bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continuous-Infusion β-Lactam Antibiotics During Continuous Venovenous Hemofiltration for the Treatment of Resistant Gram-Negative Bacteria
Authors: Moriyama Brad , Henning Stacey A , Neuhauser Melinda M , Danner Robert L , Walsh Thomas J 
Published: July 2009

Objective: To describe the rationale, principles, and dosage calculations for continuous-infusion β-lactam antibiotics to treat multidrug-resistant bacteria in patients undergoing continuous venovenous hemofiltration (CVVH). Data Sources: A MEDLINE search (1968–November 2008) of the English-language literature was performed using the terms continuous infusion and Pseudomonas or Acinetobacter, hemofiltration or CVVH or hemodiafiltration or CVVHDF or continuous renal replacement therapy or pharmacokinetics; and terms describing different β-lactam antibiotics. Study Selection and Data Extraction: In vitro, in vivo, and human studies were evaluated that used continuous-infusion β-lactam antibiotics to treat Pseudomonas aeruginosa and Acinetobacter baumannii infections. Studies were reviewed that described the pharmacokinetics of β-lactam antibiotics during CVVH as well as other modalities of continuous renal replacement therapy. Data Synthesis: Continuous infusion of β-lactam antibiotics, maintaining drug concentrations 4–5 times higher than the minimum inhibitory concentration, is a promising approach for managing infections caused by P. aeruginosa and A. baumannii. Safe yet effective continuous infusion therapy is made difficult by the occurrence of acute renal failure and the need for renal replacement therapy. Case series and pharmacokinetic properties indicate that several β-lactam antimicrobials that have been studied for continuous infusion, such as cefepime, ceftazidime, piperacillin, ticarcillin, clavulanic acid, and tazobactam, are significantly cleared by hemofiltralion. Methodology and formulas are provided that allow practitioners to calculate dosage regimens and reach target drug concentrations for continuous β-lactam antibiotic infusions during CVVH based on a literature review, pharmacokinetic principles, and our experience at the National Institutes of Health Clinical Center. Conclusions: Continuous infusion of β-lactam antibiotics may be a useful treatment strategy for multidrug-resistant gram-negative infections in the intensive care unit. Well-established pharmacokinetic and pharmacodynamic principles can be used to safely reach and maintain steady-state target concentrations of β-lactam antibiotics in critical illness complicated by acute renal failure requiring CVVH.
An Open-Label Study of Mirtazapine as Treatment for Combat-Related PTSD
Authors: Alderman Christopher P , Condon John T , Gilbert Andrew L 
Published: July 2009

Background: Posttraumatic stress disorder (PTSD) is common among war veterans. Antidepressants are effective in reducing symptoms and associated disability for some patients. Objective: To assess the effectiveness of mirtazapine for combat-related PTSD among veterans treated in an Australian hospital. Methods: This open-label prospective study assessed the effectiveness of mirtazapine as empirical treatment for combat-related PTSD. The initial dose was 15 mg at night, titrated against response to 15–45 mg. PTSD symptoms were assessed using the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder and the Clinician-Administered PTSD Scale (CAPS). Subjects also completed the Hospital Anxiety and Depression Scale (HADS). Body weight and biochemical assessments, including fasting blood glucose (FBG), total serum cholesterol, and serum triglycerides, were also measured. Baseline measurements were repeated after 12 weeks. Results: During the 18-month recruitment phase, 17 subjects were enrolled and 13 completed the protocol. The CAPS measurement decreased from a mean pretreatment score of 87.5 to 64.4 (p = 0.01). In 4 cases, the CAPS score decreased to below the diagnostic cut-point, consistent with a remission of PTSD. The Mississippi scale measurement decreased from a mean pretreatment score of 126.6 to 115.5 (p < 0.01). The mean HADS anxiety score decreased from 15.6 ± 4.2 to 13.5 ± 5.6 (p = 0.016), although the proportion of subjects with scores above the diagnostic cut-point remained high. The mean HADS depression score at baseline was not significantly different from the postintervention score. One subject had a postintervention FBG of 155 mg/dL (consistent with diabetes mellitus), which was increased from the baseline level of 83 mg/dL. All subjects experienced an increase in body weight. One subject had an increase in body weight of 8.75 kg (8.4%) from baseline. Conclusions: Although small and with methodological limitations, this study suggests that mirtazapine is an effective treatment for combat-related PTSD. Additional research incorporating an appropriately powered, double-blind, placebo-controlled study design is required.
Medication Adherence and Its Effect on Relapse Among Patients Discharged from a Veterans Affairs Posttraumatic Stress Disorder Treatment Program
Authors: Lockwood Anna , Steinke Douglas T , Botts Sheila R 
Published: July 2009

