bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the Clinical COPD Questionnaire (CCQ) in primary care
Authors: Ställberg Björn , Nokela Mika , Ehrs Per-Olof , Hjemdal Paul , Jonsson Eva Wikström 
Published: March 2009

Abstract

Background
Patient centred outcomes, such as health status, are important in Chronic Obstructive Pulmonary Disease (COPD). Extensive questionnaires on health status have good measurement properties, but are not suitable for use in primary care. The newly developed, short Clinical COPD Questionnaire, CCQ, was therefore validated against the St George's Respiratory Questionnaire (SGRQ).

Methods
111 patients diagnosed by general practitioners as having COPD completed the questionnaires twice, 2–3 months apart, without systematic changes in treatment. Within this sample of patients with "clinical COPD" a subgroup of patients with spirometry verified COPD was identified. All analyses was performed on both groups.

Results
The mean FEV1 (% predicted) was 58.1% for all patients with clinical COPD and 52.4% in the group with verified COPD (n = 83). Overall correlations between SGRQ and CCQ were strong for all patients with clinical COPD (0.84) and the verified COPD subgroup (0.82). The concordance intra-class correlation between SGRQ and CCQ was 0.91 (p < 0.05). Correlations between CCQ and SGRQ were moderate to good, regardless of COPD severity.

Conclusion
The CCQ is a valid and reliable instrument for assessments of health status on the group level in patients treated for COPD in primary care but its reliability may not be sufficient for the monitoring of individual patients.
Disagreement in physical activity assessed by accelerometer and self-report in subgroups of age, gender, education and weight status
Authors: Slootmaker Sander M , Schuit Albertine J , Chinapaw Marijke JM , Seidell Jacob C , van Mechelen Willem 
Published: March 2009

Abstract

Background
The purpose of this study is to compare self-reported time (by questionnaire) and objectively measured time (by accelerometer) spent on physical activity at moderate (MPA) and vigorous intensity (VPA) in subgroups of age, gender, education and weight status.

Methods
In total, 236 adolescents (aged 12–18) and 301 adults (aged 22–40), completed the questionnaire and wore an accelerometer for two weeks.

Results
Adolescents reported exceptionally more time spent on MPA (mean difference 596 ± 704 min/wk) and VPA (mean difference 178 ± 315 min/wk) than was assessed objectively by the accelerometer. Based on the questionnaire, high educated adolescents spent more time on MPA (205 min/wk, p = 0.002) and VPA (120 min/wk, p = 0.01) than low educated adolescents, but according to the accelerometer they spent less time on MPA (149 min/wk, p = 0.001) and VPA (47 min/wk, p = 0.001). Among adults there was moderate agreement between self-reported time and objectively measured time spent on MPA, but in general the reported time spent on MPA (mean difference 107 ± 334 min/wk) and VPA (mean difference 169 ± 250 min/wk) exceeded the time measured with the accelerometer. Overweight adults reported significantly more VPA (57 min/wk, p = 0.04) than normal weight adults, but this was not confirmed by the accelerometer data.

Conclusion
We observed large differences in time spent on MPA and VPA measured by questionnaire and accelerometer in adolescents but reasonably good agreement in adults. Differences between methods varied by gender, education and weight status. This finding raises serious questions about the use of questionnaires to quantify MPA and VPA in adolescents. There is a clear need in advanced valid assessments of PA in adolescents.

Trial number
ISRCTN93896459
Connecting extracellular metabolomic measurements to intracellular flux states in yeast
Authors: Mo Monica L , Palsson Bernhard Ø , Herrgård Markus J 
Published: March 2009

Abstract

Background
Metabolomics has emerged as a powerful tool in the quantitative identification of physiological and disease-induced biological states. Extracellular metabolome or metabolic profiling data, in particular, can provide an insightful view of intracellular physiological states in a noninvasive manner.

