Quality of care in private sector and NHS facilities for people with dementia: cross sectional survey.
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Biomedical subjects
Publications and source records attributed to P Thompson.
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We report on an infant with Robin sequence; mild developmental delay; a left ulnar ray defect with absent ulna and associated metacarpals, carpals and phalanges; and a right ulnar nerve hypoplasia. He had a de novo interstitial deletion of 4q32-->q34. The critical region involved in the 4q terminal deletion syndrome may be 4q33. This conclusion was suggested by showing that del(4)(q31qter), del(4)(q32qter), and del(4)(q33qter) result in a similarly severe phenotype. In addition, we propose that genes for distal arm development, in particular for development of the left ulnar ray, central nervous system development, and cleft lip and palate, may be located at 4q33.
BACKGROUND: Attentional deficits are described in the consensus clinical criteria for the operationalized diagnosis of dementia with Lewy bodies (DLB) as characteristic of the condition. In addition, preliminary studies have indicated that both attentional impairments and fluctuation of attentional impairments are more marked in patients with DLB than in patients with Alzheimer disease (AD), although neuropsychological function has not previously been examined in a large prospective cohort with confirmed diagnostic accuracy against postmortem diagnosis. METHODS: A detailed evaluation of attention and fluctuating attention was undertaken in 155 patients with dementia (85 with DLB and 80 with AD) from a representative hospital dementia case register and 35 elderly controls using the Cognitive Drug Research Computerized Assessment System for Dementia Patients computerized neuropsychological battery. Operationalized clinical diagnosis was made using the consensus criteria for DLB and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD. High levels of sensitivity and specificity have been achieved for the first 50 cases undergoing postmortem examination. RESULTS: The groups were well matched for severity of cognitive impairments, but the AD patients were older (mean age, 80 vs 78 years) and more likely to be female (55% vs 40%). Patients with DLB were significantly more impaired than patients with AD on all measures of attention and fluctuating attention (for all comparisons, t > or = 2.5, P<.001), and patients from both dementia groups were significantly more impaired than elderly controls for all comparisons other than cognitive reaction time, which was significantly more impaired in DLB patients than controls but was comparable in controls and AD patients. There were, however, significant associations between the severity of cognitive impairment and the severity of both attentional deficits and fluctuations in attention. CONCLUSIONS: This large prospective study confirms that slowing of cognitive processing, attention, and fluctuations of attention are significantly more pronounced in DLB and AD patients, although fluctuating attention is common in patients with moderate-to-severe AD. Deficits of cognitive reaction time appear to be specific to DLB, except in severe dementia. A detailed evaluation of attentional performance could make an important contribution to differential diagnosis, although the results need to be interpreted within the context of the overall severity of cognitive deficits.
Dendritic peptides, often presented as multiple antigen peptides (MAPs), are widely used in immunological-based fields of research, although their synthesis can be extremely challenging. In this paper, a tetrameric dendritic MAP-like presentation of the retinoblastoma protein [649-654] sequence (4RB(649-654)) has been prepared using solid-phase peptide synthesis (SPPS) methods. During the synthesis of this dendritic molecule, numerous modifications to the synthetic protocols were examined. These modifications included the introduction of a combination Boc- and Fmoc-chemistry approach and also the use of 1,8-diazabicyclo[5.4.0]-undec-7-ene as a Fmoc-deprotection agent. The use in combination of Boc- and Fmoc-based synthetic strategies resulted in the production of the desired peptide molecule, 4RB(649-654), in high purity and acceptable yields following purification by reversed phase HPLC.
Monosomy 7 and deletion of 7q are recurring abnormalities in malignant myeloid diseases. Here we extensively characterize an approximately 2-Mb commonly deleted segment (CDS) of 7q22 bounded by D7S1503 and D7S1841. Approximately 1.8 Mb of sequence have been generated from this interval, facilitating the construction of a transcript map that includes large numbers of genes and ESTs. The intron/exon organization of seven genes and expression patterns of three genes were determined, and leukemia samples were screened for mutations in five genes. We have used polymorphic markers from this region to examine leukemia cells for allelic loss within 7q22. Finally, we isolated mouse genomic clones orthologous to several of the characterized human genes. Fluorescence in situ hybridization studies using these clones indicate that a region of orthologous synteny lies on proximal mouse chromosome 5. These resources should greatly accelerate the pace of candidate gene discovery in this region.
Financial incentives of various kinds have been suggested to alleviate the chronic shortage of transplantable organs in the United States. This paper analyzes the possible consequences of financial incentives on organ supply. We show that under current practice and current law (which are not the same), inducements to donate organs or to register as an organ donor may lead to a decline in the supply of organs. Furthermore, some financial incentives that have been proposed lead to time inconsistent choices.
