bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding reasons for underuse: An approach to improve quality and reduce disparities in breast cancer treatmentrr
Authors: Bickell Nina A. , Cohen Alicia 
Published: February 2008

AbstractObjective: Effective adjuvant treatments proven to prolong survival for breast cancer exist, yet many women, particularly minority women, do not receive them. Little work has focused on improving the quality of, and reducing racial disparities in, cancer treatment. We describe the application of a conceptual model to direct, design, and implement trials to reduce underuse of effective adjuvant breast cancer treatments.Methods: Content analysis of extensive interviews and focus groups was used to construct a framework of patient, physician, and system‐level reasons for underuse. Use of the model then directed development of targeted interventions aimed at ameliorating underlying causes.Results: The process of identifying patient, physician, and system‐level reasons for underuse involved patients, surgeons, surgeon's office staff, and providers of patient assistance. Engaging these individuals both informed the design of our multi‐focused interventions and generated interest in trial participation. All 38 surgeons in six unaffiliated institutions and all 25 patient assistance programs approached agreed to participate in the intervention trials.Interpretation: Identifying reasons for underuse by interviewing patients, physicians, physician office staff, and allied care providers about episodes in which needed care failed to occur helps engage key individuals, and can inform the design and implementation of interventions targeting barriers to delivering high quality breast cancer care to all. Mt Sinai J Med 75:23–30, 2008. © 2008 Mount Sinai School of Medicine
The success of recruiting minorities, women, and elderly into a randomized controlled effectiveness trial
Authors: Sisk Jane E. , Horowitz Carol R. , Wang Jason J. , McLaughlin Mary Ann , Hebert Paul L. , Tuzzio Leah 
Published: February 2008

AbstractBackground: Heart failure, a leading cause of hospitalization among elderly people, disproportionately afflicts African‐American and other non‐White populations. Studies of health care interventions often do not include these groups in proportion to numbers in the patient population. Our objective was to assess whether a randomized controlled effectiveness trial enrolled patients by ethnicity/race, gender, and age in proportion to those eligible.Methods: We conducted a randomized controlled trial comparing nurse management and usual care among ambulatory heart failure patients at the four hospitals in East and Central Harlem, New York. We incorporated culturally sensitive and age‐appropriate strategies to enroll a demographically representative group into the trial. Recruitment proceeded in several steps: identifying patients with billing code and visit criteria, documenting systolic dysfunction, obtaining clinician permission and correct addresses, contacting patients, and enrolling eligible patients. We assessed differences by ethnicity/race and gender at successive steps in the recruitment process, and differences between enrollees and refusals regarding overall health, evaluation of medical care, and difficulty receiving care.Results: We enrolled 406 ambulatory patients by ethnicity/race and gender in proportion to the numbers eligible to be contacted (46% African‐American/Black, 33% Hispanic, and 47% female). Among patients contacted, however, those 18 through 74 years were 2.0 to 3.3 times more likely than those ≥ 75 years to enroll (p < 0.001).Conclusions: The recruitment strategy successfully enrolled patients by ethnicity/race, gender, and age through 74 years, but not those ≥ 75 years. Registries of patients who refuse to enroll in trials could provide guidance for clinical and public policy. Mt Sinai J Med 75:37–43, 2008. © 2008 Mount Sinai School of Medicine
Racial disparities in infant mortality: A quality of care perspective
Authors: Howell Elizabeth A. 
Published: February 2008

AbstractBlack infants in the United States are more than twice as likely to die as White infants in the first year of life. Reducing the existing racial disparity in infant mortality rates is a major health policy focus. Despite decades of research aimed at reducing preterm births, our efforts have been largely unsuccessful. Much greater success has been achieved in reducing the morbidity and mortality of premature infants, largely through improvements in obstetrical and neonatal care. However, it is an open question whether such improvements have reduced racial disparities in infant mortality. In this article, we recommend a new framework for addressing infant mortality disparities. We suggest that a quality of care problem may partially underlie racial disparities in infant mortality rates. Mt Sinai J Med 75:31–35, 2008. © 2008 Mount Sinai School of Medicine
Evidence of artificial cranial deformation from the later prehistory of the Acacus Mts. (southwestern Libya, Central Sahara)
Authors: Ricci F. , Fornai C. , Blos V. Tiesler , Rickards O. , di Lernia S. , Manzi G. 
Published: February 2008

