathogenic fungus Cryptococcus neoformans in India, a country now in the midst of an epidemic of AIDS-related cryptococcosis. We studied 57 clinical isolates from several regions in India, of which 51 were C. neoformans var. grubii, 1 was C. neoformans var. neoformans, and 5 were C. neoformans var. gattii. This strain set included 18 additional sequential isolates from 14 patients. Strains were characterized phenotypically by measuring the polysaccharide capsule and by determining the MICs of standard antifungals. Molecular typing was performed by a PCR-based method using the minisatellite-specific core sequence (M13), by electrophoretic karyotyping, by restriction fragment length polymorphisms with the C. neoformans transposon 1 (TCN-1), and by URA5 DNA sequence analysis. Overall, Indian isolates were less heterogeneous than isolates from other regions and included a subset that clustered into one group based on URA5 DNA sequence analysis. In summary, our results demonstrate (i) differences in genetic diversity of C. neoformans isolates from India compared to isolates from other regions in the world; (ii) that DNA typing with the TCN-1 probe can adequately distinguish C. neoformans var. grubii strains; (iii) that TCN-1 sequences are absent in many C. neoformans var. gattii strains, supporting previous studies indicating that these strains have a limited geographical dispersal; and (iv) that human cryptococcal infection can be associated with microevolution of the infecting strain and by simultaneous coinfection with two distinct C. neoformans strains.

Phenotypic switching of Cryptococcus neoformans can produce variants that elicit increased intracranial pressure in a rat model of cryptococcal meningoencephalitis.

Increased intracranial pressure (ICP) plays an important role in the morbidity and mortality of cryptococcal meningoencephalitis. The microbial and host factors that contribute to the development of increased ICP are poorly understood. We found that phenotypic switch variants of Cryptococcus neoformans (smooth and mucoid) differed in their abilities to promote increased ICP in a rat model of cryptococcal meningitis. Rats infected with the mucoid variant developed increased ICP, whereas rats infected with the smooth parent did not. This trend correlated with a shorter survival time and a higher cerebrospinal fluid (CSF) fungal burden for mucoid variant-infected rats, although brain fungal burdens were comparable between mucoid variant- and smooth parent-infected rats. Magnetic resonance imaging revealed enhanced T2 signal intensity over the surfaces of the brains of mucoid variant-infected rats. In addition, more polysaccharide accumulated in the CSF and brains of mucoid variant-infected rats. The accumulation of glucorunoxylomannan was associated with elevated levels of MCP-1 (CCL2) and, accordingly, a more pronounced but ineffective monocytic inflammatory response in the meninges of mucoid variant-infected rats. In summary, these findings suggest that strain-specific characteristics can influence the development of increased ICP and indicate a manner in which phenotypic switching could influence the outcome of a central nervous system infection.

The RAI-PC: an assessment instrument for palliative care in all settings.

Large numbers of persons in most types of healthcare settings have palliative care needs that have considerable impact on their quality of life. Therefore, InterRAI, a multinational consortium of researchers, clinicians, and regulators that uses assessment systems to improve the care of elderly and disabled persons, designed a standardized assessment tool, the Resident Assessment Instrument for Palliative Care (RAI-PC). The RAI-PC can be used for both the design of individual care plans and for case mix and outcomes research. Some elements of this instrument are taken from the resident assessment instrument (RAI) mandated for use in all nursing homes in the United States and widely used throughout the world. The RAI-PC can be used alone or in counjunction with the other assessment tools designed by the InterRAI collaboration: the RAI for homecare (RAI-HC), for acute care (RAI-AC), and for mental health care (RAI-MH). The objective of this study was to field test and carry out reliability studies on the RAI-PC. After appropriate approvals were obtained, the RAI-PC instrument was field tested on 151 persons in three countries in more than five types of settings. Data obtained from 144 of these individuals were analyzed for reliability. The reliability of the instrument was very good, with about 50 percent of the questions having kappa values of 0.8 or higher, and the average kappa value for each of the eight domains ranging from 0.76 to 0.95. The 54 men and 95 women had a mean age of 79 years. Thirty-four percent of individuals suffered pain daily. Eighty percent tired easily; 52 percent were breathless on exertion; and 19 to 53 percent had one or more other symptoms, including change in sleep pattern, dry mouth, nausea and vomiting, anorexia, breathlessness at rest, constipation, and diarrhea. The number of symptoms an individual reported increased as the estimated time until death declined. The "clinician friendly" RAI-PC can be used in multiple sites of care to facilitate both care planning and case mix and outcomes research.