If an agent does not discount the future at a constant rate, as in some forms of myopia, her optimal strategy is unattainable without some commitment device. We apply this familiar idea to a model of screening and disease prevention, and explore how financial incentives can correct suboptimal health choices. In general, myopia need not imply under-screening. While the optimal intervention for prevention effort is a state-invariant subsidy, the optimal intervention for screening may involve a tax or a subsidy. When screening and prevention are coincident, a simple and practical subsidy equal to one minus the discount factor to both screening and intervention is indicated.
OBJECTIVES: We developed a prognostic strategy for quantifying the long-term risk of coronary heart disease (CHD) events in survivors of acute coronary syndromes (ACS). BACKGROUND: Strategies for quantifying long-term risk of CHD events have generally been confined to primary prevention settings. The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study, which demonstrated that pravastatin reduces CHD events in ACS survivors with a broad range of cholesterol levels, enabled assessment of long-term prognosis in a secondary prevention setting. METHODS: Based on outcomes in 8,557 patients in the LIPID study, a multivariate risk factor model was developed for prediction of CHD death or nonfatal myocardial infarction. Prognostic indexes were developed based on the model, and low-, medium-, high- and very high-risk groups were defined by categorizing the prognostic indexes. RESULTS: In addition to pravastatin treatment, the independently significant risk factors included: total and high density lipoprotein cholesterol, age, gender, smoking status, qualifying ACS, prior coronary revascularization, diabetes mellitus, hypertension and prior stroke. Pravastatin reduced coronary event rates in each risk level, and the relative risk reduction did not vary significantly between risk levels. The predicted five-year coronary event rates ranged from 5% to 19% for those assigned pravastatin and from 6.4% to 23.6% for those assigned placebo. CONCLUSIONS: Long-term prognosis of ACS survivors varied substantially according to conventional risk factor profile. Pravastatin reduced coronary risk within all risk levels; however, absolute risk remained high in treated patients with unfavorable profiles. Our risk stratification strategy enables identification of ACS survivors who remain at very high risk despite statin therapy.
The erythropoietic porphyrias, erythropoietic protoporphyria and congenital erythropoietic porphyria, result from germline mutations in the ferrochelatase gene and uroporphyrinogen III synthase gene, respectively. Both conditions normally present in childhood but rare cases with onset past the age of 40 y have been reported. Here we show that late-onset erythropoietic protoporphyria can be caused by deletion of the ferrochelatase gene in hematopoietic cells with clonal expansion as part of the myelodysplastic process. This is the first direct demonstration of porphyria produced by an acquired molecular defect restricted to one tissue. Some other cases of late-onset erythropoietic porphyria may be explained by a similar mechanism.
The clinical effects of a patient-operated system of microwave disinfection for soft contact lenses were assessed in a prospective pilot trial involving 103 patients who were drawn from five optometric practices. Fifty-six subjects used the test system for 1 month, and 13 subjects continued use for a total of 3 months. Both test and control subjects were examined for clinical signs using slitlamp tests. After 1 month, the incidence of all signs reported in the microwave group was not significantly greater than in the control group (p = 0.267), and the same was true after 3 months (p = 0.214). There was a significantly greater incidence of edema in the 1-month test group and of staining in the control group. UV spectroscopic examination of worn lenses from test subjects exhibiting significant signs did not show a higher level of deposition than on lenses worn by control subjects (p = 0.397).
Ten brands of hydrogel contact lenses were selected from five of the six British Approved Name lens classification groups to test in vitro the effects of repeated heat disinfection by means of microwave irradiation. Each lens type was tested over a number of cycles corresponding to its scheduled number of wearing days. The total diameter and back vertex power of all 80 test and 12 control lenses were measured at the end of their relevant cycling period. The back optic zone radius, center thickness, and water content were measured for 40 test and 8 control lenses. No clinically significant change was found in any of the 10 brands tested. Statistically significant changes were found in the back optic zone radius of the Frequency 55 group and water content of the Precision UV group. Some discoloration was noted in Ciba Visitint lenses.
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OBJECTIVE: People with schizophrenia exhibit abnormalities in brain structure, often in the left hemisphere. Disturbed structural lateralization is controversial, however, and effects appear mediated by gender. The authors mapped differences between schizophrenic and normal subjects in gyral asymmetries, complexity, and variability across the entire cortex. METHOD: Asymmetry and shape profiles for 25 schizophrenic patients (15 men) and 28 demographically similar normal subjects (15 men) were obtained for 38 gyral regions, including the sylvian fissure and temporal and postcentral gyri, by using magnetic resonance data and a novel surface-based mesh-modeling approach. Cortical complexity was examined for sex and diagnosis effects in lobar regions. Intragroup variability was quantified and visualized to assess regional group abnormalities at the cortical surface. RESULTS: The patients showed greater variability in frontal areas than the comparison subjects. They also had significant deviations in gyral complexity asymmetry in the superior frontal cortex. In temporoparietal regions, significant gyral asymmetries were present in both groups. Sex differences were apparent in superior temporal gyral measures, and cortical complexity in inferior frontal regions was significantly greater in men. CONCLUSIONS: Cortical variability and complexity show regional abnormalities in the frontal cortex potentially specific to schizophrenia. The results indicate highly significant temporoparietal gyral asymmetries in both diagnostic groups, contrary to reports of less lateralization in schizophrenia. Substantially larger study groups are necessary to isolate smaller deviations in surface asymmetries, if present in schizophrenia, suggesting their diagnostic value is minimal.
