Calcium Administration Is Associated with Adverse Outcomes in Critically Ill Patients Receiving Parenteral Nutrition: Results from a Natural Experiment Created by a Calcium Gluconate Shortage.

STUDY OBJECTIVE: Parenteral calcium is frequently administered to critically ill patients. However, animal studies demonstrate that calcium administration during critical illness heightens inflammation and leads to shock, organ dysfunction, and mortality. We sought to evaluate the association between calcium administration and adverse outcomes in critically ill patients receiving parenteral nutrition (PN). DESIGN: Retrospective cohort examined before and during a calcium gluconate shortage. During the shortage, calcium was absent from PN, but calcium supplementation outside of PN was allowed. The shortage resulted in a natural experiment that included a group of patients who did not receive calcium. SETTING: Intensive care units (ICUs) in three teaching hospitals. PATIENTS: A total of 259 adults who received PN in the ICU for 48 hours or longer. MEASUREMENTS AND MAIN RESULTS: Patients were divided into quartiles based on amount of parenteral calcium received; the lowest quartile received no calcium. End points were in-hospital mortality, acute respiratory failure, new-onset shock, and a composite of any one of these end points. For patients not on mechanical ventilation or vasoactive support when PN started, logistic regression revealed that calcium administration was associated with mortality (odds ratio [OR] 2.48, 95% confidence interval [CI] 1.08-5.69), acute respiratory failure (OR 2.43, 95% CI 1.28-4.60), new-onset shock (OR 2.81, 95% CI 1.22-6.44), and the combined end point (OR 2.33, 95% CI 1.31-4.16). The odds of adverse outcomes increased as the calcium dose increased. CONCLUSION: Calcium administration correlated with adverse outcomes in critically ill patients receiving PN. The data suggest that administration of parenteral calcium to critically ill patients may be harmful.

Copper and Zinc Deficiency in a Patient Receiving Long-Term Parenteral Nutrition During a Shortage of Parenteral Trace Element Products.

Drug shortages in the United States, including parenteral nutrition (PN) components, have been common in recent years and can adversely affect patient care. Here we report a case of copper and zinc deficiency in a patient receiving PN during a shortage of parenteral trace element products. The management of the patient's deficiencies, including the use of an imported parenteral multi-trace element product, is described.

Vascular catheter tip cultures for suspected catheter-related blood stream infection in the intensive care unit: a tradition whose time has passed?

BACKGROUND: Catheter-related blood stream infections (CR-BSIs) are estimated to occur in 80,000 patients in intensive care units (ICUs) each year in the United States. We sought to determine the clinical utility of vascular catheter cultures in critically ill patients with suspected CR-BSI. METHODS: We reviewed retrospectively all positive (≥15 colony forming units/roll) vascular catheter tip cultures (CTCs) documented over a four-year period in the ICUs of two hospitals. A CR-BSI was defined as matching positive blood and catheter cultures. The time interval between catheter removal and blood culture was recorded. RESULTS: A total of 1,391 CTCs were obtained, of which 468 (34%) were positive and 143 (31% of the positive cultures) were associated with a diagnosis of CR-BSI. In 133 of these 143 cases (93%), the positive blood culture was obtained before or within 24 h after catheter removal and dictated antibiotic therapy. In only 10 of 143 cases (7%) did catheter removal and culture significantly (>1 day) precede the positive blood culture. In 55% of the CR-BSI cases, the catheter was removed empirically and close to the time of blood culture (-1.3±19.0 h). In the remaining 45%, the catheter was removed clinically (after a blood culture was positive), and this action was more remote in time (23.6±19.4 h; p<0.001 vs. empiric removal). Total microbiology laboratory costs for the CTCs were $75,300, and 600 microbiology technician hours were required. CONCLUSION: In an ICU patient population, only about one-third of vascular catheter cultures were positive, and only about one-third of the positive CTCs were associated with CR-BSI. Ninety-three percent of all CR-BSIs were identified by bacteremia either before or coinciding with catheter removal, and the results of the blood culture dictated antimicrobial therapy. Because CTCs rarely changed therapy, they may not be appropriate in the management of suspected CR-BSI in the ICU setting.

Successful use of fondaparinux for bridging early after aortic and mitral mechanical heart valve replacement.

