bluuebunny/crossref_metadata_2025 huggingface dataset:
Diurnal timing of warmer air under climate change affects magnitude, timing and duration of stream temperature change
Authors: Diabat Mousa , Haggerty Roy , Wondzell Steven M.
Published: September 2012

Stream temperature will be subject to changes because of atmospheric warming in the future. We investigated the effects of the diurnal timing of air temperature changes – daytime warming versus nighttime warming – on stream temperature. Using the physically based model, Heat Source, we performed a sensitivity analysis of summer stream temperatures to three diurnal air temperature distributions of +4 °C mean air temperature: i) uniform increase over the whole day, ii) warmer daytime and iii) warmer nighttime. The stream temperature model was applied to a 37‐km section of the Middle Fork John Day River in northeastern Oregon, USA. The three diurnal air temperature distributions generated 7‐day average daily maximum stream temperatures increases of approximately +1.8 °C ± 0.1 °C at the downstream end of the study section. The three air temperature distributions, with the same daily mean, generated different ranges of stream temperatures, different 7‐day average daily maximum temperatures, different durations of stream temperature changes and different average daily temperatures in most parts of the reach. The stream temperature changes were out of phase with air temperature changes, and therefore in many places, the greatest daytime increase in stream temperature was caused by nighttime warming of air temperatures. Stream temperature changes tended to be more extreme and of longer duration when driven by air temperatures concentrated in either daytime or nighttime instead of uniformly distributed across the diurnal cycle. Copyright © 2012 John Wiley & Sons, Ltd.
Response of streamflow to climate change and human activity in Xitiaoxi river basin in China
Authors: Zhang Canqiang , Zhang Biao , Li Wenhua , Liu Moucheng
Published: September 2012

In recent years, the Xitiaoxi river basin in China has experienced intensified human activity, including city expansion and increased water demand. Climate change also has influenced streamflow. Assessing the impact of climate variability and human activity on hydrological processes is important for water resources planning and management and for the sustainable development of eco‐environmental systems. The non‐parametric Mann–Kendall test was employed to detect the trends of climatic and hydrological variables. The Mann–Kendall–Sneyers test and the moving t‐test were used to locate any abrupt change of annual streamflow. A runoff model, driven by precipitation and potential evapotranspiration, was employed to assess the impact of climate change on streamflow. A significant downward trend was detected for annual streamflow from 1975 to 2009, and an abrupt change occurred in 1999, which was consistent with the change detected by the double mass curve test between streamflow and precipitation. The annual precipitation decreased slightly, but upward trends of annual mean temperature and potential evapotranspiration were significant. The annual streamflow during the period 1999–2009 decreased by 26.19% compared with the reference stage, 1975–1998. Climate change was estimated to be responsible for 42.8% of the total reduction in annual streamflow, and human activity accounted for 57.2%. Copyright © 2012 John Wiley & Sons, Ltd.
Effects of the Three Gorges Reservoir on the hydrological droughts at the downstream Yichang station during 2003–2011
Authors: Li Shuai , Xiong Lihua , Dong Leihua , Zhang Jun
Published: September 2012

Since the Three Gorges Reservoir (TGR) was put into operation in June 2003, the effects of the TGR on downstream hydrology and water resources have become the focus of public attention. This article examines the effects of the TGR on the hydrological droughts at the downstream Yichang hydrological station during 2003–2011. The two‐parameter monthly water balance model was used to generate the monthly discharges at the Yichang station for the period of 2003–2011 to represent the unregulated flow regime and thus to provide a comparison benchmark for the observed flow series at the Yichang station after the operation of the TGR. To provide a reference series for the observed monthly discharge series of the entire study period of 1951–2011, we constructed the naturalized monthly discharge series at the Yichang station by joining the observed monthly discharge at the Yichang station for the period of 1951–2002 and the two‐parameter monthly water balance simulated monthly runoff at the Yichang station for the period of 2003–2011. For both the observed and naturalized monthly discharge series of 1951–2011, the hydrological drought index series were calculated using the standardized streamflow index method. By comparing the drought indices of these two monthly discharge series, we investigated the effects of the TGR on the hydrological droughts at the downstream Yichang station during 2003–2011. The results show that the hydrological droughts at the downstream Yichang station are slightly aggravated by the TGR's initial operation from 2003 to 2011. The river flow reduction at the Yichang station after impoundment of the TGR might account for the downstream drought aggravation. Copyright © 2012 John Wiley & Sons, Ltd.
A method for estimating spatially variable seepage and hydraulic conductivity in channels with very mild slopes
Authors: Shanafield Margaret , Niswonger Richard G. , Prudic David E. , Pohll Greg , Susfalk Richard , Panday Sorab
Published: September 2012