AbstractThe 1999–2001 Italian–Libyan Archaeological Mission in the Acacus and Messak, southwestern Libya, resulted in the discovery of human specimens from the Wadi Tanezzuft Valley belonging to the Final Pastoral horizon (i.e. late Neolithic, about 3000 years bp). Some of these show clear traces of artificial cranial deformation. This practice, hitherto unrecorded in the central Sahara, is described and analysed in this paper. It represents an additional source of information about population movements and cultural connections in the area. It does not appear to be gender‐related, and neither does it involve all individuals in the sample, suggesting some kind of social and/or cultural differentiation within the group. The pattern of cranial deformation described here is not directly related to types most commonly encountered among recent African populations and elsewhere. It may be considered a combination of antero‐posterior and circumferential deformation and thus is referred to as a ‘pseudo‐circular type’. Archaeological and ethnographic literature related to Africa and southwestern Asia is investigated in order to identify a possible origin of such a custom and its pattern of diffusion. The evidence, according to other sources of information, contributes to interpret this area at the centre of the Sahara as a focal point of population movements and circulation of cultural traditions across North Africa in the latest phases of the Pastoral Neolithic. Copyright © 2008 John Wiley & Sons, Ltd.
Most multifocal papillary thyroid carcinomas acquire genetic and morphotype diversity through subclonal evolution following the intra‐glandular spread of the initial neoplastic clone
Authors: Jovanovic L , Delahunt B , McIver B , Eberhardt NL , Grebe SKG 
Published: February 2008

AbstractPapillary thyroid carcinoma (PTC) is frequently multifocal (mPTC), with synchronous tumour foci often showing varied morphology. The genetic mechanisms underlying the development of multiple and histologically diverse tumour foci remain uncertain. Different tumour foci might develop either through intrathyroidal dissemination of a single malignant clone, with morphotype differentiation occurring as a result of subclonal progression, or they may stem from independent transformational events involving multiple progenitor clones. To determine the clonal derivation of multiple tumour foci and to map their clonal relationships and genetic progression in mPTC, we evaluated genome‐wide allelic imbalances (AI) and BRAFV600E mutation status in 55 synchronous tumour foci from 18 mPTC patients. For apparently monoclonal tumours, we calculated the probabilities of monoclonal derivation and used phylogenetic analysis to model clonal evolution. Genome‐wide allelotyping and BRAF mutation analysis showed genetic alterations consistent with monoclonal origin in 83% of cases, mostly with evidence of subclonal evolution. BRAFV600E mutations were early events during clonal evolution of most, but not all cases. MPTC with morphologically diverse tumour foci also arose through monoclonal derivation in 75% of cases, demonstrating that morphotype‐determining genetic changes can be acquired during clonal diversification, subsequent to the spread of the original malignant progenitor clone. In 17% of patients, discordant AI or BRAFV600E profiles implied that mPTCs can occasionally develop from distinct transformation events. This study suggests that mPTC originates usually from neoplastic transformation and subsequent intrathyroidal spread of a single malignant progenitor clone. Clonal progression and morphotype differentiation occur through progressive acquisition of genetic alterations subsequent to the initial intra‐glandular spread. In monoclonal BRAFV600E‐positive mPTCs, BRAFV600E is not always present in all tumour foci, indicating that other tumour‐genetic factors in the primary progenitor clone can also trigger PTC neoplastic transformation. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Over‐expression of polycomb group protein EZH2 relates to decreased expression of p16INK4a in cholangiocarcinogenesis in hepatolithiasis
Authors: Sasaki M , Yamaguchi J , Itatsu K , Ikeda H , Nakanuma Y 
Published: February 2008

