Impact of Antimicrobial Stewardship Intervention on Coagulase-Negative Staphylococcus Blood Cultures in Conjunction with Rapid Diagnostic Testing

Rapid diagnostic testing with matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) decreases the time to organism identification by 24 to 36 h compared to the amount of time required by conventional methods. However, there are limited data evaluating the impact of MALDI-TOF with real-time antimicrobial stewardship team (AST) review and intervention on antimicrobial prescribing and outcomes for patients with bacteremia and blood cultures contaminated with coagulase-negative Staphylococcus (CoNS). A quasiexperimental study was conducted to analyze the impact of rapid diagnostic testing with MALDI-TOF plus AST review and intervention for adult hospitalized patients with blood cultures positive for CoNS. Antibiotic prescribing patterns and clinical outcomes were compared before and after implementation of MALDI-TOF with AST intervention for patients with CoNS bacteremia and CoNS contamination. A total of 324 patients with a positive CoNS blood culture were included; 246 were deemed to have contaminated cultures (117 in the preintervention group and 129 in AST the intervention group), and 78 patients had bacteremia (46 in the preintervention group and 32 in the AST intervention group). No differences in demographics were seen between the groups, and similar rates of contamination occurred between the preintervention and AST intervention groups (64.3% versus 72.6%, P = 0.173). Patients with bacteremia were initiated on optimal therapy sooner in the AST intervention group (58.7 versus 34.4 h, P = 0.030), which was associated with a similarly decreased mortality (21.7% versus 3.1%, P = 0.023). Patients with CoNS-contaminated cultures had similar rates of mortality, lengths of hospitalization, recurrent bloodstream infections, and 30-day hospital readmissions, but the AST intervention group had a decreased duration of unnecessary antibiotic therapy (1.31 versus 3.89 days, P = 0.032) and a decreased number of vancomycin trough assays performed (0.88 versus 1.95, P < 0.001). In patients with CoNS bacteremia, rapid pathogen identification integrated with real-time stewardship interventions improved timely organism identification and initiation of antibiotic therapy. Patients in the AST group with blood cultures contaminated with CoNS had decreased inappropriate antimicrobial prescribing and decreased unnecessary serum vancomycin trough assays.     

Cross-region reduction in 5-hydroxymethylcytosine in Alzheimer's disease brain

Epigenetic processes play a key role in the central nervous system and altered levels of 5-methylcytosine have been associated with a number of neurologic phenotypes, including Alzheimer's disease (AD). Recently, 3 additional cytosine modifications have been identified (5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine), which are thought to be intermediate steps in the demethylation of 5-methylcytosine to unmodified cytosine. Little is known about the frequency of these modifications in the human brain during health or disease. In this study, we used immunofluorescence to confirm the presence of each modification in human brain and investigate their cross-tissue abundance in AD patients and elderly control samples. We identify a significant AD-associated decrease in global 5-hydroxymethylcytosine in entorhinal cortex and cerebellum, and differences in 5-formylcytosine levels between brain regions. Our study further implicates a role for epigenetic alterations in AD.     

Promoting Business and Entrepreneurial Awareness in Health Care Professionals: Lessons From Venture Capital Panels at Medicine 2.0 Conferences

There are few mechanisms that bring the academic and business worlds together in a way that would maximize the success of health technology (health tech) start-ups by increasing researchers’ knowledge about how to operate in the business world. Existing solutions (eg, technology transfer offices and dual degree MD/MBA programs) are often unavailable to researchers from outside the institution or to those who have already completed their primary education, such as practicing physicians. This paper explores current solutions and offers a partial solution: include venture capital (VC) panels in medical conferences. These VC panels educate academics on 2 important and interconnected issues: how to “pitch” their ideas in the business world and what to consider when creating a company. In these sessions, academia-based start-up companies present their ideas before a VC panel composed of professional investors and receive feedback on their idea, business plan, and presentation techniques. Recent panel recommendations from Medicine 2.0 conferences fell into 7 categories: (1) the product, service, or idea you are developing into a company, (2) determine market forces and identify the target audience, (3) describe your competitive advantage, (4) the business plan, (5) current and future resources and capabilities, (6) legal aspects, and (7) general advice on the art of pitching. The academic and business literature validates many of these recommendations suggesting that VC panels may be a viable and cost-effective introduction to business and entrepreneurial education for physicians and other health care professionals. Panels benefit not only the presenting companies, but also the physicians, psychologists, and other health care professionals attending the session. Incorporating VC panels into academic conferences might also illuminate the need for incorporating relevant business training within academia.     

Transport of infants with congenital heart disease: benefits of antenatal diagnosis

Infants with significant congenital heart disease (CHD) typically require transport from their birth centre to a regional paediatric cardiac centre. Antenatal diagnosis of CHD allows early pre-emptive stabilisation, and is associated with improved early clinical status. However, the effect of antenatal diagnosis on the transport characteristics of infants with CHD has not been previously investigated. The aim of this study was to compare the transport characteristics of infants with antenatal and postnatal diagnosis of CHD. This study is a retrospective cohort study of all infants of ≤10 days and ≥34 weeks of gestation with CHD admitted to the Royal Children's Hospital, Melbourne (RCH) over 5 years. Demographic, diagnosis, and transport data were recorded. Cases of complex CHD were included in this study. Of 320 infants with complex CHD, 198 (62 %) had antenatal diagnosis (ANdx) and 122 (38 %) had postnatal diagnosis (PNdx). There was no significant difference in sex, birth weight, or gestation between ANdx and PNdx groups. Average age of referral was 15 vs. 53.4 h in ANdx vs. PNdx groups. Aggregate transfer distance in the ANdx group was 2216 km and in the PNdx group was 10,274 km (P?<?0.0001). Of the infants, 39 % in the PNdx group required highest-acuity “time critical” transports compared to 6 % of ANdx infants (P?=?0.0001). Conversely, only 11 % of the infants in the PNdx group had lowest acuity “non-urgent” transfers, compared to 24 % of ANdx infants (P?=?0.003). PNdx was associated with significantly higher rates of invasive ventilation (36 vs 20 %; P?=?0.01) and higher rates of inotrope use (19 vs. 9 %; P?=?0.007) during transport. Conclusions: Improved antenatal detection would allow for safer, less resource intense transfers of infants with CHD.     

