bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Study of Enzastaurin, a Protein Kinase C Beta Inhibitor, in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Authors: Robertson Michael J. , Kahl Brad S. , Vose Julie M. , de Vos Sven , Laughlin Mary , Flynn Patrick J. , Rowland Kendrith , Cruz Jose C. , Goldberg Stuart L. , Musib Luna , Darstein Christelle , Enas Nathan , Kutok Jeffery L. , Aster Jon C. , Neuberg Donna , Savage Kerry J. , LaCasce Ann , Thornton Donald , Slapak Christopher A. , Shipp Margaret A. 
Published: March 2007

Purpose Protein kinase C beta (PKCβ) was identified by gene-expression profiling, preclinical evaluation, and independent immunohistochemical analysis as a rational therapeutic target in diffuse large B-cell lymphoma (DLBCL). We conducted a multicenter phase II study of a potent inhibitor of PKCβ, enzastaurin, in patients with relapsed or refractory DLBCL. Patients and Methods Enzastaurin was taken orally once daily until disease progression or unacceptable toxicity occurred. Study end points included freedom from progression (FFP) for ≥ two cycles (one cycle = 28 days), objective response, and toxicity. Results Fifty-five patients (median age, 68 years) were enrolled. Patients had received a median number of two prior therapies (range, one to five); six patients relapsed after high-dose therapy and autologous stem-cell transplantation. Only one grade 4 toxicity (hypomagnesemia) occurred. Grade 3 toxicities included fatigue (n = 2), edema (n = 1), headache (n = 1), motor neuropathy (n = 1), and thrombocytopenia (n = 1). No grade 3 or 4 neutropenia occurred. No deaths or discontinuations due to toxicity were reported. Fifteen patients completed less than one cycle of therapy. Twelve of 55 patients (22%; 95% CI, 13% to 46%) experienced FFP for ≥ two cycles, and eight patients remained free from progression for ≥ four cycles (15%; 95% CI, 6% to 27%). Four patients (7%; 95% CI, 2% to 18%), including three complete responders and one patient with stable disease, continue to experience FFP 20+ to 50+ months after study entry. Conclusion Treatment with enzastaurin was well-tolerated and associated with prolonged FFP in a small subset of patients with relapsed or refractory DLBCL. Further studies of enzastaurin in DLBCL are warranted.
Serum Insulin and Inflammatory Markers in Overweight Individuals with and without Dyslipidemia
Authors: Barter Philip , McPherson Y. Ruth , Song Kijoung , Kesäniemi Y. Antero , Mahley Robert , Waeber Gérard , Bersot Thomas , Mooser Vincent , Waterworth Dawn , Grundy Scott M. 
Published: March 2007

AbstractContext: The worldwide epidemic of overweight and obesity is setting the scene for a new wave of premature cardiovascular disease.Objective: The objective of this study was to define relationships between dyslipidemia and other metabolic abnormalities in overweight subjects.Design: This study included comparison of overweight subjects with and without dyslipidemia.Setting: The setting was an institutional practice.Patients: Dyslipidemic subjects (n = 715) had plasma triglyceride greater than or equal to the 75th percentile in combination with high-density lipoprotein cholesterol (HDL-C) less than or equal to the 25th percentile. Unrelated, normolipidemic controls (n = 1073) had HDL-C higher than the median and triglyceride lower than the median. It was a requirement for the control subjects to have a body mass index (BMI) greater than 25 kg/m2.Main Outcome Measures: The main outcome measures included BMI, inflammatory markers, adipokines, blood pressure, and fasting plasma glucose and insulin.Results: The mean BMI in the subjects and controls was 28.7 and 28.2 kg/m2, respectively. Subjects had higher levels of plasma high-sensitivity C-reactive protein (3.0 vs. 2.0 mg/liter; P &lt; 0.001), lower levels of adiponectin (4.7 vs. 6.6 mg/liter; P &lt; 0.001), and, after adjustment for age, BMI, gender, smoking, statin, and β-blocker use, higher systolic (P = 0.001) and diastolic (P = 0.05) blood pressures. Fasting plasma glucose, insulin, and homeostasis model of assessment-insulin resistance were all significantly higher in subjects than controls (P &lt; 0.0001).Conclusions: Identification of people solely on the basis of an elevated plasma triglyceride and a low HDL-C uncovers an overweight group of people who have a generalized metabolic disorder. In contrast, overweight people with normal plasma lipids have normal glucose and insulin metabolism, low levels of inflammatory markers, and normal blood pressure. Such people may thus be at relatively low risk of developing diabetes and cardiovascular disease despite being overweight.
The Role of Vitamin D and Calcium in Type 2 Diabetes. A Systematic Review and Meta-Analysis
Authors: Pittas Anastassios G. , Lau Joseph , Hu Frank B. , Dawson-Hughes Bess 
Published: March 2007