AbstractPolycomb group protein EZH2 and Bmi1 are reportedly involved in the progression of malignant tumours. We examined the participation of EZH2 in multi‐step cholangiocarcinogenesis in hepatolithiasis with respect to tumour suppressor gene p16INK4a. We examined 20 hepatolithiatic livers with intrahepatic cholangiocarcinoma (ICC) and 10 histologically normal livers. Neoplastic biliary lesions were classified into biliary intraepithelial neoplasm (BilIN‐1, 2 and 3) and invasive carcinoma. We selected 15 foci of invasive carcinoma, 8 BilIN‐3 (carcinoma in situ), 12 BilIN‐2 (high‐grade dysplasia), 32 BilIN‐1 (low‐grade dysplasia) and 37 non‐neoplastic biliary epithelia from these livers. Expression of p16INK4a, EZH2 and Bmi1 were surveyed in these foci. P16INK4a promoter methylation was examined in microdissected tissues. Taking advantage of two cell lines of CC (HuCTT‐1 and TFK‐1) and small interfering RNA (siRNA), the effects of the knockdown of EZH2 on p16INK4a methylation of CC cells were examined. Expression of p16INK4a, which was frequent in BilIN1, was decreased in BilIN‐2/3 and invasive carcinoma, while EZH2 expression showed step‐wise increase from BilIN‐1, ‐2 and ‐3 to invasive carcinoma (p < 0.01). P16INK4a promoter hypermethylation was related to aberrant expression of EZH2. The knockdown of EZH2 in cultured CC cells decreased p16INK4a methylation and decreased binding of EZH2 to the p16INK4a gene promoter. The latter suggested that direct binding of EZH2 is involved in the regulation of the p16INK4a gene. Our data suggest that over‐expression of EZH2 may induce hypermethylation of p16INK4a promoter followed by decreased expression of p16INK4a in the multi‐step cholangiocarcinogenesis through intraepithelial neoplasm in hepatolithiasis. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Cadherin switching dictates the biology of transitional cell carcinoma of the bladder: ex vivo and in vitro studies
Authors: Bryan RT , Atherfold PA , Yeo Y , Jones LJ , Harrison RF , Wallace DMA , Jankowski JA 
Published: February 2008

AbstractBladder cancer is the fifth most common malignancy in the UK. Clinically, the most important process in determining prognosis is the development of invasion, initially of the lamina propria and then beyond as these transitional cell carcinomas (TCCs) progress from stage pT1 to stages T2+. Cadherins and catenins are the main mediators of cell–cell interactions in epithelial tissues, and loss of membranous E‐cadherin immunoreactivity is strongly correlated with high grade, advanced stage and poor prognosis in bladder cancer and other malignancies. However, the role of P‐cadherin is yet to be fully elucidated in bladder TCC. The objectives of this study were to establish how the expression of cadherins and catenins determines clinical and in vitro behaviour in bladder TCC. Utilizing immunohistochemistry, immunofluorescence and western blotting, we demonstrated a significant reduction in the expression of E‐cadherin and β‐catenin as grade and stage of bladder TCC progress, accompanied by a significant increase in P‐cadherin expression (all p < 0.05, Pearson's χ2 test). Increased P‐cadherin expression was also associated with a significantly worse bladder cancer‐specific survival (log rank p = 0.008), with Cox regression showing P‐cadherin to be an independent prognostic factor. Utilizing a variety of tissue culture models in a range of functional studies, we demonstrated that P‐cadherin mediates defective cell–cell adhesion and enhances anchorage‐independent growth. The results provide evidence that increased P‐cadherin expression promotes a more malignant and invasive phenotype of bladder cancer, and appears to have a novel role late in the disease. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Preimplantation genetic diagnosis for BRCA1 exon 13 duplication mutation using linked polymorphic markers resulting in a live birth
Authors: Jasper Melinda J. , Liebelt Jan , Hussey Nicole D. 
Published: February 2008

