bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iron Supplementation and Epoetin Alfa in a Jehovah's Witness with Severe Iron Deficiency Anemia
Authors: Dunn Rebecca L , Blevins Steve M 
Published: September 2013

Objective: To report a case of severe iron deficiency anemia (IDA) in a Jehovah's Witness, successfully treated with iron supplementation and epoetin alfa. Case Summary: A 69-year-old African man, a Jehovah's Witness, presented with severe IDA of unknown cause and was admitted to the general medicine service. He was treated with oral and intravenous iron and subcutaneous epoetin alfa. His serum hemoglobin concentration steadily improved. He was discharged to home on epoetin alfa and iron supplementation. His hemoglobin concentration was stable 1 month later. Discussion: Iron is a critical factor in hemoglobin synthesis and erythropoiesis, and iron deficiency is a common cause of anemia. Jehovah's Witnesses with severe anemia pose a challenge to providers because of their refusal to accept blood products. Alternative treatment regimens are few, and little evidence exists to guide treatment decisions. Recombinant human erythropoietin (rHuEpo) may play a role, but little is known about its use in IDA. Most studies on rHuEpo focus on its use in the setting of surgery, burns, trauma, pregnancy, and severe gastrointestinal bleeding. Conclusions: This case demonstrates that rHuEpo plus iron supplementation may be an acceptable alternative to blood transfusion in a Jehovah's Witness patient with severe IDA.
Phenazopyridine-Induced Toxicity in an Elderly Patient Receiving a Prolonged Regimen of Therapeutic Doses
Authors: Ronald Katie E , Demissie Asmeret 
Published: September 2013

Objective: To report a case of yellow skin pigmentation, acute renal failure, methemoglobinemia, and hemolytic anemia in a patient receiving a prolonged regimen of therapeutic doses of phenazopyridine. Case Summary: A 74-year-old female was admitted to the hospital with respiratory distress and acute renal failure, admission serum creatinine of 4.5 mg/dL (reference range 0.7–1.4 mg/dL), and blood urea nitrogen of 80 mg/dL (6–22 mg/dL). Upon admission, she had yellow skin pigmentation, methemoglobinemia with a methemoglobin level of 18.8% (0–3%), and hemolytic anemia with hemoglobin of 6.9 g/dL (12–16 g/dL), reticulocyte count of 5.1% (0.5–2%), and peripheral blood smear revealing Heinz body hemolysis. She had been taking phenazopyridine 200 mg 3 times per day for the 3 weeks prior to admission. Phenazopyridine was discontinued, and the patient was treated with intravenous methylene blue for methemoglobinemia and supportive care for acute renal failure, yellow skin discoloration, and hemolytic anemia. After 5 days in the hospital, the patient was discharged with baseline laboratory values and baseline respiratory status. An objective causality assessment revealed that acute renal failure was possibly and methemoglobinemia and hemolytic anemia were probably associated with phenazopyridine. Discussion: Phenazopyridine toxicity may occur with acute overdose or chronic administration of therapeutic doses. Severe toxicity with phenazopyridine is relatively uncommon, but when it does occur it may present as a serious clinical picture, with adverse drug reactions (ADRs) such as methemoglobinemia, hemolytic anemia, acute renal failure, and hepatitis. Removal of phenazopyridine and provision of supportive treatment for the ADRs usually results in reversal of the complications and return to baseline function. Severe cases of methemoglobinemia may need to be treated with intravenous methylene blue in addition to supportive care. This case presents the importance of understanding the risks with long-term use of therapeutic doses of phenazopyridine, especially in geriatric patients. Conclusions: The geriatric population and patients with renal insufficiency are at increased risk of phenazopyridine toxicity because of decreased renal clearance of phenazopyridine and its metabolites.
The Potential Effects of Dicloxacillin on Warfarin Management
Authors: Clarke Christina A , Patel Anita D 
Published: September 2013

