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Biomedical subjects

E Levin

Publications and source records attributed to E Levin.

At least 19 recordsLinked to original sources

Development of a new measure of health-related quality of life for people with dementia: DEMQOL.

BACKGROUND: We identified the need to develop a scientifically rigorous measure of health-related quality of life (HRQL) in dementia that would be appropriate for use at all stages of dementia severity and would be available in both self- and proxy-report versions. METHOD: We used standard psychometric methods to eliminate items with poor psychometric properties (item-reduction field test) and to assess the acceptability, reliability and validity of the item-reduced instruments (psychometric evaluation field test). We developed and validated two versions of DEMQOL: a 28-item interviewer-administered questionnaire that is self-reported by the person with dementia (DEMQOL) and a 31-item interviewer-administered questionnaire that is proxy-reported by a caregiver (DEMQOL-Proxy). RESULTS: DEMQOL shows high reliability (internal consistency and test-retest) and moderate validity in people with mild/moderate dementia. DEMQOL-Proxy shows good acceptability and internal consistency and moderate evidence of validity in people with mild/moderate and severe dementia. Test-retest reliability and performance in people with severe dementia need further testing. CONCLUSIONS: DEMQOL and DEMQOL-Proxy show psychometric properties that are comparable with the best available dementia-specific measures of HRQL. We recommend that DEMQOL and DEMQOL-Proxy are used together. Reliability and validity need to be confirmed in independent samples and responsiveness needs to be evaluated.

Adult↗

Quality of life in dementia: more than just cognition. An analysis of associations with quality of life in dementia.

OBJECTIVES: To explore the extent to which commonly used measures of specific outcomes in dementia are an appropriate proxy for quality of life in dementia. METHODS: This was a cross sectional study set in communities in London and Nottingham, comprising 101 people with dementia and their 99 main family caregivers. The main outcome measures were health related quality of life in dementia (measured by the DEMQOL-Proxy), cognition (Mini Mental State Examination), functional impairment (Barthel Index), behavioural and psychological symptoms in dementia (Neuropsychiatric Inventory; NPI), and carer mental health (General Health Questionnaire). RESULTS: On univariate analysis, decreased quality of life was statistically significantly correlated with higher levels of behavioural and psychological disturbance (NPI total score and its agitation, depression, anxiety, disinhibition, and irritability subscales); younger age of the person with dementia; and poorer mental health of the carer. Quality of life was not statistically significantly associated with cognition or carer age. In a multivariate model, psychological and behavioural disturbance and patient age remained statistically significantly associated with quality of life. Carer mental health was no longer statistically significantly associated, and cognition and functional limitation remained statistically insignificant. CONCLUSIONS: These data suggest that quality of life in dementia is complex, and that simple proxy substitutions of discrete measures such as cognition or function are likely to miss important factors.

Activities of Daily Living↗

Measurement of health-related quality of life for people with dementia: development of a new instrument (DEMQOL) and an evaluation of current methodology.

OBJECTIVES: To develop and validate a psychometrically rigorous measure of health-related quality of life (HRQoL) for people with dementia: DEMQOL. DATA SOURCES: Literature review. Expert opinion. Interviews and questionnaires. REVIEW METHODS: Gold standard psychometric techniques were used to develop DEMQOL and DEMQOL-Proxy. A conceptual framework was generated from a review of the literature, qualitative interviews with people with dementia and their carers, expert opinion and team discussion. Items for each component of the conceptual framework were drafted and piloted to produce questionnaires for the person with dementia (DEMQOL) and carer (DEMQOL-Proxy). An extensive two-stage field-testing was then undertaken of both measures in large samples of people with dementia (n = 130) and their carers (n = 126) representing a range of severity and care arrangements. In the first field test, items with poor psychometric performance were eliminated separately for DEMQOL and DEMQOL-Proxy to produce two shorter, more scientifically robust instruments. In the second field test, the item-reduced questionnaires were evaluated along with other validating measures (n = 101 people with dementia, n = 99 carers) to assess acceptability, reliability and validity. RESULTS: Rigorous evaluation in two-stage field testing with 241 people with dementia and 225 carers demonstrated that in psychometric terms: (1) DEMQOL is comparable to the best available dementia-specific HRQoL measures in mild to moderate dementia, but is not appropriate for use in severe dementia [Mini Mental State Examination (MMSE) <10]; and (2) DEMQOL-Proxy is comparable to the best available proxy measure in mild to moderate dementia, and shows promise in severe dementia. In addition, the DEMQOL system has been validated in the UK in a large sample of people with dementia and their carers, and it provides separate measures for self-report and proxy report, which allows outcomes assessment across a wide range of severity in dementia. CONCLUSIONS: The 28-item DEMQOL and 31-item DEMQOL-Proxy provide a method for evaluating HRQoL in dementia. The new measures show comparable psychometric properties to the best available dementia-specific measures, provide both self- and proxy-report versions for people with dementia and their carers, are appropriate for use in mild/moderate dementia (MMSE >/= 10) and are suitable for use in the UK. DEMQOL-Proxy also shows promise in severe dementia. As DEMQOL and DEMQOL-Proxy give different but complementary perspectives on quality of life in dementia, the use of both measures together is recommended. In severe dementia, only DEMQOL-Proxy should be used. Further research with DEMQOL is needed to confirm these findings in an independent sample, evaluate responsiveness, investigate the feasibility of use in specific subgroups and in economic evaluation, and develop population norms. Additional research is needed to address the psychometric challenges of self-report in dementia and validating new dementia-specific HRQoL measures.

