Antimicrobial use among paediatric inpatients at hospital sites within the Canadian Nosocomial Infection Surveillance Program, 2017/2018.

BACKGROUND: Antimicrobial resistance threatens the ability to successfully prevent and treat infections. While hospital benchmarks regarding antimicrobial use (AMU) have been well documented among adult populations, there is less information from among paediatric inpatients. This study presents benchmark rates of antimicrobial use (AMU) for paediatric inpatients in nine Canadian acute-care hospitals. METHODS: Acute-care hospitals participating in the Canadian Nosocomial Infection Surveillance Program submitted annual AMU data from paediatric inpatients from 2017 and 2018. All systemic antimicrobials were included. Data were available for neonatal intensive care units (NICUs), pediatric ICUs (PICUs), and non-ICU wards. Data were analyzed using days of therapy (DOT) per 1000 patient days (DOT/1000pd). RESULTS: Nine hospitals provided paediatric AMU data. Data from seven NICU and PICU wards were included. Overall AMU was 481 (95% CI 409-554) DOT/1000pd. There was high variability in AMU between hospitals. AMU was higher on PICU wards (784 DOT/1000pd) than on non-ICU (494 DOT/1000pd) or NICU wards (333 DOT/1000pd). On non-ICU wards, the antimicrobials with the highest use were cefazolin (66 DOT/1000pd), ceftriaxone (59 DOT/1000pd) and piperacillin-tazobactam (48 DOT/1000pd). On PICU wards, the antimicrobials with the highest use were ceftriaxone (115 DOT/1000pd), piperacillin-tazobactam (115 DOT/1000pd), and cefazolin (111 DOT/1000pd). On NICU wards, the antimicrobials with the highest use were ampicillin (102 DOT/1000pd), gentamicin/tobramycin (78 DOT/1000pd), and cefotaxime (38 DOT/1000pd). CONCLUSIONS: This study represents the largest collection of antimicrobial use data among hospitalized paediatric inpatients in Canada to date. In 2017/2018, overall AMU was 481 DOT/1000pd. National surveillance of AMU among paediatric inpatients is necessary for establishing benchmarks and informing antimicrobial stewardship efforts.

Trends in Severe Outcomes Among Adult and Pediatric Patients Hospitalized With COVID-19 in the Canadian Nosocomial Infection Surveillance Program, March 2020 to May 2022.

Importance: Trends in COVID-19 severe outcomes have significant implications for the health care system and are key to informing public health measures. However, data summarizing trends in severe outcomes among patients hospitalized with COVID-19 in Canada are not well described. Objective: To describe trends in severe outcomes among patients hospitalized with COVID-19 during the first 2 years of the COVID-19 pandemic. Design, Setting, and Participants: Active prospective surveillance in this cohort study was conducted from March 15, 2020, to May 28, 2022, at a sentinel network of 155 acute care hospitals across Canada. Participants included adult (aged ≥18 years) and pediatric (aged 0-17 years) patients hospitalized with laboratory-confirmed COVID-19 at a Canadian Nosocomial Infection Surveillance Program (CNISP)-participating hospital. Exposures: COVID-19 waves, COVID-19 vaccination status, and age group. Main Outcomes and Measures: The CNISP collected weekly aggregate data on the following severe outcomes: hospitalization, admission to an intensive care unit (ICU), receipt of mechanical ventilation, receipt of extracorporeal membrane oxygenation, and all-cause in-hospital death. Results: Among 1 513 065 admissions, the proportion of adult (n = 51 679) and pediatric (n = 4035) patients hospitalized with laboratory-confirmed COVID-19 was highest in waves 5 and 6 of the pandemic compared with waves 1 to 4 (77.3 vs 24.7 per 1000 patient admissions). Despite this, the proportion of patients with positive test results for COVID-19 who were admitted to an ICU, received mechanical ventilation, received extracorporeal membrane oxygenation, and died were each significantly lower in waves 5 and 6 when compared with waves 1 through 4. Admission to the ICU and in-hospital all-cause death rates were significantly higher among those who were unvaccinated against COVID-19 when compared with those who were fully vaccinated (incidence rate ratio, 4.3 and 3.9, respectively) or fully vaccinated with an additional dose (incidence rate ratio, 12.2 and 15.1, respectively). Conclusions and Relevance: The findings of this cohort study of patients hospitalized with laboratory-confirmed COVID-19 suggest that COVID-19 vaccination is important to reduce the burden on the Canadian health care system as well as severe outcomes associated with COVID-19.

