bluuebunny/crossref_metadata_2025_split huggingface dataset:
Donepezil for the symptomatic treatment of patients with mild to moderate Alzheimer's disease: a meta‐analysis of individual patient data from randomised controlled trials
Authors: Whitehead Anne , Perdomo Carlos , Pratt Raymond D. , Birks Jacqueline , Wilcock Gordon K. , Evans John Grimley 
Published: June 2004

AbstractBackgroundThe objective was to evaluate the efficacy and tolerability of donepezil (5 and 10 mg/day) compared with placebo in alleviating manifestations of mild to moderate Alzheimer's disease (AD).MethodA systematic review of individual patient data from Phase II and III double‐blind, randomised, placebo‐controlled studies of up to 24 weeks and completed by 20 December 1999. The main outcome measures were the ADAS‐cog, the CIBIC‐plus, and reports of adverse events.ResultsA total of 2376 patients from ten trials were randomised to either donepezil 5 mg/day (n = 821), 10 mg/day (n = 662) or placebo (n = 893). Cognitive performance was better in patients receiving donepezil than in patients receiving placebo. At 12 weeks the differences in ADAS‐cog scores were 5 mg/day–placebo:  − 2.1 [95% confidence interval (CI),  − 2.6 to  − 1.6;p < 0.001], 10 mg/day–placebo:  − 2.5 ( − 3.1 to  − 2.0;p < 0.001). The corresponding results at 24 weeks were  − 2.0 ( − 2.7 to  − 1.3;p < 0.001) and  − 3.1 ( − 3.9 to  − 2.4;p < 0.001). The difference between the 5 and 10 mg/day doses was significant at 24 weeks (p = 0.005). The odds ratios (OR) of improvement on the CIBIC‐plus at 12 weeks were: 5 mg/day–placebo 1.8 (1.5 to 2.1;p < 0.001), 10 mg/day–placebo 1.9 (1.5 to 2.4;p < 0.001). The corresponding values at 24 weeks were 1.9 (1.5 to 2.4;p = 0.001) and 2.1 (1.6 to 2.8;p < 0.001). Donepezil was well tolerated; adverse events were cholinergic in nature and generally of mild severity and brief in duration.ConclusionDonepezil (5 and 10 mg/day) provides meaningful benefits in alleviating deficits in cognitive and clinician‐rated global function in AD patients relative to placebo. Increased improvements in cognition were indicated for the higher dose. Copyright © 2004 John Wiley & Sons, Ltd.
Depression in frail elders: impact on family caregivers
Authors: Sewitch Maida J. , McCusker Jane , Dendukuri Nandini , Yaffe Mark J. 
Published: June 2004

AbstractObjectivesTo examine the relationship between depression among medically ill, frail elders and family caregivers' hours of care, health status, and quality of life.Design and MethodsA cross‐sectional study of 193 family caregivers of seniors treated in the emergency department (ED) was conducted. Measures included patient depression (Geriatric Depression Scale—15), and caregivers' hours of care, mental health and physical functioning (SF‐36), and quality of life (EQ‐5D).ResultsMean caregiver age was 60.0 ± 16.1 years and 70.5% were female. More caregivers of depressed seniors provided more care in the previous month (37.3% vs 22.4%, p = 0.03), had poor mental health (63.5% vs 47.0%, p = 0.03), and poor perceived quality of life (63.5% vs 50.4%, p = 0.04) compared to caregivers of non‐depressed seniors. Multiple logistic regression analyses indicated that patient depression was associated with poor caregiver quality of life (OR = 3.15, 95% CI 1.48, 6.73), and poor mental health in spousal and adult child caregivers (OR = 2.72, 95% CI = 0.88, 8.39, and OR = 3.29, 95% CI = 1.10, 9.86, respectively).ConclusionsPsychosocial support may be needed for caregivers of depressed seniors. Copyright © 2004 John Wiley & Sons, Ltd.
Risk indicators of depression in residential homes
Authors: Eisses A. M. H. , Kluiter H. , Jongenelis K. , Pot A. M. , Beekman A. T. F. , Ormel J. 
Published: June 2004