Infiltration along ephemeral channels plays an important role in groundwater recharge in arid regions. A model is presented for estimating spatial variability of seepage due to streambed heterogeneity along channels based on measurements of streamflow‐front velocities in initially dry channels. The diffusion‐wave approximation to the Saint‐Venant equations, coupled with Philip's equation for infiltration, is connected to the groundwater model MODFLOW and is calibrated by adjusting the saturated hydraulic conductivity of the channel bed. The model is applied to portions of two large water delivery canals, which serve as proxies for natural ephemeral streams. Estimated seepage rates compare well with previously published values. Possible sources of error stem from uncertainty in Manning's roughness coefficients, soil hydraulic properties and channel geometry. Model performance would be most improved through more frequent longitudinal estimates of channel geometry and thalweg elevation, and with measurements of stream stage over time to constrain wave timing and shape. This model is a potentially valuable tool for estimating spatial variability in longitudinal seepage along intermittent and ephemeral channels over a wide range of bed slopes and the influence of seepage rates on groundwater levels. Copyright © 2012 John Wiley & Sons, Ltd.
Feasibility of real time next generation sequencing of cancer genes linked to drug response: Results from a clinical trial
Authors: Tran Ben , Brown Andrew M.K. , Bedard Philippe L. , Winquist Eric , Goss Glenwood D. , Hotte Sebastien J. , Welch Stephen A. , Hirte Hal W. , Zhang Tong , Stein Lincoln D. , Ferretti Vincent , Watt Stuart , Jiao Wei , Ng Karen , Ghai Sangeet , Shaw Patricia , Petrocelli Teresa , Hudson Thomas J. , Neel Benjamin G. , Onetto Nicole , Siu Lillian L. , McPherson John D. , Kamel‐Reid Suzanne , Dancey Janet E.
Published: September 2012

The successes of targeted drugs with companion predictive biomarkers and the technological advances in gene sequencing have generated enthusiasm for evaluating personalized cancer medicine strategies using genomic profiling. We assessed the feasibility of incorporating real‐time analysis of somatic mutations within exons of 19 genes into patient management. Blood, tumor biopsy and archived tumor samples were collected from 50 patients recruited from four cancer centers. Samples were analyzed using three technologies: targeted exon sequencing using Pacific Biosciences PacBio RS, multiplex somatic mutation genotyping using Sequenom MassARRAY and Sanger sequencing. An expert panel reviewed results prior to reporting to clinicians. A clinical laboratory verified actionable mutations. Fifty patients were recruited. Nineteen actionable mutations were identified in 16 (32%) patients. Across technologies, results were in agreement in 100% of biopsy specimens and 95% of archival specimens. Profiling results from paired archival/biopsy specimens were concordant in 30/34 (88%) patients. We demonstrated that the use of next generation sequencing for real‐time genomic profiling in advanced cancer patients is feasible. Additionally, actionable mutations identified in this study were relatively stable between archival and biopsy samples, implying that cancer mutations that are good predictors of drug response may remain constant across clinical stages.
Addition of interferon‐α to the p53‐SLP® vaccine results in increased production of interferon‐γ in vaccinated colorectal cancer patients: A phase I/II clinical trial
Authors: Zeestraten Eliane C.M. , Speetjens Frank M. , Welters Marij J.P. , Saadatmand Sepideh , Stynenbosch Linda F.M. , Jongen Rogier , Kapiteijn Ellen , Gelderblom Hans , Nijman Hans W. , Valentijn A. Rob P.M. , Oostendorp Jaap , Fathers Lorraine M. , Drijfhout Jan W. , van de Velde Cornelis J.H. , Kuppen Peter J.K. , van der Burg Sjoerd H. , Melief Cornelis J.M.
Published: September 2012

We previously established safety and immunogenicity of a p53 synthetic long peptides (p53‐SLP®) vaccine. In the current trial, we investigated whether combination of interferon‐alpha (IFN‐α) with p53‐SLP® is both safe and able to improve the induced p53‐specific IFN‐γ response. Eleven colorectal cancer patients successfully treated for metastatic disease were enrolled in this study. Of these, nine patients completed follow‐up after two injections with p53‐SLP® together with IFN‐α. Safety and p53‐specific immune responses were determined before and after vaccination. Furthermore, cryopreserved PBMCs were compared head‐to‐head to cryopreserved PBMCs obtained in our previous trial with p53‐SLP® only. Toxicity of p53‐SLP® vaccination in combination with IFN‐α was limited to Grade 1 or 2, with predominantly small ongoing swellings at the vaccination site. All patients harbored p53‐specific T cells after vaccination and most patients showed p53‐specific antibodies. Compared to the previous trial, addition of IFN‐α significantly improved the frequency of p53‐specific T cells in IFN‐γ ELISPOT. Moreover, in this trial, p53‐specific T cells were detectable in blood samples of all patients in a direct ex vivo multiparameter flowcytometric assay, opposed to only 2 of 10 patients vaccinated with p53‐SLP® only. Finally, patients in this trial displayed a broader p53‐specific immunoglobulin‐G response, indicating an overall better p53‐specific T‐helper response. Our study shows that p53‐SLP® vaccination combined with IFN‐α injection is safe and capable of inducing p53‐specific immunity. When compared to a similar trial with p53‐SLP® vaccination alone the combination was found to induce significantly more IFN‐γ producing p53‐specific T cells.
Distressing Adverse Events After Antidepressant Switch in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Trial: Influence of Adverse Events During Initial Treatment with Citalopram on Development of Subsequent Adverse Events with an Alternative Antidepressant
Authors: Katz Aaron J. , Dusetzina Stacie B. , Farley Joel F. , Ellis Alan R. , Gaynes Bradley N. , Castillo Wendy C. , Stürmer Til , Hansen Richard A.
Published: September 2012

Study Objective

To determine whether distressing adverse events (DAEs) experienced during initial antidepressant treatment are associated with subsequent DAEs after switching to a second antidepressant.

Design

Secondary analysis of data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.

Setting

Primary care and psychiatric care facilities.