AbstractBackgroundThe risk of breast cancer associated with inheriting a BRCA1 mutation is extremely high, in addition, there is a 50% chance of transmitting this familial cancer mutation to any offspring.MethodsA 31‐year‐old woman with a strong maternal family history of early onset of breast cancer had experienced 3 years of primary infertility. Presymptomatic testing confirmed the woman had inherited a 6 kb duplication of exon 13 (ins6KbEx13) in BRCA1 from her mother. Neither gamete donation or adoption were acceptable options for this infertile couple, and as termination of pregnancy after prenatal diagnosis following in vitro fertilization (IVF) was not ethically acceptable, preimplantation genetic diagnosis (PGD) was sought. A single‐cell PCR protocol for PGD for the breast and ovarian cancer predisposing BRCA1 exon 13 duplication mutation was developed which involved amplification of three specific gene regions, including the BRCA1 mutation (ins6KbEx13), an intragenic marker (D17S855) and a flanking marker (D17S1185).ResultsIn the first cycle of IVF, three embryos were analyzed and two were determined to be at low risk of having inherited the maternal BRCA1 mutation. Following the transfer of both embryos on day 5, a singleton pregnancy resulted. Declining confirmatory prenatal diagnosis, a male baby was subsequently delivered at term.ConclusionsSuccessful PGD for BRCA1 resulted in the delivery of a live‐born male. PGD using linked polymorphic markers provides an alternate option for reproduction for couples with or at risk of having inherited a BRCA1 mutation. Copyright © 2008 John Wiley & Sons, Ltd.
Optimized criteria for using fluorescence in situ hybridization in the prenatal diagnosis of common aneuploidies
Authors: Leclercq Sandrine , Lebbar Aziza , Grange Gilles , Tsatsaris Vassilis , Le Tessier Dominique , Dupont Jean‐Michel 
Published: February 2008

AbstractObjectiveTo evaluate the medical and economic performance of three strategies for selecting patients eligible for interphase FISH in the prenatal diagnosis of common aneuploidies.MethodsWe evaluated three protocols on the same population that was referred for prenatal diagnosis between June 2001 and December 2006. The number of aneuploidies detected by FISH and the relative cost (reagent and technical staff cost) are reported for each strategy.Results2707 women were referred for prenatal diagnosis either because of advanced maternal age over 38 (48%), abnormal maternal serum screening (35%) or prenatal ultrasound anomalies (17%). A total of 4.8% chromosomal anomalies (balanced and unbalanced) were diagnosed after karyotyping. Theoretically, interphase FISH should have detected 79.4% of the unbalanced anomalies. We observed a significant improvement in the trisomy 21 detection by selecting the probes according to the reason for referral. The last protocol adopted, which offers a rapid test to 57% of women undergoing amniocentesis, presents the best aneuploidy detection rate (68% of total aneuploidies, 87% of trisomy 21).ConclusionSelecting probes according to medical criteria patients combined with a technical procedure modification allows medico‐economic improvement of interphase FISH in routine diagnosis. Copyright © 2008 John Wiley & Sons, Ltd.
Monochorionic and dichorionic twin pregnancies discordant for fetal anencephaly: a systematic review of prenatal management options
Authors: Lust Annelies , De Catte Luc , Lewi Liesbeth , Deprest Jan , Loquet Philippe , Devlieger Roland 
Published: February 2008

AbstractThe aim of this study was to evaluate the effect of selective feticide (SF) compared to expectant management (EM) on perinatal outcome in dichorionic and monochorionic twins discordant for anencephaly. For this purpose, we conducted a systematic review of literature and added ten unpublished cases. As a result, we found that in dichorionic twins, mean gestational age (GA) at birth in the SF group was 38.0 weeks versus 34.9 weeks (P = 0.0002). Mean birth weight was 2922 g in the SF group versus 2474 g (P = 0.03). In monochorionic twins, mean GA at birth was 35.2 weeks versus 32.7 weeks (P = 0.1). Mean birth weight was 2711 g versus 1667 g (P = 0.0001).We conclude that while SF does not reduce perinatal mortality, it does result in significantly longer gestations and higher birth weight, and appears to be the management of choice in dichorionic twins discordant for anencephaly. In monochorionic twins, SF also increases birth weight, but in view of the complexity of this group, no clear recommendations can be made. Copyright © 2008 John Wiley & Sons, Ltd.
Evidence for prolonged prescribing of aspirin–clopidogrel combination in Scottish primary care
Authors: Simpson Colin R. , Alford Karen , Williams David 
Published: February 2008

AbstractPurposeTo identify whether patients were prescribed the combination of aspirin–clopidogrel in primary care after the generally recommended 12‐month period.MethodsA population based cross‐sectional study using data from 61 general practices (1st April 2003–31st March 2004).Results691 patients (0.18% of total population) were prescribed aspirin–clopidogrel in combination. 27.78% of these patients had undergone coronary stenting or angioplasty and 34.30% were prescribed this combination for more than 1 year. 96 (13.9%) patients had a previous history of ischaemic stroke or transient ischaemic attack.ConclusionsPatients were prescribed the combination of aspirin–clopidogrel beyond the generally accepted 12‐month period, which may lead to increased safety and cost concerns. Copyright © 2008 John Wiley & Sons, Ltd.
The association between antidepressant use and hypoglycaemia in diabetic patients: a nested case–control study
Authors: Derijks Hieronymus J. , Heerdink Eibert R. , De Koning Fred H. , Janknegt Robert , Klungel Olaf H. , Egberts Antoine C. 
Published: February 2008

