bluuebunny/crossref_metadata_2025_split huggingface dataset:
An economic model of long-term use of celecoxib in patients with osteoarthritis
Authors: Loyd Michael , Rublee Dale , Jacobs Philip 
Published: July 2007

Abstract

Background
Previous evaluations of the cost-effectiveness of the cyclooxygenase-2 selective inhibitor celecoxib (Celebrex, Pfizer Inc, USA) have produced conflicting results. The recent controversy over the cardiovascular (CV) risks of rofecoxib and other coxibs has renewed interest in the economic profile of celecoxib, the only coxib now available in the United States. The objective of our study was to evaluate the long-term cost-effectiveness of celecoxib compared with nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) in a population of 60-year-old osteoarthritis (OA) patients with average risks of upper gastrointestinal (UGI) complications who require chronic daily NSAID therapy.

Methods
We used decision analysis based on data from the literature to evaluate cost-effectiveness from a modified societal perspective over patients' lifetimes, with outcomes expressed as incremental costs per quality-adjusted life-year (QALY) gained. Sensitivity tests were performed to evaluate the impacts of advancing age, CV thromboembolic event risk, different analytic horizons and alternate treatment strategies after UGI adverse events.

Results
Our main findings were: 1) the base model incremental cost-effectiveness ratio (ICER) for celecoxib versus nsNSAIDs was $31,097 per QALY; 2) the ICER per QALY was $19,309 for a model in which UGI ulcer and ulcer complication event risks increased with advancing age; 3) the ICER per QALY was $17,120 in sensitivity analyses combining serious CV thromboembolic event (myocardial infarction, stroke, CV death) risks with base model assumptions.

Conclusion
Our model suggests that chronic celecoxib is cost-effective versus nsNSAIDs in a population of 60-year-old OA patients with average risks of UGI events.
Particular distribution and expression pattern of endoglin (CD105) in the liver of patients with hepatocellular carcinoma
Authors: Yu Decai , Zhuang Linyuan , Sun Xitai , Chen Jun , Yao Yongzhong , Meng Kui , Ding Yitao 
Published: July 2007

Abstract

Background
Endoglin (CD105) has been considered a prognostic marker for hepatocellular carcinoma (HCC), and widely used as an appropriate targeting for antiangenesis therapy in some cancers. Our aim was to evaluate the distribution and expression of CD105 in the liver of patients with HCC, and to discuss whether CD105 may be used as an appropriate targeting for antiangenesis therapy in HCC.

Methods
Three parts of liver tissues from each of 64 patients with HCC were collected: tumor tissues (TT), adjacent non-tumor (AT) liver tissues within 2 cm, and tumor free tissues (TF) 5 cm far from the tumor edge. Liver samples from 8 patients without liver diseases served as healthy controls (HC). The distribution and expression of CD105 in tissues were evaluated by immunohistochemistry, Western blotting analysis, and real-time PCR. HIF-1alpha and VEGF165 protein levels in tissues were analyzed by Immunohistochemistry and Western blotting analysis or ELISA.

Results
CD105 was positively stained mostly in a subset of microvessels 'endothelial sprouts' in TT of all patients while CD105 showed diffuse positive staining, predominantly on hepatic sinus endothelial cells in the surrounding of draining veins in TF and AT. The mean score of MVD-CD105 (mean ± SD/0.74 mm2) was 19.00 ± 9.08 in HC, 153.12 ± 53.26 in TF, 191.12 ± 59.17 in AT, and 85.43 ± 44.71 in TT, respectively. Using a paired t test, the expression of CD105 in AT and TF was higher than in TT at protein (MVD, p = 0.012 and p = 0.007, respectively) and mRNA levels (p < 0.001 and p = 0.009, respectively). Moreover, distribution and expression of CD105 protein were consistent with those of HIF-1alpha and VEGF165 protein in liver of patients with HCC. The level of CD105 mRNA correlated with VEGF165 level in TF (r = 0.790, p = 0.002), AT (r = 0.723, p < 0.001), and TT (r = 0.473, p = 0.048), respectively.