Patients

A total of 727 outpatients aged 18–75 years with nonpsychotic major depressive disorder who failed first‐step therapy with citalopram and were switched to second‐step monotherapy with an alternative antidepressant.

Measurements and Main Results

In the STAR*D trial, patient‐reported DAEs were entered into the Patient‐Rated Inventory of Side Effects (PRISE). In this secondary analysis, data from PRISE were used to determine the incidence of DAEs during first‐step treatment with citalopram and second‐step treatment with sustained‐release bupropion, sertraline, or extended‐release venlafaxine. Regression models were used to compare the risk of adverse events during second‐step treatment between those who reported similar adverse events during first‐step treatment and those who did not, while controlling for potential confounders. Of the 727 patients analyzed, DAEs were reported by 514 patients (70.7%) during first‐step treatment and 626 (86.1%) during second‐step treatment; no significant differences were observed among the three second‐step treatment groups. Overall, patients reporting DAEs during first‐step treatment were more likely to report DAEs during second‐step treatment (risk ratio [RR] 1.11, 95% confidence interval [CI] 1.03–1.20). After controlling for confounders, patients were significantly more likely to report DAEs specific to a body function or organ system, such as those involving the genitourinary system (RR 3.39, 95% CI 2.41–4.78) or sexual functioning (RR 2.75, 95% CI 2.29–3.29), if the patients had reported similar events during initial treatment.

Conclusion

Patients who experienced DAEs with initial antidepressant treatment were likely to report similar adverse events after switching to an alternative antidepressant, even when subsequent treatment is from a different class of antidepressants.
Severe Prolonged Sedation Associated with Coadministration of Protease Inhibitors and Intravenous Midazolam During Bronchoscopy
Authors: Hsu Alice Jenh , Carson Kathryn A. , Yung Rex , Pham Paul A.
Published: September 2012

Study Objective

To determine whether human immunodeficiency virus (HIV)‐positive patients who received intravenous midazolam during an inpatient bronchoscopy procedure were more likely to experience severe prolonged sedation if they were taking antiretroviral therapy that included a protease inhibitor versus those who were not taking any antiretroviral therapy.

Design

Retrospective cohort study.

Setting

Tertiary care academic medical center.

Patients

Two hundred forty‐one HIV‐positive adults who received intravenous midazolam while undergoing bronchoscopy between January 1, 2003, and December 31, 2006, were analyzed; 51 patients were taking an antiretroviral regimen that included a protease inhibitor (exposed group), whereas 190 patients were not taking any antiretroviral agents (nonexposed group).

Measurements and Main Results

Patient demographics, medication administration records, and bronchoscopy data were collected from electronic databases and patient medical records. The exposed and nonexposed groups had similar demographic characteristics except that patients in the exposed group had lower HIV viral loads and were less likely to have altered mental status or respiratory distress before bronchoscopy. In addition, the exposed group had a higher proportion of males and patients with hepatitis B or C virus coinfection. The incidence of severe prolonged sedation was 9.80% in the exposed group versus 1.58% in the nonexposed group (relative risk [RR] 6.21, 95% confidence interval [CI] 1.53–25.12). Specific protease inhibitors associated with severe prolonged sedation were atazanavir‐ritonavir and lopinavir‐ritonavir. Length of hospital stay was approximately 3 days longer in the exposed group compared with the nonexposed group.

Conclusion

Although the interaction between intravenous midazolam and protease inhibitors is well known, this study was the first systematic evaluation, to our knowledge, of the risk of severe prolonged sedation in a cohort of hospitalized HIV‐positive patients. Coadministration of protease inhibitors with intravenous midazolam was associated with severe prolonged sedation as well as increased length of hospital stay. Therefore, concomitant use of these drugs should be closely monitored, or alternative sedatives for procedural sedation should be considered.
Key Articles of Dietary Interventions that Influence Cardiovascular Mortality
Authors: Finks Shannon W. , Airee Anita , Chow Sheryl L. , Macaulay Tracy E. , Moranville Michael P. , Rogers Kelly C. , Trujillo Toby C.
Published: September 2012

Lifestyle modifications, particularly diet, are a key component to the reduction of cardiovascular events. Diets high in carbohydrates and saturated fat have been shown to negatively affect blood cholesterol, thereby increasing the risk for cardiovascular disease (CVD). Dietary interventions that emphasize the consumption of whole grains, fruits, and vegetables have been shown to be successful in reducing cardiovascular risk. Clinical pharmacist practitioners need to be knowledgeable regarding lifestyle modifications, specifically dietary issues, to develop a comprehensive, effective, and evidence‐based plan for patients who are either at risk for or who have established CVD. Numerous studies have been published over the past few years with regard to the rapidly growing field of dietary interventions that influence cardiovascular risk, and the amount of literature can be overwhelming. Thus we chose to focus our review on articles that assess changes in dietary patterns that affect overall mortality risk from CVD. As such, literature describing the impact of dietary factors that influence weight, lipid changes, or other risk factors alone were not included in this review. A group of practitioners with expertise and interest in CVD were involved in the compilation of this article.
Immunoassay Cross‐Reactivity of Phenylephrine and Methamphetamine
Authors: Curtin Lindsay B. , Cawley Michael J.
Published: September 2012

