Advanced glycation end product (AGE) targeting antibody SIWA318H is efficacious in preclinical models for pancreatic cancer.

SIWA318H is a novel monoclonal antibody that selectively targets an advanced glycation end product biomarker found in damaged/dysfunctional cells exhibiting (a) aerobic glycolysis, and (b) oxidative stress. Cells with this biomarker are dysfunctional and are associated with stresses and/or damages relating to aging, cancer and other disease processes. In this study, we evaluated the biological effects and antitumor activity of SIWA318H in preclinical models for pancreatic cancer. SIWA318H binds to pancreatic cancer cells and cancer-associated fibroblasts, as well as tumor xenografts derived from pancreatic cancer patients. Furthermore, SIWA318H induced significant antibody-dependent cell-mediated cytotoxicity (ADCC) against pancreatic cancer cells. In a humanized CD34+ NSG mouse xenograft model for pancreatic cancer, tumors in mice treated with SIWA318H grew significantly slower compared to those in control mice (p < 0.001). After 3 weeks of treatment with SIWA318H, the tumor growth was suppressed by 68.8% and 61.5% for the high and low dose regimens, respectively, when compared to the isotype antibody control (ANOVA p < 0.002). Moreover, a significant increase in complete remission (CR) rate was observed in mice receiving the high dose (60%, p < 0.04) or low dose (77.8%, p < 0.02) of SIWA318H treatment compared with control mice (6.7%). Immunohistochemical analyses of the tumor tissues showed a significant decrease in senescent cells in the tumor microenvironment of SIWA318H treated mice compared to that of control treated mice (p < 0.05). These results provide compelling evidence that SIWA318H is a promising novel therapeutic against pancreatic cancer.

Developing Connections Between LINC00298 RNA and Alzheimer's Disease Through Mapping Its Interactome and Through Biochemical Characterization.

BACKGROUND: Long non-coding RNAs are ubiquitous throughout the human system, yet many of their biological functions remain unknown. LINC00298 RNA, a long intergenic non-coding RNA, has been shown to have preferential expression in the central nervous system where it contributes to neuronal differentiation and development. Furthermore, previous research has indicated that LINC00298 RNA is known to be a genetic risk factor for the development of Alzheimer's disease. OBJECTIVE: To biochemically characterize LINC00298 RNA and to elucidate its biological function within hippocampal neuronal cells, thereby providing a greater understanding of its role in Alzheimer's disease pathogenesis. METHODS: LINC00298 RNA was in vitro transcribed and then subjected to structural analysis using circular dichroism, and UV-Vis spectroscopy. Additionally, affinity column chromatography was used to capture LINC00298 RNA's protein binding partners from hippocampal neuronal cells, which were then identified using liquid chromatography and mass spectrometry (LC/MS). RESULTS: LINC00298 RNA is comprised of stem-loop secondary structural elements, with a cylindrical tertiary structure that has highly dynamic regions, which result in high positional entropy. LC/MS identified 24 proteins within the interactome of LINC00298 RNA. CONCLUSION: Through analysis of LINC00298 RNA's 24 protein binding partners, it was determined that LINC00298 RNA may play significant roles in neuronal development, proliferation, and cellular organization. Furthermore, analysis of LINC00298 RNA's interactome indicated that LINC00298 RNA is capable of intracellular motility with dual localization in the nucleus and the cytosol. This biochemical characterization of LINC00298 RNA has shed light on its role in Alzheimer's disease pathogenesis.

Examining the relative influence of dispersal and competition on co-occurrence and functional trait patterns in response to disturbance.

Disturbance gradients are particularly useful for understanding the relative influences of competition and dispersal. Shortly after disturbance, plant composition should be influenced more strongly by dispersal than competition; over time, this should reverse, with competition becoming more important. As such, we predicted that plant functional traits associated with high dispersal ability would be over-represented shortly after a disturbance event occurs, while those associated with high competitive ability would have increased representation as time progresses. Additionally, it has been suggested that competitive interactions may contribute to negative co-occurrence patterns; if this is the case, negative co-occurrence patterns should also increase as time-since-disturbance increases. Here, we examine how functional trait and co-occurrence patterns change over time following a herbicide-based disturbance, compared to undisturbed vegetation, in a temperate, old-field grassland dominated by herbaceous perennials. In our study system, negative co-occurrence patterns were most pronounced in disturbed plots one year after herbicide application, consistent with several lines of evidence that dispersal can strongly impact both composition and co-occurrence patterns. Over three years post-disturbance, co-occurrence patterns in disturbed plots decreased, becoming more similar to control plots. This pattern is inconsistent with the expectation that competition contributes to negative co-occurrence patterns, at least over three growing seasons. More pronounced negative co-occurrence patterns were associated with higher species evenness among plots. Functional traits related to increased dispersal (mean seed mass, and proportion of stoloniferous/rhizomatous species) and competitive ability (mean species height, and mean specific leaf area) did not differ significantly across treatments, with the exception of mean height in the third-year post-disturbance; however, the overall trajectory of this trait was inconsistent with theoretical expectations. Overall, co-occurrence patterns changed across the gradient of time-since disturbance, but not as expected; functional trait patterns (trait means, functional diversity measures) were not responsive to our experimental disturbance gradient.

