Comparison of survival of stage I-III colon cancer by travel distance and hospital volume.

BACKGROUND: Previous studies have demonstrated improved outcomes at high-volume colorectal surgery centers; however, the benefit for patients who live far from such centers has not been assessed relative to local, low-volume facilities. METHODS: The 2010-2015 National Cancer Database (NCDB) was queried for patients with stage I-III colon adenocarcinoma undergoing treatment at a single center. A 'local, low-volume' cohort was constructed of 12,768 patients in the bottom quartile of travel distance at the bottom quartile of institution surgical volume and a 'travel, high-volume' cohort of 11,349 patients in the top quartile of travel distance at the top quartile of institution surgical volume. RESULTS: In unadjusted analysis, patients in the travel cohort had improved rates of positive resection margins (3.7% vs. 5.5%, p < 0.001), adequate lymph-node harvests (92% vs. 83.6%, p < 0.001), and 30- (2.2% vs. 3.9%, p < 0.001) and 90-day mortality (3.7% vs. 6.4%, p < 0.001). On multivariable logistic regression analysis adjusting for patient demographic, tumor, and facility characteristics, the cohorts demonstrated equivalent overall survival (HR: 0.972, p = 0.39), with improved secondary outcomes in the 'travel' cohort of adequate lymph-node harvesting (OR: 0.57, p < 0.001), and 30- (OR 0.79, p = 0.019) and 90-day mortality (OR 0.80, p = 0.004). CONCLUSIONS: For patients with stage I-III colon cancer, traveling to high-volume institutions compared to local, low-volume centers does not convey an overall survival benefit. However, given advantages including 30- and 90-day mortality and adequate lymph-node harvest, nuanced patient recommendations should consider both these differences and the unquantified benefits to local care, including cost, travel time, and support systems.

A "Stone in the Pond" Approach to Contact Tracing: Responding to a Large-Scale, Nosocomial Tuberculosis Exposure in a Moderate TB-Burden Setting.

A "stone in the pond" strategy is a practical approach to investigating large-scale nosocomial tuberculosis (TB) exposures. Here, we describe such a risk-stratified approach to contact tracing after a TB exposure that occurred over 5 months in a pediatric inpatient ward in a country with a moderate TB burden. Infect Control Hosp Epidemiol 2017;38:1509-1511.

Association between neoadjuvant chemoradiation and survival for patients with locally advanced rectal cancer.

AIM: To examine the overall survival differences for the following neoadjuvant therapy modalities - no therapy, chemotherapy alone, radiation alone and chemoradiation - in a large cohort of patients with locally advanced rectal cancer. METHOD: Adults with clinical Stage II and III rectal adenocarcinoma were selected from the National Cancer Database and grouped by type of neoadjuvant therapy received: no therapy, chemotherapy only, radiotherapy only or chemoradiation. Multivariable regression methods were used to compare adjusted differences in perioperative outcomes and overall survival. RESULTS: Among 32 978 patients included, 9714 (29.5%) received no neoadjuvant therapy, 890 (2.7%) chemotherapy only, 1170 (3.5%) radiotherapy only and 21 204 (64.3%) chemoradiation. Compared with no therapy, chemotherapy or radiotherapy alone were not associated with any adjusted differences in surgical margin positivity, permanent colostomy rate or overall survival (all P > 0.05). With adjustment, neoadjuvant chemoradiation vs no therapy was associated with a lower likelihood of surgical margin positivity (OR 0.74, P < 0.001), decreased rate of permanent colostomy (OR 0.77, P < 0.001) and overall survival [hazard ratio (HR) 0.79, P < 0.001]. When compared with chemotherapy or radiotherapy alone, chemoradiation remained associated with improved overall survival (vs chemotherapy alone HR 0.83, P = 0.04; vs radiotherapy alone HR 0.83, P < 0.019). CONCLUSION: Neoadjuvant chemoradiation, not chemotherapy or radiotherapy alone, is important for sphincter preservation, R0 resection and survival for patients with locally advanced rectal cancer. Despite this finding, one-third of patients in the United States with locally advanced rectal cancer fail to receive stage-appropriate chemoradiation.

