Rapid Fabrication of Superhydrophobic Virtual Walls for Microfluidic Gas Extraction and Sensing.

Based on the virtual walls concept, where fluids are guided by wettability, we demonstrate the application of a gas phase extraction microfluidic chip. Unlike in previous work, the chip is prepared using a simple, rapid, and low-cost fabrication method. Channels were cut into double-sided adhesive tape (280 µm thick) and bonded to hydrophilic glass slides. The tape was selectively made superhydrophobic by 'dusting' with hydrophobic silica gel to enhance the wettability contrast at the virtual walls. Finally, the two glass slides were bonded using tape, which acts as a spacer for gas transport from/to the guided liquids. In our example, the virtual walls create a stable liquid-vapor-liquid flow configuration for the extraction of a volatile analyte (ammonia), from one liquid stream to the other through the intermediate vapor phase. The collector stream contained a pH indicator to visualize the mass transport. Quantitative analysis of ammonium hydroxide in the sample stream (<1 mM) was possible using a characteristic onset time, where the first pH change in the collector stream was detected. The effect of gap length, flow rates, and pH of the collector stream on the onset time is demonstrated. Finally, we demonstrate the analysis of ammonium hydroxide in artificial human saliva to show that the virtual walls chip is suitable for extracting volatile analytes from biofluids.

Solid organ transplant patients: are there opportunities for antimicrobial stewardship?

OBJECTIVE: Rising incidence of Clostridium difficile and multidrug-resistant organisms' infections and a dwindling development of new antimicrobials are an impetus for antimicrobial stewardship in organ transplant recipients. We sought to understand antimicrobial prescribing practices and identify opportunities for interdisciplinary collaboration among the transplant, antimicrobial stewardship, and infectious diseases teams. METHODS: In 2013, two assessors conducted four real-time audits on all antimicrobial therapy in transplant patients, assessing each regimen against stewardship principles established by the Centers for Disease Prevention and Control, supplemented by applicable transplant-specific infection guidelines. Chi-square test was used to compare stewardship-concordant and stewardship-discordant audit results relative to transplant infectious diseases consultation. RESULTS: Analysis was performed on 176 audits. Fifty-eight percent (103/176) received at least one antimicrobial, of which 69.9% (72/103) were stewardship-concordant. Infections were confirmed or suspected in 52.3% (92/176). Of those, 98.9% (91/92) received antimicrobials, and 41.8% (38/91) were prescribed by transplant clinicians. Infectious diseases consultation was associated with more stewardship-concordant prescriptions (78.5% vs. 59.6%, p = 0.03). The most common stewardship-discordant categories were lack of de-escalation, empiric antimicrobial spectrum being too broad, and therapy duration being too long. CONCLUSIONS: Opportunities exist for antimicrobial stewardship in transplant recipients, especially those who do not require infectious diseases consultation.

Impact of Antimicrobial Stewardship on Physician Practice in a Geriatric Facility.

BACKGROUND: There is a paucity of literature describing the implementation of antimicrobial stewardship programs (ASPs) in long-term care (LTC) facilities. The current study evaluated the impact of an ASP that was implemented across a geriatric facility, which included an inpatient specialty hospital and an LTC facility. The program included prospective audits with feedback, multidisciplinary education, information technology interventions, and guideline development. OBJECTIVE: To investigate the impact of the ASP on physicians' prescribing practices in this geriatric facility. METHODS: Utilization data for antibiotics commonly used to treat urinary tract infections were retrieved for the period September 1, 2011, to August 31, 2013. The study examined whether there were significant changes in overall antibiotic use, ciprofloxacin use, and physician prescribing behaviour after program implementation in September 2012. RESULTS: There was no significant change in the total number of antibiotic prescriptions for urinary tract infections in the hospital or the LTC facility after ASP implementation. Significant reductions were seen in the average days of therapy initially prescribed and the actual days of therapy after ASP implementation in the LTC facility but not the hospital. Across both facilities, significant reductions were seen in the number of ciprofloxacin prescriptions. CONCLUSIONS: The current study showed that an ASP can affect physicians' antibiotic prescribing behaviour and antibiotic usage in an LTC environment.

Il n'existe que très peu de documentation qui porte sur la mise en œuvre de programmes de gérance des antimicrobiens dans les établissements de soins de longue durée. La présente étude a évalué l'effet d'un programme de gérance des antimicrobiens mis en œuvre dans l'ensemble d'un centre gériatrique, qui comprenait un hôpital spécialisé et un établissement de soins de longue durée. Le programme comprenait des audits prospectifs accompagnés de rétroaction, des séances de formation multidisciplinaire, des interventions s'appuyant sur les technologies de l'information et l'élaboration de lignes directrices.

The ever-evolving landscape of candidaemia in patients with acute leukaemia: non-susceptibility to caspofungin and multidrug resistance are associated with increased mortality.