Epidemiology of Primary and Recurrent Healthcare-Associated and Community-Associated Pediatric Clostridioides difficile Infection in Canada, 2015-2020.

Clostridioides difficile infection (CDI) among children remains a concerning cause of morbidity in hospital settings. We present epidemiological and molecular trends in healthcare- and community-associated CDI among children in Canadian inpatient and outpatient settings, including those who experienced recurrent infections.

Cerebrospinal fluid shunt-associated surgical site infection with three-month versus twelve-month surveillance periods in Canadian hospitals.

Cerebrospinal fluid shunt-associated surgical site infection surveillance for 3 months compared to 12 months after surgery captures 83% of cases with no significant differences in patient characteristics, surgery types, or pathogens. A shorter 3-month follow-up can reduce resource use and allow for more timely reporting of healthcare-associated infection rates for hospitals.

Trends in Clostridioides difficile infection rates in Canadian hospitals during the coronavirus disease 2019 (COVID-19) pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.

Characterization of Healthcare-Associated and Community-Associated Clostridioides difficile Infections among Adults, Canada, 2015-2019.

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015-2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015-2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.

Patients in hospital with laboratory-confirmed COVID-19 in a network of Canadian acute care hospitals, Mar. 1 to Aug. 31, 2020: a descriptive analysis.

BACKGROUND: Information on the epidemiology of patients in hospital with laboratory-confirmed coronavirus disease 2019 (COVID-19) in Canadian acute care hospitals is needed to inform infection prevention and control strategies and public health measures. The aim of this surveillance was to describe the epidemiology of patients in hospital with laboratory-confirmed COVID-19 in a network of Canadian acute care hospitals between Mar. 1 and Aug. 31, 2020. METHODS: Through prospective surveillance, we identified adult and pediatric patients in hospital with laboratory-confirmed COVID-19 using a standard definition between Mar. 1 and Aug. 31, 2020, through the Canadian Nosocomial Infection Surveillance Program (CNISP), a network of 78 hospitals. Patient demographic and clinical characteristics and data on treatment, interventions and outcomes were reviewed and described. RESULTS: As of Aug. 31, 2020, the CNISP had received data for 1906 patients in hospital with COVID-19 in 49 sentinel hospitals in 9 provinces. The majority of patients in hospital with COVID-19 were older (median age 71 yr) and had underlying medical conditions (85.8%). Few children with COVID-19 were admitted to a participating hospital (n = 37, 1.9%). Acquisition of COVID-19 in hospitals was infrequent (6.4% of all cases). A total of 32.8% of patients were admitted from a long-term care facility or retirement home. Health care workers constituted 10.6% of adult patients aged 18-65 years in hospital with COVID-19. Thirty-day attributable mortality was 16.2%. Hospital admission rates peaked in mid-April and were highest in Ontario and Quebec. INTERPRETATION: Surveillance findings indicate that a high proportion of Canadian patients in hospital with COVID-19 during the first 6 months of the pandemic were older adults with underlying medical conditions. Active surveillance of patients in hospital with COVID-19 is critical to enhancing our knowledge of the epidemiology of COVID-19 and to identifying populations at risk for severe outcomes, which will help guide Canada's response in the coming months.

The National Dental Practice-Based Research Network Adult Anterior Open Bite Study: Patient satisfaction with treatment.