Ebola virus disease: An update on current prevention and management strategies.

Ebola virus disease (EVD) is characterised by systemic viral replication, immuno-suppression, abnormal inflammatory responses, large volume fluid and electrolyte losses, and high mortality in under-resourced settings. There are various therapeutic strategies targeting EVD including vaccines utilizing different antigen delivery methods, antibody-based therapies and antiviral drugs. These therapies remain experimental, but received attention following their use particularly in cases treated outside West Africa during the 2014-15 outbreak, in which 20 (80%) out of 25 patients survived. Emerging data from current trials look promising and are undergoing further study, however optimised supportive care remains the key to reducing mortality from EVD.

Mass cytometry analysis reveals hyperactive NF Kappa B signaling in myelofibrosis and secondary acute myeloid leukemia.

Myeloproliferative neoplasms (MPNs) feature a malignant clone containing the JAK2 V617F mutation, or another mutation causing dysregulated JAK2 kinase activity. The multiple disease phenotypes of MPNs, and their tendency to transform phenotypically, suggest pathophysiologic heterogeneities beyond a common phenomenon of JAK2 hyperactivation. JAK2 has the potential to activate multiple other signaling molecules, either directly through downstream effectors, or indirectly through induction of target gene expression. We have interrogated myeloproliferative signaling in myelofibrosis (MF) and secondary acute myeloid leukemia (sAML) patient samples using mass cytometry, which allows the quantitative measurement of multiple signaling molecules simultaneously at the single-cell level, in cell populations representing a nearly complete spectrum of hematopoiesis. MF and sAML malignant cells demonstrated a high prevalence of hyperactivation of the JAK-STAT, MAP kinase, PI3 kinase and NFκB signaling pathways. Constitutive NFκB signaling was evident across MF and sAML patients. A supporting gene set enrichment analysis (GSEA) of MF showed many NFκB target genes to be expressed above normal levels in MF patient CD34+ cells. NFκB inhibition suppressed colony formation from MF CD34+ cells. This study indicates that NFκB signaling contributes to human myeloproliferative disease and is abnormally activated in MF and sAML.

A comparison of paediatric and adult infectious diseases consultations in Australia and New Zealand.

The objective of this paper is to describe paediatric infectious diseases consultations across Australia and New Zealand. We surveyed infectious diseases physicians at 51 hospitals over a period of 2 weeks in 2012. Compared with adult consults, paediatric consults were more frequently received from general paediatricians/physicians and intensive care, yet less frequently from surgeons and emergency. Respiratory, skin/soft tissue and bone/joint infections were the most frequent consultations in children. These data demonstrate the breadth of formal infectious diseases consults in children. Differences between paediatric and infectious diseases consultations need to be considered when planning both paediatric and adult physician training and future curriculum development.

Clonal evolution revealed by whole genome sequencing in a case of primary myelofibrosis transformed to secondary acute myeloid leukemia.

Clonal architecture in myeloproliferative neoplasms (MPNs) is poorly understood. Here we report genomic analyses of a patient with primary myelofibrosis (PMF) transformed to secondary acute myeloid leukemia (sAML). Whole genome sequencing (WGS) was performed on PMF and sAML diagnosis samples, with skin included as a germline surrogate. Deep sequencing validation was performed on the WGS samples and an additional sample obtained during sAML remission/relapsed PMF. Clustering analysis of 649 validated somatic single-nucleotide variants revealed four distinct clonal groups, each including putative driver mutations. The first group (including JAK2 and U2AF1), representing the founding clone, included mutations with high frequency at all three disease stages. The second clonal group (including MYB) was present only in PMF, suggesting the presence of a clone that was dispensable for transformation. The third group (including ASXL1) contained mutations with low frequency in PMF and high frequency in subsequent samples, indicating evolution of the dominant clone with disease progression. The fourth clonal group (including IDH1 and RUNX1) was acquired at sAML transformation and was predominantly absent at sAML remission/relapsed PMF. Taken together, these findings illustrate the complex clonal dynamics associated with disease evolution in MPNs and sAML.