Results
We used an updated genome-scale metabolic network model of Saccharomyces cerevisiae, i MM904, to investigate how changes in the extracellular metabolome can be used to study systemic changes in intracellular metabolic states. The i MM904 metabolic network was reconstructed based on an existing genome-scale network, i ND750, and includes 904 genes and 1,412 reactions. The network model was first validated by comparing 2,888 in silico single-gene deletion strain growth phenotype predictions to published experimental data. Extracellular metabolome data measured in response to environmental and genetic perturbations of ammonium assimilation pathways was then integrated with the i MM904 network in the form of relative overflow secretion constraints and a flux sampling approach was used to characterize candidate flux distributions allowed by these constraints. Predicted intracellular flux changes were consistent with published measurements on intracellular metabolite levels and fluxes. Patterns of predicted intracellular flux changes could also be used to correctly identify the regions of the metabolic network that were perturbed.

Conclusion
Our results indicate that integrating quantitative extracellular metabolomic profiles in a constraint-based framework enables inferring changes in intracellular metabolic flux states. Similar methods could potentially be applied towards analyzing biofluid metabolome variations related to human physiological and disease states.
The child and adolescent psychiatry trials network (CAPTN): infrastructure development and lessons learned
Authors: Shapiro Mark , Silva Susan G , Compton Scott , Chrisman Allan , DeVeaugh-Geiss Joseph , Breland-Noble Alfiee , Kondo Douglas , Kirchner Jerry , March John S 
Published: March 2009

Abstract

Background
In 2003, the National Institute of Mental Health funded the Child and Adolescent Psychiatry Trials Network (CAPTN) under the Advanced Center for Services and Intervention Research (ACSIR) mechanism. At the time, CAPTN was believed to be both a highly innovative undertaking and a highly speculative one. One reviewer even suggested that CAPTN was "unlikely to succeed, but would be a valuable learning experience for the field."

Objective
To describe valuable lessons learned in building a clinical research network in pediatric psychiatry, including innovations intended to decrease barriers to research participation.

Methods
The CAPTN Team has completed construction of the CAPTN network infrastructure, conducted a large, multi-center psychometric study of a novel adverse event reporting tool, and initiated a large antidepressant safety registry and linked pharmacogenomic study focused on severe adverse events. Specific challenges overcome included establishing structures for network organization and governance; recruiting over 150 active CAPTN participants and 15 child psychiatry training programs; developing and implementing procedures for site contracts, regulatory compliance, indemnification and malpractice coverage, human subjects protection training and IRB approval; and constructing an innovative electronic casa report form (eCRF) running on a web-based electronic data capture system; and, finally, establishing procedures for audit trail oversight requirements put forward by, among others, the Food and Drug Administration (FDA).

Conclusion
Given stable funding for network construction and maintenance, our experience demonstrates that judicious use of web-based technologies for profiling investigators, investigator training, and capturing clinical trials data, when coupled to innovative approaches to network governance, data management and site management, can reduce the costs and burden and improve the feasibility of incorporating clinical research into routine clinical practice. Having successfully achieved its initial aim of constructing a network infrastructure, CAPTN is now a capable platform for large safety registries, pharmacogenetic studies, and randomized practical clinical trials in pediatric psychiatry.
Triple-negative breast cancers are increased in black women regardless of age or body mass index
Authors: Stead Lesley A , Lash Timothy L , Sobieraj Jerome E , Chi Dorcas D , Westrup Jennifer L , Charlot Marjory , Blanchard Rita A , Lee John C , King Thomas C , Rosenberg Carol L 
Published: March 2009

Abstract
Introduction
We investigated clinical and pathologic features of breast cancers (BC) in an unselected series of patients diagnosed in a tertiary care hospital serving a diverse population. We focused on triple-negative (Tneg) tumours (oestrogen receptor (ER), progesterone receptor (PR) and HER2 negative), which are associated with poor prognosis.

Methods
We identified female patients with invasive BC diagnosed between 1998 and 2006, with data available on tumor grade, stage, ER, PR and HER2 status, and patient age, body mass index (BMI) and self-identified racial/ethnic group. We determined associations between patient and tumour characteristics using contingency tables and multivariate logistic regression.