Phase II study of dichloroacetate, an inhibitor of pyruvate dehydrogenase, in combination with chemoradiotherapy for unresected, locally advanced head and neck squamous cell carcinoma.

Chemoradiotherapy (CRT) for locally-advanced head and neck squamous cell carcinoma (LA-HSNCC) yields 5-year survival rates near 50% despite causing significant toxicity. Dichloroacetate (DCA), a pyruvate dehydrogenase kinase metabolic inhibitor, reduces tumor lactate production and has been used in cancer therapy previously. The safety of adding this agent to CRT is unknown. Our randomized, placebo-controlled, double-blind phase II study added DCA to cisplatin-based CRT in patients with LA-HNSCC. The primary endpoint was safety by adverse events (AEs). Secondary endpoints compared efficacy via 3-month end-of-treatment response, 5-year progression-free and overall survival. Translational research evaluated pharmacodynamics of serum metabolite response. 45 participants (21 DCA, 24 Placebo) were enrolled from May 2011-April 2014. Higher rates of all-grade drug related fevers (43% vs 8%, p = 0.01) and decreased platelet count (67% vs 33%, p = 0.02) were seen in DCA versus placebo. However, there were no significant differences in grade 3/4 AE rates. Treatment compliance to DCA/placebo, radiation therapy, and cisplatin showed no significant difference between groups. While end-of-treatment complete response rates were significantly higher in the DCA group compared to placebo (71.4% vs 37.5%, p = 0.0362), survival outcomes were not significantly different between groups. Treatment to baseline metabolites demonstrated a significant drop in pyruvate (0.47, p < 0.005) and lactate (0.61, p < 0.005) in the DCA group. Adding DCA to cisplatin-based CRT appears safe with no detrimental effect on survival and expected metabolite changes compared to placebo. This supports further investigation into combining metabolic agents to CRT. Trial registration number: NCT01386632, Date of Registration: July 1, 2011.

Point-of-sale Naloxone: Novel Community-based Research to Identify Naloxone Availability.

INTRODUCTION: Expanding naloxone availability is important to reduce opioid-related deaths. Recent data suggest low, variable urban naloxone availability. No reports describe naloxone availability at the point of sale (POSN). We characterize POSN without prescription across a Midwestern metropolitan area, via a unique poison center-based study. METHODS: Pharmacies were randomly sampled within a seven-county metropolitan area, geospatially mapped, and distributed among seven investigators, who visited pharmacies and asked, "May I purchase naloxone here without a prescription from my doctor?" Following "No," investigators asked, "Are you aware of the state statute that allows you to dispense naloxone to the public under a standing order?" Materials describing statutory support for POSN were provided. Responses were uploaded to REDCap in real time. We excluded specialty (veterinary, mail order, or infusion) pharmacies a priori. POSN availability is presented as descriptive statistics; characteristics of individual sites associated with POSN availability are reported. RESULTS: In total, 150 pharmacies were prospectively randomized, with 52 subsequently excluded or unavailable for survey. Thus, 98 were included in the final analysis. POSN was available at 71 (72.5%) of 98 pharmacies. POSN availability was more likely at chain than independent pharmacies (84.7% vs 38.5%, p<0.001); rural areas were more commonly served by independent than chain pharmacies (47.4% vs 21.5%, p = 0.022). Five chain and five independent pharmacies (18.5% each) were unaware of state statutory support for collaborative POSN agreements. Statutory awareness was similar between independent and chain pharmacies (68.8% vs 54.6%, p = 0.453). Rationale for no POSN varied. CONCLUSION: POSN is widely available in this metropolitan area. Variability exists between chain and independent pharmacies, and among pharmacies of the same chain; awareness of statutory guidance does not. Poison centers can act to define local POSN availability via direct inquiry in their communities.