AbstractObjectivesTo assess risk indicators of depressive symptoms in social and personal domains of residents of residential homes.MethodsIn a cross‐sectional study risk indicators for depressive symptoms (Geriatric Depression Scale) were examined in bivariate and multivariate analyses, four hundred and seventy‐nine elderly subjects from 11 residential homes took part in the study.ResultsFunctional impairment, loneliness, higher education levels, a family history of depression and neuroticism are associated with depressive symptom.ConclusionThe risk indicators of depression found in residential homes are similar to those in the community. Copyright © 2004 John Wiley & Sons, Ltd.
Plasma homocysteine concentration relates to the severity but not to the duration of Alzheimer's disease
Authors: Nilsson Karin , Gustafson Lars , Hultberg Björn 
Published: June 2004

AbstractBackgroundIt has been reported that plasma tHcy concentration is elevated in patients with Alzheimer's disease (AD) and relates to the progress or the development of AD. In the present study we have compared plasma tHcy concentrations at different times during the course of AD and with measures corresponding to the severity and the progress rate of AD.MethodsThe study population consisted of 159 patients with AD. Three measures corresponding to the progress rate of AD were created by dividing the actual scores of the severity of the dementia, the Berger scale and the Katz index by the estimated duration.ResultsAD patients without a history of cardiovascular disease did not show a significant increase of plasma tHcy concentration compared to the control subjects, whereas AD patients with cardiovascular disease exhibited a significant increase of plasma tHcy concentration compared to both control subjects and patients without cardiovascular disease. However, after creatinine adjustment of plasma tHcy in control subjects and AD patients a significant increase of plasma tHcy was observed also in AD patients without cardiovascular disease compared to controls. The concentration of plasma tHcy in AD patients with and without cardiovascular history did not increase with time after disease onset. Plasma tHcy concentration correlated with the severity of the disease. The correlations between plasma tHcy and measures of rate progression of AD did not improve compared with the correlations between plasma tHcy and the severity of dementia.ConclusionAn interpretation of these findings may be that plasma tHcy is additionally increased in AD patients when a complication occurs, such as folate/cobalamin deficiency or a cardiovascular disease. Copyright © 2004 John Wiley & Sons, Ltd.
The effect of private insurance access on the choice of GP/specialist and public/private provider in Spain
Authors: Rodríguez Marisol , Stoyanova Alexandrina 
Published: June 2004

AbstractThis paper sheds light into the investigation of differential patterns of utilisation of physician services by populations subgroups that is emerging in a number of studies. Using Spanish data from the National Health Survey of 1997 we try to explain the distinct role of the type of insurance on the choice between specialists and GPs and its intertwining with the choice between private and public providers. We estimate a two‐stages probit to conclude that differences in insurance access is the main determinant of both, the choice of sector and the kind of physician contacted, giving rise to very different patterns of consumption of GP and specialist visits. People with only public insurance go 2.8 times to the GP per one time that they visit a specialist; individuals with duplicate coverage have a ratio of GP/specialist visits equal to 1.4 (the combination being public GP and private specialist) and people with only private insurance access actually have an ‘inverted’ pattern of visits: they contact specialists more often than GPs. Age, sex and health and public supply characteristics also have a distinct and interesting impact on these choices. Finally, equity concerns based on the implied assumption that specialists care is superior to general practitioner care are discussed. Copyright © 2003 John Wiley & Sons, Ltd.
To what extent do people prefer health states with higher values? A note on evidence from the EQ‐5D valuation set
Authors: Roberts Jennifer , Dolan Paul 
Published: June 2004

AbstractThe EQ‐5D general population valuation set (or ‘tariff’) is increasingly being used in the evaluation of health care interventions and has been recommended by the National Institute for Clinical Excellence (NICE) for use in cost‐utility analyses of health technologies. To be of use to decision‐makers, the health gain implied by changes in health state values must reflect individual preferences. At the simplest level, if State A has a higher mean value than State B, then the majority of people should consider a move from B to A to be a good thing. In this paper, we examine the extent to which this is true by re‐analysing data from the general population study used to derive the EQ‐5D tariff. We show that, on average, the difference in value between two states has to be as large as 0.20 (on a scale where one represents full and zero represents death) for 70% of respondents to agree with the sign of that difference (never mind its size). Results such as these have important implications for the use of the EQ‐5D tariff that has been generated from these data. Copyright © 2004 John Wiley & Sons, Ltd.
Molecular pathology of head‐and‐neck cancer
Authors: Kim Michael M. , Califano Joseph A. 
Published: June 2004