Objective: To illustrate the effect that dicloxacillin may have on the anticoagulant properties of warfarin. Case Summary: A 69-year-old white male presented to the emergency department following a motor vehicle accident. He had been receiving a stable dose of warfarin of approximately 35–37.5 mg/wk for more than 2 years for atrial fibrillation. Computed tomography and magnetic resonance imaging revealed a 1 × 1.3 cm lesion in the anterior aspect of the pancreatic body. During a subsequent hospital stay for a distal pancreatectomy and splenectomy, the patient began a 6-week course of dicloxacillin to treat osteomyelitis of the elbow. During the course of treatment, the patient's warfarin dose was increased by 114% to reach a therapeutic international normalized ratio (INR) approximately 11 days after the antibiotic was discontinued. Discussion: Compared with previously published cases documenting the interaction between dicloxacillin and warfarin, to our knowledge, this is the first case to comprehensively assess and document other factors that potentially influenced the patient's INR. At every clinic visit, the patient was assessed for several factors that could have contributed to fluctuations in INR, none of which proved to have a significant effect. Conclusions: The addition of dicloxacillin to our patient's stable warfarin regimen resulted in a significant interaction that placed the patient at risk for thromboembolic complications. Careful monitoring of INR from the start of dicloxacillin therapy until 2 weeks after its discontinuation should be considered in patients who are taking warfarin and require dicloxacillin therapy.
Risperidone for Night Terrors and Sleepwalking in an Adult: A Case Report
Authors: Detweiler Mark B 
Published: September 2013

Objective: To report the successful treatment of a case of night terrors and sleepwalking in an adult using low-dose risperidone. Case Summary: A 30-year-old female with a history of nightmares as a teen, but with no prior psychiatric history, presented with new-onset night terrors and sleepwalking related to psychosocial stressors. She recalled images of being chased by monsters and of people trying to hurt her. Sleepwalking sometimes involved self-injurious behavior, as she ran through the house screaming. Intake diagnoses included general anxiety disorder (GAD), obsessive-compulsive disorder (OCD) and obsessive-compulsive personality disorder (OCPD). She reported compulsive counting since childhood and episodes of compulsive eating. Risperidone 1 mg was started and eventually titrated to 2 mg at night for night terror and sleepwalking suppression. For GAD, OCD, and OCPD, paroxetine 10 mg was started and titrated to 50 mg. Temazepam 30 mg was added to prolong sleep and cyproheptadine 4 mg was prescribed for anorgasmia. Symptoms were well controlled with the medications for about 8 months. The patient chose to stop the paroxetine and temazepam on day 655, but continued to take risperidone 2 mg for approximately 45 days. When she discontinued the risperidone, the night terrors and sleepwalking returned within 3 days. Discussion: Low-dose risperidone has been shown to modulate combat posttraumatic stress disorder nightmares. Its effectiveness for night terrors and sleepwalking has not been reported. In this case, risperidone was the sole medication suppressing night terrors and sleepwalking for a month and a half. As found in previous studies, 2 mg of risperidone seemed to be the optimal dose. Conclusions: Risperidone dosed at 1–2 mg at night may be a pharmacologic alternative for the symptoms of sleep terrors with sleepwalking.
Compliance with Antibiotic Dosing Guidelines in Critically Ill Patients Receiving Renal Replacement Therapy
Authors: Udani Suneel , Chen Ling-Xin , Daley Mitchell , Lat Ishaq , Koyner Jay L 
Published: September 2013

Background: Compliance with antibiotic dosing guidelines and achievement of target serum concentrations in patients with infection who are on renal replacement therapy (RRT) is complex, essential for supportive care, and not well studied. Objective: To determine adherence rates to antibiotic dosing guidelines in the setting of RRT in the intensive care unit (ICU). Methods: We conducted a retrospective, single-center, cohort study evaluating antibiotic dosing in all patients in the ICU receiving RRT between July 2007 and June 2009. Appropriate dosing was determined by comparing dose administered with established guidelines. Dosing was denoted as accurate if adjustment occurred prior to the third administered dose or, if appropriate dosing is every 12 hours or more, within 24 hours. We compared rates according to modality of RRT (intermittent hemodialysis [IHD] vs continuous veno-venous hemodialysis [CVVHD]), indication for RRT (acute kidney injury [AKI] vs end-stage renal disease [ESRD]), and presence of a clinical pharmacist on rounds. Results: Adherence rates of 546 patients receiving RRT, with 1761 individual antibiotic prescriptions, were analyzed. Dosing errors were more common in the group receiving CVVHD than in the IHD group (58.1% vs 49.5%; p < 0.001). Frequency of dosing errors did not differ significantly between patients receiving RRT for AKI versus those with ESRD (55.4% vs 51.3%; p = 0.24) or in ICUs with or without a pharmacist on rounds (53.0% vs 54.6%; p = 0.67). Underdosing occurred less frequently with a clinical pharmacist on rounds (18.7% vs 31.3%; p < 0.001). However, in-hospital mortality was not significantly different in underdosed individuals compared with the rest of the cohort (52.3% vs 51.6%; p = 0.92). Conclusions: Antibiotic underdosing is common. Increased awareness of dose adjustment guidelines for CVVHD and having a clinical pharmacist on rounds may improve rates of underdosing.
Patient Attitudes concerning Pharmacist Inquiry of Spirituality in a Community Pharmacy
Authors: Twigg Geoffrey , Johnson Mark S 
Published: September 2013

