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Attitudes of patients with mild dementia and their carers towards disclosure of the diagnosis.

OBJECTIVE: To determine the attitudes of patients with mild dementia and their carers towards the disclosure of diagnoses of cancer and dementia and whether there are differences between these groups. To determine whether any major adverse events occurred following disclosure of diagnosis of dementia. DESIGN: A prospective study followed by a retrospective case-note study after 1 year. PARTICIPANTS AND SETTING: Fifty patients with mild dementia and their carers were recruited from a memory clinic in Nottingham, UK, and an old-age psychiatrist, using a semistructured questionnaire, separately interviewed them. MEASURES: Questions related to whether patients and their carers wished to be told diagnoses of cancer and dementia; the reasons for this; whether they would want treatment and make use of predictive testing if available were included. At 1-year follow-up whether antidepressants had been prescribed and whether any catastrophic reaction had occurred following disclosure of diagnosis. RESULTS: An overwhelming majority of patients with mild dementia wished to be informed of their diagnosis (92%); even more (98%) of the same patient sample reported wanting disclosure of a hypothetical diagnosis of cancer. A higher proportion (98%) of carers would wish to be told if they were to develop either dementia or cancer. All patients and carers would like access to treatment for dementia. A total of 88% of patients and 86% of carers would make use of a predictive test of Alzheimer's disease. Before receiving a diagnosis of mild dementia, only 28% of patients had insight that they may have dementia. Only a quarter (26%) of carers did not want the doctor to disclose the diagnosis of dementia to the patient. After 1 year, 6% of the original sample had developed a depressive illness requiring antidepressant treatment and no major incidents had occurred following disclosure of diagnosis. CONCLUSIONS: There has been a growing debate on whether patients with dementia should be informed of their diagnosis. Until recently, little was known about the views of patients themselves. This study shows that the vast majority of patients with mild dementia wish to be fully informed. Despite increasing awareness, a quarter of carers still do not wish their relative to be informed, though wish to be informed if they themselves were to develop the illness. This is significantly lower, however, than previously reported, suggesting a shift in attitudes. This study adds support to the weight of evidence that disclosure of a diagnosis of dementia does not cause depression or any irreversible harm to the patient.

Adaptation, Psychological↗

Phytohaemagglutinin (PHA) skin test in predicting prognosis in cancer patients.

The response to intradermal injection of 1 mug of purified PHA was found to correlate with survival of patients with advanced solid tumours treated by chemotherapy, with responders surviving longer than non-responders. In patients with prolonged survival, the reaction was enhanced. Negative intradermal response to PHA was found to be less common in cancer patients than negative responses to tuberculin or streptokinase, and was more easily reversed by successful chemotherapy.

Adult↗

Use of impact testing to predict softness, cow preference, and hardening over time of stall bases.

The objective of this study was to assess the softness and durability of commercially available free-stall bases, and to determine the relationship of stall base softness to cow preference. Clegg impact values were recorded at the University of Wisconsin-Madison Arlington Agricultural Research Station on June 19, 2002, and again on July 24, 2003. The Clegg Impact Soil Tester (model 95051, Lafayette Instruments, Lafayette, IN) with a 20-kg hammer was used in this study. The impact of the hammer on the free-stall base results in a digital display based on peak deceleration of the hammer's impact with the free-stall base in tens of gravities (CIV/H). The CIV/H value, as measured by the Clegg Impact hammer, is based on peak deceleration of the 20-kg hammer's impact with the surface, from a height of 30 cm. Clegg impact measures were highly correlated with cow preference measurements. This relationship suggests that Clegg impact measures of compressibility were good indicators for predicting stall-base acceptance. A cork mattress, 4 foam mattresses, 4 rubber mattresses, 4 rubber mats, and a waterbed were evaluated in this study. Foam-based mattresses lost cushioning ability faster than rubber mattresses or rubber mats. Clegg impact values increased over the 13-mo time period for most stall base types, which indicated a tendency of stall bases to harden.

Animals↗

An in vitro cytotoxicity test to predict the ocular irritation potential of detergents and detergent products.

Two in vitro cytotoxicity procedures, the measurement of cell-membrane integrity using fluorescein diacetate and ethidium bromide, and the quantitation of the release of a cell-membrane-bound enzyme, alkaline phosphatase, were used to assess the cytotoxicity of a range of cationic, anionic and nonionic detergents. The in vitro results were compared with the in vivo irritancy of these compounds in the rabbit eye. Although in general the decreasing order of potency of cationic, anionic and nonionic detergents was similar in vivo and in vitro, there were some apparent anomalies which may be due to the differing penetration characteristics of the detergents, as indicated by electrical impedance measurements of the isolated cornea. The study was extended to an examination of the cytotoxicity of a range of completely soluble, detergent-based formulations in a suspension culture of mouse fibroblasts. In this case the in vitro results correlated more closely with those from the in vivo tests.