Background: Clinical outcomes in patients with posttraumatic stress disorder (PTSD) can be affected by several factors, including medication adherence. PTSD is associated with an increased likelihood of missed appointments, medication underuse or abuse, and treatment nonadherence. Objective: To evaluate medication adherence and its effect on relapse following discharge of veterans from a PTSD residential rehabilitation program (PRRP). Methods: A retrospective evaluation of drug adherence and relapse in the 12 months following discharge of patients from a PRRP was performed. All veterans who were discharged from January 1, 2005, to December 31, 2006, and were receiving antidepressant therapy were included. Adherence to antidepressant therapy was assessed by electronic prescription claims and defined as a medication possession ratio of at least 0.8 in the year following discharge. Relapse was defined as a hospitalization for psychiatric symptomatology. Predictive factors of adherence were also explored. Results: Twenty-eight of the 82 (34%) veterans included in our study were adherent to medication during the 12 months following discharge. Seventeen (20.7%) veterans were re hospitalized for psychiatric symptoms, but nonadherence was not significantly associated with relapse (p = 0.91). The total number of drugs that a veteran received was related to adherence; patients who had a higher median number of medications were more adherent (p = 0.014). Age, comorbid substance abuse, combat service, and service connection were not associated with drug adherence. Conclusions: The majority of patients who were discharged from a residential PTSD treatment program were nonadherent to antidepressant drug therapy. One in 5 veterans with PTSD was rehospitalized within 1 year; however, medication adherence did not affect this outcome.
Safety and Clinical Outcomes when Utilizing High-Dose (≥8 mg/kg) Daptomycin Therapy
Authors: Moise Pamela A , Hershberger Ellie , Amodio-Groton Maria I , Lamp Kenneth C 
Published: July 2009

Background: Daptomycin is approved for the treatment of skin and skin-structure infections (4 mg/kg) and Staphylococcus aureus bacteremia, including right-sided endocarditis (β mg/kg). In vitro and animal studies have reported increased activity with increased daptomycin doses. There are limited clinical data on use of daptomycin at doses greater than 6 mg/kg. Objective: To evaluate the safety and efficacy of higher doses (≥8 mg/kg) of daptomycin when administered for a variety of gram-positive infections. Methods: Data were collected retrospectively as part of an ongoing registry (the Cubicin Outcomes Registry and Experience database) for the 2005–2007 program years. For the purpose of this study, the safety and efficacy of daptomycin were evaluated in patients who received doses of 8 m/kg or higher. Results: Ninety-four (2.6%) of 3617 patients received daptomycin doses of 6 mg/kg or higher; 18 (19%) of those patients received doses of 10 mg/kg or higher. The most common infections were bacteremia (30/94), skin and skin-structure infections (22/94), and endocarditis (15/94). The most common pathogens were Enterococcus spp. (37/94; 57% vancomycin-resistant) and S. aureus (28/94; 68% methicllin-resistant). Fifty-one percent of the patients were male. 39% were aged 66 years or older, 27% had an initial creatinine clearance less than 30 mL/min, and 17% were on dialysis. The median duration of daptomycin therapy was 15 days (minimum 1, maximum 90). Six (6.4%) of the 94 patients experienced 1 or more adverse events or abnormal laboratory value changes possibly related to daptomycin; in 2 (2.1%) of the 94 patients, daptomycin was discontinued due to treatment-related adverse events. Seventy-four (79%) patients were considered evaluable for efficacy. The overall clinical success rate was 89% (bacteremia, 91 %; skm and skin-structure infections. 88%: endocarditis. 67%) Conclusions: Daptomycin was well tolerated and effective at doses of 8 mg/kg or higher in patients with gram-positive infections. Further prospective and comparative studies of daptomycin at doses greater than 6 mg/kg are warranted.
Ordering Off the Menu: Assessing Compliance with a Nonformulary Medication Policy
Authors: Pummer Tara L , Shalaby Karen M , Erush Sarah C 
Published: July 2009