Background: Health care professionals, including physicians and nurses, are becoming more aware of the importance of addressing and incorporating spirituality into patient care. Less is known concerning pharmacist inquiry of patient spiritual beliefs. Objective: To observe patients' attitudes in having the pharmacist inquire about their spiritual beliefs in the community pharmacy setting and to determine patient characteristics that may be predictive of these attitudes. Methods: This study was conducted in an independent pharmacy on the Eastern Shore of Maryland over a 2-week period. Patients voluntarily filled out an 11-question survey assessing baseline religiosity, using the Duke University Religion Index (DUREL) and attitudes on inquiry by the pharmacist regarding spirituality. The results were analyzed to assess patient attitudes and correlations predictive of these attitudes. Results: A total of 105 participants completed the survey. Participants scored high on organizational, nonorganizational, and intrinsic religiosity as assessed by DUREL. Survey results revealed that most patients felt that it was appropriate for both physicians (69%) and pharmacists (57%) to inquire about spiritual beliefs, most (86%) patients believed that prayer was important in treatment, 57% of patients felt comfortable having their pharmacist offer prayer, and 93% felt that spiritual health positively impacts physical and mental health. Organizational religiosity proved to be the best baseline predictor of patient desire in having spirituality acknowledged in pharmacy care (OR 1.733; p = 0.002). Other strong predictors included intrinsic religiosity (OR 1.271; p = 0.004), the patient's desire to have physicians inquire about spirituality (OR 10.365; p = 0.001), and patient comfort level with pharmacist prayer (OR 3.729; p = 0.039). Conclusions: This pilot study provides initial evidence that patients are generally supportive of pharmacist inquiry concerning their spiritual and religious beliefs in the community pharmacy setting, with more frequent organized religious attendance being the best predictor. Further studies are needed to validate these results.
Adherence, Persistence, and Predictors Associated with Early Niacin Termination
Authors: Christian Jennifer Briley , Rabatin Vincent , Lowe Kimberly A 
Published: September 2013

Background: Niacin is the most effective therapy currently available to increase high-density lipoprotein cholesterol. However, adherence to niacin may be limited by a number of factors and it is important to characterize who is likely to discontinue the medicine. Objective: To measure adherence and persistence to niacin, estimate the influence of niacin dose on adherence, and identify factors associated with early termination of niacin. Methods: This retrospective study estimated adherence to niacin by calculating the medication possession ratio, persistence, number of refills, and termination proportion in a large, deidentified US health claims database consisting of 42,685 insurance-carrying adults who were new users of niacin. Results: We identified 29,801 new users of niacin who were not taking statins or fibric acid, 12,298 new users of niacin plus statin, 441 new users of niacin plus fibric acid, and 145 new users who initiated all 3 agents. Persistence was lowest among individuals taking less than 1 g/day and was highest among those taking niacin plus fibric acid plus statin (5.10 vs 7.17 months, respectively). However, lower niacin dose was associated with greater adherence, regardless of statin use. Termination of niacin within 1 year of initiation was significantly associated with being female or having 1 of the following conditions: peripheral vascular disease, chronic pulmonary disease, diabetes mellitus, rheumatic disease, or liver disease. Increased age, taking niacin in combination with a statin, or taking drugs from 2 or more concomitant prescription medication classes were significantly associated with a reduced likelihood of termination within 1 year. Conclusions: We observed relatively high adherence rates to niacin; however, most patients failed to persist with use of the drug beyond 7 months.
A randomized, controlled trial to evaluate the effect of an anti-interleukin-9 monoclonal antibody in adults with uncontrolled asthma
Authors: Oh Chad K , Leigh Richard , McLaurin Kimmie K , Kim Keunpyo , Hultquist Micki , Molfino Nestor A 
Published: September 2013

Abstract

Background
Preclinical studies suggest that interleukin-9 may be a central mediator in the development and maintenance of airway inflammation in asthma. The aim of this study was therefore to evaluate the effects of MEDI-528, an anti-interleukin-9 monoclonal antibody, in adults with confirmed uncontrolled moderate-to-severe asthma.