AbstractContext: Altered vitamin D and calcium homeostasis may play a role in the development of type 2 diabetes mellitus (type 2 DM).Evidence Acquisition and Analyses: MEDLINE review was conducted through January 2007 for observational studies and clinical trials in adults with outcomes related to glucose homeostasis. When data were available to combine, meta-analyses were performed, and summary odds ratios (OR) are presented.Evidence Synthesis: Observational studies show a relatively consistent association between low vitamin D status, calcium or dairy intake, and prevalent type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM prevalence, 0.36 (0.16–0.80) among nonblacks for highest vs. lowest 25-hydroxyvitamin D; metabolic syndrome prevalence, 0.71 (0.57–0.89) for highest vs. lowest dairy intake]. There are also inverse associations with incident type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM incidence, 0.82 (0.72–0.93) for highest vs. lowest combined vitamin D and calcium intake; 0.86 (0.79–0.93) for highest vs. lowest dairy intake]. Evidence from trials with vitamin D and/or calcium supplementation suggests that combined vitamin D and calcium supplementation may have a role in the prevention of type 2 DM only in populations at high risk (i.e. glucose intolerance). The available evidence is limited because most observational studies are cross-sectional and did not adjust for important confounders, whereas intervention studies were short in duration, included few subjects, used a variety of formulations of vitamin D and calcium, or did post hoc analyses.Conclusions: Vitamin D and calcium insufficiency may negatively influence glycemia, whereas combined supplementation with both nutrients may be beneficial in optimizing glucose metabolism.
Phosphorylation of a Conserved Serine in the Deoxyribonucleic Acid Binding Domain of Nuclear Receptors Alters Intracellular Localization
Authors: Sun Kai , Montana Vedrana , Chellappa Karthikeyani , Brelivet Yann , Moras Dino , Maeda Yutaka , Parpura Vladimir , Paschal Bryce M. , Sladek Frances M. 
Published: March 2007

AbstractNuclear receptors (NRs) are a superfamily of transcription factors whose genomic functions are known to be activated by lipophilic ligands, but little is known about how to deactivate them or how to turn on their nongenomic functions. One obvious mechanism is to alter the nuclear localization of the receptors. Here, we show that protein kinase C (PKC) phosphorylates a highly conserved serine (Ser) between the two zinc fingers of the DNA binding domain of orphan receptor hepatocyte nuclear factor 4α (HNF4α). This Ser (S78) is adjacent to several positively charged residues (Arg or Lys), which we show here are involved in nuclear localization of HNF4α and are conserved in nearly all other NRs, along with the Ser/threonine (Thr). A phosphomimetic mutant of HNF4α (S78D) reduced DNA binding, transactivation ability, and protein stability. It also impaired nuclear localization, an effect that was greatly enhanced in the MODY1 mutant Q268X. Treatment of the hepatocellular carcinoma cell line HepG2 with PKC activator phorbol 12-myristate 13-acetate also resulted in increased cytoplasmic localization of HNF4α as well as decreased endogenous HNF4α protein levels in a proteasome-dependent fashion. We also show that PKC phosphorylates the DNA binding domain of other NRs (retinoic acid receptor α, retinoid X receptor α, and thyroid hormone receptor β) and that phosphomimetic mutants of the same Ser/Thr result in cytoplasmic localization of retinoid X receptor α and peroxisome proliferator-activated receptor α. Thus, phosphorylation of this conserved Ser between the two zinc fingers may be a common mechanism for regulating the function of NRs.
The Construction of the Two-dimensional Array of the Fibrous Objects from the Mixture of RFDF16–PEG and RFDF16 at Air/Water Interface
Authors: Tanaka Masayoshi , Hattori Makoto , Kinoshita Takatoshi 
Published: March 2007