What do infectious diseases physicians do? A 2-week snapshot of inpatient consultative activities across Australia, New Zealand and Singapore.

The practice of an infectious diseases (ID) physician is evolving. A contemporary understanding of the frequency and variety of patients and syndromes seen by ID services has implications for training, service development and setting research priorities. We performed a 2-week prospective survey of formal ID physician activities related to direct inpatient care, encompassing 53 hospitals throughout Australia, New Zealand and Singapore, and documented 1722 inpatient interactions. Infections involving the skin and soft tissue, respiratory tract and bone/joints together accounted for 49% of all consultations. Suspected/confirmed pathogens were primarily bacterial (60%), rather than viral (6%), fungal (4%), mycobacterial (2%) or parasitic (1%). Staphylococcus aureus was implicated in 409 (24%) episodes, approximately four times more frequently than the next most common pathogen. The frequency of healthcare-related infections (35%), immunosuppression (21%), diabetes mellitus (19%), prosthesis-related infections (13%), multiresistant pathogens (13%) and non-infectious diagnoses (9%) was high, although consultation characteristics varied between geographical settings and hospital types. Our study highlights the diversity of inpatient-related ID activities and should direct future teaching and research. ID physicians' ability to offer beneficial consultative advice requires broad understanding of, and ability to interact with, a wide range of referring specialities.

Bad design, bad practices, bad bugs: frustrations in controlling an outbreak of Elizabethkingia meningoseptica in intensive care units.

BACKGROUND: Elizabethkingia meningoseptica is a nosocomial-adapted Gram-negative bacillus intrinsically resistant to antibiotics commonly used in the intensive care setting. An outbreak investigation commenced when five patients developed E. meningoseptica infection in two intensive care units (ICUs). METHODS: Analysis of laboratory data, case reviews, ICU workflows and extensive environmental sampling were undertaken. Molecular typing was performed using repetitive element palindromic polymerase chain reaction. Follow-up studies after interventions included environmental monitoring and a survey of staff compliance with interventions. FINDINGS: Laboratory data revealed increasing incidence of E. meningoseptica colonization or infection in ICU patients compared with preceding years. E. meningoseptica was cultured from 44% (35/79) of taps, but not from other sources. Hand hygiene sinks were used for disposal of patient secretions and rinsing re-usable patient care items. Sinks misused in this way were contaminated more often than sinks that were not misused (odds ratio 4.38, 95% confidence interval 1.68-11.39; P = 0.004). Molecular typing revealed that patient isolates had identical patterns to several isolates from hand hygiene taps. An urgent education programme was instituted to change these practices. Taps were cleaned systematically and aerators were changed. A temporary reduction in case numbers was achieved. Recolonization of taps was demonstrated on follow-up environmental screening, and cases recurred after two months. A survey revealed that 77.3% (163/213) of nursing staff still misused sinks due to time constraints or other problems adhering to the interventions. CONCLUSION: Introduction of non-sanctioned practices due to suboptimal unit design may have unintentional consequences for ICU patients. Room design and staff workflows must be optimized for patient safety as lapses in procedure can inadvertently put patients at risk.

Hot and steamy: outbreak of Bacillus cereus in Singapore associated with construction work and laundry practices.