Phenylephrine, an α1‐adrenergic agonist, and methamphetamine, a prescription drug and substance of abuse, have similar chemical structures and thus have the potential to cross‐react in qualitative screening tools such as a urine drug screening (UDS) performed by immunoassay. This cross‐reactivity may yield a false‐positive result that may affect the provision of care in certain patient populations and clinical situations. We describe a 36‐year‐old woman with confirmed brain death after a short hospital stay who had an initial UDS that was negative for methamphetamine. The patient was assessed for potential organ donation, which included obtaining a follow‐up UDS. A urine sample was obtained after being hospitalized for 36 hours, which tested positive for methamphetamine, with no suspected ingestion of the target substance. Confirmatory laboratory testing indicated that intravenous phenylephrine and its metabolites were the likely cause of the false‐positive UDS. However, the patient was not deemed to be a suitable candidate for organ donation, but clear documentation of the reason for denial of organ donation was not available in the patient's medical record. To our knowledge, this is the first case published in the English‐language literature that describes the clinical occurrence of apparent immunoassay cross‐reactivity of methamphetamine and phenylephrine that resulted in a false‐positive UDS for methamphetamine. In addition, this report describes the potential implications of this situation on clinical care, including organ donation acceptance. Toxicology screening in the emergency department and intensive care unit is a tool to assist in the diagnosis of medical conditions, but it may not always be reliable. Therefore, positive immunoassay results that may change the management of a patient's condition should be quickly verified with confirmatory testing to minimize unfavorable consequences.
Influence of Pill Burden and Drug Cost on Renal Function After Transplantation
Authors: Hardinger Karen L. , Hutcherson Timothy , Preston David , Murillo Daniel
Published: September 2012

Study Objective

To determine the influence of pill burden and drug cost on outcomes after renal transplantation.

Design

Retrospective medical record review.

Setting

Kidney and pancreas transplantation center.

Patients

Sixty‐eight adults who underwent kidney or kidney‐pancreas transplantation during 2007.

Measurements and Main Results

The median pretransplantation pill burden was 15 pills/day, which increased to 25 pills/day at 1 month after transplantation and returned to 16 pills/day by 1 year after transplantation. Pretransplantation pill burden was lower than the burden at 1, 3, 6, 12, and 24 months after transplantation (p<0.05). The mean pretransplantation drug cost of $1918/month was lower than the cost at 1 month after transplantation ($2564/mo, p=0.04) but was similar thereafter. Higher pretransplantation pill burden was associated with increased serum creatinine concentration at 6 months after transplantation (r=0.288, p=0.017). Higher pill burdens at 1 month (r=0.364, p=0.002), 3 months (r=0.332, p=0.006), and 6 months (r=0.374, p=0.002) were associated with increased 3‐month serum creatinine concentration. Higher drug costs were associated with increased serum creatinine concentrations throughout the study.

Conclusion

Higher pretransplantation pill burden and higher drug cost may be associated with poor renal function after transplantation. Further study addressing factors associated with nonadherence is needed.
Use of the Chromogenic Factor X Assay in Patients Transitioning from Argatroban to Warfarin Therapy
Authors: Austin Jennifer H. , Stearns Candace R. , Winkler Anne M. , Paciullo Christopher A.
Published: September 2012

Study Objective

To assess the correlation between the chromogenic factor X assay and the international normalized ratio (INR) in patients transitioning from argatroban to warfarin therapy.

Design

Retrospective medical record review.

Setting

Academic medical center and community‐based teaching hospital.

Patients

One hundred thirty‐nine patients who had chromogenic factor X levels measured during the transition from argatroban to warfarin therapy between January 1, 2006, and July 31, 2010.

Measurements and Main Results

The correlation between chromogenic factor X levels and INRs during the transition period was assessed by calculating the sensitivity, specificity, positive predictive value, and negative predictive value for chromogenic factor X levels that were less than or equal to 45% in predicting a therapeutic INR (2.0–3.5). Patients received an average of 4.4 doses of warfarin before argatroban was discontinued. In 60 patients (43.2%), chromogenic factor X levels were subtherapeutic at the time of argatroban discontinuation. Chromogenic factor X levels could predict a therapeutic INR with a sensitivity of 63.2%, a specificity of 80%, a positive predictive value of 93.5, and a negative predictive value of 32.3. In patients who received 5 or more days of warfarin overlap with argatroban, the sensitivity of chromogenic factor X levels to predict an INR greater than 2.0 was 78.2%, with a specificity of 77.8%, a positive predictive value of 95.6, and a negative predictive value of 36.8. The correlation of chromogenic factor X levels and a therapeutic INR was 18.1%; however, this poor correlation may have been due to increases in the INR values of the patients who received less than 5 days of warfarin overlap with argatroban. During the transition period, nine patients developed thrombi and eight patients experienced clinically significant bleeding.

Conclusion

Measuring chromogenic factor X levels is recommended before transitioning patients from argatroban to warfarin therapy. Patients should receive at least 5 days of overlap with warfarin and have a chromogenic factor X level of 45% or less before discontinuing argatroban.
Relationship Between Changes in Inhaled Corticosteroid Use and Markers of Uncontrolled Asthma During Pregnancy
Authors: Blais Lucie , Firoozi Faranak , Kettani Fatima‐Zohra , Ducharme Francine M. , Lemière Catherine , Beauchesne Marie‐France , Bérard Anick
Published: September 2012

Study Objective

To describe changes in inhaled corticosteroid use during pregnancy and markers of uncontrolled asthma, and to evaluate the association between them.

Design

Population‐based, cross‐sectional study.