Alkaline Phosphatase↗

Use of serologic tests to predict resistance to feline herpesvirus 1, feline calicivirus, and feline parvovirus infection in cats.

OBJECTIVE: To determine whether detection of virus-specific serum antibodies correlates with resistance to challenge with virulent feline herpesvirus 1 (FHV-1), feline calicivirus (FCV), and feline parvovirus (FPV) in cats and to determine percentages of client-owned cats with serum antibodies to FHV-1, FCV, and FPV. DESIGN: Prospective experimental study. ANIMALS: 72 laboratory-reared cats and 276 client-owned cats. PROCEDURES: Laboratory-reared cats were vaccinated against FHV-1, FCV, and FPV, using 1 of 3 commercial vaccines, or maintained as unvaccinated controls. Between 9 and 36 months after vaccination, cats were challenged with virulent virus. Recombinant-antigen ELISA for detection of FHV-1-, FCV-, and FPV-specific antibodies were developed, and results were compared with results of hemagglutination inhibition (FPV) and virus neutralization (FHV-1 and FCV) assays and with resistance to viral challenge. RESULTS: For vaccinated laboratory-reared cats, predictive values of positive results were 100% for the FPV and FCV ELISA and 90% for the FHV-1 ELISA. Results of the FHV-1, FCV, and FPV ELISA were positive for 195 (70.7%), 255 (92.4%), and 189 (68.5%), respectively, of the 276 client-owned cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that for cats that have been vaccinated, detection of FHV-1-, FCV-, and FPV-specific antibodies is predictive of whether cats are susceptible to disease, regardless of vaccine type or vaccination interval. Because most client-owned cats had detectable serum antibodies suggestive of resistance to infection, use of arbitrary booster vaccination intervals is likely to lead to unnecessary vaccination of some cats.

Animals↗

[The use of the M-cholinomimetic test in predicting treatment efficacy in neurogenic bladder dysfunctions].

Presented are the first-hand correlations between therapeutic responses and hyper-response of the bladder of M-cholinomimetic drugs made by the authors on the basis of a follow-up of 98 children with hyper-reflex dysfunctions of the urinary bladder. The study revealed a definite relationship: the more pronounced hyper-response was, the more difficult it was to get a persistent effect of recovered function of the bladder. Out of 63 M-cholinomimetic-positive patients, the effective response was noted in 61.9 per cent, recovery, in 31.7 and improvement in 30.2. All of 35 cholinoceptive-negative patients (100 per cent) responded to the treatment: 77.1 per cent recovered, 22.9 per cent improved. Higher treatment response observed in cholinomimetic-negative patients could be explained by the fact that in the absence of hypersensitivity, i.e. in case of minimal "immaturity" of neuromuscular structures, it was much easier to recover the function of the bladder. And on the contrary, it was difficult to make the final prognosis for those with pronounced cholinoceptive hypersensitivity (positive tests) because of high possibility of therapeutically resistant patterns of disease. Thus, the efficacy on the treatment in children with hyper-reflex dysfunction of the urinary bladder was in inverse proportion to cholinoceptive hypersensitivity. Taking into account the currently absent methods of prognosis for therapeutic response of neurogenic dysfunctions of the urinary bladder the authors advised to use the M-cholinomimetic test for these purposes.

Adolescent↗

Screening for mild cognitive impairment (MCI) utilizing combined mini-mental-cognitive capacity examinations for identifying dementia prodromes.