Phenotypic switching of Cryptococcus neoformans occurs in vivo and influences the outcome of infection.

Phenotypic switching has been linked to the virulence of many pathogens, including fungi. However, it has not been conclusively shown to occur in vivo or to influence the outcome of infection. Cryptococcus neoformans undergoes phenotypic switching in vitro to colony types that differ in their virulence in mice. In this study, we asked whether C. neoformans undergoes phenotypic switching in vivo and whether this phenomenon contributes to virulence. By using a small inoculum to preclude the introduction of variants that had already switched during in vitro propagation, we demonstrated that in vivo switching to a mucoid phenotype occurred in two mice strains and was associated with a lethal outcome. Phenotypic switching resulted in changes of the capsular polysaccharide that inhibited phagocytosis by alveolar macrophages. This promoted a more vigorous inflammatory response and rapid demise. These data document in vivo switching in a fungus and associate this phenomenon with enhanced virulence and a lethal outcome. The importance of this finding is underscored by the increased likelihood of phenotypic switching in chronic cryptococcosis; thus this mechanism may account for the inability to eradicate the organism in immunocompromised hosts.

Pain in U.S. nursing homes: validating a pain scale for the minimum data set.

PURPOSE: The aim of this study was to validate a pain scale for the Minimum Data Set (MDS) assessment instrument and examine prevalence of pain in major nursing home subpopulations, including type of admission and cognitive status. DESIGN AND METHODS: This study considered validation of the MDS pain items and derivation of scale performed against the Visual Analogue Scale (VAS), using Automatic Interaction Detection. The derivation data describe 95 postacute care nursing home patients who are able to communicate. The scale is then used in retrospective analysis of 34,675 Michigan nursing home residents. RESULTS: A four-group scale was highly predictive of VAS pain scores (variance explanation 56%) and therefore quite valid in detecting pain. In the prevalence sample, only 47% of postacute patients compared to 63% of postadmission patients reported no pain, and these percentages rose with increasing cognitive impairment. IMPLICATIONS: Pain is prevalent in nursing home residents, especially in those with cognitive dysfunction, and often untreated.

Clinical characteristics and six-month outcomes of nursing home residents with low activities of daily living dependency.

BACKGROUND: Up to 30% of nursing home residents have very little dependency in activities of daily living (ADLs). We compared the characteristics and six-month outcomes of a sample of low-ADL--dependent nursing home residents (LDR) with other residents. METHODS: This is a cross-sectional, six-month follow-up study using secondary data analysis. We combined the separate 1990 and 1993 cohorts in the Resident Assessment Instrument evaluation study. In each case these data were collected in the same 254 nursing homes in 10 states. We studied residents with a length of stay greater than 60 days and age 65 years and older (N = 3955). We compared the baseline characteristics of LDR (n = 985) with all other residents. We then compared six-month outcomes of LDR with other residents and characteristics of LDR with poor outcomes (death or worsened ADL disability) with LDR who remained stable. RESULTS: The LDR had a significantly decreased frequency of geriatric syndromes (i.e., cognitive impairment, urinary incontinence, under-nutrition, vision problems, poor balance, and pressure ulcers) and neurological disease but had the same frequency of non-neurological chronic diseases and were on more medications. Thirty-one percent had poor six-month outcomes associated with baseline poor cognition, incontinence, poor appetite, and presence of vascular disease, daily pain, shortness of breath, and multiple medications. CONCLUSION: Our research identified 29% of nursing home residents with higher physical function (LDR) who had fewer geriatric syndromes and neurological disease diagnoses; 69% of these remained stable at 6 months. Those LDR with a higher risk of poor outcomes could be prospectively identified. LDR who remained stable for 6 months may represent a group who could potentially be maintained in the community.