Data Source

Three administrative claims databases in Québec, Canada.

Patients

A cohort of 4434 asthmatic women (4920 pregnancies) who delivered their infants between 1990 and 2002 and who used inhaled corticosteroids before their pregnancy.

Measurements and Main Results

The average daily doses of inhaled corticosteroids during pregnancy and during the 9 months before conception were compared; the change in use was categorized as discontinuation (reduction of ≥75%), reduction (26–75% reduction), no change (±25% change), or increase (increase of ≥25%). The markers of uncontrolled asthma included at least one asthma exacerbation and the use of three or more doses/week of a short‐acting β2‐agonist during pregnancy. Generalized estimating equation models were used for statistical analyses. In nearly 50% of the pregnancies (2388 [48.5%] of 4920), the women either stopped or reduced their doses of corticosteroid during pregnancy, and these doses were already quite low before pregnancy. The proportion of women who had an asthma exacerbation during pregnancy was 8.2% among women who discontinued corticosteroids and greater than 20% in all of the other groups. All of the groups used frequent doses of short‐acting β2‐agonists. Discontinuing inhaled corticosteroid use during pregnancy was associated with a lower risk of exacerbations (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.33–0.54), whereas increasing inhaled corticosteroid use was associated with a higher risk (OR 1.42, 95% CI 1.17–1.72), compared with no change in use.

Conclusion

Because of residual confounding by asthma severity, our study was not able to show that women who stopped inhaled corticosteroids during pregnancy were at increased risk of having an asthma exacerbation. However, women who stopped corticosteroids tended to have a milder form of asthma, which is reassuring and suggests that women can recognize, to a certain extent, the need to continue taking their controller agents if necessary.
Incidence of Amiodarone Hypersensitivity in Patients with Previous Allergy to Iodine or Iodinated Contrast Agents
Authors: Lakshmanadoss Umashankar , Lindsley John , Glick Daryl , Twilley Charles H. , Lewin John J. , Marine Joseph E.
Published: September 2012

Study Objective

To determine the incidence and nature of allergic reactions to amiodarone in hospitalized patients with a listed allergy to iodine or iodinated radiocontrast agents.

Design

Retrospective medical record review.

Setting

Two academic medical centers.

Patients

A total of 234 sequential hospitalized patients with a listed iodine and/or iodinated radiocontrast agent allergy who received oral or intravenous amiodarone between January 2006 and December 2010.

Measurements and Main Results

Demographic and clinical data, as well as documentation of an allergic reaction to amiodarone, were collected for each patient from electronic medical records. Mean ± SD age was 69 ± 12 years, and 51% were male. Of the 234 patients, 167 (71%) had a listed previous allergy to iodinated contrast agents, 55 (24%) to iodine, and 12 (5%) to both. Patients received an average inpatient total dose of 2.9 ± 3.2 g of either oral (106 patients [45%]), intravenous (39 patients [17%]), or both oral and intravenous (89 patients [38%]) amiodarone. Only 1 (0.4%) of the 234 patients was identified as having a probable allergic reaction to amiodarone (score of 6 on the Naranjo adverse drug reaction probability scale). One additional patient receiving intravenous amiodarone experienced a rash that was determined to be caused by an antibiotic. All other patients received amiodarone without any identifiable allergic reactions.

Conclusion

The incidence of hypersensitivity reaction to amiodarone in hospitalized patients with a listed allergy to iodine or iodinated contrast agents was less than 1%, and all identified reactions were without long‐term sequelae. Allergy to iodine and iodinated contrast agents may not be a valid absolute contraindication to amiodarone administration in the inpatient setting.
Evaluation of Serum Creatinine Concentration–Based Glomerular Filtration Rate Equations in Pediatric Patients with Chronic Kidney Disease
Authors: Lee Carlton K. K. , Swinford Rita D. , Cerda Ruby D. , Portman Ronald J. , Hwang Wenke , Furth Susan L.
Published: September 2012

Study Objective

To evaluate the accuracy of four equations based on serum creatinine concentration—the original Schwartz equation and the Leger, Bedside Chronic Kidney Disease in Children (CKiD), and Counahan‐Barratt equations—for determining glomerular filtration rate (GFR) in pediatric patients with chronic kidney disease.

Design

Retrospective, observational, cross‐sectional study.

Setting

Single‐center, academic, outpatient pediatric nephrology clinic.

Patients

Fifty‐three pediatric patients with stages 2–5 chronic kidney disease who completed GFR assessment with 125I‐iothalamate between January 2002 and January 2005.

Measurement and Main Results

Data were collected from each patient's medical record. Glomerular filtration rate data were analyzed using 59 evaluations from the 53 pediatric patients. 125I‐iothalamate clearance was used as the index GFR. The Bedside CKiD and Counahan‐Barratt equations outperformed the Schwartz and Leger equations when the index GFR was less than 60 ml/minute/1.73 m2; the Schwartz and Counahan‐Barratt equations performed best for index GFRs of 60 ml/minute/1.73 m2 or greater. Overestimation was highest with the Schwartz and Leger equations (> 20% index GFR in 57.6% and 62.7% of patients, respectively). Underestimation was highest with the Bedside CKiD and Counahan‐Barratt equations (> 20% index GFR in 30.5% and 28.8%, respectively).