OBJECTIVES: The epidemiology and clinical course of candidaemia in patients with acute leukaemia, a population frequently exposed to antifungals, have not been extensively studied. In the present contemporary series of acute leukaemia patients, we describe patient characteristics, Candida species and MIC distributions and investigate the association between antifungal resistance and all-cause mortality. METHODS: We performed a retrospective review of medical records and microbiological data of adult patients with acute leukaemia or high-risk myelodysplastic syndrome with at least one positive blood culture for Candida species at the MD Anderson Cancer Center between January 2008 and October 2012. Susceptibility was defined according to the 2012 epidemiological cut-off values and clinical breakpoints. RESULTS: We identified 67 episodes of candidaemia in 65 patients. Almost all episodes (94%) occurred in patients who were receiving antifungal agents, 71% in patients receiving an echinocandin. Almost all isolates (99%) were of non-albicans Candida species [most frequently Candida parapsilosis (32%), Candida tropicalis (23%) and Candida glabrata (20%)]. Caspofungin non-susceptibility was significantly associated with fluconazole resistance (P < 0.001). Non-susceptibility to caspofungin and multidrug resistance were associated with excess 14 day [adjusted HR (aHR) 3.02 (95% CI 1.28-7.09), P = 0.011 and aHR 3.02 (95% CI 1.27-7.14), P = 0.012, respectively] and 30 day [aHR 2.96 (95% CI 1.38-6.37), P = 0.005 and aHR 2.86 (95% CI 1.31-6.21), P = 0.008, respectively] all-cause mortality. CONCLUSIONS: In patients with acute leukaemia, a shift in candidaemia epidemiology was noted with a 99% predominance of non-albicans species. Non-susceptibility of Candida strains to caspofungin or multidrug resistance were independent markers of poor outcome in this patient population.

A retrospective study of venous thromboembolism in acute leukemia patients treated at the University of Texas MD Anderson Cancer Center.

The purpose was to determine the incidence and prevalence of venous thromboembolism (VTE) in acute leukemia patients from our institution. We conducted a retrospective study on newly diagnosed acute leukemia patients who presented at our institution from November 1999 to May 2005. Descriptive statistics and cross-tabulation were used to describe patient characteristics. Measures of morbidity were used to address VTE risk. Chi-square testing, Fisher's exact testing, Mann-Whitney analyses, or median testing were used to determine between-group differences. Data analyses were conducted using Stata version 11 (Stata Corp., College Station, TX). Two hundred and ninety-nine patients with acute lymphoblastic leukemia (ALL) and 996 patients with acute myeloid leukemia (AML) were included. After excluding patients diagnosed with VTE prior to or at the time of leukemia diagnosis, during the mean time follow-up period of 2.5 years (range: 0.0025-10.3 years), the overall incidence rate of VTE was 3.7 per 100 person-years: 4.2 per 100 person-years for ALL and 3.4 per 100 person-years for AML. Among all patients, the majority (80.6%) developed VTE within 12 months after diagnosis and during thrombocytopenia. The most common VTE was central venous catheter (CVC)-associated upper-extremity deep venous thrombosis. Pulmonary embolism occurred in 15% of ALL patients and 8% of AML patients. VTE recurred in 20.7% of ALL patients and 18.6% of AML patients. VTE occurs frequently in patients with acute leukemia. Studies are needed to identify risk factors for the development and recurrence of VTE among patients with acute leukemia and to establish more effective methods for preventing and treating VTEs in leukemia patients who have thrombocytopenia and/or CVC.

Glucarpidase Intervention for Delayed Methotrexate Clearance.

OBJECTIVE: To review and evaluate the current published literature on the effectiveness and safety of glucarpidase and to determine its potential role in clinical practice. DATA SOURCES: A PubMed literature search from 1946 to January 2014 was performed using the search terms carboxypeptidase G2, glucarpidase, high-dose methotrexate, and leucovorin rescue. Additional references were identified by reviewing the references from the PubMed search articles. STUDY SELECTION AND DATA EXTRACTION: English-language clinical trials and retrospective studies assessing the safety and effectiveness of glucarpidase were included. Case reports were excluded. DATA SYNTHESIS: A total of 5 non-randomized, prospective studies and 1 retrospective study evaluated the effectiveness and safety of glucarpidase in patients receiving high-dose methotrexate. In these studies, glucarpidase conferred a >87% reduction in serum methotrexate concentrations (sMTX) and was well tolerated. Although a substantial reduction in sMTX was observed, clinically significant outcomes such as the need for dialysis, time to administration of next chemotherapy cycle, and methotrexate toxicity-related mortality were not consistently evaluated. CONCLUSIONS: Glucarpidase is effective in lowering sMTX in patients with delayed methotrexate clearance and renal dysfunction. Considering the relatively high cost of glucarpidase, it should be reserved for specific patients who have not responded to standard supportive care measures.

Clofarabine in the treatment of newly diagnosed acute myeloid leukemia in older adults.