Results
415 cases were identified. Patients were racially and ethnically diverse (born in 44 countries, 36% white, 43% black, 10% Hispanic and 11% other). 47% were obese (BMI > 30 kg/m2). 72% of tumours were ER+ and/or PR+, 20% were Tneg and 13% were HER2+. The odds of having a Tneg tumour were 3-fold higher (95% CI 1.6, 5.5; p = 0.0001) in black compared with white women. Tneg tumours were equally common in black women diagnosed before and after age 50 (31% vs 29%; p = NS), and who were obese and non-obese (29% vs 31%; p = NS). Considering all patients, as BMI increased, the proportion of Tneg tumours decreased (p = 0.08).

Conclusions
Black women of diverse background have 3-fold more Tneg tumours than non-black women, regardless of age and BMI. Other factors must determine tumour subtype. The higher prevalence of Tneg tumours in black women in all age and weight categories likely contributes to black women's unfavorable breast cancer prognosis.
Integrated analysis of breast cancer cell lines reveals unique signaling pathways
Authors: Heiser Laura M , Wang Nicholas J , Talcott Carolyn L , Laderoute Keith R , Knapp Merrill , Guan Yinghui , Hu Zhi , Ziyad Safiyyah , Weber Barbara L , Laquerre Sylvie , Jackson Jeffrey R , Wooster Richard F , Kuo Wen Lin , Gray Joe W , Spellman Paul T 
Published: March 2009

Abstract
Background
Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EgfR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes.

Results
We were interested in identifying subnetworks within the EgfR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EgfR-MAPK signaling. This model was composed of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype-specific subnetworks, including one that suggested Pak1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that Pak1 over-expressing cell lines would have increased sensitivity to Mek inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three Mek inhibitors. We found that Pak1 over-expressing luminal breast cancer cell lines are significantly more sensitive to Mek inhibition compared to those that express Pak1 at low levels. This indicates that Pak1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to Mek inhibitors.

Conclusions
All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.
Acute Pancreatitis in Primary Hyperparathyroidism: A Population-Based Study
Authors: Khoo Teck Kim , Vege Santhi Swaroop , Abu-Lebdeh Haitham S. , Ryu Euijung , Nadeem Sarah , Wermers Robert A. 
Published: March 2009

Abstract
Context: The association between acute pancreatitis and primary hyperparathyroidism (PHPT) is controversial.
Objective: The aim of the study was to address the incidence and disease characteristics of acute pancreatitis in PHPT from a large inception cohort of community residents.
Design and Setting: Patients with acute pancreatitis were identified in an Olmsted County, Minnesota, cohort of PHPT subjects diagnosed from 1965–2001 and compared to matched control subjects.
Main Outcome Measures: The estimated rate of developing acute pancreatitis was calculated by person-years method. Cox models assessed the effect of PHPT disease status on the development of acute pancreatitis.
Results: Of 684 patients with PHPT, 10 patients (1.5%) developed acute pancreatitis, compared to 32 of 1364 control patients (2.3%). The estimated rate of development of acute pancreatitis in PHPT was 114 per 100,000 person-years, compared to 140 per 100,000 person-years in control subjects (P = 0.56). The estimated hazard ratio of acute pancreatitis for PHPT relative to the control subjects was 0.84 (P = 0.89). The majority of subjects with PHPT and acute pancreatitis were women (n = 7), and the mean age was 70.6 yr at the time of acute pancreatitis. PHPT was present an average of 137 months before the development of acute pancreatitis, and contributing causes for acute pancreatitis were in identified in four patients. Maximal serum calcium levels in PHPT were not significantly associated with the development of acute pancreatitis.
Conclusions: Acute pancreatitis was not increased in community patients with PHPT, and therefore, there does not appear to be a causal relationship between PHPT and acute pancreatitis.
Conjugated Oral versus Transdermal Estrogen Replacement in Girls with Turner Syndrome: A Pilot Comparative Study
Authors: Nabhan Zeina M. , DiMeglio Linda A. , Qi Rong , Perkins Susan M. , Eugster Erica A. 
Published: March 2009