Conclusion
It is demonstrated that CD105 was not only present in neovessels in tumor tissues, but also more abundant in hepatic sinus endothelium in non-tumor tissues with cirrhosis. Therefore, CD105 may not be an appropriate targeting for antiangenesis therapy in HCC, especially with cirrhosis.
Expression and localization of hepcidin in macrophages: a role in host defense against tuberculosis
Authors: Sow Fatoumata B , Florence William C , Satoskar Abhay R , Schlesinger Larry S , Zwilling Bruce S , Lafuse William P 
Published: July 2007

AbstractHepcidin is an antimicrobial peptide produced by the liver in response to inflammatory stimuli and iron overload. Hepcidin regulates iron homeostasis by mediating the degradation of the iron export protein ferroportin 1, thereby inhibiting iron absorption from the small intestine and release of iron from macrophages. Here, we examined the expression of hepcidin in macrophages infected with the intracellular pathogens Mycobacterium avium and Mycobacterium tuberculosis. Stimulation of the mouse RAW264.7 macrophage cell line and mouse bone marrow-derived macrophages with mycobacteria and IFN-γ synergistically induced high levels of hepcidin mRNA and protein. Similar results were obtained using the human THP-1 monocytic cell line. Stimulation of macrophages with the inflammatory cytokines IL-6 and IL-β did not induce hepcidin mRNA expression. Iron loading inhibited hepcidin mRNA expression induced by IFN-γ and M. avium, and iron chelation increased hepcidin mRNA expression. Intracellular protein levels and secretion of hepcidin were determined by a competitive chemiluminescence ELISA. Stimulation of RAW264.7 cells with IFN-γ and M. tuberculosis induced intracellular expression and secretion of hepcidin. Furthermore, confocal microscopy analyses showed that hepcidin localized to the mycobacteria-containing phagosomes. As hepcidin has been shown to possess direct antimicrobial activity, we investigated its activity against M. tuberculosis. We found that hepcidin inhibited M. tuberculosis growth in vitro and caused structural damage to the mycobacteria. In summary, our data show for the first time that hepcidin localizes to the phagosome of infected, IFN-γ-activated cells and has antimycobacterial activity.
Replication and Identification of Novel Variants at TCF7L2 Associated with Type 2 Diabetes in Hong Kong Chinese
Authors: Ng Maggie C. Y. , Tam Claudia H. T. , Lam Vincent K. L. , So Wing-Yee , Ma Ronald C. W. , Chan Juliana C. N. 
Published: July 2007

Abstract
Objective: Variations at a large linkage disequilibrium (LD) block of transcription factor 7-like 2 gene (TCF7L2) were reported to be associated with type 2 diabetes (T2D) in Icelandic, Danish and European-American populations and further replicated in other populations of European, African, and Asian ancestries. However, data for Chinese and comprehensive survey of the whole gene are lacking.
Design: We attempted to examine 22 tagging single-nucleotide polymorphisms (SNPs) spanning across the TCF7L2 gene for association with T2D in Hong Kong Chinese. We first studied a case-control sample involving 433 hospital cases with familial early-onset T2D and 419 normal controls and further studied the associated SNPs in 450 members of 142 diabetic families.
Results: Two of the previously reported risk alleles at rs11196205 (C) and rs7903146 (T) were rare in Chinese (0.013 and 0.024, respectively, in controls). Rs11196205 was associated with T2D [odds ratio (OR) [95% confidence interval (CI)] = 2.11 (1.04–4.26)], whereas the association for rs7903146 [OR (95% CI) = 1.27 (0.71–2.29)] was not significant in the case-control sample. Interestingly, another SNP (rs11196218 G allele) located in adjacent LD block conferred independent risk for T2D [OR (95%CI) =1.43 (1.14–1.79)] and contributed high-population attributable risk of 42%. The association finding of rs11196218 and its haplotype for T2D was also replicated in the family sample (P &lt; 0.05).
Conclusions: Our results are consistent with others’ findings that variations at TCF7L2 contribute to T2D, including Chinese. The presence of association signals spanning several LD blocks warrants further examination of extended regions to reveal the causal variant(s) for this important T2D gene.
Thyroid Echogenicity Predicts Outcome of Radioiodine Therapy in Patients with Graves’ Disease
Authors: Marković Vinko , Eterović Davor 
Published: July 2007