Conclusion

The new Bedside CKiD equation performed well for pediatric patients with moderate‐to‐severe chronic kidney disease, but less well for pediatric patients with mild disease. Additional studies are needed to develop more precise GFR equations using serum creatinine concentration.
Proarrhythmic Potential of Dronedarone: Emerging Evidence from Spontaneous Adverse Event Reporting
Authors: Kao David P. , Hiatt William R. , Krantz Mori J.
Published: September 2012

Study Objective

To characterize the frequency and type of cardiac events, including torsade de pointes, associated with dronedarone and its structural analog, amiodarone, outside of the clinical trial setting.

Design

Retrospective analysis.

Data Source

Spontaneous reports in the United States Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database generated between July 1, 2009, and June 30, 2011.

Measurements and Main Results

All reports of adverse events during the study period were reviewed to identify cardiac events associated with any approved drug in the United States. The type and number of cardiac events associated with dronedarone and amiodarone were determined. Active ingredients were identified using the Drugs@FDA database, and the Medical Dictionary for Regulatory Activities (MedDRA) was used to aggregate related adverse events. To avoid redundant reporting, all statistics were generated in reference to unique case identifiers. Dronedarone was associated with more adverse cardiovascular event reports than amiodarone (810 vs 493 reports) during the study period. Dronedarone was also associated with the most reports of torsade de pointes of any approved drug in the United States (37 reports), followed by amiodarone (29 reports). Reports of ventricular arrhythmias and cardiac arrest (138 vs 113 reports) as well as heart failure (179 vs 126 reports) were more common with dronedarone than amiodarone.

Conclusion

Dronedarone was associated with reports of ventricular arrhythmia, cardiac arrest, and torsade de pointes in clinical practice. Whether this observation accounts for the increased risk of fatal arrhythmia observed in a recent prospective trial requires further investigation.
Characterization of Continued Antibacterial Therapy After Diagnosis of Hospital‐Onset Clostridium difficile Infection: Implications for Antimicrobial Stewardship
Authors: Harpe Spencer E. , Inocencio Timothy J. , Pakyz Amy L. , Oinonen Michael J. , Polk Ronald E.
Published: September 2012

Study Objectives

To determine the proportion of hospitalized adults with hospital‐onset
Clostridium difficile infection (CDI) who continued to receive concomitant non‐CDI antibacterial agents, to characterize the antibacterial therapy that these patients received before and after the diagnosis of CDI, and to compare hospital outcomes between those patients who did and those who did not have their previous antibacterial therapy discontinued after CDI diagnosis.

Design

Retrospective cohort study.

Data Source

Drug use and administrative discharge data from 42 United States academic medical centers.

Patients

A total of 5968 adult inpatients with hospital‐onset CDI between January 1, 2002, and June 30, 2006.

Measurements and Main Results

We characterized patient‐level antibacterial agent use before and after CDI diagnosis. Overall, 3479 patients (58.3%) continued antibacterial therapy for 2 or more days after CDI diagnosis (interhospital range 6.7–72.2%). Although the number of different antibacterial agents received in the week preceding CDI diagnosis was positively associated with continued antibacterial therapy, the relationship between continuation and severity of illness was statistically significant but nonlinear. Patients who were receiving oral vancomycin alone were less likely to have antibacterial therapy continued (28/61 patients [45.9%]) than patients receiving metronidazole alone (1154/2333 patients [49.5%]) or receiving both metronidazole and oral vancomycin (2297/3576 [64.2%]). After adjusting for confounders, patients who continued to receive antibacterial therapy had a 62.7% (95% confidence interval [CI] 48.6–78.0%, p<0.001) longer length of hospital stay after CDI diagnosis than those who did not continue therapy; the adjusted odds of mortality and odds of readmission were 1.7 (95% CI 1.4–2.1, p<0.001) and 1.2 (95% CI 1.1–1.5, p=0.025) times higher, respectively, with continued antibacterial therapy.

Conclusion

A majority of patients with CDI continued to receive antibacterial agents after their CDI diagnosis, although the interhospital range was large. Compared with patients who did not continue therapy, hospital length of study, mortality, and subsequent admissions among patients who continued their antibacterial therapy remained significantly higher after adjusting for confounders. The adverse outcomes associated with continued therapy likely reflect the severity of the underlying primary infection and/or a poorer response to CDI therapy, suggesting an opportunity for antimicrobial stewardship programs to make important contributions to patient care.
Inappropriate Antibiotic Use Due to Decreased Compliance with a Ventilator‐Associated Pneumonia Computerized Clinical Pathway: Implications for Continuing Education and Prospective Feedback
Authors: Wilde Ashley M. , Nailor Michael D. , Nicolau David P. , Kuti Joseph L.
Published: September 2012

Study Objective

To assess the impact of noncompliance with a ventilator‐associated pneumonia (VAP) computerized clinical pathway (CCP) on antibiotic use after removal of prospective antibiotic stewardship resources.

Design

Retrospective, observational, quasi‐experimental study.

Setting

Three intensive care units (medical, surgical, and neurotrauma) in a large, tertiary care hospital.

Patients

A total of 136 patients with culture‐positive VAP; 72 were treated from September 2006–August 2007 (period 1), during which use of the CCP was mandatory along with aggressive stewardship support, and 64 were treated from September 2009–April 2010 (period 2), during which use of the CCP was voluntary.