AbstractBackground: The optimal route of estrogen replacement in Turner syndrome (TS) is unknown.Objective: The objective of the study was to compare conjugated oral vs. transdermal estrogen (TD E2) on bone accrual, uterine growth, pubertal development, IGF-I, and lipids in girls with TS.Methods: Prepubertal GH-treated girls aged 10 yr or older with TS were eligible. Subjects were randomized to conjugated oral estrogen or TD E2 for 1 yr. Assessments included dual-emission x-ray absorptiometry, pelvic ultrasound, Tanner staging, growth velocity, IGF-I, and lipid profile.Results: Twelve girls (14.0 ± 1.7 yr) were enrolled. TD E2 resulted in a significantly greater change in spine bone density at 12 months compared with conjugated oral estrogen (bone mineral content 9.0 ± 0.9 vs. 5.8 ± 0.9 g, P = 0.04; bone mineral density 0.12 ± 0.01 vs. 0.06 ± 0.01 g/cm2, P = 0.004; Z-score 0.7 ± 0.1 vs. 0.3 ± 0.1, P = 0.03). Greater increases in uterine length (4.13 ± 0.39 vs. 1.98 ± 0.39 cm, P = 0.003) and volume (22.2 ± 4.4 vs. 4.0 ± 4.4 ml, P = 0.02) were also found in the TD vs. the oral group at 1 yr. At study end, 66% of subjects in the TD group had a mature uterus vs. 0% in the oral group. No significant differences in other parameters examined were seen.Conclusion: In girls with TS, TD E2 resulted in faster bone accrual at the spine and increased uterine growth compared with conjugated oral estrogen. This pilot study provides preliminary information for optimizing estrogen replacement in this population.
Association of Serum C-Reactive Protein Level with Sex-Specific Type 2 Diabetes Risk: A Prospective Finnish Study
Authors: Hu Gang , Jousilahti Pekka , Tuomilehto Jaakko , Antikainen Riitta , Sundvall Jouko , Salomaa Veikko 
Published: March 2009

AbstractObjective: Our objective was to assess whether the association of serum C-reactive protein (CRP) with type 2 diabetes risk is modified by sex.Design and Subjects: We prospectively followed 12,861 Finnish men and women who were 35–74 yr of age, and free of diabetes, coronary heart disease, stroke, and cancer at baseline. Hazard ratios of type 2 diabetes were estimated for different levels of serum CRP.Results: During the follow-up, 208 men and 113 women developed diabetes. The multivariable-adjusted (age, physical activity, education, smoking, alcohol and coffee drinking, family history of diabetes, use of antihypertensive drugs, cholesterol-lowering agents, and hormone replacement therapy in women, systolic blood pressure, serum high-density lipoprotein cholesterol, serum triglycerides, and body mass index) hazard ratios of diabetes at three different levels of CRP (0.05–0.99, 1.0–2.99, and ≥3.0 mg/liter) based on the recommendation by Centers for Disease Control and the American Heart Association were 1.00, 1.46, and 1.85 (P for trend = 0.006) in men, and 1.00, 3.83, and 8.37 (P for trend &lt;0.001) in women, respectively. CRP had a stronger association with diabetes risk in women than men (P for interaction: χ2 = 6.42; 1 df; P &lt; 0.025). This positive association between CRP and diabetes risk did not change when participants were stratified by age group, smoking status, level of obesity, alcohol drinking habit, or family history of diabetes.Conclusions: High baseline level of serum CRP was associated with an increased risk of diabetes among both men and women, but this association was stronger in women than men.
Adrenal Androgen Production Capacity Remains High up to Menopause in Women with Polycystic Ovary Syndrome
Authors: Puurunen Johanna , Piltonen Terhi , Jaakkola Päivi , Ruokonen Aimo , Morin-Papunen Laure , Tapanainen Juha S. 
Published: March 2009