AbstractEach year approximately 40,000 people in the United States and 500,000 people worldwide are diagnosed with head‐and‐neck squamous cell carcinoma (HNSC). Although there have been significant improvements in the treatment of this disease, leading to decreased morbidity, over the past few decades the 5‐year survival rate has remained largely unchanged at 50%. Genetic and epigenetic alterations as well as viral agents have been implicated in the development of head‐and‐neck cancer. Advances in our understanding of the molecular biology underlying these processes have spawned numerous, diverse strategies to exploit this understanding in applied pathology. Preliminary investigations have analyzed body fluids and margins for the presence of cancer cells. Specific molecular alterations have been associated with improved treatment response and prognosis. Molecular therapy has been shown to have some clinical efficacy in HNSC. Expression profiles may be generated for specific primary tumors and compared to known markers of disease. Improved molecular characterization of primary tumors, surgical margins and body fluids may allow clinicians to detect and treat earlier lesions, predict a tumor's response to treatment, tailor treatment to specific molecular alterations and ultimately improve clinical outcomes related to HNSC. © 2004 Wiley‐Liss, Inc.
Arsenic trioxide sensitizes CD95/Fas‐induced apoptosis through ROS‐mediated upregulation of CD95/Fas by NF‐κB activation
Authors: Woo Sang Hyeok , Park In‐Chul , Park Myung‐Jin , An Sungkwan , Lee Hyung‐Chahn , Jin Hyeon‐Ok , Park Sin‐Ae , Cho Hyeyoung , Lee Su‐Jae , Gwak Ho‐Shin , Hong Young‐Joon , Hong Seok‐Il , Rhee Chang Hun 
Published: June 2004

AbstractCD95/Fas is a cell surface protein that belongs to the tumor necrosis factor receptor family. Signals through CD95/Fas are able to induce apoptosis in sensitive cells. Therefore, modalities to regulate the CD95/Fas expression level in tumor cells are called for. In the present study, we show that sublethal doses of arsenic trioxide (As2O3) sensitized CD95/Fas‐induced apoptosis in human cervical cancer cells, and the sensitizing effects resulted from As2O3‐mediated increase in the expression of the CD95/Fas. N‐acetyl‐L‐cysteine, a specific scavenger of reactive oxygen species, abrogated As2O3‐induced upregulation of CD95/Fas and enhancement of CD95/Fas‐mediated apoptosis. Furthermore, inhibition of NF‐κB by transient transfection of IκBα supersuppressor blocked the increase of CD95/Fas expression following As2O3 treatment. Antisense oligonucleotide of CD95/Fas and ZB4, an antibody that blocks the binding of CD95/Fas ligand to CD95/Fas, reduced the amount of As2O3‐sensitized CD95/Fas‐induced apoptosis, demonstrating the specificity of CD95/Fas‐binding ligands in the As2O3‐sensitized CD95/Fas‐induced apoptosis. These findings demonstrate that sensitization of human cervical cancer cells to CD95/Fas‐mediated apoptosis by As2O3 can be partly due to induction of ROS and subsequent upregulation of CD95/Fas gene expression by NF‐κB activation. © 2004 Wiley‐Liss, Inc.
Inherited predisposition to early onset lung cancer according to histological type
Authors: Li Xinjun , Hemminki Kari 
Published: June 2004