Aged↗

Miscarriage in the first trimester according to the presence or absence of the progesterone-induced blocking factor at three to five weeks from conception in progesterone supplemented women.

PURPOSE: To determine if the failure to detect the immonomodulatory protein progesterone induced blocking factor (PIBF) at three to five weeks of seemingly normal pregnancies in women supplemented by extra progesterone is associated with a higher miscarriage rate. METHODS: Progesterone-induced blocking factor expression by lymphocytes was measured by an immunocytochemistry technique. The serum beta human chorionic gonadotropin (hCG) and/or ultrasound were also deemed appropriate so that by these criteria there was no evidence of a poor pregnancy. The minimum progesterone dosage was 200 mg twice daily vaginal suppositories. RESULTS: Progesterone-induced blocking factor was detected in 17/39 (43.5%) of pregnant patients at this early time. There were three miscarriages by 12 weeks in this group (17.6%). The miscarriage rate was 6/21 (28.5%) in those where it was not detected. CONCLUSIONS: There was insufficient power to show significance. However there seems to be a trend for higher rates of miscarriage when PIBF is absent so these preliminary data encourage continuation of the study.

Abortion, Spontaneous↗

Hepatitis B vaccination: long-term follow-up of the immune response of preterm infants and comparison of two vaccination protocols.

BACKGROUND: We conducted a 3-year follow-up study of long-term antibody persistence following vaccination of low-risk preterm infants with recombinant hepatitis B vaccine (HBV). Two three-dose protocols were compared: vaccination beginning within 24 h of birth to initial vaccination delayed until a weight of 2,000 g was reached. SUBJECTS AND METHODS: The study population included 136 children, divided into three groups: children born prematurely (< or = 35 weeks, n = 57), children born at term (> or = 37 weeks, n = 39), both groups receiving the first dose of HBV within 24 h of birth, and children born prematurely (< or = 35 weeks, n = 40), who received the first dose of HBV when a weight of 2,000 g was reached. All infants received the second hepatitis vaccination 1 month after the first, and the third dose 6 months after the first. Hepatitis B surface antibody (AntiHBs) was measured at an age of 3-3.5 years (at least 2.5 years after completion of the three-dose HBV series). An AntiHBs level of > or = 10 IU/l was considered positive. RESULTS: At 3-3.5 years of age, a higher percentage of the premature-delayed vaccination group had a positive AntiHBs level (92.5%) compared to both the premature (54.4%, p < 0.001) and full-term groups (71.8%, p < 0.05) vaccinated soon after birth. The premature-delayed vaccination group also had a significantly higher geometric mean concentration (GMC) (119 vs 14.2 IU/l, p < 0.001 and 119 vs 32.7 IU/l, p < 0.005, respectively). CONCLUSION: Delaying vaccination of premature infants against hepatitis B until a weight of 2,000 g was reached resulted in both a significantly higher percentage of children with positive antibody levels and a significantly higher GMC at 3-3.5 years of age as compared to early-vaccinated preterm and full-term infants. The known short-term advantage of delayed vaccination of preterm infants was shown to persist for at least the first 3 years of life.