Abstract
The mixture of β-sheet peptide–PEG diblock copolymer and β-sheet peptide spread at air/water interface formed a two-dimensional array of the fibrous objects. The fibrous objects constructed by intermolecular hydrogen bonding of β-sheet peptides were regulated by compressing of the monolayer. When the spread peptide moieties fully located on the water surface, the distance between the fibers was efficiently modulated by the fraction of PEG segments.
Di-2-methoxyethyl Azodicarboxylate (DMEAD): An Inexpensive and Separation-friendly Alternative Reagent for the Mitsunobu Reaction
Authors: Sugimura Takashi , Hagiya Kazutake 
Published: March 2007

Abstract
Di-2-methoxyethyl azodicarboxylate (DMEAD) was prepared as an alternative of DEAD or DIAD for the Mitsunobu reaction. Removal of the hydrazinedicarboxylate generated from DMEAD becomes much easier owing to the polar and water-soluble property.
Prioritizing health technologies in a Primary Care Trust
Authors: Wilson Edward , Sussex Jon , Macleod Christine , Fordham Richard 
Published: March 2007

Background: In the English National Health Service (NHS), Primary Care Trusts (PCTs) are responsible for commissioning health-care services on behalf of their populations. As resources are finite, decisions are required as to which services best fulfil population needs. Evidence on effectiveness varies in quality and availability. Nevertheless, decisions still have to be made. Methods: We report the development and pilot application of a multi-criteria prioritization mechanism in an English PCT, capable of accommodating a wide variety of evidence to rank six service developments. Results: The mechanism proved valuable in assisting prioritization decisions and feedback was positive. Two community-based interventions were expected to save money in the long term and were ranked at the top of the list. Based on weighted benefit score and cost, two preventive programmes were ranked third and fourth. Finally, two National Institute for Health and Clinical Excellence (NICE)-approved interventions were ranked fifth and sixth. Sensitivity analysis revealed overlap in benefit scores for some of the interventions, representing diversity of opinion among the scoring panel. Conclusion: The method appears to be a practical approach to prioritization for commissioners of health care, but the pilot also revealed interesting divergences in relative priority between nationally mandated service developments and local health-care priorities.
Commoditization of the international teleradiology market
Authors: McLean Thomas 
Published: March 2007

Telemedicine improves access to medical care. However, telemedicine will also increase market volatility because of its ability to stimulate price competition and the insidious way it shifts liability for providing medical services. To cope with increased volatility, other economic sectors have evolved commodities markets by making greater use of standardized forward/future contracts. In the past, the need for medical services to be produced and consumed locally and a lack of an objective definition for medical quality, prohibited the use of forward contracts for health-care services. However, telemedicine, and the increasing use of statistical definitions of medical quality now make standardized forward contracts for health-care services conceivable. Commoditization of teleradiology would offer several advantages including increasing market transparency, a mechanism for ensuring medical quality, and a means for bringing capital into the health-care sector. To reap the benefits of a commodities market in teleradiology, the key will be for market stakeholders to overcome their fear of the unknown in order to organize a central exchange.
How should cost-effectiveness analysis be used in health technology coverage decisions? Evidence from the National Institute for Health and Clinical Excellence approach
Authors: Williams Iestyn , Bryan Stirling , McIver Shirley 
Published: March 2007