Within a stereoscopic display the field of view (FOV) was held constant at 13.86 degrees while the geometric field of view (GFOV) was varied across four levels: 0 degrees (parallel), 13.86 degrees (veridical), 50 degrees and 100 degrees. Participants performed a distance-matching task where they adjusted the distance of a standard track from the centre of the display to match the distance of a target track from the same point. The results indicated that while the least error occurred in the veridical GFOV condition, small variations of GFOV away from the veridical have little effect. Large differences between FOV and GFOV (36 degrees and 86 degrees) increased errors markedly. A trend toward better performance in the veridical GFOV condition relative to the parallel GFOV condition suggests that the use of linear perspective information in a stereoscopic display may facilitate more accurate spatial perception. Actual or potential applications of this work include stereoscopic display design in aviation and non-aviation settings.
BACKGROUND: Few data are available regarding the natural course of psychiatric symptoms in dementia with Lewy bodies and Alzheimer's disease. To acquire this information is essential to inform differential diagnosis and treatment decisions. METHOD: The current study provides prospective data regarding a representative case-register cohort of patients with operationalized clinical diagnoses of dementia with Lewy bodies (N = 82) or Alzheimer's disease (N = 132), with verified accuracy of clinical diagnosis against postmortem examination. Psychosis (Columbia University Scale for Psychopathology in Alzheimer's Disease) and depression (Cornell Scale for Depression in Dementia) were assessed at baseline and annual follow-up. RESULTS: Visual hallucinations were significantly more likely to be persistent in patients suffering from dementia with Lewy bodies (chi2 = 19.1, df = 1, p < .0001). Although a number of other psychiatric symptoms were also more frequent at baseline in dementia with Lewy body patients, they were not significantly more likely to persist. Delusions and auditory hallucinations did, however, persist in more than 40% of patients across both diagnostic groups. Patients suffering from dementia with Lewy bodies were significantly more likely to develop new auditory hallucinations over the year of follow-up (chi2 = 14.4, df= 1, p < .0001). CONCLUSION: These results confirm that, although a number of psychiatric symptoms are common in dementia with Lewy bodies, it is only visual hallucinations that are significantly more persistent, with important treatment implications.
BACKGROUND: A logical progression of the widely used microtiter plate ELISA is toward a protein array format that allows simultaneous detection of multiple analytes at multiple array addresses within a single well. Here we describe the construction and use of such a multiplex ELISA to measure prostate-specific antigen (PSA), alpha1-antichymotrypsin-bound PSA (PSA-ACT), and interleukin-6 (IL-6). METHODS: We silanized glass plates and printed the appropriate capture antibodies to allow for the construction of "sandwich" ELISA quantification assays. We examined specificity of the assay for appropriate antigen, assembled calibration curves, and obtained PSA concentrations for 14 human serum samples. We compared the serum PSA concentrations derived through the use of our array with values obtained independently using a standard ELISA method. RESULTS: R2 values generated by our microarray for the PSA and PSA-ACT calibration curves were 0.989 and 0.979, respectively. Analyte concentrations used for the construction of these curves were 0.31-20 microg of protein/L of diluent. IL-6 calibration curve concentrations were 4.9-300 ng of IL-6/L of diluent. The R2 value for the IL-6 calibration curve was 0.983. The 14 human serum samples screened by this micro-ELISA technique for PSA concentrations generated a regression equation (linear) with a slope of 0.83 +/- 0.10 and intercept of 0.74 +/- 0.70 (R2 = 0.88). CONCLUSIONS: Multiplexed ELISA arrays are a feasible option for analyte quantification in complex biologic samples.
The new guidelines reflect a worldwide change to more sensitive diagnostic strategies and more aggressive management of unstable angina. Stratification to high risk now includes those patients with only a minor degree of electrocardiographic ST depression (0.5 mm) or a significant elevation of cardiac troponin. High-risk patients are recommended to be treated with intensive medical and invasive management. Intermediate-risk patients may be best evaluated using an accelerated diagnostic strategy over an 8-12 h period before being reclassified as high or low risk.