OBJECTIVE: To report a case of successful use of fondaparinux for bridging early after aortic and mitral mechanical heart valve replacement (MHVR). CASE SUMMARY: A 71-year-old female underwent aortic and mitral valve replacements with St. Jude medical bileaflet prostheses, as well as DeVega tricuspid annuloplasty and coronary artery bypass graft. Anticoagulation was initially withheld following the procedure because of thrombocytopenia, large amount of chest tube drainage (~1 L/day), and concerns regarding postoperative bleeding. The thrombocytopenia (baseline platelet count 183 x 10(3)/µL; postoperative platelet count 44 × 10(3)/µL) was thought to be a consequence of the cardiopulmonary bypass; there was a low probability of heparin-induced thrombocytopenia. However, the care team preferred to avoid heparin products and initiated fondaparinux 7.5 mg subcutaneously once daily on postoperative day 8 once the patient's platelet count had recovered to >100 x 10(3)/µL. The treatment was bridged to warfarin on postoperative day 13 and the patient was discharged home after receiving 8 days of fondaparinux. Throughout the patient's hospitalization and upon follow-up on postoperative day 31, there were no signs or symptoms of thromboembolic events or bleeding. DISCUSSION: Unfractionated heparin and low-molecular-weight heparins are the standard of care for bridging to warfarin in patients with MHVR. The use of fondaparinux following MHVR has not been studied in randomized controlled trials. In vitro studies support the effectiveness of fondaparinux in preventing thrombus formation on mechanical heart valves. However, the only data available in humans as of December 2011 are 3 case reports. Two of these case reports described the successful use of fondaparinux for anticoagulation in a patient with an aortic valve replacement. In the third case report, the patient had an aortic and mitral valve replacement. Our case report is novel because it describes the use of fondaparinux early after MHVR, which is the most critical time period for effective thromboprophylaxis. CONCLUSIONS: The use of fondaparinux for postoperative bridging in our patient early after combined aortic and mitral MHVR was effective. However, until studies evaluate the efficacy and safety of fondaparinux in patients with MHVR, its use should be considered only when heparin products are contraindicated.

Prevalence of articles with honorary and ghost authors in three pharmacy journals.

PURPOSE: The prevalence of honorary and ghost authors in articles published in 2009 in three peer-reviewed pharmacy journals was studied. METHODS: A 20-question survey was e-mailed to corresponding authors of articles with two or more authors published in 2009 in the American Journal of Health-System Pharmacy, Annals of Pharmacotherapy, and Pharmacotherapy. The survey solicited the following information: demographic characteristics of the corresponding author, information about the published article, information to determine whether any of the authors did not meet the International Committee of Medical Journal Editors criteria for authorship, and information to determine if an individual contributed substantially to the research or writing of the article but was not listed as an author. RESULTS: Of the 491 corresponding authors to whom the survey was sent, 457 had a working e-mail address; 114 surveys were completed (24.9% response rate). Usable responses were provided by 112 authors. The prevalence of articles with honorary and ghost authors was 14.3% and 0.9%, respectively. Honorary authorship was more common in original research than review articles. Articles with honorary authors had longer bylines than articles without honorary authors (mean number of authors, 4.9 versus 3.7; p = 0.002). The proportion of articles with an honorary author was 1.9% for articles with fewer than 4 authors, 25% for articles with 4 or 5 authors, and 29.4% for articles with more than 5 authors (p = 0.001). CONCLUSION: A survey sent to the corresponding authors of articles published in 2009 in three peer-reviewed pharmacy journals revealed that a substantial percentage of articles demonstrated evidence of honorary or ghost authorship.

Women as authors in the pharmacy literature: 1989-2009.

PURPOSE: Trends in the authorship of original research articles by female U.S. pharmacists in three peer-reviewed pharmacy journals over the period 1989-2009 were evaluated. METHODS: The sex distribution of the authors of all original research articles published in 1989, 1999, and 2009 in three prominent pharmacy journals (American Journal of Health-System Pharmacy, Annals of Pharmacotherapy, and Pharmacotherapy) was evaluated. A total of 608 original research articles were assessed to determine the sex of the first listed author (typically the person with primary responsibility for the research and article preparation) and the last listed, or "senior," author (usually a senior faculty member under whose academic purview the research was conducted). Pharmacist authors with U.S. affiliations were included in the analysis. RESULTS: In each of the three journals evaluated, female authorship increased from 1989 to 2009. Overall, the proportion of articles listing a woman as the first author increased significantly during the study period, from 29.9% in 1989 to 44.3% in 1999 and to 52.2% in 2009. However, after a significant rise in the proportion of articles listing a woman as the last author from 1989 to 1999 (from 16.8% to 37.0%), female last authorship in the three journals declined to 33.8% in 2009. CONCLUSION: There was a significant overall increase in female authorship of original research articles in the pharmacy literature from 1989 to 2009, but gender difference persists among pharmacists serving as last listed authors.