Background: In the National Health Service in England and Wales, technology coverage decisions are taken by the National Institute for Health and Clinical Excellence (NICE). The intention formally to apply cost-effectiveness analysis to the decision-making process distinguishes NICE from most other bodies making similar policy recommendations. We carried out a case study of the NICE Appraisals Committee to explore the influence and use of economic evaluation in the decision-making process. Methods: Qualitative case study methodology. This involved analysis of all relevant secondary sources, observations of Appraisals Committee deliberations and interviews with a cross-section of Committee members. Findings: Economic evaluation is integrated into the Committee's work. There are two main ways in which the use of economic analysis is understood by Committee members: an ordinal approach, whereby cost-effectiveness is only considered if the technology has passed a clinical effectiveness hurdle; and a framework approach, whereby the economic evaluation and model provide a structure for considering the decision problem and the evidence. These two approaches appear to operate simultaneously but are, in essence, inconsistent. Conclusions: The NICE 'experiment' has seen cost-effectiveness analysis move to the centre-ground of UK national policy deliberations regarding technology coverage. However, our case study implies that there may be room for further refinement of the appraisal process in order to resolve the observed tension between two different ways of incorporating cost-effectiveness analysis in NICE's decision-making.
The effect of telephone reminders on attendance in respiratory outpatient clinics
Authors: Roberts Nicola , Meade Karen , Partridge Martyn 
Published: March 2007

Introduction: Patient non-attendance is an area of concern for all health care providers. A randomized controlled trial was undertaken to investigate whether reminder telephone calls improved attendance at respiratory outpatient clinics in the English National Health Service (NHS). Methods: Patients were randomly allocated into one of two groups, either telephone reminder group or usual care. The telephone reminder group received a reminder telephone call between 9 am and 5 pm during the week prior to their appointment. Attendance and demographic information (age, sex, diagnosis and home postcode) were recorded. Results: A total of 504 patients were recruited, 258 patients were allocated to the control group and 246 patients were allocated to the telephone reminder group. Fifty-eight percent of the patients allocated to the telephone reminder group were not contactable. Within the telephone reminder group, of the 104 patients who could be contacted, 86% attended. There was a significant 15% increase in attendance in the contacted group ( n = 104) when compared both with the control group (71%, n = 258) and with the patients who could not be contacted (68%, n = 142) ( P = 0.007; P = 0.004). It was estimated that the cost of telephoning 200 patients could be offset by preventing one non-attendance. Conclusion: Routine telephoning of outpatients should become standard practice if reducing non-attendance is thought to be desirable, but general practitioner (GP) referral letters and hospital records of current hospital outpatients need to include an up-to-date telephone number. Consideration should be given to 'out-of-hours' reminder calls to maximize the contact rate.
Inequality in the face of death? Public expenditure on health care for different socioeconomic groups in the last year of life
Authors: Hanratty Barbara , Burström Bo , Walander Anders , Whitehead Margaret 
Published: March 2007

Objective: To investigate the association between public expenditure on health care in the last year of life and individual socioeconomic status in Sweden. Methods: Population-based study of public expenditure using linked registers for all 16,617 deaths among Stockholm County Council residents in 2002 (population 1.8 million). Age-standardized, total and per capita spend were calculated by income categories, age and specialty. Multivariate analysis examined the association between socioeconomic status and public expenditure. Results: County council expenditure on health care in the last year of life rose with increasing income of the deceased person. Median per capita expenditure increased from 55,417 Swedish Kronor (SEK) (US&dollar; 7542) in the lowest income group to SEK 94,678 (US&dollar; 12,887) in the highest. Total age-standardized spend increased by 60% across the same interval (80,227 [95% confidence interval (CI) 79,946&ndash;80,497] to SEK 127,344 [95% CI 126,969&ndash;127,719]). Expenditure decreased with increasing age over 65 years in all income groups. Higher income was independently associated with greater total public health spend in multivariate analysis, adjusting for age, sex, health-care utilization and major diagnostic groups. Conclusions: There is inequality in public expenditure on health care at the end of life across socioeconomic groups in Stockholm. This phenomenon merits attention within Sweden, and beyond, in countries with less comprehensive welfare systems.
Shifting care from hospitals to the community: a review of the evidence on quality and efficiency
Authors: Sibbald Bonnie , McDonald Ruth , Roland Martin 
Published: March 2007