INTRODUCTION: This article evaluates and reports on the satisfaction of adult patients across the United States who received orthodontic treatment for anterior open bite malocclusion. The factors that influence satisfaction are also described. METHODS: Practitioners were recruited from the National Dental Practice-Based Research Network. On joining the Network, practitioner demographics and information on their practices were acquired. Practitioners enrolled their adult patients in active treatment for anterior open bite. Patient demographics, patient dentofacial characteristics, and details regarding previous and current treatment were collected through questionnaires at enrollment (T1). Pretreatment lateral cephalograms and intraoral frontal photographs were submitted. Treatment performed, and details related to treatment outcome were recorded through questionnaires at the end of active treatment (T2). Posttreatment lateral cephalograms and intraoral frontal photographs were submitted. Patient satisfaction at T2 was assessed using a 5-point Likert-type scale and open-ended responses. Predictive univariate models were developed to evaluate the factors that affect patient satisfaction. Open-ended responses were reviewed for general trends. RESULTS: T2 data were received for 260 patients, and 248 of these patients completed and returned the patient satisfaction questionnaires. High levels of satisfaction were found in this sample of adult patients receiving treatment for anterior open bite malocclusion. Specifically, 96% of the sample reported being very or somewhat satisfied. Only 10 patients (4%) were not satisfied with the treatment provided or an element of the final result. Successful open bite closure, treatment modality, and certain patient characteristics may affect patient satisfaction. However, there was insufficient power to demonstrate statistical significance because of the very low number of dissatisfied patients. Open-ended responses directly associated with patient satisfaction were received from 23 patients (9%). They relayed positive, neutral, and negative feelings about the treatment received and final results. Additional responses regarding the orthodontic treatment in general, but not specifically linked to patient satisfaction, were received from 119 patients (48%). These comments depict an overwhelmingly positive experience. CONCLUSIONS: Adult patients who received orthodontic treatment for anterior open bite malocclusion were generally satisfied with the treatment provided, as well as the final esthetic and functional results.

The National Dental Practice-Based Research Network Adult Anterior Open Bite Study: Treatment success.

INTRODUCTION: Anterior open bite (AOB) continues to be a challenging malocclusion for orthodontists to treat and retain long-term. There is no consensus on which treatment modality is most successful. This study reports on the overall success rate of AOB orthodontic treatment in the adult population across the United States, as well as 4 major treatment modalities and other factors that may influence treatment success. METHODS: Practitioners and their adult patients with AOB were recruited through the National Dental Practice-Based Research Network. Patient dentofacial and demographic characteristics, practitioner demographic and practice characteristics, and factors relating to orthodontic treatment were reported. Treatment success was determined from posttreatment (T2) lateral cephalometric films and intraoral frontal photographs. Treatment was categorized into 4 main groups: aligners, fixed appliances, temporary anchorage devices (TADs), and orthognathic surgery. Extractions were also evaluated. Bivariate and multivariable models were used to investigate the association between treatment success and treatment modality, pretreatment (T1) dentofacial characteristics, patient and practitioner demographics, and practice characteristics, adjusting for clustering of patients within practice. RESULTS: A total of 254 patients, enrolled by 84 practitioners, contributed to T2 data for this study. There were 29 patients in the aligner group, 152 in fixed appliances, 20 in TADs, and 53 in surgery. A total of 49 patients underwent extractions of teeth other than third molars. Ninety-three percent finished treatment with a positive overbite on the T2 lateral cephalogram, and 84% finished with a positive vertical overlap of all incisors. The small number of aligners and TAD patients limited the ability to compare success rates in these groups. Patients treated with orthognathic surgery had a higher rate of success compared with those treated with fixed appliances only. Treatment success was also associated with academic practice setting, T1 mandibular plane angle ≤30°, no to mild T1 crowding, and treatment duration <30 months. CONCLUSIONS: The overall success of orthodontic treatment in adult patients with AOB who participated in this study was very high. Orthognathic surgery was the only treatment modality that exhibited a statistically higher odds of successful outcomes. Some T1 dentofacial characteristics and treatment factors were associated with the successful closure of AOB.

Antimicrobial use among adult inpatients at hospital sites within the Canadian Nosocomial Infection Surveillance Program: 2009 to 2016.