Methods
In this prospective double-blind, multicenter, parallel-group study, 329 subjects were randomized (1:1:1:1) to subcutaneous placebo or MEDI-528 (30, 100, 300 mg) every 2 weeks for 24 weeks, in addition to their usual asthma medications. The primary endpoint was change in mean Asthma Control Questionnaire-6 (ACQ-6) score at week 13. Secondary endpoints included weighted asthma exacerbation rates and pre-bronchodilator forced expiratory volume in 1 second (FEV1) at weeks 13 and 25, as well as Asthma Quality of Life Questionnaire scores at weeks 12 and 25 and the safety of MEDI-528 throughout the study period. The primary endpoint was analyzed using analysis of covariance.

Results
The study population (n = 327) was predominantly female (69%) with a mean age of 43 years (range 18–65). The mean (SD) baseline ACQ-6 score for placebo (n = 82) and combined MEDI-528 (n = 245) was 2.8 (0.7) and 2.8 (0.8); FEV1 % predicted was 70.7% (15.9) and 71.5% (16.7). Mean (SD) change from baseline to week 13 in ACQ-6 scores for placebo vs combined MEDI-528 groups was −1.2 (1.0) vs −1.2 (1.1) (p = 0.86). Asthma exacerbation rates (95% CI) at week 25 for placebo vs MEDI-528 were 0.58 (0.36–0.88) vs 0.49 (0.37–0.64) exacerbations/subject/year (p = 0.52). No significant improvements in FEV1 % predicted were observed between the placebo and MEDI-528 groups. Adverse events were comparable for placebo (82.9%) and MEDI-528 groups (30 mg, 76.5%; 100 mg, 81.9%; 300 mg, 85.2%). The most frequent were asthma (placebo vs MEDI-528, 30.5% vs 33.5%), upper respiratory tract infection (14.6% vs 17.1%), and headache (9.8% vs 9.8%).

Conclusions
The addition of MEDI-528 to existing asthma controller medications was not associated with any improvement in ACQ-6 scores, asthma exacerbation rates, or FEV1 values, nor was it associated with any major safety concerns.

Trial registration
ClinicalTrials.gov: NCT00968669.
Feature ranking based on synergy networks to identify prognostic markers in DPT-1
Authors: Adl Amin Ahmadi , Qian Xiaoning , Xu Ping , Vehik Kendra , Krischer Jeffrey P 
Published: September 2013

Abstract
Interaction among different risk factors plays an important role in the development and progress of complex disease, such as diabetes. However, traditional epidemiological methods often focus on analyzing individual or a few ‘essential’ risk factors, hopefully to obtain some insights into the etiology of complex disease. In this paper, we propose a systematic framework for risk factor analysis based on a synergy network, which enables better identification of potential risk factors that may serve as prognostic markers for complex disease. A spectral approximate algorithm is derived to solve this network optimization problem, which leads to a new network-based feature ranking method that improves the traditional feature ranking by taking into account the pairwise synergistic interactions among risk factors in addition to their individual predictive power. We first evaluate the performance of our method based on simulated datasets, and then, we use our method to study immunologic and metabolic indices based on the Diabetes Prevention Trial-Type 1 (DPT-1) study that may provide prognostic and diagnostic information regarding the development of type 1 diabetes. The performance comparison based on both simulated and DPT-1 datasets demonstrates that our network-based ranking method provides prognostic markers with higher predictive power than traditional analysis based on individual factors.
Production of biodiesel from soybean and Jatropha Curcas oils with KSF and amberlyst 15 catalysts in the presence of co-solvents
Authors: Calgaroto Cleber , Calgaroto Selma , Mazutti Marcio A , de Oliveira Debora , Pergher Sibele , de Oliveira J Vladimir 
Published: September 2013