Systematic review of ablation techniques for the treatment of malignant or aggressive benign lesions in children

Background

Ablation techniques are widely used for solid malignant tumors in adults. There is no large series assessing the effectiveness of local ablative therapies in the treatment of malignant or aggressive benign lesions in children.

Objective

To review the existing evidence on the techniques and results of ablation for pediatric solid malignant or aggressive benign tumors.

Materials and methods

We searched MEDLINE for papers published between 1995 and 2012 that reported outcomes of radiofrequency, microwave and cryoablation, interstitial laser therapy, irreversible electroporation and percutaneous ethanol injection for patients younger than 18 years old. Data collection included factors related to the patient, tumor biology, ablation technique and cancer-specific endpoints. Additional series of predominantly adults including data on patients younger than 18 years old were also identified.

Results

We identified 28 patients treated by ablation in 29 regions: 5 patients undergoing ablation for liver lesions, 9 patients for lung metastases, 11 patients for bone and/or soft tissue and 4 patients for kidney or pancreas. The ablation was performed to treat primary tumors, local recurrences and metastases. The histology of the tumors was osteosarcoma in 6 patients, Wilms tumor in 3, rhabdomyosarcoma in 3, hepatoblastoma in 3, desmoid tumor in 3, adrenocortical carcinoma in 2 and a single case each of leiomyosarcoma, Ewing sarcoma, paraganglioma, solid-pseudopapillary neoplasm, sacrococcygeal teratoma, hepatic adenoma, juxtaglomerular cell tumor and plantar fibromatosis. Eighteen of the patients (64%) experienced a complication, but only 6 (21%) of these needed treatment other than supportive care.

Conclusions

Although ablative techniques are feasible and promising treatments for certain pediatric tumors, large multicenter prospective trials will be needed to establish efficacy.     

Single-Center Outcome Analysis Comparing Reintervention Rates of Surgical Arterioplasty With Stenting for Branch Pulmonary Artery Stenosis in a Pediatric Population

Although catheter-based intervention is generally accepted as the treatment of choice for branch pulmonary artery (PA) stenosis, there are no data directly comparing both the need for reintervention and time to reintervention in patients undergoing transcatheter stenting versus surgical arterioplasty. We compared children who underwent surgical branch pulmonary arterioplasty and branch PA stent placement between January 2008 and May 2012 at a single tertiary center. Need for reintervention and mean time to reintervention were assessed using chi-square and independent sample Student t test. Thirty-seven patients were included (surgery n = 18, stent n = 19). Mean weight at initial intervention was 11.3 ± 8.8 kg for surgical and 20.1 ± 15.5 kg for stent (p = 0.041). Intervention was performed on the left PA in 17 patients, the right PA in 12 patients, and both PAs in 8 patients. Five patients had undergone previous intervention. On mean follow-up of 807 ± 415 days, 50 % (9 of 18) of the surgery cohort and 5.3 % (1 of 19) of the stent cohort required reintervention (p = 0.002). In all but one case reintervention was catheter-based. Mean time to reintervention for the surgery cohort was 272 ± 162 days and for the single stent cohort it was 150 days. When comparable age and weight groups were analyzed, reintervention was still more common in the surgery cohort (p = 0.007). Children undergoing surgical branch pulmonary arterioplasty are more likely to require reintervention than those undergoing stent placement.     

Patient Radiation Exposure in a Modern,Large-Volume,Pediatric Cardiac Catheterization Laboratory

Radiation exposure from pediatric cardiac catheterization may be substantial, although published estimates vary. We sought to report patient radiation dose across a range of diagnostic and interventional cases in a modern, high-volume pediatric catheterization laboratory. We retrospectively reviewed diagnostic and interventional cases performed in our pediatric catheterization laboratory from 1 April 2009 to 30 September 2011 for which radiation usage data were available as reported by the Artis Zee^® (Siemens Medical Solutions) system. Electrophysiology cases were excluded. Radiation dose was quantified as air kerma dose (mGy) and dose-area product (DAP; μGy m²). The DAP was converted to an effective dose millisievert (mSv) using the Monte Carlo method. Radiation usage data were available from 2,265 diagnostic and interventional cases with an overall median air kerma dose of 135 mGy [interquartile range (IQR) 59–433], median DAP of 760 μGy m² (IQR 281–2,810), of which 75 % (IQR 59–90 %) was derived from fluoroscopy, and median effective dose of 6.2 mSv (IQR 2.7–14.1). Air kerma dose from a single camera >2,000 mGy occurred in 1.8 % of cases. Significant differences in all measures of radiation exposure existed based on procedural and interventional types (p = 0.0001), with interventional cases associated with the highest effective dose after adjusting for patient weight category (p < 0.001). Patient weight, age, fluoroscopy time, and proportional use of digital acquisition were independent predictors of exposure (p ≤ 0.001; R ² = 0.59–0.64). In a modern, large-volume pediatric catheterization laboratory, the median effective dose is 6.2 mSv with a wide range of exposure based on patient- and procedure-specific factors. Radiation monitoring is an important component of a pediatric laboratory and further dose reduction strategies are warranted.