Abstract
Context: Despite accounting for variations in gland size and iodine kinetics, the success of radioiodine therapy in patients with Graves’ disease remains moderately common and unpredictable.
Objectives: We hypothesized that hypoechogenic glands, with large, densely packed cells, are more radiosensitive than normoechogenic glands, in which much radiation is wasted on more abundant colloid. We evaluated this hypothesis in a cohort of patients with Graves’ disease.
Design: This was a prospective trial of patients recruited during 4 yr and followed up 1 yr after radioiodine therapy.
Setting: This trial was held in a university hospital-outpatient clinic.
Patients: A total of 177 consecutive patients with first presentation of Graves’ disease (28 males), 23–76 yr old, who relapsed after antithyroid therapy were included in the study.
Intervention: The patients were assigned to an ablative target-absorbed dose of 200 Gy (n = 78) or randomly to 100 or 120 Gy of nonablative dose (n = 99).
Main Outcome Measures: The measures were incidences of hyperthyroidism, euthyroidism, and hypothyroidism at 12-month follow-up.
Results: At follow-up there were 25 hyperthyroid, 44 euthyroid, and 108 hypothyroid patients. Compared with 96 patients with a hypoechogenic gland, in 81 patients with a normoechogenic gland, there were more hyperthyroid (22 vs. 7%) and euthyroid (41 vs. 11%), but less hypothyroid outcomes (37 vs. 81%; P &lt; 0.0001). The other independent predictor of increased radioresistance was the large gland volume.
Conclusion: In patients with Graves’ disease, normoechogenic and large glands are associated with increased radioresistance.
Selective Regulation of Somatostatin Receptor Subtype Signaling: Evidence for Constitutive Receptor Activation
Authors: Ben-Shlomo Anat , Pichurin Oxana , Barshop Nicole J. , Wawrowsky Kolja A. , Taylor John , Culler Michael D. , Chesnokova Vera , Liu Ning-Ai , Melmed Shlomo 
Published: July 2007

Abstract
Anterior pituitary hormone secretion is under tonic suppression by hypothalamic somatostatin signaling through somatostatin receptor subtypes (SSTs). Because some hormonal axes are known to be abnormally regulated by ligand-independent constitutively active G protein-coupled receptors, we tested pituitary SSTs for selective constitutive signaling. We therefore differentially silenced endogenous SST2, SST3, and SST5 in somatostatin-sensitive ACTH-secreting mouse AtT-20 pituitary corticotroph cells using small inhibitory RNA (siRNA) and analyzed downstream SSTs-regulated pathways. Transfection with siRNA reduced specific receptor subtype mRNA expression up to 82%. Specificity of receptor silencing was validated against negative controls with different gene-selective siRNAs, concordance of mRNA and cAMP changes, reduced potency of receptor-selective agonists, and phenotype rescue by overexpression of the silenced receptor. Mouse SST3 &gt; SST5 &gt; SST2 knockdown increased basal cAMP accumulation (up to 200%) and ACTH secretion (up to 60%). SST2- and SST5-selective agonist potencies were reduced by SST3- and SST5-silencing, respectively. SST5 &gt; SST2 = SST3 silencing also increased basal levels of ERK1/2 phosphorylation. SST3- and SST5-knockdown increased cAMP was only partially blocked by pertussis toxin. The results show that SST2, SST3, and SST5 exhibit constitutive activity in mouse pituitary corticotroph cells, restraining adenylate cyclase and MAPK activation and ACTH secretion. SST3 mainly inhibits cAMP accumulation and ACTH secretion, whereas SST5 predominantly suppresses MAPK pathway activation. Therefore, SST receptor subtypes control pituitary cell function not only through somatostatin binding to variably expressed cell membrane receptor subtypes, but also by differential ligand-independent receptor-selective constitutive action.
Elevation of Low-Density Lipoprotein Cholesterol Concentration with Over-the-Counter Fish Oil Supplementation
Authors: Malinowski Jennifer M , Metka Kimberly 
Published: July 2007