OBJECTIVE: To test correctness of results when combining Mini-Mental State Examination (MMSE) and Cognitive Capacity Screening Examination (CCSE) for identifying mild cognitive impairment (MCI) among non-demented elderly subjects at risk for developing dementia. METHODS: A retrospective study was conducted among consecutively referred volunteers with memory complaints to a research out-patient clinic. Two cognitive screening tests (MMSE and CCSE) were performed according to established protocol. Resulting combined screening test (termed by acronym as CMC) combined the non-overlapping test items derived from both MMSE and CCSE. Conversion to dementia at follow-up served as the 'gold-standard' for evaluating correctness of CMC for identifying MCI. RESULTS: Of 351 subjects completing cognitive assessments and meeting requirements for study protocol, 84 (23.9%) developed dementia of different types within 3-6 years (3.89 +/- 2.17) of follow-up. Among these, 47 met criteria for probable Alzheimer disease (AD), 22 for probable vascular dementia (VaD), 12 for mixed AD/VaD and three for probable frontotemporal dementia. When final diagnosis of AD was used as the 'gold standard' for testing correctness of MCI identified by cognitive screening tests, sensitivities of MMSE, CCSE and CMC for identifying MCI were relatively 61.0%, 74.3% and 83.1% with minimum specificity set at 80%. When diagnosis of all types of dementia was used as the standard for testing predictive correctness of MCI, CCSE emerged as an optimal MCI screening test. CONCLUSION: Combining the CCSE and MMSE screening tests resulted in higher sensitivity than was achieved by MMSE alone and maintained specificity at comparable levels for identifying MCI. The results confirmed that CMC has optimal correctness and utility as a brief cognitive test for screening MCI as a prodrome for dementia among non-demented elderly populations.

Aged↗

Expression of prolactin receptor mRNA in oestrogen receptor positive breast cancers pre- and post-tamoxifen therapy.

AIM: Previous in vitro studies have shown that tamoxifen down-regulates prolactin receptors in breast cancer cells. The aim of this study was to determine whether similar changes might provide the basis for a predictive test in patients. METHODS: Biopsy specimens were obtained from 28 post-menopausal women immediately before initiation of treatment with tamoxifen (20 mg daily) and after treatment for 7 days. Prolactin receptor mRNA, determined by reverse-transcription polymerase chain reaction, was then expressed relative to 18S ribosomal RNA. RESULTS: There was good evidence for a decline in receptor expression in response to treatment with tamoxifen in the whole group (p = 0.036) but with a particularly marked decrease (>60%) in a sub-group of 11 patients. No clear correlation with tumour type or grade, or with several other markers (progesterone receptor, c-erb B-2, pS2, or Bcl-2) was apparent. CONCLUSION: Tamoxifen reduces expression of mRNA encoding the prolactin receptor in a sub-group of breast tumours and might provide the basis for a predictive test for tamoxifen therapy.

Aged↗

Developing and testing measures predictive of hepatitis A vaccination in a sample of men who have sex with men.

Studies continue to show that the majority of men who have sex with men (MSM) in the US remain unvaccinated against the hepatitis A virus (HAV). Such limited vaccination coverage is a missed opportunity to prevent disease. This study was designed to develop reliable and valid theory-based quantitative measures to understand beliefs and attitudes regarding HAV vaccination among MSM. A convenience sample of 358 patrons of two gay bars in Birmingham, Alabama, completed a theory-based questionnaire. Data were randomly split into two groups. Exploratory factor analysis (EFA) was performed on the first split-half sample to identify factor structure using standard principal component analysis. Confirmatory factor analysis (CFA) was performed on the remaining half sample using structural equation modeling. EFA revealed five scales measuring beliefs about HAV vaccination, including: perceived barriers and benefits associated with HAV vaccination; perceived severity and susceptibility related to hepatitis A infection; and perceived self- efficacy to complete the two-dose vaccine series. CFA revealed acceptable absolute model fits for four scales and excellent comparative model fits for all five scales. Multivariable analysis further validated the scales. Although the results should be tested further, these findings propose standardized measures that may be useful in assessing the beliefs and attitudes of MSM towards HAV vaccination to guide intervention design and evaluation.

Adult↗

Attitudes of subjects at risk and their relatives towards genetic counselling in Huntington's chorea.

Ninety-two patients suffering from Huntington's chorea (HC) and their spouses, and 91 subjects with an affected parent and their spouses, living in three counties of industrial South Wales, have been studied regarding their knowledge of their inheritance of the disorder. Particular attention was paid to its influence on their attitudes towards child-bearing, telling their children of the risks, and predictive tests. Only 12% of the patients were known to have received professional advice before completing their families, in contrast to 68% of the sample at risk. It is estimated that 82% of the patients and 60% of the subjects at risk had, or might have, restricted their family size had they known in time. The majority found genetic counselling helpful, but did not necessarily wish to alter their child-bearing plans in consequence. It was clear that information provided by the family alone was usually inadequate and that this applied to the present generation at risk as well as to previous generations. It was concluded that the burden of telling children the risks is too great for most parents and that professional help is needed. The long term impact of genetic counselling on the incidence of the disease is impossible to assess without continued monitoring, but preliminary results are encouraging. Attitudes towards a predictive test reflected much conflict: although 56% overall wished to take one, only 40% of those who were parents wished to know if they were at risk of passing the gene on to their children. Few subjects reported severe social stress on learning of their genetic risks, but about one in four reported experiencing significant anxiety.