Measurements and Main Results

Compliance with use of the CCP was 100% during period 1 and 44% (28/64 patients) during period 2. For the 36 patients (56%) whose antibiotic selection did not comply with the CCP, empiric antibiotics were selected by provider discretion. Most patients had late‐onset VAP and were similar with respect to age, sex, and comorbidities between the two periods.
Staphylococcus aureus (11–17% methicillin‐resistant S. aureus) and
Pseudomonas aeruginosa were the most common pathogens during both periods. The proportion of patients with appropriate antibiotics within 24 hours of VAP identification was not significantly different between period 1 (70.8%) and period 2 (56.3%, p=0.112). During period 2, patients who were treated according to the CCP were more likely to receive appropriate antibiotic therapy compared with patients treated according to provider discretion (82.1% vs 36.1%, p≤0.001). Time to appropriate therapy was also shorter for patients treated according to the CCP (mean ± SD 0.43 ± 1.14 vs 1.29 ± 1.36 days, p=0.003). Treatment with the CCP was the only variable significantly associated with appropriate antibiotic therapy (odds ratio 4.8, 95% confidence interval 2.1–10.9). Mortality was not significantly different between period 1 and period 2, and only Acute Physiology and Chronic Health Evaluation II score and admission with a head injury were predictive of death. Finally, a greater proportion of patients treated with the CCP were de‐escalated from anti‐
Pseudomonas β‐lactams (85.0% vs 33.3%, p=0.006) when they were not necessary.

Conclusion

These data highlight the importance of continued stewardship resources after CCP implementation to ensure compliance and to maximize antibiotic stewardship outcomes.
Appropriate description of intermolecular interactions in the methane hydrates: An assessment of DFT methods
Authors: Liu Yuan , Zhao Jijun , Li Fengyu , Chen Zhongfang
Published: September 2012

Accurate description of hydrogen‐bonding energies between water molecules and van der Waals interactions between guest molecules and host water cages is crucial for study of methane hydrates (MHs). Using high‐level ab initio MP2 and CCSD(T) results as the reference, we carefully assessed the performance of a variety of exchange–correlation functionals and various basis sets in describing the noncovalent interactions in MH. The functionals under investigation include the conventional GGA, meta‐GGA, and hybrid functionals (PBE, PW91, TPSS, TPSSh, B3LYP, and X3LYP), long‐range corrected functionals (ωB97X, ωB97, LC‐ωPBE, CAM‐B3LYP, and LC‐TPSS), the newly developed Minnesota class functionals (M06‐L, M06‐HF, M06, and M06‐2X), and the dispersion‐corrected density functional theory (DFT) (DFT‐D) methods (B97‐D, ωB97X‐D, PBE‐TS, PBE‐Grimme, and PW91‐OBS). We found that the conventional functionals are not suitable for MH, notably, the widely used B3LYP functional even predicts repulsive interaction between CH4 and (H2O)6 cluster. M06‐2X is the best among the M06‐Class functionals. The ωB97X‐D outperforms the other DFT‐D methods and is recommended for accurate first‐principles calculations of MH. B97‐D is also acceptable as a compromise of computational cost and precision. Considering both accuracy and efficiency, B97‐D, ωB97X‐D, and M06‐2X functional with 6‐311++G(2d,2p) basis set without basis set superposition error (BSSE) correction are recommended. Though a fairly large basis set (e.g., aug‐cc‐pVTZ) and BSSE correction are necessary for a reliable MP2 calculation, DFT methods are less sensitive to the basis set and BSSE correction if the basis set is sufficient (e.g., 6‐311++G(2d,2p)). These assessments provide useful guidance for choosing appropriate methodology of first‐principles simulation of MH and related systems. © 2012 Wiley Periodicals, Inc.
Are Kissing Gourami Specialized for Substrate‐Feeding? Prey Capture Kinematics of Helostoma temminckii and Other Anabantoid Fishes
Authors: Ferry Lara A. , Konow Nicolai , Gibb Alice C.
Published: September 2012

Helostoma temminckii are known for a “kissing” behavior, which is often used in intraspecific interactions, and an unusual cranial morphology that is characterized by an intramandibular joint (IMJ). The IMJ is located within the lower jaw and aids in generating the eponymous kissing movement. In other teleost linages the IMJ is associated with the adoption of a substrate‐grazing foraging habit. However, because of anatomical modifications of the gill‐rakers, Helostoma has been considered a midwater filter‐feeding species. We offered midwater, benthic, and attached food to Helostoma, Betta, and two “true” osphronemid gouramis, to ask: (1) how do food capture kinematics differ in different foraging contexts; and (2) are Helostoma feeding kinematics distinct when compared with closely related anabantoids that lack an IMJ? For all anabantoid species except Helostoma, benthic prey were captured using a greater contribution of effective suction relative to midwater prey, though Helostoma was rarely willing to feed in the midwater. Helostoma individuals produced relatively less suction than other species regardless of the food type. Helostoma produced a much larger gape and more premaxillary protrusion than other species, but also took longer to do so. We suggest that the jaw morphology of Helostoma facilitates an extremely large mouth‐gape to enhance substrate‐scraping. The large amplitude mouth‐opening that characterizes substrate‐feeding may represent a functional trade‐off, whereby the enhanced ability to procure food from the substrate is accompanied by a concomitant reduction in the ability to produce suction. J. Exp. Zool. 317A:571–579, 2012. © 2012 Wiley Periodicals, Inc.
Ol4E‐T, a Eukaryotic Translation Initiation Factor 4E‐Binding Protein of Medaka Fish (Oryzias latipes), Can Interact With Nanos3 and Vasa In Vitro
Authors: Zhao Haobin , Guan Guijun , Duan Jundan , Cheng Nana , Wang Jialin , Matsuda Masaru , Paul‐Prasanth Bindhu , Nagahama Yoshitaka
Published: September 2012