AbstractThe role of hereditary factors in lung cancer is less well understood than in many other human neoplastic diseases. We used a nation‐wide family dataset to search for evidence for a genetic predisposition in lung cancer. The Swedish Family‐Cancer Database includes all Swedes born in 1932 and later (0‐ to 68‐year‐old offspring) with their parents, totaling over 10.2 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry up to year 2000. Standardized incidence ratios (SIR) and 95% confidence limits (CI) were calculated for age‐specific familial risks in offspring by parental or sibling proband, separately. A Kappa test was used to examine the association between familial risk and histology. Compared to the rate of lung cancers among persons without family history, a high risk by parental family history in adenocarcinoma (2.03) and large cell carcinoma (2.14) was found, and only a slightly lower risk was found among patients with squamous cell carcinoma (1.63) and small cell carcinoma (1.55). Among siblings, an increased risk was shown for concordant adenocarcinoma and small cell carcinoma at all ages and for all histological types when cancer was diagnosed before age 50. At young age, risks between siblings were higher than those between offspring and parents. The present data suggest that a large proportion of lung cancers before age 50 years appears to be heritable and probably due to a high‐penetrant recessive gene or genes that predispose to tobacco carcinogens; however, this hypothesis needs to be tested in segregation analysis with a large number of pedigrees. © 2004 Wiley‐Liss, Inc.
Different types of microsatellite instability in ovarian carcinoma
Authors: Singer Gad , Kallinowski Thore , Hartmann Arndt , Dietmaier Wolfgang , Wild Peter J. , Schraml Peter , Sauter Guido , Mihatsch Michael J. , Moch Holger 
Published: June 2004

AbstractMicrosatellite instability at mono‐ and dinucleotide repeats is the hallmark of the hereditary non‐polyposis cancer syndrome (HNPCC) and is related to deficient DNA mismatch repair. In contrast, a distinct form of microsatellite instability at selective tetranucleotide repeats (EMAST or elevated microsatellite alterations at selected tetranucleotides) was described in several non‐HNPCC cancer types. EMAST is probably unrelated to mismatch repair defects. We investigated the frequency of microsatellite instability at mononucleotide, dinucleotide and tetranucleotide repeats in a series of 75 ovarian carcinomas (53 serous and 22 non‐serous). Microsatellite analysis was carried out using 5 mono‐ and dinucleotide markers from the National Cancer Institute Consensus Panel and 6 tetranucleotide markers, which have been reported as frequently unstable in the literature. High frequency of microsatellite instability (MSI‐H) at mono‐ and dinucleotide repeats was observed in 9% and a low frequency (MSI‐L) in 21% of serous carcinomas. MSI‐H was detected in 4% and MSI‐L in 18% of non‐serous carcinomas. Nine percent of serous carcinomas showed instability at multiple and 9% at single tetranucleotide loci. All non‐serous carcinomas were stable at tetranucleotide loci. In summary, EMAST (e.g., tumors with tetranucleotide instability without concomitant MSI‐H) was observed in 13% of ovarian serous carcinomas. All EMAST positive tumors were of advanced stage. We conclude that EMAST occurs as a distinct form of microsatellite instability in ovarian cancer. EMAST seems to be particularly frequent in advanced serous carcinomas. Its clinical significance needs to be investigated. © 2004 Wiley‐Liss, Inc.
Genetic counseling program in familial breast cancer: Analysis of its effectiveness, cost and cost‐effectiveness ratio
Authors: Balmaña Judith , Sanz Judit , Bonfill Xavier , Casado Alfonso , Rué Montse , Gich Ignasi , Díez Orland , Sabaté Josep M. , Baiget Montserrat , Alonso M. Carmen 
Published: June 2004

AbstractWomen with a family history of breast cancer are at increased risk for developing this neoplasm. Starting surveillance more frequently at a younger age than the general population and the possibility of undergoing genetic testing are options for their medical management. We analyzed the benefits and costs of our clinical program in familial breast cancer (FBC) and carried out a cost‐effectiveness analysis of such procedure. The benefits and costs of performing genetic counseling and a screening program in FBC based on 143 high‐risk families registered in our database between June 1995 and December 2001 were analyzed. A decision tree was constructed to estimate the survival benefit and cost‐effectiveness of the clinical genetic counseling program compared with the strategy of not performing any screening protocol. We estimated that the prevalence of a BRCA mutation in an unaffected relative of our high‐risk cohort was 10% and that 53% of the mutations are found in the BRCA1 gene. We assigned a 58.5% lifetime risk of breast cancer for a 30‐year‐old mutation carrier according to the SEER data. The effectiveness of the screening was obtained from our experience and data for estimating survival were derived from other studies with longer follow‐up. We used our local payment data to calculate the costs of the program. A mutation in the BRCA1 or BRCA2 genes was identified in 20% of the probands. Seventy primary breast cancer cases were recorded since the onset of the program. Thirty percent of the tumors were diagnosed through the screening program and 71% of them were lymph node‐negative compared to 49% of the tumors diagnosed outside the program (p = 0.1). The cost‐effectiveness ratio of our FBC genetic counseling and screening program was 4,294 euros per life‐year gained. The model was sensitive to the prevalence of mutation carriers, the lifetime risk of breast cancer and the effectiveness of the screening. In our setting and according to our model, this analysis suggests that a program of genetic testing and screening for breast cancer in a high‐risk population may be cost‐effective. These results need to be confirmed as more effective interventions for cancer prevention and screening are being implemented. © 2004 Wiley‐Liss, Inc.
Annual Cycle of Planktothrix agardhii(Gom.) Anagn. & Kom. Nature Population
Authors: Poulíčková Aloisie , Hašler Petr , Kitner Miloslav 
Published: June 2004