Fertility Awareness-Based Methods for Family Planning: A Literature Review.

A review of 23 research articles to examine fertility awareness-based methods revealed biologic indicators and tracking methods to identify the fertile window in reproductive-aged women. This literature review indicated that a woman's cycle regularity is a major determinant of which method is best. Additionally, the woman's desire to achieve a pregnancy and her preference regarding the intensity of training are factors in method choice. Some evidence suggests that use of at least two biologic indicators is most effective for determining the fertility window. Recommended web and mobile applications also are discussed.

Potential risk of drug-drug interactions with hormonal contraceptives and antiretrovirals: prevalence in women living with HIV.

BACKGROUND: Family planning services are vital for women living with HIV (WLH); however, the use of concomitant antiretroviral therapy (ART) and hormonal contraceptives (HCs) may pose challenges due to the risk of potential drug-drug interactions (DDIs). The objectives of this study were to assess ART and HC use among WLH and quantify the frequency of potential DDIs between ART and HCs. METHODS: This was a retrospective, observational, cohort study of WLH aged 18-55 years, prescribed ART, with at least one clinic visit from January 1, 2010 to April 30, 2014. Potential DDIs between HCs and ART were assessed using the University of Liverpool HIV Drug Interactions website (www.hiv-druginteractions.org) and categorized as 'weak potential interaction,' 'potential interaction,' or 'do not co-administer.' RESULTS: Overall, a contraceptive method was reported in 167 (54%) of the 309 women included in the study. Of those using contraception, 73 (43.7%) reported using HCs, which was most frequently a progestin intrauterine device (n=43), progestin injection (n=17), or combination oral contraceptive pills (n=9). Out of a total of 449 ART regimens, a potential DDI was identified in 21 of 115 (18.3%) ART-HC combinations from 19 women using ART and HCs. Atazanavir/ritonavir was the most common potentially interacting ART (10, 47.6%); for HCs, these were combination oral contraceptive pills (16, 76.2%) and progestin implants (2, 9.5%). CONCLUSION: In this cohort, one-quarter of WLH on ART-HCs had a potential DDI. Future studies should investigate the impact of DDIs on unintended pregnancies, the side effects of DDIs, and the effects of HC DDIs on ART concentrations.

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study.

PURPOSE: Pembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC. PATIENTS AND METHODS: Eligible patients included those with oral cavity (excluding lip), oropharyngeal, hypopharyngeal, or laryngeal stage III to IVB HNSCC (according to American Joint Committee on Cancer, 7th edition, staging system) eligible for cisplatin-based, standard-dose (70 Gy) chemoradiotherapy. Pembrolizumab was administered concurrently with and after chemoradiotherapy with weekly cisplatin. Safety was the primary end point and was determined by incidence of chemoradiotherapy adverse events (AEs) and immune-related AEs (irAEs). Efficacy was defined as complete response (CR) rate on end-of-treatment (EOT) imaging or with pathologic confirmation at 100 days postradiotherapy completion. Key secondary end points included overall (OS) and progression-free survival (PFS). RESULTS: The study accrued 59 patients (human papillomavirus [HPV] positive, n = 34; HPV negative, n = 25) from November 2015 to October 2018. Five patients (8.8%) required discontinuation of pembrolizumab because of irAEs, all of which occurred during concurrent chemoradiotherapy; 98.3% of patients completed the full planned treatment dose (70 Gy) of radiotherapy without any delays ≥ 5 days; 88.1% of patients completed the goal cisplatin dose of ≥ 200 mg/m2. EOT CR rates were 85.3% and 78.3% for those with HPV-positive and -negative HNSCC, respectively. CONCLUSION: Pembrolizumab in combination with weekly cisplatin-based chemoradiotherapy is safe and does not impair delivery of curative radiotherapy or chemotherapy in HNSCC. Early efficacy data support further investigation of this approach.

The Calgary student run clinic in context: a mixed-methods case study.