Abstract
Experimental conditions for the production of fatty acid methyl esters (FAME) from Jatropha curcas and soybean oils using two acid heterogeneous catalysts (Amberlyst15 and KSF) was optimized, in the presence of different co-solvents (THF, acetone, petroleum ether and n-hexane) in a batch reactor at fixed conditions: oil to methanol molar ratio (1:9), catalyst concentration (4.8 wt%), co-solvent mass ratio (1:1), 160°C and 6 hours. Results showed that the use of co-solvents led to a reduction in the FAME conversion. Higher conversions were obtained for Jatropha curcas compared to soybean oil. The Amberlyst15 presented an enhancement in the catalytic activity after regeneration, providing high biodiesel conversions compared to the fresh resin. The catalyst also presented stability after 5 cycles of reuse. Activity lost was observed for KSF after 2 successive batch experiments, probably due to a deactivation of acid sites.
Proteomic analysis of mismatch repair-mediated alkylating agent-induced DNA damage response
Authors: Chen Xi , Zhao Yong , Li Guo-Min , Guo Lin 
Published: September 2013

Abstract

Background
Mediating DNA damage-induced apoptosis is an important genome-maintenance function of the mismatch repair (MMR) system. Defects in MMR not only cause carcinogenesis, but also render cancer cells highly resistant to chemotherapeutics, including alkylating agents. To understand the mechanisms of MMR-mediated apoptosis and MMR-deficiency-caused drug resistance, we analyze a model alkylating agent (N-methyl-N’-nitro-N-nitrosoguanidine, MNNG)-induced changes in protein phosphorylation and abundance in two cell lines, the MMR-proficient TK6 and its derivative MMR-deficient MT1.

Results
Under an experimental condition that MNNG-induced apoptosis was only observed in MutSα-proficient (TK6), but not in MutSα-deficient (MT1) cells, quantitative analysis of the proteomic data revealed differential expression and phosphorylation of numerous individual proteins and clusters of protein kinase substrates, as well differential activation of response pathways/networks in MNNG-treated TK6 and MT1 cells. Many alterations in TK6 cells are in favor of turning on the apoptotic machinery, while many of those in MT1 cells are to promote cell proliferation and anti-apoptosis.

Conclusions
Our work provides novel molecular insights into the mechanism of MMR-mediated DNA damage-induced apoptosis.
GREM1, FRZB and DKK1 mRNA levels correlate with osteoarthritis and are regulated by osteoarthritis-associated factors
Authors: Leijten Jeroen CH , Bos Steffan D , Landman Ellie BM , Georgi Nicole , Jahr Holger , Meulenbelt Ingrid , Post Janine N , van Blitterswijk Clemens A , Karperien Marcel 
Published: September 2013

Abstract
Introduction
Osteoarthritis is, at least in a subset of patients, associated with hypertrophic differentiation of articular chondrocytes. Recently, we identified the bone morphogenetic protein (BMP) and wingless-type MMTV integration site (WNT) signaling antagonists Gremlin 1 (GREM1), frizzled-related protein (FRZB) and dickkopf 1 homolog (Xenopus laevis) (DKK1) as articular cartilage’s natural brakes of hypertrophic differentiation. In this study, we investigated whether factors implicated in osteoarthritis or regulation of chondrocyte hypertrophy influence GREM1, FRZB and DKK1 expression levels.

Methods
GREM1, FRZB and DKK1 mRNA levels were studied in articular cartilage from healthy preadolescents and healthy adults as well as in preserved and degrading osteoarthritic cartilage from the same osteoarthritic joint by quantitative PCR. Subsequently, we exposed human articular chondrocytes to WNT, BMP, IL-1β, Indian hedgehog, parathyroid hormone-related peptide, mechanical loading, different medium tonicities or distinct oxygen levels and investigated GREM1, FRZB and DKK1 expression levels using a time-course analysis.

Results
GREM1, FRZB and DKK1 mRNA expression were strongly decreased in osteoarthritis. Moreover, this downregulation is stronger in degrading cartilage compared with macroscopically preserved cartilage from the same osteoarthritic joint. WNT, BMP, IL-1β signaling and mechanical loading regulated GREM1, FRZB and DKK1 mRNA levels. Indian hedgehog, parathyroid hormone-related peptide and tonicity influenced the mRNA levels of at least one antagonist, while oxygen levels did not demonstrate any statistically significant effect. Interestingly, BMP and WNT signaling upregulated the expression of each other’s antagonists.

Conclusions
Together, the current study demonstrates an inverse correlation between osteoarthritis and GREM1, FRZB and DKK1 gene expression in cartilage and provides insight into the underlying transcriptional regulation. Furthermore, we show that BMP and WNT signaling are linked in a negative feedback loop, which might prove essential in articular cartilage homeostasis by balancing BMP and WNT activity.