AbstractChanges in abundance, biovolume and morphology of Planktothrix agardhii in a natural population were followed over one year period in shallow fishpond Bílá Lhota (Central Moravia, Czech Republic). The selected environmental parameters (pH, oxygen, temperature, conductivity, nutrients, light) were measured at the surface and at the bottom of the fishpond, together with the Planktothrix abundances and filament morphology – filament length, width, shape, aerotopes (gas vacuoles) formation. The annual cycle of P. agardhii in this hypertrophic fishpond starts in March with the germination of hormogonia and the growth of overwintered filaments. The filament length quickly increases to a maximum length in April. The following summer period can be characterized by filament shortening and by changes in the aerotopes shape. On the other hand the abundance and biomass of P. agardhii is increasing until the maximum in August. Further shortening of filaments, loss of aerotopes and hormogoniae formation is typical for the autumn (October) with the average temperature of 9.4 °C. The population overwinters near the pond bottom in the form of hormogonia (60%) and filaments (40%). (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Relative Distributions of Dreissena bugensis and Dreissena polymorpha in the Lower Don River System, Russia
Authors: Zhulidov A. V. , Pavlov D. F. , Nalepa T. F. , Scherbina G. H. , Zhulidov D. A. , Gurtovaya T. Yu. 
Published: June 2004

AbstractA survey was conducted in the lower Don River system in Russia to confirm the presence of Dreissena bugensis, and to compare its distribution relative to that of Dreissena polymorpha. In 1999 and 2001–2002, dreissenid mussels were collected at 15 sites in the main river, in connecting reservoirs, and in a major tributary, the Manych River. Collections were made near stations where long‐term monitoring data on total mineral (sum of principal ions) and calcium content were available. Both dreissenid species were found at all sites, with D. bugensis comprising 4–75% of all dreissenids at individual sites. D. bugensis was relatively more abundant than D. polymorpha in the Manych River where total mineral and calcium content was significantly higher than in the Don River, suggesting the two species may have different calcium requirements. Examination of archived samples indicated that D. bugensis was present in the Don River system as early as the 1980s, presenting the unresolved enigma of why D. bugensis has not displaced D. polymorpha as the dominant species as typically found over shorter time periods in other water bodies. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Reactions of the Heavy Metal Cycle to Industrial Activities in the Deep Sea: An Ecological Assessment
Authors: Koschinsky Andrea , Borowski Christian , Halbach Peter 
Published: June 2004

AbstractThis article focuses on possible geochemical consequences of potential industrial activities in the deep sea, such as manganese nodule mining, for the heavy metal cycle of the deep sea and possible reactions of the benthic ecosystem. The metal fluxes induced by sediment resuspension are compared with fluvial, atmospheric, and hydrothermal metal fluxes into the ocean. The results of geochemical laboratory experiments and analyses of deep‐sea benthic organisms are discussed with respect to their ecological importance in case of a seabed disturbance.A limited short‐term increase of heavy metal concentrations in the benthic layer will probably cause only negligible harmful effects on the biota. An essential precondition is that the geochemical milieu remains largely unchanged; especially variations of the redox conditions would result in changes in metal speciation, bioavailability, and toxicity.