BACKGROUND: A sudden increase in invasive infections caused by Bacillus cereus group organisms prompted an investigation at the National University Hospital in Singapore. AIM: To describe the investigation and management and subsequent difficulties controlling the outbreak. METHODS: Clinical case reviews were performed on all patients with B. cereus group recovered from clinical samples. Widespread environmental sampling was performed followed by review of hospital ventilation systems, domestic cleaning and laundry practices. FINDINGS: B. cereus was recovered from 171 patients during a six-month period coinciding with large-scale construction work beside the hospital. Most patients presented with bacteraemia (146/171; 85.4%) with 46/171 (26.9%) requiring extended treatment courses with vancomycin or other interventions. Sampling confirmed extensive airborne dispersal inside the hospital, including isolation rooms and air-conditioned wards. Hospital linen was heavily contaminated [7403 cfu/cm(2); 95% confidence interval (CI): 6349-8457; for 30 towels sampled], encouraged by inappropriate storage in airtight plastic bags (4437 cfu/cm(2); CI: 3125-5750) compared with storage in porous canvas bags (166 cfu/cm(2); CI: 76-256; P < 0.001). Interventions introduced included revision of laundry practices, transport and storage of hospital linen and towels; bleach-based environmental cleaning; and upgrading of ventilation systems throughout the hospital. Clinical case numbers returned to baseline levels within three months, only to rise again following relaxation of laundry practices. CONCLUSIONS: Construction work beside this Singapore hospital encouraged heavy contamination of air and environment with Bacillus spp., assumed to be responsible for the outbreak described. Failure to maintain revised laundry practices allowed resurgence of clinical cases, particularly among immunocompromised patients.

The impact of multidrug resistance in healthcare-associated and nosocomial Gram-negative bacteraemia on mortality and length of stay: cohort study.

Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an emerging public health threat. Accurate estimates of their clinical impact are vital for justifying interventions directed towards preventing or managing infections caused by these pathogens. A retrospective observational cohort study was conducted between 1 January 2007 and 31 July 2009, involving subjects with healthcare-associated and nosocomial Gram-negative bacteraemia at two large Singaporean hospitals. Outcomes studied were mortality and length of stay post-onset of bacteraemia in survivors (LOS). There were 675 subjects (301 with MDR-GNB) matching study inclusion criteria. On multivariate analysis, multidrug resistance was not associated with 30-day mortality, but it was independently associated with longer LOS in survivors (coefficient, 0.34; 95% CI, 0.21-0.48; p < 0.001). The excess LOS attributable to multidrug resistance after adjustment for confounders was 6.1 days. Other independent risk factors for higher mortality included male gender, higher APACHE II score, higher Charlson comorbidity index, intensive care unit stay and presence of concomitant pneumonia. Concomitant urinary tract infection and admission to a surgical discipline were associated with lower risk of mortality. Appropriate empirical antibiotic therapy was neither associated with 30-day mortality nor LOS, although the study was not powered to assess this covariate adequately. Our study adds to existing evidence that multidrug resistance per se is not associated with higher mortality when effective antibiotics are used for definitive therapy. However, its association with longer hospitalization justifies the use of control efforts.

Barrett's esophagus, esophageal and esophagogastric junction adenocarcinomas: the role of diet.

Identification of modifiable risk factors is an attractive approach to primary prevention of esophageal adenocarcinoma (EAC) and esophagogastric junction adenocarcinoma (EGJAC). We conducted a review of the literature to investigate the association between specific dietary components and the risk of Barrett's esophagus (BE), EAC and EGJAC, supposing diet might be a risk factor for these tumors. Consumption of meat and high-fat meals has been found positively associated with EAC and EGJAC. An inverse association with increased intake of fruit, vegetables and antioxidants has been reported but this association was not consistent across all studies reviewed. Few studies have examined the association between diet and BE. Additional research is needed to confirm the aforementioned association and clarify the mechanisms by which dietary components affect the risk of developing EAC and EGJAC. Future studies could advance our knowledge by emphasizing prospective designs to reduce recall bias, by using validated dietary intake questionnaires and biological measures and by considering important confounders such as gastro-esophageal reflux disease (GERD) symptoms, tobacco and alcohol use, biometrics, physical activity, and socioeconomic factors.

Cap-assisted endoscopic mucosal resection of large polyps involving the ileocecal valve.

Standard endoscopic mucosal resection (EMR) is limited with regard to lesions below or involving the ileocecal valve. We describe the treatment and outcomes when using cap-assisted EMR (EMR-C) to remove large laterally spreading tumors (LSTs) with ileal infiltration in seven patients (median age 74 years). Each LST (median size 40 mm) was successfully resected in one session (median procedure time 50 minutes). Intraprocedural and early bleeding occurred in two patients, and delayed hemorrhage in one. Circumferential resection of the ileum caused asymptomatic strictures in six patients, with regression during follow-up for five. We conclude that the novel EMR-C method is a potentially effective treatment for cecal LST involving the distal ileum. Serious complications such as perforation or symptomatic strictures of the ileocecal valve were not observed and any procedure-related bleeding was easily controlled.