BACKGROUND: Student Run Clinics (SRCs) provide students with clinical education while caring for underserved populations. While much of the research on SRCs comes from the USA, SRCs in other contexts need to be appraised in the context of the systems they interact with. This study explored how stakeholders in the University of Calgary's SRC perceived its purpose and beneficiaries with respect to patients, students, undergraduate medical education, and its intersections within the healthcare system in Calgary. METHODS: Data came from the SRC's EMR and stakeholder interviews at the Inn from the Cold (IFTC) shelter. Qualitative data were analyzed using standard grounded theory techniques. RESULTS: There were 13 interviews - seven with student clinicians and six with preceptors and other stakeholders. Interviews highlighted the uncertainty of the SRCs role. Majority of participants saw the SRC as facilitating further access to other healthcare services, while some commented on its primarily education-focused role. Major limitations in the SRC's scope of care and its integration with other services were identified. CONCLUSION: SRCs need to consider their accountabilities, both educational and healthcare-focused at individual and organization levels, in order to function as responsible healthcare providers in Calgary.

Partial sequence analyses of exon 7 of the ABO locus of cynomolgus (Macaca fascicularis) and rhesus (M. mulatta) macaques: Indeterminate phenotypes show the presence of the O blood group.

Compatibility tests to identify A, B, and O alleles are critical for establishing suitable donor-recipient matches among experimental animals. Using a qPCR-based SNP probe assay, we have identified A, B, AB, and indeterminate blood group phenotypes in cynomolgus and rhesus macaques. We have hypothesized, albeit without molecular confirmation, that the indeterminate phenotype represents homozygosity for the null O allele at the macaque ABO locus. The indeterminate phenotype represents the unsuccessful detection of either A or B alleles using primers targeting the A-specific and B-specific single nucleotide polymorphisms (SNPs) in a variable region of exon 7 of the ABO locus. These SNPs are associated with two functional sites, detected using two allele-specific probes in the qPCR assay where the codons leucine and methionine (at codon 266) and glycine and alanine (at codon 268) are required for the synthesis of the A and B transferases, respectively. While reference sequences for the A and B alleles exhibited no novel mutations in the functional exon, plasmid Sanger sequence analyses showed unique mutations within the diagnostic target sites in 10 macaques exhibiting the indeterminate phenotype. Eight of these indeterminate individuals exhibited SNPs at codon 268 that should prevent the syntheses of an A or B transferase. While the two other indeterminate samples had functional codons that were consistent with A or B alleles, mutations in either their probe- or primer-binding sites that altered their peptide sequences probably impeded their detection by our assay.

Landscape effects on the contemporary genetic structure of Ruffed Grouse (Bonasa umbellus) populations.

The amount of dispersal that occurs among populations can be limited by landscape heterogeneity, which is often due to both natural processes and anthropogenic activity leading to habitat loss or fragmentation. Understanding how populations are structured and mapping existing dispersal corridors among populations is imperative to both determining contemporary forces mediating population connectivity, and informing proper management of species with fragmented populations. Furthermore, the contemporary processes mediating gene flow across heterogeneous landscapes on a large scale are understudied, particularly with respect to widespread species. This study focuses on a widespread game bird, the Ruffed Grouse (Bonasa umbellus), for which we analyzed samples from the western extent of the range. Using three types of genetic markers, we uncovered multiple factors acting in concert that are responsible for mediating contemporary population connectivity in this species. Multiple genetically distinct groups were detected; microsatellite markers revealed six groups, and a mitochondrial marker revealed four. Many populations of Ruffed Grouse are genetically isolated, likely by macrogeographic barriers. Furthermore, the addition of landscape genetic methods not only corroborated genetic structure results, but also uncovered compelling evidence that dispersal resistance created by areas of unsuitable habitat is the most important factor mediating population connectivity among the sampled populations. This research has important implications for both our study species and other inhabitants of the early successional forest habitat preferred by Ruffed Grouse. Moreover, it adds to a growing body of evidence that isolation by resistance is more prevalent in shaping population structure of widespread species than previously thought.

Evidence of temporal niche separation via low flowering time overlap in an old-field plant community.

Flowering time is a trait that reflects the timing of specific resource requirements by plants. Consequently, several predictions have been made related to how species are assembled within communities according to flowering time. Strong overlap in flowering time among coexisting species may result from clustered abiotic resources, or contribute to improved pollination success. Conversely, low flowering time overlap (asynchrony) among coexisting species may reduce competition for soil, light, or pollinator resources and alleviate interspecific pollen transfer. Here, we present evidence that coexisting species in an old-field community generally overlap less in flowering time than expected under a commonly used and statistically validated null model. Flowering time asynchrony was more pronounced when abundance data were used (compared to presence-absence data), and when analyses focused on species that share bees as pollinators. Control and herbivore-exclusion plots did not differ in flowering time overlap, providing no evidence of the reduction in overlap expected to result from increased competition. Our results varied with the randomization algorithm used, emphasizing that the choice of algorithm can influence the outcome of null models. Our results varied between 2 years, with patterns being less clear in the second year, when both growing season and flowering times were contracted. Finally, we found evidence that further supports a previous finding that higher plot-level flowering time overlap was associated with higher proportions of introduced species. Reduced flowering time overlap among species in our focal community may promote coexistence via temporal niche differentiation and reduced competition for pollinators and other abiotic resources.