Background: Use of nonformulary medications (NFMs) may create added costs and potential safety issues. Institutional policies can support compliance with formulary systems and address these issues. However, periodic review is needed to assess the effectiveness of NFM policies. Objective: To evaluate NFM use at a large university medical center and assess for compliance with the established policy as well as for prescribing errors, procurement procedures, and delivery times. Methods: All new medication orders entered as NFM in the computerized order entry system during a 6-week period were evaluated and followed until administration of the first NFM dose. Orders were categorized as NFMs, formulary medications (FMs), or the patient's own medications. Each order was evaluated to determine the prescriber, service and location of the patient, and any prescribing errors. Additional information, such as the indication, location where the medication was obtained, and the delivery time, was obtained through patient chart review and the pharmacist intervention database. Results: A total of 237 orders were entered as nonformulary; 72 (30%) were FMs and 165(70%) were NFMs. Of the 165 NFM orders, 71 (43%) were orders for the patient's own medication. Of the remaining 94 NFMs, only 39% met the institution's established policy criteria. Overall, 28% of all orders entered as nonformulary had a prescribing error. Of these, 49% were incorrect dosages and 33% were misspelled orders. Seventy percent of NFMs were obtained from the institution's standard locations. The institution's nonformulary turnaround time was achieved with 96% of NFMs. Conclusions: The majority of NFM orders did not meet the institution's established criteria and these orders frequently contained prescribing errors. Routine assessment of NFM use and policy compliance can present opportunities for improvement.
Acquired Fanconi Syndrome After Treatment with Capecitabine, Irinotecan, and Bevacizumab
Authors: Shaikh Aisha , Wiisanen Matthew E , Gunderson Heidi D , Leung Nelson 
Published: July 2009

Objective: To describe a case of acquired Fanconi syndrome after treatment with capecitabine, irinotecan, and bevacizumab. Case Summary: A 77-year-old female with metastatic colon cancer presented with vomiting and diarrhea. The patient had been diagnosed with stage IIIC (T3, N2, M0) colon cancer 18 months earlier and was initially treated with FOLFOX6 (regimen of oxaliplatin, fluorouracil, and leucovorin) after her hemicolectomy. She was switched to a capecitabine/oxaliplatin regimen after 4 cycles due to central access problems. She did well until 10 months after her cancer diagnosis, when metastasis was discovered. She was started on reduced doses of capecitabine, irinotecan, and bevacizumab. After her eleventh cycle, she presented to the hospital with the above symptoms. Laboratory test results showed hypokalemia, hypocalcemia, hypophosphatemia, and hypouricemia. The patient had not been started on any new medications other than chemotherapy for over 1 year. The electrolyte derangements were new, since the patient had laboratory values checked every 3 weeks. Despite daily intravenous replacements, the electrolyte abnormalities persisted. Laboratory evaluations demonstrated the presence of euglycemic glucosuria and a high fractional excretion of phosphorus in the setting of hypophosphatemia. Fanconi syndrome was confirmed by demonstration of aminoaciduria. Discussion: Fanconi syndrome is a disorder characterized by proximal tubular dysfunction resulting in electrolyte wasting. In the acquired form, medications and multiple myeloma are the most common causes. Based on the Naranjo probability scale, a drug was the probable cause of Fanconi syndrome in our patient. However, because multiple drugs were involved, it was not possible to determine which one was the culprit. Conclusions: This is the first case of Fanconi syndrome reported after the administration of capecitabine, irinotecan, and bevacizumab. More studies are needed to confirm this association.
Sex Differences in Inappropriate Drug Use: a Register-Based Study of Over 600,000 Older People
Authors: Johnell Kristina , Weitoft Gunilla Ringbäck , Fastbom Johan 
Published: July 2009