BACKGROUND: Antimicrobial resistance is a growing threat to the world's ability to prevent and treat infections. Links between quantitative antibiotic use and the emergence of bacterial resistance are well documented. This study presents benchmark antimicrobial use (AMU) rates for inpatient adult populations in acute-care hospitals across Canada. METHODS: In this retrospective surveillance study, acute-care adult hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP) submitted annual AMU data on all systemic antimicrobials from 2009 to 2016. Information specific to intensive care units (ICUs) and non-ICU wards were available for 2014-2016. Data were analyzed using defined daily doses (DDD) per 1000 patient days (DDD/1000pd). RESULTS: Between 2009 and 2016, 16-18 CNISP adult hospitals participated each year and provided their AMU data (22 hospitals participated in ≥1 year of surveillance; 11 in all years). From 2009 to 2016, there was a significant reduction in use (12%) (from 654 to 573 DDD/1000pd, p = 0.03). Fluoroquinolones accounted for the majority of this decrease (47% reduction in combined oral and intravenous use, from 129 to 68 DDD/1000pd, p < 0.002). The top five antimicrobials used in 2016 were cefazolin (78 DDD/1000pd), piperacillin-tazobactam (53 DDD/1000pd), ceftriaxone (49 DDD/1000pd), vancomycin (combined oral and intravenous use was 44 DDD/1000pd; 7% of vancomycin use was oral), and ciprofloxacin (combined oral and intravenous use: 42 DDD/1000pd). Among the top 10 antimicrobials used in 2016, ciprofloxacin and metronidazole use decreased significantly between 2009 and 2016 by 46% (p = 0.002) and 26% (p = 0.002) respectively. Ceftriaxone (85% increase, p = 0.0008) and oral amoxicillin-clavulanate (140% increase, p < 0.0001) use increased significantly but contributed only a small component (8.6 and 5.0%, respectively) of overall use. CONCLUSIONS: This study represents the largest collection of dispensed antimicrobial use data among inpatients in Canada to date. Between 2009 and 2016, there was a significant 12% decrease in AMU, driven primarily by a 47% decrease in fluoroquinolone use. Modest absolute increases in parenteral ceftriaxone and oral amoxicillin-clavulanate use were noted but contributed a small amount of total AMU. Ongoing national surveillance is crucial for establishing benchmarks and antimicrobial stewardship guidelines.

The National Dental Practice-Based Research Network adult anterior open bite study: A description of the practitioners and patients.

OBJECTIVES:: To describe the demographic and practice characteristics of the clinicians enrolled in a large, prospective cohort study examining recommendations and treatment for adult anterior open bite (AOB) and the relationship between these characteristics and practitioners' self-reported treatment preferences. The characteristics of the AOB patients recruited were also described. MATERIALS AND METHODS:: Practitioners were recruited from the National Dental Practice-Based Research Network. Participants in the study consisted of practitioners and their adult AOB patients in active treatment. Upon enrollment, practitioners completed questionnaires enquiring about demographics, treatment preferences for adult AOB patients, and treatment recommendations for each patient. Patients completed questionnaires on demographics and factors related to treatment. RESULTS:: Ninety-one practitioners and 347 patients were recruited. Demographic characteristics of recruited orthodontists were similar to those of American Association of Orthodontists members. The great majority of practitioners reported using fixed appliances and elastics frequently for adult AOB patients. Only a third of practitioners reported using aligners frequently for adult AOB patients, and 10% to 13% frequently recommended temporary anchorage devices (TADs) or orthognathic surgery. Seventy-four percent of the patients were female, and the mean age was 31.4 years. The mean pretreatment overbite was -2.4 mm, and the mean mandibular plane angle was 38.8°. Almost 40% of patients had undergone orthodontic treatment previously. CONCLUSIONS:: This article presents the demographic data for 91 doctors and 347 adult AOB patients, as well as the practitioners' self-reported treatment preferences.

The evolving epidemiology of Clostridium difficile infection in Canadian hospitals during a postepidemic period (2009-2015).