Age Factors↗

Deposition of whole blood platelets on extracellular matrix under flow conditions in preterm infants.

BACKGROUND: A previous study showed greater adhesion by platelets of healthy full term infants to subendothelial extracellular matrix (ECM) under flow conditions compared with healthy adult platelets. AIM: To investigate the adhesion and aggregation of platelets from preterm infants on ECM under defined shear conditions. METHODS: In vitro platelet function was investigated in 106 preterm infants, 74 full term infants, and 26 healthy adults. Blood samples were obtained from all infants within 24 hours of birth, and weekly until discharge from preterm infants only. Citrated whole blood was placed in ECM precoated tissue culture plates and subjected to shear stress (1300 s-1) for two minutes using a rotating Teflon cone. Platelet adhesion (surface coverage) and aggregation (average size) to ECM were assayed using an image analyser. Assays for von Willebrand factor (vWF) antigen, ristocetin cofactor, and vWF collagen-binding activity were performed on samples from an additional 70 preterm infants, 23 healthy full term infants, and 24 healthy adults. Preterm infants with hyaline membrane disease (HMD) were analysed separately in both cohorts. RESULTS: Platelets from preterm infants displayed significantly less platelet adhesion than those from full term infants but similar aggregation and levels of vWF antigen, ristocetin cofactor, and collagen binding activity. Mean surface coverage was 22.0 (8.4)% for preterm infants with HMD, 28.7 (8.0)% for healthy preterm infants, and 35.7 (7.9)% for full term infants. Surface coverage in the preterm infants correlated with gestational age during the first 24 hours only, and did not reach full term levels during 10 weeks of follow up. CONCLUSION: Platelet adhesion to ECM is significantly poorer in preterm than in full term infants, and poorer in preterm infants with HMD than in healthy preterm infants. Intrinsic platelet properties rather than the concentration or activity of vWF may be responsible for this difference.

Adult↗

[Detection of anti-Borrelia antibodies by immunoblotting in Lyme borreliosis].

IgM and IgG were detected in the sera from 25 Russian patients with Lyme disease by immunoblotting test with Immunetics kit (USA). Early stage of the disease was diagnosed in 12 patients and late stage in 13. Specific protein lines were detected in virtually all patients but their number and combination in the sera were different. Eleven (43%) sera were regarded as positive according to the American criteria of seropositive test, 3 of them by IgM and 10 by IgG. In patients with short disease serum reaction was either negative or confined to 1-2 lines per strip. Patients with late stage showed a more manifest extensive reaction, which was the most pronounced in patients with a long lasting disease and articular involvement; the reaction was similar to that characteristic of chronic Lyme arthritis. Parallel testing of IgG antibodies in 25 sera from American patients with Lyme disease (confirmed by direct isolation of the agent) showed notable similarity of reactions of both American and Russian sera. More essential differences were observed only for low molecular weight proteins (p28, p23, p21).

Antibodies, Bacterial↗

Outcome of referral to social services departments for people with cognitive impairment.

The objective of this study was to determine how the entry into long term care of people assessed by their local social services department (SSD) under the National Health Service and Community Care Act 1990 is predicted by the severity of their cognitive impairment, care provided by family members, and the receipt of community care services. The design involved a cohort study of people over one and a half years following referral (min-max: 1-2 years) from three SSDs (county council, metropolitan and inner London boroughs). Consecutive recruitment of 141 people with cognitive impairment aged 65 and over took place over a 4 month period. The main outcome measure was survival analysis of time taken from referral to entering long term care at follow-up. The receipt and intensity of community care services increased the probability of remaining at home. People with mild or moderate cognitive impairment were more likely to remain at home if they had a spouse or daughter carer. Analysis of the interaction between three main effects predicting entry to long term care (severity of cognitive impairment, access to a carer, and the receipt of home care or day care) suggests that while carers are central in determining whether older people with cognitive impairment are able to remain living in the community, there are limits to the care they can provide.

Aged↗

Depression and the response of residential homes to physical health needs.