[Integrated health information system based on Resident Assessment Instruments]. / Geïntegreerd gezondheidsinformatiesysteem op basis van Resident Assessment Instrumenten.

The paper explores the meaning of Resident Assessment Instruments. It gives a summary of existing RAI instruments and derived applications. It argues how all of these form the basis for an integrated health information system for "chain care" (home care, home for the elderly care, nursing home care, mental health care and acute care). The primary application of RAI systems is the assessment of client care needs, followed by an analysis of the required and administered care with the objective to make an optimal individual care plan. On the basis of RAI, however, applications have been derived for reimbursement systems, quality improvement programs, accreditation, benchmarking, best practice comparison and care eligibility systems. These applications have become possible by the development on the basis of the Minimum Data Set of RAI of outcome measures (item scores, scales and indices), case-mix classifications and quality indicators. To illustrate the possibilities of outcome measures of RAI we present a table and a figure with data of six Dutch nursing homes which shows how social engagement is related to ADL and cognition. We argue that RAI/MDS assessment instruments comprise an integrated health information system because they have consistent terminology, common core items, and a common conceptual basis in a clinical approach that emphasizes the identification of functional problems.

State practice variations in the use of tube feeding for nursing home residents with severe cognitive impairment.

OBJECTIVE: To describe the differences in prevalence of tube feeding among states and to examine possible factors that could explain practice patterns. DESIGN: Analysis of random samples from an interstate data bank comprised of the Minimum Data Set (MDS), a standardized, federally mandated assessment instrument for nursing home residents. SETTING: Nursing homes in four states participating in a federal demonstration project of case mix payment plus five others with existing MDS data systems. PARTICIPANTS: Individuals 65 years of age and older (N = 57,029), who had very severe cognitive impairment, including total dependence in eating, and who resided in nursing homes during 1994, the most recent year for which uniform data were available. MEASUREMENTS: State-by-state differences in prevalence of tube feeding, controlling for demographic and clinical variables. RESULTS: The prevalence of tube feeding ranged from 7.5% in Maine to 40.1% in Mississippi. Each state had a significantly elevated prevalence of tube feeding compared with Maine, with odds ratios (ORs) ranging from 1.50 to 5.83, P < .001. Specific directives not to provide tube feeding (OR 0.41, P < .001), and white race (OR 0.45, P < .001) were strongly and negatively associated with tube feeding. CONCLUSIONS: Wide regional variations exist in the use of tube feeding of nursing home residents with equivalent impairments. Sociodemographic factors could be important, but more study is needed to determine whether physician characteristics, such as race, attitudes, or knowledge, have an impact and to clarify medical standards for the use of tube feeding in this population.

Accelerated dysfunction among the very oldest-old in nursing homes.

BACKGROUND: The population aged 65 and older is often analyzed in three categories: young-old (65-74), middle-old (75-84), and oldest-old (> or = 85). This may blind heterogeneity within the oldest category. New, large data sets allow examination of the very oldest-old (e.g., aged > or = 95) and contrasts with those who are younger. METHODS: We determined the annual change of prevalence of physical and cognitive function, and of disease problems in the old to very oldest-old, using data from existing Resident Assessment Instrument records from nursing homes in seven states during 1992-1994. We used data from 193,467 unique residents aged 80 or older, including 6,556 residents aged 100 or older. We computed the prevalence, by age, of selected conditions: physical and cognitive function, diseases, problem behavior, mood disturbance, restraint use, falls, weight loss, eating less, body mass index, chewing and swallowing problems, incontinence (bowel and bladder), catheter use, and selected diagnoses. RESULTS: Prevalence of all measures of physical and cognitive dysfunction increased most rapidly with each year of age among the very oldest-old. Most of the slope changes occurred from 95 to 100 years of age. Such changes are less pronounced or not seen in measures of disease prevalence. CONCLUSIONS: Accelerated change in prevalence of dysfunction seen in the nursing home population may suggest a change in the mechanisms of aging that occur after the mid-nineties. Examination of the very oldest-old may provide new insight into the nature of the aging process.