BACKGROUND: The clinical and molecular epidemiology of health care-associated Clostridium difficile infection in nonepidemic settings across Canada has evolved since the first report of the virulent North American pulsed-field gel electrophoresis type 1 (NAP1) strain more than 15 years ago. The objective of this national, multicentre study was to describe the evolving epidemiology and molecular characteristics of health care-associated C. difficile infection in Canada during a post-NAP1-epidemic period, particularly patient outcomes associated with the NAP1 strain. METHODS: Adult inpatients with C. difficile infection were prospectively identified, using a standard definition, between 2009 and 2015 through the Canadian Nosocomial Infection Surveillance Program (CNISP), a network of 64 acute care hospitals. Patient demographic characteristics, severity of infection and outcomes were reviewed. Molecular testing was performed on isolates, and strain types were analyzed against outcomes and epidemiologic trends. RESULTS: Over a 7-year period, 20 623 adult patients admitted to hospital with health care-associated C. difficile infection were reported to CNISP, and microbiological data were available for 2690 patients. From 2009 to 2015, the national rate of health care-associated C. difficile infection decreased from 5.9 to 4.3 per 10 000 patient-days. NAP1 remained the dominant strain type, but infection with this strain has significantly decreased over time, followed by an increasing trend of infection with NAP4 and NAP11 strains. The NAP1 strain was significantly associated with a higher rate of death attributable to C. difficile infection compared with non-NAP1 strains (odds ratio 1.91, 95% confidence interval [CI] 1.29-2.82). Isolates were universally susceptible to metronidazole; one was nonsusceptible to vancomycin. The proportion of NAP1 strains within individual centres predicted their rates of health care-associated C. difficile infection; for every 10% increase in the proportion of NAP1 strains, the rate of health care-associated C. difficile infection increased by 3.3% (95% CI 1.7%-4.9%). INTERPRETATION: Rates of health care-associated C. difficile infection have decreased across Canada. In nonepidemic settings, NAP4 has emerged as a common strain type, but NAP1, although decreasing, continues to be the predominant circulating strain and remains significantly associated with higher attributable mortality.

Real-world economic value of a 21-gene assay in early-stage breast cancer.

OBJECTIVES: Value-based payment reforms shift cost-containment responsibilities to the physician. Although gene expression profiling (GEP) utilizing a 21-gene panel among patients with early-stage, axillary lymph node-negative, hormone receptor-positive, HER2/neu oncogene-negative breast cancer is able to identify a cohort that may achieve excellent outcomes without adjuvant chemotherapy, high up-front costs (list price, $4175) could dissuade usage. STUDY DESIGN: Retrospective review of consecutive patients with breast cancer treated at a single cancer center. METHODS: Chart review of 227 patients 70 years or younger with outpatient costs (ie, drug average sales price, reagent costs, physician charges) during first 6 months of treatment. RESULTS: Of these patients, 68% underwent GEP, with 52%, 43%, and 5% having low, intermediate, and high recurrence risk scores, respectively. Adjuvant chemotherapy was utilized less in genomically profiled cohorts (19% vs 29%; P = .08) and was consistent with recommendations of the recurrence scores. The mean 6-month outpatient costs were $24,955 with adjuvant chemotherapy and $2654 with hormonal therapy. Patients with stage II cancer undergoing GEP received adjuvant chemotherapy at a lower frequency (28.6% vs 86.7%), but patients with stage I cancer who underwent testing were slightly more likely to receive chemotherapy (15.8% vs 14%) because the test identified patients with higher-risk tumors. Universal GEP testing of patients with stage II cancer would have resulted in net savings of $11,494 per patient inclusive of test cost; stage I testing would have increased costs by $4505. Similar trends for grade 2/3 tumors (-$2394) and grade 1 tumors (+$6047) were noted. CONCLUSIONS: Universal GEP testing of women 70 years or younger with stage II or grade 2/3 lymph node-negative breast cancers would result in lower outpatient costs, inclusive of the diagnostic test, within the first 6-month episode of care.

Treatment of Peripheral T-Cell Lymphoma in Community Settings.