OBJECTIVE: To investigate the response of residential homes to four specific health problems of residents and the relationship between the quality of this response and the prevalence of depression. DESIGN AND SAMPLE: Post hoc analysis of data collected for a cross-sectional survey of homes chosen to represent "excellent" and "standard" care; resident sample sufficient to detect difference between 20% and 40% depression prevalence between two groups of homes (90% power, 5% significance). Three hundred and nine residents were assessed. SETTING: Seventeen residential homes in different areas of England. METHODS: Data were collected about aspects of the care provided, including quality rating of care plans. Standard instruments were used to collect resident data by direct and informant interviews, including assessments of dementia, depression, dependency, medication and specific health problems. RESULTS: Seventy-nine per cent of the sample were suffering from dementia; 40% of 194 residents who could be assessed for depression were depressed. Of residents assessed by research nurses, 72% had problems with mobility, 67% with stability, 40% with hearing and 46% with vision. Quality of response to these problems was variable. In a combined assessment of care plan quality and key worker awareness, 7% of homes' responses to these four problems in residents were rated as good. Seventeen per cent of depressed residents were so identified by their key workers. Good interventions by key workers were associated with less depression in residents. DISCUSSION: The response of home staff and community health professionals to physical health needs in residential homes is variable and should be improved. This study suggests that improving this aspect of care provision might reduce depression and thus improve quality of life.

Aged↗

Hemostatic parameters and platelet activation marker expression in cyanotic and acyanotic pediatric patients undergoing cardiac surgery in the presence of tranexamic acid.

We have investigated hemostatic parameters including platelet activation in 56 pediatric patients with or without cyanosis undergoing cardiopulmonary bypass (CPB) and cardiac surgery to repair congenital defects. Patients were participants in a study assessing the effects of tranexamic acid on surgery-related blood loss. Parameters monitored included blood loss, prothrombin F1.2, thrombin-antithrombin complexes, t-PA, PAI-1, plasminogen, fibrin D-dimer, and plasma factor XIII. Additionally, flow cytometry monitored platelet degranulation (P-selectin or CD63), as well as surface-bound fibrinogen, von Willebrand factor and factor XIIIa. Cyanotic patients had evidence of supranormal coagulation activation as both fibrin D-dimer and PAI-1 levels were elevated prior to surgery. While the extent of expression of P-selectin or CD63 was not informative, platelet-associated factor XIIIa was elevated in cyanotic patients at baseline. In both patient groups, CPB altered platelet activation state and coagulation status irrespective of the use of tranexamic acid.

Antifibrinolytic Agents↗

Patterns of medication use before and after bone densitometry: factors associated with appropriate treatment.

OBJECTIVE: We examined the medications used by women before and after bone densitometry to determine whether patient or physician factors were associated with appropriate osteoporosis therapy. METHODS: Appropriate osteoporosis treatment was defined as alendronate, etidronate, calcitonin, or hormone replacement therapy (HRT) for women with any bone mineral density (BMD) t score < -2.5 or no osteoporosis therapy, except HRT, for women with t scores > -1.0. We observed a cohort of women who underwent bone densitometry at one outpatient osteoporosis clinic. Medical history, medication use, and demographic data were collected at the time of bone densitometry. A followup questionnaire assessed the medication use patterns since bone densitometry and attitudes about osteoporosis therapy. RESULTS: We recruited 553 women who underwent bone densitometry in 1996. Their mean age was 62 years and 95% were postmenopausal. Prior to bone density scans, 27% of patients used HRT, 15% used bisphosphonates, and 6% used calcitonin. Scan results and surveys revealed that 40% of patients had BMD below a t score of -2.5 at any site. Of women with osteoporosis 78% reported taking an appropriate medication after their scans. Patients most likely to receive appropriate treatment were those who understood their bone densitometry results (odds ratio, OR, 2.5; 95% confidence interval, CI, 1.3 to 4.8) and patients who were taking an osteoporosis medication (OR 1.9; 95% CI 1.0 to 3.6). Neither the specialty of the referring physician nor patients' medical history was associated with use of appropriate osteoporosis therapy. CONCLUSION: Of women with osteoporosis who underwent bone densitometry 78% received appropriate therapy after this test. Patient factors were associated with the likelihood that they received appropriate therapy, suggesting that strategies aimed at educating patients may improve the use of osteoporosis medications.

Aged↗

Inhibition of angiogenesis by nonsteroidal anti-inflammatory drugs: insight into mechanisms and implications for cancer growth and ulcer healing.