Background: Several studies have observed a higher rate of inappropriate drug use in elderly women than in elderly men, although few have focused explicitly on sex differences. Also, educational level (a measure of socioeconomic status) has been associated with both polypharmacy and inappropriate drug use in the elderly population, which could explain sex differences in inappropriate drug use. Objective: To investigate whether sex is associated with inappropriate drug use in a large general population of older people, after adjustment for age, socioeconomic status (ie, educational level), and comorbidity (ie, number of drugs). Methods: We conducted an analysis of data on sex, age, dispensed drugs, and education for people aged 75–89 years who were registered in the Swedish Prescribed Drug Register between July and October 2005 (N = 645,429). The main outcome measures were the filling of prescriptions for anticholinergic drugs or long-acting benzodiazepines, concurrent use of 3 or more psychotropic drugs, and potentially serious drug–drug interactions. Results: Potentially inappropriate drug use was more common in women (24.6%) than in men (19.3%). More women than men were exposed to all types of inappropriate drug use, except for potentially serious drug–drug interactions. Logistic regression analysis showed that women were more likely to be exposed to potentially inappropriate drug use than were men (OR 1.24; 95% CI 1.23 to 1.26) after adjustment for age, education, and number of drugs (used as a proxy for comorbidity). In particular, female sex was highly associated with Inappropriate psychotropic use (eg, long-acting benzodiazepines: adjusted OR [ORadjusted] 1.45; 95% CI 1.42 to 1.49; >3 psychotropic drugs: QRadjusted 1.50; 95% CI 1.47 to 1.53). In contrast, women had a lower probability of potentially serious drug-drug interactions than did men (ORadjusted 0.81; 95% CI 0.80 to 0.83). Conclusions: Inappropriate drug use in the elderly should be monitored separately for women and men. Our results suggest that neither socioeconomic status nor comorbidity seem to explain sex differences in inappropriate drug use. Future research in other large study populations is needed for investigation of other explanations behind these sex differences.
Dapagliflozin for the Treatment of Type 2 Diabetes
Authors: Brooks Amie McCord , Thacker Stacey M 
Published: July 2009

Objective: To review the literature and describe the pharmacology, pharmacokinetics, clinical safety, and efficacy of dapagliflozin, a compound currently in Phase 3 clinical trials. Data Sources: A search of the literature was conducted via MEDLINE (1995–March 2009) and ClinicalTrials.gov using the search terms dapagliflozin, SGLT2 inhibitor, sodium-glucose co-transport inhibition, and renal glucose reabsorption inhibition. Bibliographies of identified articles were also used to identify useful references. Study Selection and Data Extraction: All English-language reports evaluating dapagliflozin were included in this review, including abstracts and scientific presentations. Data Synthesis: Due to the increasing prevalence of type 2 diabetes, suboptimal management of the associated hyperglycemia, morbidity and mortality associated with the disease, and the limitations of currently available therapies, novel therapeutic strategies are needed for its treatment. Dapagliflozin represents the first selective, sodium-glucose cotransporter 2 inhibitor that functions by regulating renal glucose reabsorption. Clinical trial data are limited, but available evidence supports clinically significant reductions in fasting plasma glucose, postprandial plasma glucose, hemoglobin A1c, and body weight with this agent. In addition, dapagliflozin has demonstrated excellent tolerability with safety data demonstrated in both Phase 1 and Phase 2 studies. Conclusions: Dapagliflozin represents the first in a new class of drugs that may represent a promising new option in the treatment of type 2 diabetes. Results of ongoing Phase 3 clinical trials are necessary to demonstrate efficacy and safety of this agent across various patient populations and clinical scenarios.
Regression From Pre-Diabetes to Normal Glucose Regulation in the Diabetes Prevention Program
Authors: Perreault Leigh , Kahn Steven E. , Christophi Costas A. , Knowler William C. , Hamman Richard F. ,   the Diabetes Prevention Program Research Group
Published: July 2009

OBJECTIVE
Participants in the Diabetes Prevention Program (DPP) randomized to intensive lifestyle modification (ILS) or metformin had a significantly reduced incidence of diabetes compared with those randomized to placebo, yet most were still at risk because they had pre-diabetes. We explored the effect of baseline characteristics, weight change, ILS, and metformin on regression from pre-diabetes to the lowest-risk state of normal glucose regulation (NGR) defined by American Diabetes Association criteria.