BACKGROUND: Peripheral T-cell lymphomas (PTCLs) represent a rare and heterogeneous group of malignancies that do not have consensus treatment recommendations. Strategies extrapolated from B-cell lymphoma have met with limited efficacy, although T-cell-specific salvage therapies have been recently developed. METHODS: To determine treatment patterns and associated outcomes in PTCL not otherwise specified (PTCL-NOS), anaplastic large T-cell lymphoma (ALCL), and angioimmunoblastic T-cell lymphoma (AITL), a retrospective analysis was undertaken at a large US community oncology network among patients treated between January 2010 and April 2015. RESULTS: Among 93 patients (44 PTCL-NOS, 30 ALCL, 19 AITL), 23 unique treatments were used in 66 first-line patients and 12 unique second-line treatments were used in 24 relapsed/refractory patients. First-line CHOP and CHOP-like regimens were used in 74% of patients, providing 4-year overall survival (OS) outcomes of 34% (95% confidence interval [CI], 14%-83%) in patients without transplant consolidation (82% in ALCL, 37% in PTCL-NOS, and 0% in AITL). Upfront stem cell transplantation trended toward improved 4-year progression-free survival 77% (95% CI, 54%-100%) versus 34% (95% CI, 14%-80%); (P = .08; hazard ratio [HR] 0.29) with 4-year OS 77% (95% CI, 54%-100%) versus 34% (P = .22; HR 0.41). Brentuximab was the most common second-line therapy, with multiple additional regimens used in sequence (up to 5 salvage regimens) in many. CONCLUSIONS: The significant variability in treatments used for PTCL emphasizes the lack of consensus therapy in this rarer lymphoma and calls for additional organized prospective and registry studies to evaluate comparative effectiveness.

Genomic Profiling of Advanced Non-Small Cell Lung Cancer in Community Settings: Gaps and Opportunities.

BACKGROUND: National guidelines have advocated broad molecular profiling as a part of the standard diagnostic evaluation for advanced non-small cell lung cancer (NSCLC), with the goal of identifying driver mutations for which effective therapies or clinical trials are available. However, adherence to genomic testing guidelines could present challenges to community oncologists. PATIENTS AND METHODS: We performed a retrospective review of genomic testing patterns in patients with nonsquamous NSCLC treated by 89 oncologists at 15 sites throughout New Jersey and Maryland from January 2013 to December 2015. RESULTS: A total of 814 patients (89% with stage IV; 11% with stage IIIB) were identified in the COTA Inc database. Of the 814 patients, 479 (59%) met the guideline recommendations for EGFR (epidermal growth factor receptor) and ALK (anaplastic lymphoma kinase) biomarker testing; 63 (8%) underwent comprehensive genomic profiling for all 4 major types of alterations (point mutations, indels, fusions, and copy number amplifications). Gender, age, race, site of care (referral vs. community center), and practice size did not influence comprehensive genomic profiling frequency. Active smokers and patients who died within 30 days were tested less frequently (P < .05). Among those not tested for EGFR and ALK, 52% received chemotherapy without documented reasons for no testing, 32% did not receive antineoplastic therapy, and 13% had insufficient tissue for genotyping. CONCLUSION: Genomic testing presents multiple logistical challenges for the community-based oncologist, including coordination of sample handling, long turnaround times, test reimbursement, access to targeted therapies, insufficient tissue, and patient harm from the repeat biopsies necessary if the tissue sample is insufficient. Opportunities exist for improvement in guideline adherence, possibly through new technologies such as "liquid biopsies," which obviates the need tissue biopsy samples in select settings.

A Patient-Reported Outcome Instrument to Facilitate Timing of End-of-Life Discussions among Patients with Advanced Cancers.

BACKGROUND: Honoring the wishes of cancer patients is a responsibility of oncologists; however, end-of-life care (EOLC) discussions are frequently delayed past the point of usefulness. OBJECTIVE: To develop a patient-reported outcome (PRO) screening tool that facilitates timing of EOLC discussions. DESIGN: A seven-item PRO instrument covering four clinical and personhood domains [performance status, pain, burden (financial and family), and depression] was administered to patients with advanced malignancies undergoing noncurative therapy. The PRO instrument included the patient's assessment of the importance of each domain. Results were correlated with the oncologist's assessment of appropriateness of continuing aggressive therapy. SETTING/SUBJECTS: Four hundred thirty-three patients fully completed the PRO instrument between February and March 2015 at a single outpatient cancer center. RESULTS: There was a difference (p < 0.0001) in median scores among cohorts deemed by their oncologists appropriate to continue noncurative treatments versus patients whose physicians were contemplating or actively engaged in EOLC discussions. The scores for the four individual domains also differed among cohorts. An upper threshold score comprising 46% of patients deemed appropriate to curtail treatment (but inclusive of only 26% of patients deemed appropriate to continue) was determined, facilitating identification of patients for EOLC discussions. CONCLUSIONS: A seven-item patient-centric PRO instrument was able to separate advanced malignancy patients into cohorts who their physicians deemed were at differing stages in their cancer journey with increasing needs for advance care planning. A study to determine if the threshold scores identified in this pilot correlate with palliative/EOL consultation frequency and patient survival is underway.