Contraception Behavior↗

Early preclinical diagnosis of dominant pseudoxanthoma elasticum by specific ultrastructural changes of dermal elastic and collagen tissue in a family at risk.

The preferred description for the Grönblad-Strandberg syndrome, pseudoxanthoma elasticum (PXE), refers only to the cutaneous aspect of the disease, although the skin is the least severely involved organ. The potential catastrophic manifestation of this heterogeneous heritable disorder is described in a dominant pedigree where mother and grandmother died because of major vascular problems. The family requested predictive testing of the three children. Diagnosis of PXE is usually performed by morphological examination of skin lesions, which reveal incrustations formed by inorganic ions (mainly calcium) and various organic (degraded?) materials in the elastin moiety of the elastic fibers. The ubiquitous elastic fibers in other organs and arteries may be similarly involved. Moreover, there is co-involvement of collagen fibrils at the electron microscopical level. The three adolescent siblings did not show any clinical PXE symptoms. However, ultrastructural investigation of overtly normal skin in predilection sites gave a positive diagnosis for this dominant PXE type. Dermal connective tissue showed a specific aberrant pattern: elastin of elastic fibers regularly contained small foci of calcification resembling those in perilesional skin of the mother and other PXE patients; in collagen bundles adjacent to altered elastic fibers, collagen fibrils occurred with thickened diameters and flower-like contours; ground substance material was increased. The possible pathogenetic mechanism and problems posed by predictive testing of adult-onset diseases are discussed.

Adolescent↗

Relationship between radiosensitivity and normal tissue complications in Saudi cancer patients treated with radiotherapy.

PURPOSE: To assess the variations in radiosensitivity, its relationship with clinical complications and the potential application of predictive testing in Saudi radiotherapy patients. MATERIALS AND METHODS: Forty-one patients included in this study, during (17) or after (24) their radiation treatment for head and neck (26), breast (9), gynecological (3) or other (3) cancer. Skin fibroblasts were established and radiosensitivity was measured. The surviving fraction at 2 Gy (SF2) was calculated and compared to the maximum grade of acute (erythema, desquamation, mucositis, ulceration) and late reactions (atrophy, fibrosis, xerostomia, telangiectasia). Follow-up ranged between 12 and 178 months (median 30). RESULTS: SF2 ranged between 0.16 and 0.56 (mean 0.34). The inter-patients coefficient of variation (CV) was 26%. The intra-patient CV was 18%. There was a statistically significant correlation between fibroblasts SF2 and the maximum grade of late (p = 0.012; 40 patients), but not acute complications (p = 0.70; 36 patients). There was no correlation between acute and late reactions (p > 0.05; 34 patients). CONCLUSIONS: These data revealed wide variations in cellular radiosensitivity that correlated with late reactions to radiation treatment. Radiotherapy patients, particularly those at risk to sustain severe complications may well benefit from individualizing the doses prescription. However, a predictive test alternative to SF2 is required.

Journal Article↗

Use of coagulation tests to predict the clinical progress of pre-eclampsia.

The clinical manifestations of severe pre-eclampsia are normally separated from those of mild pre-eclampsia and normal pregnancy on arbitrary grounds. A clinical index, based on the increase in diastolic blood-pressure and the presence of proteinuria, was developed to reflect the spectrum of disease from mild to severe pre-eclampsia. This was related to a coagulation index based on the platelet-count, plasma-factor-VIII, and serum-fibrinolytic-degradation-products. The two indices were shown to be strongly correlated. All cases of perinatal death associated with pre-eclampsia had coagulation indices in the most severely abnormal range. These results suggest that intravascular coagulation is a highly characteristic feature of pre-eclampsia and that the coagulation index may be of value in monitoring the progress of the disease.

Blood Cell Count↗

The important role of fitness determination and stress testing in predicting coronary incidence.

The question of whether there is some effect of status of cardiorespiratory fitness and exercise ECG abnormalities on occurrence of CHD other than their effect on the risk factors of serum cholesterol, blood pressure, glucose, and smoking seems to have been answered in the affirmative by this study. The relative prognostic importance of the measures considered here, the role of exercise, and the interrelationships between fitness, exercise, other risk factors, and CHD provide many interesting hypotheses for continued study. A future investigation will involve a large prospective study in which the risk function to be derived would include stress ECG and treadmill performance as predictor variables. The retrospective approach reported in this paper had certain limitations. It did, however, permit demonstration of new results because, essentially for the first time, all of the important risk factors are measured in the study population and can be evaluated simultaneously.