RESEARCH DESIGN AND METHODS
The DPP was a prospective randomized trial. Cox proportional hazards modeling was used to identify predictors of regression from pre-diabetes to NGR over 3 years of follow-up.

RESULTS
Lower baseline fasting (hazard ratio 1.52, P &lt; 0.01) and 2-h (1.24, P &lt; 0.01) glucose predicted regression to NGR, as did younger age (1.07, P &lt; 0.01) and greater insulin secretion (1.09, P = 0.04). ILS (2.05, P &lt; 0.01) and weight loss (1.34, P &lt; 0.01) had significant and independent effects on regression. A nonsignificant trend for regression was also observed for metformin (1.25, P = 0.06), male sex (1.17, P = 0.08), and insulin sensitivity (1.07, P = 0.09). In those entering the study with both impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), male sex and insulin sensitivity predicted regression to isolated IFG, whereas ILS, metformin, female sex, and greater insulin secretion predicted regression to isolated IGT.

CONCLUSIONS
Insulin secretion, and other biologic processes retained with younger age, are key in restoring NGR in people with pre-diabetes. However, NGR may also be attained through weight loss and additional aspects of ILS.
Differentiation of Embryonic Stem Cells into Anterior Definitive Endoderm
Authors: Livigni Alessandra , Villegas Santiago Nahuel , Oikonomopoulou Ifigenia , Rahman Afifah , Morrison Gillian M. , Brickman Joshua M. 
Published: July 2009

AbstractAnterior definitive endoderm (ADE) is both an important embryonic signaling center and a unique multipotent precursor of liver, pancreas, and other visceral organs. Here we describe a method for the differentiation of mouse embryonic stem (ES) cells to endoderm with pronounced anterior character. ADE‐containing cultures can be produced in vitro by suspension (aggregation or embryoid body) culture and in a serum‐free adherent monolayer culture. Purified ES cell–derived ADE cells appear committed to endodermal fates and can undergo further differentiation in vitro towards liver and pancreas with enhanced efficiency. Curr. Protoc. Stem Cell Biol. 10:1G.3.1‐1G.3.10. © 2009 by John Wiley & Sons, Inc.
Lithium Storage in Carbon Nanostructures
Authors: Kaskhedikar Nitin A. , Maier Joachim 
Published: July 2009

AbstractIn this review article we discuss the progress of lithium storage in different carbon forms starting from intercalation in graphite to the lithium storage in fullerenes, nanotubes, diamond and most recently, graphene. The recent advances in lithium storage in various novel morphological variants of carbons prepared by a variety of techniques are also discussed with the most important models in literature that have been set out to explain the excess lithium storage. The major emphasis lies on the real structure.
A numerical study of mixing in a microchannel with circular mixing chambers
Authors: Ansari Mubashshir Ahmad , Kim Kwang‐Yong 
Published: July 2009

AbstractThe mixing of fluids in a microchannel is numerically investigated using three‐dimensional Navier–Stokes equations. The microchannel has circular mixing chambers that are designed to create a self‐circulating flow that operates at low Reynolds numbers. The investigations have been performed on a design that comprises of four circular mixing chambers that are joined together with constriction channels. The study has been carried out in two parts. Firstly, the mixing and the flow field are analyzed for a wide range (1–250) of the Reynolds number. Secondly, the effects of two design parameters, namely, the ratio, w/d, of the width of the constriction channel to the diameter of the circular chamber, and the angle, θ, between the outer walls of the chamber and the connection channel, on the mixing and the flow field have been evaluated. The mixing has been evaluated using a parameter, called mixing index, which is based on the variance of the mass fraction. The mixing index at the end of the device increases rapidly with the Reynolds number. The presence of a flow recirculation zone in the circular chamber is found to be effective in enhancing mixing, especially for larger Reynolds numbers. The mixing performance improves with an increase in θ, and with a decrease in w/d. The characteristics of the pressure drop have also been investigated as a function of the Reynolds number and geometric parameters. © 2009 American Institute of Chemical Engineers AIChE J, 2009