Maternal factors have essential roles in the specification and development of germ cells in metazoans. In Drosophila, a number of genes such as oskar, vasa, nanos, and tudor are required for specific steps in pole cell formation and further germline development. Drosophila cup, another maternal factor, is confirmed as a main factor in normal oogenesis, maintenance, and survival of female germ‐line stem cells by interaction with Nanos. Through searching for the homolog of Drosophila cup in the medaka, the homolog of eukaryotic translation initiation factor 4E (eIF4E)‐transporter, named Ol4E‐T, was identified. Reverse transcription‐polymerase chain reaction (RT‐PCR) and in situ hybridization revealed that Ol4E‐T is maternally deposited in the embryo and Ol4E‐T expression is maintained throughout embryogenesis. Ol4E‐T is predominantly expressed in the adult gonads. In the testes, Ol4E‐T is expressed in the same regions where medaka vasa, named olvas is expressed. In the ovary, expression of Ol4E‐T conforms to that of nanos3 and olvas. Ol4E‐T harbors a well‐conserved eIF4E‐binding motif, YTKEELL, by which Ol4E‐T interacts with eIF4E in medaka. Additionally, Ol4E‐T can interact with medaka Nanos3 and Olvas, as shown by yeast two hybridization. The spatial expression and interactions between Ol4E‐T with germ cell markers Olvas and Nanos3 suggest a role for Ol4E‐T in germ‐line development in medaka. J. Exp. Zool. (Mol. Dev. Evol.) 320B:10–21, 2013. © 2012 Wiley Periodicals, Inc.
Theria‐Specific Homeodomain andcis‐Regulatory Element Evolution of theDlx3–4Bigene Cluster in 12 Different Mammalian Species
Authors: Sumiyama Kenta , Miyake Tsutomu , Grimwood Jane , Stuart Andrew , Dickson Mark , Schmutz Jeremy , Ruddle Frank H. , Myers Richard M. , Amemiya Chris T.
Published: September 2012

The mammalianDlx3andDlx4genes are configured as a bigene cluster, and their respective expression patterns are controlled temporally and spatially bycis‐elements that largely reside within the intergenic region of the cluster. Previous work revealed that there are conspicuously conserved elements within the intergenic region of theDlx3–4bigene clusters of mouse and human. In this paper we have extended these analyses to include 12 additional mammalian taxa (including a marsupial and a monotreme) in order to better define the nature and molecular evolutionary trends of the coding and non‐coding functional elements among morphologically divergent mammals.Dlx3–4regions were fully sequenced from 12 divergent taxa of interest. We identified three theria‐specific amino acid replacements in homeodomain ofDlx4gene that functions in placenta. Sequence analyses of constrained nucleotide sites in the intergenic non‐coding region showed that many of the intergenic conserved elements are highly conserved and have evolved slowly within the mammals. In contrast, a branchial arch/craniofacial enhancer I37‐2 exhibited accelerated evolution at the branch between the monotreme and therian common ancestor despite being highly conserved among therian species. Functional analysis of I37‐2 in transgenic mice has shown that the equivalent region of the platypus fails to drive transcriptional activity in branchial arches. These observations, taken together with our molecular evolutionary data, suggest that theria‐specific episodic changes in the I37‐2 element may have contributed to craniofacial innovation at the base of the mammalian lineage. J. Exp. Zool. (Mol. Dev. Evol.) 9999B:639–650, 2012. © 2012 Wiley Periodicals, Inc.
DNA Methylation as a Mechanism of Nutritional Plasticity: Limited Support From Horned Beetles
Authors: Snell‐Rood Emilie C. , Troth Ashley , Moczek Armin P.
Published: September 2012

Epigenetic changes to DNA, potentially heritable alterations above the sequence level, such as DNA methylation, are thought to underlie many instances of adaptive phenotypic plasticity. Our understanding of the links between epigenetic variation and adaptive phenotypic plasticity in natural populations is limited. If DNA methylation underlies adaptive responses to different nutritional environments, methylation patterns should be correlated with differences in performance across nutritional environments, and respond to changes in the environment. Additionally, genotypes that can cope with a broader range of nutritional environments are expected to have greater flexibility in methylation patterns. We tested these predictions using horned beetles (genus Onthophagus), which can cope with a wide range of variation in larval nutrition. We surveyed levels of methylation across several methylated loci in lab‐reared beetles originating from natural populations using a methylation‐specific amplified fragment length polymorphism (AFLP) analysis. For less than half the of the loci investigated, methylation level was correlated with performance, measured as adult body size attained on a given diet, in different nutritional environments, with an overall greater effect in males (the more nutritionally plastic sex) than females. Methylation levels at most sites were influenced more by genotype (iso‐female line) than by environment (dung type). Only 1 site (of 12) showed a significant genotype‐by‐environment interaction. Taken together, our results provide modest support for the hypothesis that DNA methylation underlies nutritional plasticity, as only 8–16% of methylated sites conformed to all of our predictions. J. Exp. Zool. (Mol. Dev. Evol.) 320B:22–34, 2013. © 2012 Wiley Periodicals, Inc.