Objective: To report a case of elevated low-density lipoprotein cholesterol (LDL-C) concentration in a patient taking fish oil supplements for hypertriglyceridemia. Case Summary: A 63-year-old white woman had been taking 2.7 g of eico-sapentaenotc acid (EPA) and docosahexaenoic acid (DHA) daily in 9 g of over-the-counter (OTC) fish oil capsules for triglyceride lowering. Prior to the adverse event, she had baseline fasting triglyceride (TG) and LDL-C concentrations of 278 mg/dL and 106 mg/dL, respectively. After 6 weeks of treatment with fish oil, fasting TG levels decreased by 47.5% (-132 mg/dL) and the LDL-C increased by 75% (+80 mg/dL). Discontinuation of therapy for 6 weeks resulted in TG returning to high concentrations (334 mg/dL; +56 mg/dL change from baseline) and LDL-C decreasing toward baseline (143 mg/dL; +37 mg/dL change from baseline). Discussion: Fish oil, an omega-3 polyunsaturated fatty acid, consists of EPA and DHA. EPA and DHA are thought to inhibit the synthesis of triglycerides in the liver. Type IV dyslipidemic patients may develop increased LDL-C levels while taking fish oil to lower triglycerides due to possible down-regulation of the LDL-C receptor in hepatic cells and formation of larger LDL particles. Use of the Naranjo probability scale indicates a probable relationship between elevations in LDL-C from baseline and initiation of fish oil treatment for hypertriglyceridemia. It is unknown whether any component within this particular product could have contributed to such an unusual elevation in LDL-C. Conclusions: This case documents a much higher LDL-C elevation associated with OTC fish oil supplementation than has been previously identified in the literature. Healthcare providers should be advised that LDL-C levels may increase with use of OTC fish oil and should monitor patients periodically for such elevations. The significance of this Increase on clinical outcomes is not known.
Antidepressant-lnduced Liver Injury
Authors: DeSanty Kevin P , Amabile Celene M 
Published: July 2007

Objective: To review principles of drug-induced liver injury (DILI), summarize characteristics of antidepressant-mediated liver Injury, and provide recommendations for monitoring and management. Data Sources: A search relating to antidepressant-induced liver injury was performed using MEDLINE (1966–March 2007). Search terms included antidepressant, cholestasis, hepatotoxicity, jaundice, liver injury, toxic hepatitis, and transaminases. Reference citations not Identified in the initial database search were also utilized. Study Selection and Data Extraction: All English-language case reports, letters, and review articles identified from the data sources were used. Case reports and letters relating to hepatotoxicity from antidepressant overdose were excluded. Data Synthesis: Antidepressant-induced liver injury described in published cases were of the idiopathic type and, by definition, cannot be predicted based on dose or specific risk factors. Paroxetine had the largest number of cases within the selective serotonin-reuptake inhibitor class. Nefazodone, a serotonin–norepinephrine reuptake inhibitor, appeared to have the most serious cases and is the only antidepressant agent that carries a Food and Drug Administration Black Box Warning regarding hepatotoxiciiy. The tricyclic antidepressants and monoamine oxidase Inhibitors are capable of producing hepatotoxicity, but fewer cases with these agents have been reported in the past 15 years, possibly due to a decline in their use. Causality has not been well established in all reports due to the concurrent use of other drugs and/or underlying liver disease. Conclusions: Most antidepressant agents have the potential to produce idiopathic liver injury. There is no way to prevent idiopathic DILI, but the severity of the reaction may be minimized with prompt recognition and early withdrawal of the agent. The clinician must be careful to provide ongoing therapy of the underlying depressive disorder and be aware of possible drug discontinuation syndromes should potential hepatotoxicity be suspected.
Rabeprazole and Psychiatric Symptoms
Authors: Polimeni Giovanni , Cutroneo Paola , Gallo Adele , Gallo Salvatore , Spina Edoardo , Caputi Achille P 
Published: July 2007