Objectives: A key objective in many health-care systems is to shift specialist services from acute hospitals to the community and so bring care closer to home for patients. Our aim was to review published research into the effectiveness of strategies for achieving this objective. Methods: We conducted a 'scoping' review and qualitative data synthesis of four strategies: transfer of services from hospital to primary care; relocation of hospital services to primary care; joint working between primary and acute care; and interventions to alter the referral behaviour of primary care practitioners. Results: One hundred and nineteen studies were identified and data systematically extracted. The findings suggest that transferring hospital services to primary care, and interventions that change the referral behaviour of primary care practitioners generally reduced outpatient activity but also risked reducing quality. Savings in cost were offset by increases in overall service volume and loss of economies of scale. Relocating specialists to primary care, and joint working between primary and acute care, improved access without jeopardizing quality. However, outpatient activity was rarely reduced and costs were generally increased due to loss of economies of scale. Conclusions: Our findings suggest that the policy may be effective in improving access to specialist care for patients and reducing demand on acute hospitals. There is a risk, however, that the quality of care may decline and costs may increase.
Open-ended questions in surveys of patients' satisfaction with family doctors
Authors: Marcinowicz Ludmiła , Chlabicz Sławomir , Grębowski Ryszard 
Published: March 2007

Objective: To compare replies to open-ended and closed questions about patient satisfaction with family doctors. Methods: Two centres of primary health care in Białystok in northeast Poland were chosen. A self-administered questionnaire was mailed to 1000 people (500 from each centre) aged 18 years and over, randomly selected from the practices. Possible responses to the one closed question were: very good, good, bad, very bad or difficult to say. Replies to two open-ended questions were categorized as positive, neutral, negative or ambivalent. Results: The response rate was 57.9%. There were some discrepancies between the closed-question response and the open-ended question replies. Some of those who replied good or very good to the closed question expressed negative views in response to the two open-ended questions (14.0% and 12.4%). Conclusions: Answers to open-ended questions add value to a patient satisfaction survey by providing information that answers to closed questions may not elicite.
How useful are Cochrane reviews in identifying research needs?
Authors: Clarke Lorcan , Clarke Mike , Clarke Thomas 
Published: March 2007

Objectives: To determine the extent to which reports of Cochrane reviews recommend the need for further research and, if so, the extent to which they make suggestions regarding that research. Methods: We examined all 2535 reviews in Issue 4, 2005 of The Cochrane Library. Each review was categorized on the basis of whether a suggestion was included about specific interventions, participants, or outcome measures that should be included in future research. We also identified the frequency with which reviews conclude that no more research is needed or feasible, noted the need for further systematic reviewing, and refered to a relevant ongoing or planned study. We also report the number of studies listed in the 'Ongoing Studies' section in each review. Results: Only 3.2% of reviews suggested explicitly that no more research is needed or feasible. In 82.0% of reviews, suggestions were made as to the specific interventions that need evaluating, in 30.2% the appropriate participants were suggested, and in 51.9% outcome measures were suggested. Suggestions for all three domains were made in 16.9% of the reviews. While 11.6% did not include a specific suggestion about any of these domains, 21.2% of reviews mention a relevant ongoing or planned study in one or both of the 'Implications for Research' and the 'Ongoing Studies' sections. Conclusions: Most Cochrane reviews identify residual uncertainty and are a rich source of suggestions for further health-care research.
Is the metaphor of 'barriers to change' useful in understanding implementation? Evidence from general medical practice
Authors: Checkland Kath , Harrison Stephen , Marshall Martin 
Published: March 2007

Objectives: To investigate how general medical practices in the UK react to bureaucratic initiatives, such as National Health Service (NHS) National Service Frameworks (NSFs), and to explore the value of the metaphor of 'barriers to change' for understanding this. Methods: Interviews, non-participant observation and documentary analysis within case studies of four practices in northern England. Results: The practices had not actively implemented NSFs. At interview, various 'barriers' that had prevented implementation were listed, including the complexity of the documents and lack of time. Observation suggested that these barriers were constructions used by the participants to make sense of the situation in which they found themselves. Conclusion: The metaphor of 'removing barriers to change' was of limited use in a context where non-implementation of policy was an emergent property of underlying organizational realities, likely to be modifiable only if these realities were addressed.