Adult↗

Radiation-induced micronuclei in human fibroblasts in relation to clonogenic radiosensitivity.

As part of our programme for developing predictive tests for normal tissue response to radiotherapy, we have investigated the efficacy of the cytokinesis-block micronucleus (MN) assay as a means of detecting interindividual differences in cellular radiosensitivity. A study was made of nine fibroblast strains established from vaginal biopsies of pretreatment cervical cancer patients and an ataxia telangiectasia (A-T) cell strain. Cells were irradiated in plateau phase, replated and treated with cytochalasin B 24 h later. MN formation was examined 72 h after irradiation as the number of MN in 100 binucleate cells. The method yielded low spontaneous MN yields (<7 per 100 cells), and mean induced MN frequencies after 3.5 Gy varied between cell strains from 18 to 144 per 100 cells. However, in repeat experiments, considerable intrastrain variability was observed (CV = 32%), with up to twofold differences in MN yields, although this was less than interstrain variability (CV = 62%). An analysis was made of the relationship between MN results and previously obtained clonogenic survival data. There was a significant correlation between MN yields and clonogenic survival. However, when the A-T strain was excluded from the analysis, the correlation lost significance, mainly because of one slow-growing strain which was the most sensitive to cell killing but had almost the lowest MN frequency. With current methodology, the MN assay on human fibroblasts does not appear to have a role in predictive testing of normal tissue radiosensitivity.

Cell Survival↗

Utility of amino-terminal pro-brain natriuretic peptide testing for prediction of 1-year mortality in patients with dyspnea treated in the emergency department.

BACKGROUND: Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is useful for diagnosis and triage of patients with dyspnea, but its role for predicting outcomes in such patients remains undefined. METHODS: A total of 599 breathless patients treated in the emergency department were prospectively enrolled, and a sample of blood was obtained for NT-proBNP measurements. After 1 year, the vital status of each patient was ascertained, and the association between NT-proBNP values at presentation and mortality was assessed. RESULTS: At 1 year, 91 patients (15.2%) had died. Median NT-proBNP concentrations at presentation among decedents were significantly higher than those of survivors (3277 vs 299 pg/mL; P<.001). The optimal NT-proBNP cut point for predicting 1-year mortality was 986 pg/mL. In a multivariable model, an NT-proBNP concentration greater than 986 pg/mL at presentation was the single strongest predictor of death at 1 year (hazard ratio [HR], 2.88; 95% confidence interval, 1.64-5.06; P<.001), independent of a diagnosis of heart failure. Other factors associated with death included age (by decade; HR, 1.20), heart rate (by decile; HR, 1.13), urea nitrogen level (by decile; HR, 1.20), systolic blood pressure less than 100 mm Hg (HR, 1.94), heart murmur (HR, 1.92), and New York Heart Association classification (HR, 1.38 for each increase in class). The NT-proBNP concentration alone had an area under the receiver operating characteristic curve (AUC) of 0.76 for predicting mortality; the other significant covariates combined had an AUC of 0.80. The final model for predicting death, combining NT-proBNP with other covariates associated with mortality, had a superior AUC of 0.82. CONCLUSION: In addition to assisting in emergency department diagnosis and triage, NT-proBNP concentrations at presentation are strongly predictive of 1-year mortality in dyspneic patients.

Age Factors↗

Correlations between triplet repeat expansion and clinical features in Huntington's disease.

OBJECTIVE: To investigate possible correlations between the length of the (CAG)n trinucleotide repeat in Hungtington's disease gene IT15 and clinical features (age at onset, symptoms at onset, and mode of progression) in Huntington's disease. DESIGN: In 59 patients with Huntington's disease, the expansion of the (CAG)n trinucleotide repeat was determined and clinical data were obtained retrospectively. SETTING: The Center for Human Genetics, affiliated with a university hospital. PATIENTS: All patients belonged to an initial group of 248 individuals tested in an indirect predictive testing procedure. RESULTS: A good correlation was found between the expansion of the (CAG)n trinucleotide repeat and the age at onset (r = -.71). No correlation was found between the repeat length of the normal allele and the age at onset. No correlations were found between repeat expansion and other clinical features, such as the nature of the symptoms at onset (neurologic, psychiatric/cognitive, or both) and the mode of progression. CONCLUSION: Factors that determine the nature of symptoms at onset and the mode of progression of Huntington's disease seem to be operating independently of the (CAG)n trinucleotide repeat in gene IT15.

Age Factors↗