Objective: To report the case of a patient who developed marked anxiety associated with episodes of panic attacks after starting rabeprazole therapy. Case Summary: An otherwise healthy 55-year-old woman was prescribed rabeprazole 20 mg/day administered in the morning tor persistent symptoms of dyspepsia. Ten days later, she presented with a 7 day history of marked anxiety associated with panic attacks, night terror (pavor nocturnus), episodic mental confusion, and attention deficit. Within 2 days of discontinuing rabeprazole, the patient recovered completely from the neuropsychiatric manifestations. Subsequent esomeprazole therapy did not cause psychiatric symptoms. Discussion: Rabeprazole-induced hypergastrinemia may have played a role in this neuropsychiatric adverse reaction. Several lines of evidence have indicated that gastrin-releasing peptide, whose release is mediated by proton pump inhibitor (PPI)–induced secretion of gastrin, is involved in regulating aspects of behavior that might be altered in disorders such as anxiety, depression, and dementia. The fact that rabeprazole has the highest capacity of inducing gastrin increase compared with other PPIs might explain why our patient's panic symptoms disappeared after switching to esomeprazole. Based on the Naranjo probability scale, rabeprazole was the probable cause of the adverse reaction. Conclusions: Specific studies are needed to investigate the potential role of PPI-induced hypergastrinemia in neuropsychiatrie adverse reactions.
Home-Based Physical Therapy Intervention With Adherence-Enhancing Strategies Versus Clinic-Based Management for Patients With Ankle Sprains
Authors: Bassett Sandra F , Prapavessis Harry 
Published: July 2007

Background and Purpose: To some extent, favorable treatment outcomes for physical therapy intervention programs depend on patients attending their clinic appointments and adhering to the program requirements. Previous studies have found less-than-optimal levels of clinic attendance, and a viable option might be physical therapy intervention programs with a large component of home treatment. This study investigated the effects of a standard physical therapy intervention program—delivered primarily at either the clinic or home—on ankle function, rehabilitation adherence, and motivation in patients with ankle sprains.
Subjects: Forty-seven people with acute ankle sprains who were about to start a course of physical therapy intervention participated in the study.
Methods: Using a prospective design, subjects were randomly assigned to either a clinic intervention group or a home intervention group. Ankle function and motivation were measured before and after rehabilitation, and adherence to the clinic- and home-based programs was measured throughout the study.
Results: The groups had similar scores for post-treatment ankle function, adherence, and motivation. The home intervention group had a significantly higher percentage of attendance at clinic appointments and better physical therapy intervention program completion rate.
Discussion and Conclusion: Home-based physical therapy intervention appears to be a viable option for patients with sprained ankles.
Effectiveness of an Artificial Intelligence–Enabled Intervention for Detecting Clinical Deterioration
Authors: Gallo Robert J. , Shieh Lisa , Smith Margaret , Marafino Ben J. , Geldsetzer Pascal , Asch Steven M. , Shum Kenny , Lin Steven , Westphal Jerri , Hong Grace , Li Ron Chen 
Published: March 2024

ImportanceInpatient clinical deterioration is associated with substantial morbidity and mortality but may be easily missed by clinicians. Early warning scores have been developed to alert clinicians to patients at high risk of clinical deterioration, but there is limited evidence for their effectiveness.ObjectiveTo evaluate the effectiveness of an artificial intelligence deterioration model–enabled intervention to reduce the risk of escalations in care among hospitalized patients using a study design that facilitates stronger causal inference.Design, Setting, and ParticipantsThis cohort study used a regression discontinuity design that controlled for confounding and was based on Epic Deterioration Index (EDI; Epic Systems Corporation) prediction model scores. Compared with other observational research, the regression discontinuity design facilitates causal analysis. Hospitalized adults were included from 4 general internal medicine units in 1 academic hospital from January 17, 2021, through November 16, 2022.ExposureAn artificial intelligence deterioration model–enabled intervention, consisting of alerts based on an EDI score threshold with an associated collaborative workflow among nurses and physicians.Main Outcomes and MeasuresThe primary outcome was escalations in care, including rapid response team activation, transfer to the intensive care unit, or cardiopulmonary arrest during hospitalization.ResultsDuring the study, 9938 patients were admitted to 1 of the 4 units, with 963 patients (median [IQR] age, 76.1 [64.2-86.2] years; 498 males [52.3%]) included within the primary regression discontinuity analysis. The median (IQR) Elixhauser Comorbidity Index score in the primary analysis cohort was 10 (0-24). The intervention was associated with a −10.4–percentage point (95% CI, −20.1 to −0.8 percentage points; P = .03) absolute risk reduction in the primary outcome for patients at the EDI score threshold. There was no evidence of a discontinuity in measured confounders at the EDI score threshold.Conclusions and RelevanceUsing a regression discontinuity design, this cohort study found that the implementation of an artificial intelligence deterioration model–enabled intervention was associated with a significantly decreased risk of escalations in care among inpatients. These results provide evidence for the effectiveness of this intervention and support its further expansion and testing in other care settings.