Angiogenesis, the formation of new capillary blood vessels, is essential not only for the growth and metastasis of solid tumors, but also for wound and ulcer healing, because without the restoration of blood flow, oxygen and nutrients cannot be delivered to the healing site. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, indomethacin and ibuprofen are the most widely used drugs for pain, arthritis, cardiovascular diseases and, more recently, the prevention of colon cancer and Alzheimer disease. However, NSAIDs produce gastroduodenal ulcers in about 25% of users (often with bleeding and/or perforations) and delay ulcer healing, presumably by blocking prostaglandin synthesis from cyclooxygenase (COX)-1 and COX-2 (ref. 10). The hypothesis that the gastrointestinal side effects of NSAIDs result from inhibition of COX-1, but not COX-2 (ref. 11), prompted the development of NSAIDs that selectively inhibit only COX-2 (such as celecoxib and rofecoxib). Our study demonstrates that both selective and nonselective NSAIDs inhibit angiogenesis through direct effects on endothelial cells. We also show that this action involves inhibition of mitogen-activated protein (MAP) kinase (ERK2) activity, interference with ERK nuclear translocation, is independent of protein kinase C and has prostaglandin-dependent and prostaglandin-independent components. Finally, we show that both COX-1 and COX-2 are important for the regulation of angiogenesis. These findings challenge the premise that selective COX-2 inhibitors will not affect the gastrointestinal tract and ulcer/wound healing.

Animals↗

Effects of prestorage white cell reduction on platelet aggregate formation and the activation state of platelets and plasma enzyme systems.

BACKGROUND: The introduction of prestorage white cell (WBC) reduction in random-donor platelet concentrates in Canada has increased the occurrence of particulate material in PCs. The effects of filtration on platelet activation state and the activation of plasma enzyme systems were assessed. STUDY DESIGN AND METHODS: Particulate material was examined by light microscopy, electron microscopy, protein electrophoresis, and biochemical analysis. Thirty PCs (10 unfiltered, 20 filtered) were examined during processing and 5-day storage for pH, platelet count and mean volume, morphology, activation marker expression, and hypotonic shock response. Complement activation, thrombin generation, and fibrinolysis were assessed by using specific enzyme immunoassays or chromogenic assays. RESULTS: By all analyses, the particulate material appeared to be platelet aggregates. Platelets exposed to WBC-reduction filters expressed a significantly higher level of activation markers CD62 and CD63, altered morphology, and increased platelet microparticles throughout the storage period than did unfiltered platelets. Complement activation at the C3 level was significantly increased in filtered units with little evidence of coagulation or fibrinolytic system activation. CONCLUSION: Exposure of platelets to filters during prestorage WBC reduction increased platelet activation and mildly increased complement activation over the levels during the storage period. These alterations can contribute to the formation of irreversible platelet aggregates during processing.

Antigens, CD↗

Prednisolone treatment of respiratory syncytial virus infection: a randomized controlled trial of 147 infants.

OBJECTIVE: To evaluate the effect of systemic prednisolone as an adjunct to conventional treatment with beta2-agonist, respiratory support, and fluid replacement in hospitalized infants <24 months of age with respiratory syncytial virus (RSV) infection. METHODS: The study was randomized, double-blind, and placebo-controlled. During the winter of 1995-1996, 147 infants <2 years of age, hospitalized with RSV infection, were allocated to treatment with either systemic prednisolone mixture 2 mg/kg daily or placebo for 5 days. MAIN OUTCOME MEASURES: The acute effect variables were duration of stay in hospital, use of medicine, and supportive measures while in hospital. At follow-up 1 month after discharge, the acute effect variables were duration of illness, start in day care center, morbidity, and use of medicine. At follow-up 1 year after discharge, the acute effect variables were morbidity, use of medicine, and skin prick tests with allergens. RESULTS: Prednisolone treatment had no effect on any of the outcome measures. CONCLUSIONS: Our randomized prospective study in infants hospitalized with acute RSV infection showed no effect of systemic prednisolone treatment either in the acute state of RSV infection, nor in the follow-up 1 month and 1 year after admission to hospital. We find our results in agreement with the largest studies reported earlier; therefore, corticosteroid, whether by the systemic route or by inhalation, should not be prescribed to infants with RSV infection.

Double-Blind Method↗