Healthcare-Associated Clostridium difficile Infections and Strain Diversity in Pediatric Hospitals in the Canadian Nosocomial Infection Surveillance Program, 2007-2011.

Children with healthcare-associated Clostridium difficile infection were identified. The incidence increased from 3.2/10,000 patient days in 2007 to 5.2/10,000 patient days in 2011 (p < 0.001). Of 169 isolates, the most common North American Pulsed-Field (NAP) types were NAP4 (n = 43; (25.4%), and NAP1 (n = 25;14.8%) while 55 (32.6%) were non-assigned NAP types.

Effect of PEL exopolysaccharide on the wspF mutant phenotypes in Pseudomonas aeruginosa PA14.

Pseudomonas aeruginosa is an opportunistic human pathogen that produces and secretes exopolysaccharides (EPS), in which cells are embedded to form a highly organized community structure called biofilm. Here, we characterized the role of cyclic diguanylate (c-di-GMP) and EPS (PEL) overproduction in the wspF mutant phenotypes of P. aeruginosa PA14 (wrinkly appearance, hyperadherence, impaired motilities, and reduced virulence in acute infections). We confirmed that the elevated c-di-GMP level plays a key role in all the wspF mutant phenotypes listed above, as assessed by ectopic expression of a c-di-GMP-degrading phophodiesterase (PvrR) in the wspF mutant. In contrast, PEL EPS, which is overproduced in the wspF mutant, was necessary for wrinkly appearance and hyperadherence, but not for the impaired flagellar motilities and the attenuated virulence of the wspF mutant. These results suggest that cdi- GMP affects flagellar motility and virulence, independently of EPS production and surface adherence of this bacterium.

Derivation of infectious HIV-1 molecular clones with LTR mutations: sensitivity to the CD8+ cell noncytotoxic anti-HIV response.

CD8(+) cells from healthy, asymptomatic HIV-1-infected individuals can inhibit HIV-1 replication in naturally or acutely infected CD4(+) cells in the absence of cell killing. This CD8(+) cell noncytotoxic anti-HIV response (CNAR) is mediated by a soluble CD8(+) cell antiviral factor (CAF). CNAR/CAF inhibits HIV-1 replication by blocking viral RNA transcription. HIV transcription is regulated by a variety of cis-acting DNA sequence elements within the proviral long terminal repeat (LTR). We hypothesized that one of the HIV-1 LTR proviral DNA sequence elements that binds host cell transcriptional factors is involved in this antiviral activity. To assess this possibility, we constructed full-length infectious HIV-1 molecular clones with mutations in the LTR elements NFAT, AP-1, IL-2 homology region, and the downstream ISRE. We also tested full-length infectious molecular clones that had deletions of either the NF-kappaB or Sp1 sites of the LTR or lacked functional Tat and TAR elements. Viruses generated from these molecular clones were used to acutely infect CD4(+) cells that subsequently were either co-cultured with CD8(+) cells from individuals that exhibited strong CNAR or cultured with CAF-containing fluids. The replication of all of the mutant HIV-1 viruses tested was substantially reduced in the presence of CNAR/CAF. These findings suggest that other regions in the viral LTR or other host cell processes are involved in the transcriptional block elicited by CNAR/CAF.

R-type pyocin is required for competitive growth advantage between Pseudomonas aeruginosa strains.

R-type pyocin is a bacteriophage tail-shaped bacteriocin produced by Pseudomonas aeruginosa, but its physiological roles are relatively unknown. Here we describe a role of R-type pyocin in the competitive growth advantages between P. aeruginosa strains. Partial purification and gene disruption revealed that the major killing activity from the culture supernatant of PA14 is attributed to R-type pyocin, neither F-type nor S-type pyocins. These findings may provide insight into the forces governing P. aeruginosa population dynamics to promote and maintain its biodiversity.