Holocene thinning of the Greenland ice sheet.

On entering an era of global warming, the stability of the Greenland ice sheet (GIS) is an important concern, especially in the light of new evidence of rapidly changing flow and melt conditions at the GIS margins. Studying the response of the GIS to past climatic change may help to advance our understanding of GIS dynamics. The previous interpretation of evidence from stable isotopes (delta(18)O) in water from GIS ice cores was that Holocene climate variability on the GIS differed spatially and that a consistent Holocene climate optimum-the unusually warm period from about 9,000 to 6,000 years ago found in many northern-latitude palaeoclimate records-did not exist. Here we extract both the Greenland Holocene temperature history and the evolution of GIS surface elevation at four GIS locations. We achieve this by comparing delta(18)O from GIS ice cores with delta(18)O from ice cores from small marginal icecaps. Contrary to the earlier interpretation of delta(18)O evidence from ice cores, our new temperature history reveals a pronounced Holocene climatic optimum in Greenland coinciding with maximum thinning near the GIS margins. Our delta(18)O-based results are corroborated by the air content of ice cores, a proxy for surface elevation. State-of-the-art ice sheet models are generally found to be underestimating the extent and changes in GIS elevation and area; our findings may help to improve the ability of models to reproduce the GIS response to Holocene climate.

Readiness exercise to combat avian influenza.

AIM: To examine the readiness of our hospital for the potential pandemic threat of avian influenza, we developed and implemented simulation case scenarios in our hospital. METHODS: Two volunteers, who assumed the identity of 'actual' patients, were trained to simulate acute respiratory symptoms following a visit to an avian influenza-affected area, and their identities and locations were kept confidential prior to the readiness exercise. A team of auditors was stationed at high-risk areas to assess adherence to the use of personal protective equipment (PPE) and infection control procedures. RESULTS: A total of 324 healthcare workers and 84 administrators participated in this hospital-wide exercise. Following disclosure of their symptoms, the 'patients' were masked and isolated in negative-pressure rooms. A quarantine order was enforced on 38 inpatients and 45 healthcare workers who were present in the affected wards at the time of the exercise, which mandated the use of PPE. Although all affected healthcare workers were competent in the use of PPE, we observed breaches in PPE and isolation procedures in eight medical and nursing students, and 10 healthcare attendants. The exercise concluded after H5N1 tests returned negative. CONCLUSION: We recommend the use of case simulation as an effective means of assessing potential breaches in infection control procedures.

The relationship of 16 underage drinking laws to reductions in underage drinking drivers in fatal crashes in the United States.

The minimum legal drinking age 21 (MLDA 21) legislation in the United States (U.S.) has been documented as one of the most effective public health measures adopted in recent times. This study reports on an effort to evaluate and interrelate a basic set of 16 laws directed at younger than age 21 youth that are designed to (a) control the sales of alcohol to youth, (b) prevent possession and consumption of alcohol by youth, and (c) prevent alcohol impaired driving by those younger than age 21. The first objective of this study was to determine whether there was any relationship between the existence and strength of the various underage drinking laws in a State and the percentage of younger than age 21 drivers involved in fatal crashes who were drinking. After controlling for various factors, the only significant finding that emerged was for the existence and strength of the law making it illegal for an underage person to use fake identification ( p <0.016). The second objective was to determine if the enactment of two of the sixteen provisions (possession and purchase laws) was associated with a reduction in the rate of underage drinking driver involvements in fatal crashes. Analysis of variance (ANOVA) showed that there was a national 11.2% reduction ( p <0.05) in the ratio of underage drinking drivers to underage non-drinking drivers in fatal crashes after the possession and purchase laws were adopted in 36 States and the District of Columbia (DC). This suggests that the two mandatory elements of the Federal MLDA 21 law are having the desired effect of reducing underage alcohol-related highway deaths.