OBJECTIVE: To review the literature evaluating the efficacy and tolerability of clofarabine, a second-generation purine nucleoside analogue, for the treatment of previously untreated acute myeloid leukemia (AML) in older adults. DATA SOURCE: A literature search of the PubMed database (1972-October 2011) using the search terms clofarabine and acute myeloid leukemia was performed. STUDY SELECTION AND DATA EXTRACTION: All relevant English-language articles were reviewed, and clinical trials with patients aged 50 years or older who were newly diagnosed with AML were included. DATA SYNTHESIS: Two studies evaluating clofarabine as monotherapy and 2 studies evaluating clofarabine in combination with cytarabine were reviewed. Clofarabine demonstrated activity in older adults with previously untreated AML. Response rates and median overall survival (OS) for patients receiving clofarabine were similar to those reported for conventional intensive chemotherapy regimens. Responses to the 2 types of treatment remained similar in the presence of unfavorable prognostic factors, such as secondary AML or adverse cytogenetics. Although clofarabine was associated with a lower induction mortality rate versus intensive chemotherapy regimens, a significant percentage of patients experienced severe complications, including sepsis. Compared to single-agent clofarabine, response rates and median OS were higher for clofarabine combined with cytarabine. CONCLUSIONS: Based on published data, adverse effect profiles, and cost, clofarabine may be an appropriate alternative to intensive chemotherapy regimens in certain subsets of older patients with newly diagnosed AML. These include patients with a baseline decreased performance status or history of cardiovascular disease who may not tolerate anthracyclines, which are typically a component of most intensive chemotherapy regimens. Additional randomized controlled trials are needed to directly compare the efficacy of clofarabine with that of intensive chemotherapy regimens and to evaluate the potential benefit of combining clofarabine with cytarabine.

Differentiation syndrome in patients with acute promyelocytic leukemia.

OBJECTIVE: To review the pathophysiology, risk factors, and management of differentiation syndrome (DS) associated with acute promyelocytic leukemia (APL). DATA SOURCE: A MEDLINE search was conducted (1977-November 2010) using the terms APL, DS, all-trans retinoic acid (ATRA), retinoic acid syndrome, and arsenic trioxide (ATO). METHODS OF STUDY SELECTION: English articles identified from the MEDLINE search were evaluated. DATA EXTRACTION AND SYNTHESIS: With ATRA, ATO, and chemotherapy, a complete remission is achievable for most newly diagnosed APL patients. However, treatment with the differentiating agents, ATRA and ATO, can lead to the development of DS. Signs and symptoms of this syndrome include hyperleukocytosis and cardiorespiratory compromise. Severe complications can develop, if DS is not recognized early and treated promptly with corticosteroids. In addition, patients with a high white blood cell count at diagnosis may benefit from prophylactic steroids. CONCLUSIONS: Early recognition and prompt initiation of corticosteroids are key factors in the management of DS. Healthcare professionals need to be familiar with this complication which can arise from differentiation agents.

A review of pharmacologic options for previously untreated chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and has a heterogeneous clinical course. Some patients experience an indolent disease course, which does not require treatment or affect their overall quality of life. Other patients present with symptomatic advanced disease that rapidly progresses and requires therapy. For these patients, chemotherapy is the mainstay of treatment and has undergone significant evolution in the past few decades. From alkylating agents to purine analogs, response rates have greatly improved with new chemotherapy regimens. The development of chemoimmunotherapy regimens has also transformed the treatment of CLL. This article will review front-line treatment options for CLL and discuss the updated National Comprehensive Cancer Network guidelines.

Treatment of acute promyelocytic leukemia during pregnancy.

Management of the pregnant patient with acute promyelocytic leukemia (APL) is a challenge. Immediate treatment of APL is critical, as it is an oncologic emergency, with a high risk of morbidity and mortality associated with disseminated intravascular coagulation. However, administration of chemotherapy and differentiating agents in pregnancy is controversial because of potential teratogenic effects. In addition, complications associated with APL, including retinoic acid syndrome, add to the complexity of management. To better understand how to manage this complex patient care situation, we searched the PubMed database (January 1972-May 2008) for English-language articles about maternal and fetal outcomes resulting from APL treatment during pregnancy. A total of 42 cases from 35 articles were identified: 12 first-trimester, 21 second-trimester, and 9 third-trimester cases. The most commonly administered agents were all-trans-retinoic acid (ATRA), anthracyclines, and antimetabolites. Complete remission was reported in 35 (83%) of 42 patients. Administration of ATRA or chemotherapy in the first trimester was associated with an increased risk of fetal malformations and spontaneous abortion, whereas administration in the second and third trimesters was associated with relatively favorable fetal outcomes. The overall treatment of the pregnant patient with APL should include a discussion about pregnancy termination, especially if APL is diagnosed in the first trimester. If the pregnancy is to continue, then the appropriate chemotherapy regimen needs to be determined. Frequent fetal monitoring, along with aggressive management of potential APL-related complications, is necessary to allow for optimal maternal and fetal outcomes.