Abstract
Introduction: Hyperandrogenism is one of the main features of polycystic ovary syndrome (PCOS). Of circulating androgens, 50% of androstenedione and testosterone are of ovarian and adrenal origin, whereas dehydroepiandrosterone (DHEA) and DHEA sulfate are almost uniquely of adrenal origin. Our previous studies have indicated that ovarian androgen production capacity is enhanced in women with PCOS, and it remains high until late reproductive age. To study whether this also applies to adrenal androgen production, ACTH tests were performed in healthy women and in women with PCOS.
Materials: Sixty-nine healthy women (aged 19–62 yr; body mass index 19.2–35.0 kg/m2) and 58 women with previously diagnosed PCOS (aged 18–59 yr; body mass index 19.0–42.9 kg/m2) participated in the study.
Methods: The subjects underwent ACTH stimulation tests, and serum cortisol, 17-hydroxyprogesterone, androstenedione, testosterone, DHEA, and DHEA sulfate levels were analyzed at 0, 30, and 60 min.
Results: Basal and ACTH-stimulated levels of most adrenal androgens decreased in healthy women with age, whereas in women with PCOS, only the concentrations of basal serum 17-hydroxyprogesterone decreased, and all areas under the curve (AUCs) remained unchanged and significantly higher (except for DHEA) than those in control women. Likewise, at the menopausal transition, pre- and postmenopausal women with PCOS exhibited mainly unchanged and higher basal androgen and AUC levels.
Conclusions: Similarly to ovarian endocrine function, serum adrenal steroid levels and adrenal steroid production capacity remain enhanced at least up to menopause in women with PCOS.
OR Practice—Supporting 3PL Decisions in the Automotive Industry by Generating Diverse Solutions to a Large-Scale Location-Routing Problem
Authors: Schittekat Patrick , Sörensen Kenneth 
Published: March 2009

For the distribution of spare parts to car dealers, many automotive companies use a transport network of intermediate hubs or transport platforms, operated by a set of third-party logistics (3PL) partners. The optimization of this network, particularly the selection of 3PL providers and corresponding transport platforms, is a complex decision that needs to be supported by appropriate software tools. In this paper, we develop such a tool, implement it, and show its results on a real-life case study provided by Toyota. The tool is currently in active use at Toyota to study and improve the distribution of spare parts in Germany. Using a tabu search metaheuristic, the developed tool essentially solves a large location-routing problem, but has several innovative features to increase its usefulness. First, the tool generates a set of high-quality but structurally different solutions, rather than a single one. This increases Toyota's negotiating power, increases its ability to analyze its current transport network against possible alternatives, and allows it to quickly switch between different transport networks if unexpected events occur. Second, a commercial vehicle-routing solver is integrated into the tool, to allow for a far more realistic modeling of the vehicle-routing decision.
Clinical Outcomes and Pharmacists' Acceptance of a Community Hospital's Anticoagulation Management Service Utilizing Decentralized Clinical Staff Pharmacists
Authors: Airee Anita , Guirguis Alexander B , Mohammad Rima A 
Published: March 2009

Background: In 2008, the Joint Commission released an updated National Patient Safety Goals document that requires institutions to implement practices that reduce the likelihood of patient harm associated with use of anticoagulation therapy. One of the expectations associated with this goal was that each organization would establish an anticoagulant management program. To our knowledge, few data exist to describe the implementation and assessment of anticoagulation programs in smaller, nonteaching community hospitals using decentralized pharmacists in an integrated practice model. Objective: To compare the performance of a protocol-driven anticoagulation management service led by decentralized pharmacists in a nonteaching community hospital with that of usual medical care provided by hospitalist physicians before this program was implemented. Based on these results, as well as a pharmacist satisfaction survey, evaluate the service and identify barriers to expansion. Methods: We conducted a retrospective cohort study comparing 50 consecutive patients who were starting warfarin for the first time beginning in November 2003 with 50 patients managed by hospitalist physicians prior to November 2002 (the time of program implementation). Results: There were no significant differences between groups with regard to time in therapeutic range once therapeutic, length of stay, international normalized ratios (INRs) greater than 3.5, or INRs less than 2. Patients in the pharmacy management group had significantly fewer drug interactions with antimicrobials than did the usual medical care group. Although time to therapeutic range was longer in the pharmacy protocol group, there were fewer patients with INRs greater than 3.5, although this did not reach statistical significance. Conclusions: The efficacy of the pharmacist-led anticoagulation management service was no different from that of usual medical care. Patient safety appeared improved, in part due to more careful initial dose selection based on patient-specific factors. Although this program was accepted by pharmacists, time limitations were perceived to be a major barrier to quality care and expansion of the service.