Prior antibiotic exposure and risk of type 2 diabetes among Veterans.

BACKGROUND: Exposure to antibiotics may increase the risk of type 2 diabetes. Veterans are at increased risk for diabetes and for exposure to antibiotics. OBJECTIVE: To determine the impact of antibiotic exposure for risk of diabetes. DESIGN: Retrospective cohort study. PARTICIPANTS: Veterans at the New York Harbor Healthcare System enrolled in primary care, 2004-2014, with ≥2 glycosylated hemoglobin test results <6.5%. MAIN MEASURES: The primary exposure was any antimicrobial prescribed >6 months prior to the date of diabetes diagnosis, loss to follow-up, death, or the end of the study, measured as the number of courses of antimicrobial prescriptions filled and the mean daily dose (MDD). The primary outcome was incident diagnosis of diabetes through 2014, defined ≥2 ICD-9 codes for diabetes or ≥2 prescriptions of diabetes medications, other than metformin. Cox proportional hazards regression was used to model antimicrobial medications, demographic and anthropometric measures, and comorbid cardiovascular conditions to incident diabetes. Models incorporated time varying covariates of antimicrobial medication and MDD to analyze associations by antimicrobial class. KEY RESULTS: Among 14,361 Veterans, 9922 (69.1%) were prescribed any antimicrobial medication during the study period. 1413 (9.8%) individuals developed type 2 diabetes. Increased risk of diabetes was associated with >1 prescription (HR 1.13 [1.01-1.26]) compared to none. Time varying analysis of the total number of cumulative courses prescribed showed increased diabetes risk for cephalosporin (HR 1.17 [1.04-1.31]), macrolide (HR 1.08 [1.03-1.13]) and penicillin (HR 1.05 [1.02-1.07]). MDD showed increased risk per 100-unit (mg) increase in antibiotic exposure from (HR 1.05 [1.02-1.08]) for sulfonamide to (HR 1.70 [1.51-1.92]) for cephalosporin. CONCLUSION: Any and repeated exposure to certain antibiotics may increase diabetes risk among Veterans. Results from this study add to the growing evidence suggesting that antibiotic exposure increases risk for diabetes. Antibiotic stewardship may be enhanced by better understanding this risk, and may lower the incidence of diabetes in populations at risk.

HbA1c, lipid profiles and risk of incident type 2 Diabetes in United States Veterans.

United States Veterans are at excess risk for type 2 diabetes, but population differentials in risk have not been characterized. We determined risk of type 2 diabetes in relation to prediabetes and dyslipidemic profiles in Veterans at the VA New York Harbor (VA NYHHS) during 2004-2014. Prediabetes was based on American Diabetes Association hemoglobin A1c (HbA1c) testing cut-points, one of several possible criteria used to define prediabetes. We evaluated transition to type 2 diabetes in 4,297 normoglycemic Veterans and 7,060 Veterans with prediabetes. Cox proportional hazards regression was used to relate HbA1c levels, lipid profiles, demographic, anthropometric and comorbid cardiovascular factors to incident diabetes (Hazard Ratio [HR] and 95% confidence intervals). Compared to normoglycemic Veterans (HbA1c: 5.0-5.6%; 31-38 mmol/mol), risks for diabetes were >2-fold in the moderate prediabetes risk group (HbA1c: 5.7-5.9%; 39-41 mmol/mol) (HR 2.37 [1.98-2.85]) and >5-fold in the high risk prediabetes group (HbA1c: 6.0-6.4%; 42-46 mmol/mol) (HR 5.59 [4.75-6.58]). Risks for diabetes were increased with elevated VLDL (≥40mg/dl; HR 1.31 [1.09-1.58]) and TG/HDL (≥1.5mg/dl; HR 1.34 [1.12-1.59]), and decreased with elevated HDL (≥35mg/dl; HR 0.80 [0.67-0.96]). Transition to diabetes in Veterans was related in age-stratified risk score analyses to HbA1c, VLDL, HDL and TG/HDL, BMI, hypertension and race, with 5-year risk differentials of 62% for the lowest (5-year risk, 13.5%) vs. the highest quartile (5-year risk, 21.9%) of the risk score. This investigation identified substantial differentials in risk of diabetes in Veterans, based on a readily-derived risk score suitable for risk stratification for type 2 diabetes prevention.