AbstractPurposeHypoglycaemia is a limiting factor for glycaemic management of diabetes with intensive insulin and/or oral antidiabetic drug (OAD) regimen. Case reports suggest that antidepressants may interfere with blood glucose metabolism in patients with diabetes mellitus potentially increasing the risk of clinically relevant hypoglycaemia. Comorbid depression treated with antidepressants could therefore further complicate glycaemic control. We have carried out a nested case–control study among diabetic patients to assess the risk of hypoglycaemia requiring hospitalisation associated with the use of antidepressants.MethodsDiabetic patients treated with insulin and/or OADs were selected from the Dutch Pharmo system. Exposure to antidepressants was the primary determinant investigated. Use of antidepressants was further subclassified based on the receptor binding profile to investigate whether specific pharmacological properties could explain a potential influence on glucose homeostasis. Conditional logistic regression was used to estimate odds ratios and to adjust for confounding factors.ResultsFrom the base cohort (40 600 patients), 549 (1.35%) cases were identified and 1897 controls were selected. Current use of any antidepressant was not associated with a significantly higher risk of hypoglycaemia requiring hospitalisation (OR: 1.36 (95%CI: 0.84–2.20)). A trend for a higher risk on hypoglycaemia was identified for antidepressants with high affinity for the serotonin reuptake transporter. The risk on severe hypoglycaemia was increased after 3 years of use (OR: 2.75 (95%CI: 1.31–5.77)).ConclusionsIt is important for diabetic patients using antidepressants for more than 3 years to pay attention for symptoms of hypoglycaemia and strict blood glucose self‐monitoring. Copyright © 2008 John Wiley & Sons, Ltd.
Adverse drug reaction‐related hospitalisations: a population‐based cohort study
Authors: van der Hooft Cornelis S. , Dieleman Jeanne P. , Siemes Claire , Aarnoudse Albert‐Jan L.H.J. , Verhamme Katia M.C. , Stricker Bruno H.C.H. , Sturkenboom Miriam C.J.M. 
Published: February 2008

AbstractPurposeTo evaluate the extent, characteristics and determinants of adverse drug reaction (ADR)‐related hospitalisations on a population‐based level in 2003.MethodsWe performed a cohort study in the Integrated Primary Care Information (IPCI) database, a general practitioners (GPs) research database with longitudinal data from electronic patient records of a group of 150 GP throughout the Netherlands. Hospital discharge letters and patient records were reviewed to evaluate ADR‐related hospitalisations applying WHO causality criteria. The prevalence of ADR‐related hospitalisations per total admissions and the incidence per drug group were calculated. Avoidability and seriousness of the ADRs causing admission were assessed applying the algorithm from Hallas.ResultsWe identified 3515 hospital admissions, 1277 elective and 2238 acute. Of the acute admissions, 115 were caused by an ADR giving a prevalence of 5.1% (95% confidence intervals (CI): 4.3–6.1%). The prevalence of ADR‐related acute admissions increased with age up to 9.8% (95%CI: 7.5–12.7) for persons >75 years. The ADRs that most frequently caused hospitalisations were gastro‐intestinal bleeding with anti‐thrombotics, bradycardia/hypotension with cardiovascular drugs and neutropenic fever with cytostatics. The incidence rate of ADR‐related hospitalisations per drug group was highest for anti‐thrombotics and anti‐infectives and was relatively low for cardiovascular drugs. Fatality as a direct consequence of the ADR‐related admission was 0.31%. In elderly patients 40% of the ADRs causing hospitalisation were judged to be avoidable.ConclusionsThe extent and potential avoidability of ADR‐related hospitalisations is still substantial, especially in elderly patients. Measures need to be put into place to reduce the burden of ADRs. Copyright © 2008 John Wiley & Sons, Ltd.