Authorship and characteristics of articles in pharmacy journals: changes over a 20-year interval.

BACKGROUND: To our knowledge, no studies have evaluated authorship patterns and characteristics of articles in pharmacy journals. OBJECTIVE: To investigate changes over a 20-year period in authorship and characteristics of articles in pharmacy journals. METHODS: All articles published in the American Journal of Health-System Pharmacy, The Annals of Pharmacotherapy, and Pharmacotherapy in 1989, 1999, and 2009 were reviewed. Data collected for each article included article type, number of authors, number of physician authors, whether any author was affiliated with a pharmaceutical company, and source of funding. RESULTS: The number of articles included was 574 in 1989, 659 in 1999, and 589 in 2009. The mean number of authors per article increased from 2.5 in 1989 to 2.8 in 1999 and 3.6 in 2009 (p<0.001). Conversely, the proportion of articles with a single author decreased from 35% in 1989 to 23% in 1999 and 11% in 2009 (p<0.001), while the proportion of multi-authored articles (>6 authors) increased from 2% in 1989 to 3% in 1999 and 9% in 2009 (p<0.001). A physician author was listed on 25% of papers in 1989, which increased to 38% in 1999 and 41% in 2009 (p<0.001). Among research articles with declared funding from industry, there was an increase over time in reported author affiliation with an industry sponsor (10% of articles in 1989, 17% in 1999, and 66% in 2009; p<0.001). CONCLUSIONS: Significant changes in authorship patterns and characteristics of articles were observed from 1989 to 2009. We found an increase in the number of authors per article over time, with fewer single-author papers now published. The explanations for the changes are likely multifactorial, including increased pressure to publish, increased research complexity, and inappropriate authorship. To prevent inappropriate author-number inflation and to preserve authorship's meaning and value, authors should adhere to the criteria for authorship from the International Committee of Medical Journal Editors.

Physical compatibility of 4% sodium citrate with selected antimicrobial agents.

PURPOSE: The physical compatibility of 4% sodium citrate with vancomycin, gentamicin, tobramycin, daptomycin, and linezolid was evaluated. METHODS: Admixtures were prepared by mixing 4% sodium citrate with clinically relevant concentrations of antimicrobial agents (vancomycin 5 mg/mL, vancomycin 10 mg/mL, vancomycin 20 mg/mL, daptomycin 5 mg/mL, gentamicin 2.4 mg/mL, tobramycin 2.4 mg/mL, and linezolid 1 mg/mL). Three samples of each admixture were incubated (1) at 22-23 degrees C and exposed to light, (2) in a water bath at 37 degrees C and exposed to light, (3) at 22-23 degrees C and protected from light, and (4) in a water bath at 37 degrees C and protected from light. Visual compatibility, spectrophotometric absorbance, and pH were evaluated immediately after mixing (baseline) and at 8, 24, and 48 hours. Physical compatibility was defined as the absence of visible precipitation, a pH value at 48 hours that did not vary by more than 10% from baseline, and an absorbance value of <0.015. RESULTS: There was no visual evidence of precipitation and no clinically important changes in pH observed during the 48-hour study period in any admixture. However, turbidity, based on absorbance, was noted with vancomycin 20 mg/mL at each time point. CONCLUSION: No evidence of incompatibility was observed when vancomycin 5 mg/ mL, vancomycin 10 mg/mL, daptomycin 5 mg/mL, gentamicin 2.4 mg/mL, tobramycin 2.4 mg/mL, or linezolid 1 mg/mL was mixed with 4% sodium citrate as might occur in an antimicrobial lock. Vancomycin 20 mg/mL mixed with 4% sodium citrate displayed spectrophotometric evidence of incompatibility.