Electron cryotomography of Mycoplasma pneumoniae mutants correlates terminal organelle architectural features and function.

The Mycoplasma pneumoniae terminal organelle functions in adherence and gliding motility and is comprised of at least eleven substructures. We used electron cryotomography to correlate impaired gliding and adherence function with changes in architecture in diverse terminal organelle mutants. All eleven substructures were accounted for in the prkC, prpC and P200 mutants, and variably so for the HMW3 mutant. Conversely, no terminal organelle substructures were evident in HMW1 and HMW2 mutants. The P41 mutant exhibits a terminal organelle detachment phenotype and lacked the bowl element normally present at the terminal organelle base. Complementation restored this substructure, establishing P41 as either a component of the bowl element or required for its assembly or stability, and that this bowl element is essential to anchor the terminal organelle but not for leverage in gliding. Mutants II-3, III-4 and topJ exhibited a visibly lower density of protein knobs on the terminal organelle surface. Mutants II-3 and III-4 lack accessory proteins required for a functional adhesin complex, while the topJ mutant lacks a DnaJ-like co-chaperone essential for its assembly. Taken together, these observations expand our understanding of the roles of certain terminal organelle proteins in the architecture and function of this complex structure.

Effect of application score strategy on interviews offered to postgraduate year 1 pharmacy residency applicants.

OBJECTIVES: Residency programs may need to spend a large amount of time on the application review process in order to invite the best candidates for interviews. By using a different scoring strategy, this process could be made more efficient while still resulting in selection of the most appropriate candidates to interview. The objective of this study was to explore hypothetical scoring strategies for past residency applicants and to determine the percentage of these applicants that would have received an interview offer compared with the program's standard scoring strategy. METHODS: Two years of residency applications to a postgraduate year 1 (PGY1) program providing the majority of clinical experience in ambulatory care were analyzed. Four models were explored: 1) standard model (original method); 2) simplified model (derived from statistical methods); 3) intuition model (criteria thought to best exemplify program success); and 4) objective model (criteria easy to objectively record, e.g., grade point average). All 3 new models were compared with the standard model to determine the percentage of candidates who would have received an interview if their applications had been scored according to the new model. RESULTS: A total of 110 applications were reviewed (42 interviews offered). After a multivariable analysis, academics, leadership, interest in ambulatory care, and professionalism were included in the simplified model, which predicted 81% of the interviews offered through the standard model. The intuition and objective models predicted 71% and 48% of interviews offered through the standard model, respectively. CONCLUSION: Models scoring only 4 of the initial 12 criteria would have likely predicted 71% to 81% of original interview offers. Residency programs should consider periodically reviewing their application review processes to determine areas for improved efficiency.

Sulfamethoxazole/trimethoprim versus fluoroquinolones for the treatment of Stenotrophomonas maltophilia bloodstream infections.

OBJECTIVES: Stenotrophomonas maltophilia causes high mortality rates, especially in bloodstream infections (BSIs) where there is a lack of comparative data with fluoroquinolones (FQs) and sulfamethoxazole/trimethoprim (SXT). The objective of this study was to evaluate outcomes in patients with S. maltophilia BSI who were treated with FQs versus SXT. METHODS: A retrospective study was conducted to compare FQs (levofloxacin, ciprofloxacin and moxifloxacin) versus SXT for the treatment of S. maltophilia BSI. RESULTS: A total of 54 patients were included in this retrospective study, including 32 treated with SXT and 22 treated with FQs (11 ciprofloxacin, 5 levofloxacin and 6 moxifloxacin). There were 3 deaths (13.6%) in the FQ group versus 10 (31.3%) in the SXT group (P=0.20). Modified Acute Physiology and Chronic Health Evaluation (APACHE) II score [odds ratio (OR)=1.4, 95% confidence interval (CI) 1.1-1.8] and broad-spectrum antibiotics prior to culture (OR=8, 95% CI 1.3-49.8) were significant predictors of mortality. CONCLUSIONS: Ciprofloxacin, moxifloxacin and levofloxacin are possible alternatives to SXT for S. maltophilia BSI; however, further investigation is needed to confirm these findings.