A prospective multi-center quality improvement initiative (NINJA) indicates a reduction in nephrotoxic acute kidney injury in hospitalized children.

Nephrotoxic medication (NTMx) exposure is a common cause of acute kidney injury (AKI) in hospitalized children. The Nephrotoxic Injury Negated by Just-in time Action (NINJA) program decreased NTMx associated AKI (NTMx-AKI) by 62% at one center. To further test the program, we incorporated NINJA across nine centers with the goal of reducing NTMx exposure and, consequently, AKI rates across these centers. NINJA screens all non-critically ill hospitalized patients for high NTMx exposure (over three medications on the same day or an intravenous aminoglycoside over three consecutive days), and then recommends obtaining a daily serum creatinine level in exposed patients for the duration of, and two days after, exposure ending. Additionally, substitution of equally efficacious but less nephrotoxic medications for exposed patients starting the day of exposure was recommended when possible. The main outcome was AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) serum creatinine criteria (increase of 50% or 0.3 mg/dl over baseline). The primary outcome measure was AKI episodes per 1000 patient-days. Improvement was defined by statistical process control methodology and confirmed by Autoregressive Integrated Moving Average (ARIMA) modeling. Eight consecutive bi-weekly measure rates in the same direction from the established baseline qualified as special cause change for special process control. We observed a significant and sustained 23.8% decrease in NTMx-AKI rates by statistical process control analysis and by ARIMA modeling; similar to those of the pilot single center. Thus, we have successfully applied the NINJA program to multiple pediatric institutions yielding decreased AKI rates.

Derivation of a site-specific assessment criterion for benzo[a]pyrene in red shale at a former coking works.

A former coking works in England is being remediated to enable its redevelopment. We have developed site specific human health risk assessment criteria (SSAC) for benzo[a]pyrene (BaP) based on detailed characterisation of red shale proposed for reuse in an area allocated for residential development. Samples of red shale were analysed using the Colon-enhanced Physiologically Based Extraction Test (CEPBET) to estimate the bioaccessibility of BaP. The results indicate that between 5% and 28% of the red shale BaP is bioaccessible. A cautious value of 50% was used in calculating an SSAC. The CLEA human health assessment model was used to calculate the SSAC and any changes to the default input parameters have been discussed and justified. Based on the fact that BaP appears to be a point-of-contact, rather than a systemic, carcinogen in animal studies, individual assessment criteria were estimated for the oral, inhalation and dermal routes of entry in-line with current UK guidance. An overall SSAC of 2.5 mg/kg for BaP in red shale for the residential with home-grown produce land use was then derived as the lowest of the three route-specific assessment criteria. This value is specific to both the site and the material being assessed. The approach adopted however can be applied on other sites and for other materials to inform detailed quantitative risk assessments.

Making sense of outliers.

Phonetic inquiry, particularly of the kind which looks at large numbers of items, frequently asks what a 'typical' example of a phenomenon of speech is like. For example, in describing the plosives of a language, it is common to calculate average closure durations or voice onset times in some contexts. In this paper, the focus is on examples from natural conversation where there are untypical patterns, and where the item of interest is, in statistical terms, an outlier. Outliers are generally excluded from linguistic analysis, and may be treated as e.g. production errors. The paper shows instead that at least some outliers are in fact part of a meaningful practice, and an orderly method by which speakers can create meaning. The phenomenon more precisely is that of intensifying emphasis, which has been described for German. We consider its phonetic exponents in American English, which are both 'prosodic' and 'segmental'. We provide an account of function based on participants' own use and displayed understanding of the phenomenon, and argue for a structurally rich account of the phenomenon which includes aspects of turn construction and sequential organisation.

The phonetics of talk in interaction--introduction to the special issue.

This overview paper provides an introduction to work on naturally-occurring speech data, combining techniques of conversation analysis with techniques and methods from phonetics. The paper describes the development of the field, highlighting current challenges and progress in interdisciplinary work. It considers the role of quantification and its relationship to a qualitative methodology. It presents the conversation analytic notion of sequence as a version of context, and argues that sequences of talk constrain relevant phonetic design, and so provide one account for variability in naturally occurring speech. The paper also describes the manipulation of speech and language on many levels simultaneously. All of these themes occur and are explored in more detail in the papers contained in this special issue.

Effectiveness and safety of mandatory antimicrobial indications and durations and a pharmacist-driven 48-hour time-out in a pediatric hospital.

PURPOSE: To evaluate the effectiveness and safety of mandatory antimicrobial indications and durations (MAID) and a pharmacist-driven 48-hour time-out in a pediatric hospital. METHODS: MAID and a 48-hour time-out were implemented on February 14, 2017. Antibiotic days of therapy (DOT) per 1,000 patient days were compared between the pre- and postperiod for select antibiotics using unadjusted Poisson models. A prepost comparison was used to compare antimicrobial stewardship program (ASP) intervention rates between time periods. A 2-step process, including distribution of a discontinuation (DC) report to pharmacists and ASP-prompted reorders, was instituted to reduce unintentional antimicrobial discontinuation with MAID. ASP-prompted reorders occurred only when a discrepancy persisted between the order and provider-desired duration. Missed antimicrobial doses were identified by ASP and the institutional event reporting system. Safety of MAID was assessed by reviewing the rate and details of ASP-prompted reorders and missed antimicrobial doses. RESULTS: A significant decrease in DOT per 1,000 patient days was observed for cefazolin (39.7 to 36.9; P < 0.001), ampicillin (39.9 to 35.7; P < 0.001), clindamycin (38.2 to 35.9; P < 0.001), ceftriaxone (46.5 to 43.4; P < 0.001), and meropenem (8.7 to 6.6; P < 0.001) following implementation. No change in ASP intervention rate occurred between the pre- and postperiod (16.9 vs 16.8%; P = 0.94). With MAID, ASP-prompted reorder occurred on 7.3% of orders. Unintentional discontinuations resulting in missed antimicrobial doses occurred in 3 orders (0.07%); no patient harm resulted. CONCLUSION: MAID and a 48-hour time-out significantly reduced DOT of select antibiotics. No patient harm occurred with the 2-step safety process.

Evidence-based development of a nephrotoxic medication list to screen for acute kidney injury risk in hospitalized children.

PURPOSE: Medications are commonly associated with acute kidney injury (AKI). However, in both clinical practice and research, consideration of specific medications as nephrotoxic varies widely. The Nephrotoxic Injury Negated by Just-in-time Action quality improvement collaborative was formed to focus on prevention or reduction of nephrotoxic medication-associated AKI in noncritically ill hospitalized children. However, there were discrepancies among institutions as to which medications should be considered nephrotoxic. The collaborative convened a Nephrotoxic Medication (NTMx) Subcommittee to develop a consensus for the classification of nephrotoxic medications. SUMMARY: The NTMx Subcommittee initially included pediatric nephrologists, a pharmacist, and a pediatric intensivist. The committee reviewed NTMx lists from the collaborative and identified changes from the initial NTMx list. The NTMx Subcommittee conducted a literature review of the disputed medications and assigned an evidence grade based on the reported association with nephrotoxicity and the quality of the data. The association between medication exposure and AKI was also determined using administrative data from the Pediatric Health Information Systems database. The NTMx Subcommittee then came to a majority consensus regarding which medications should be included on the list. The subcommittee's recommendations were presented to the larger collaborative for approval, and consensus was achieved. The list continues to be reviewed and updated annually. CONCLUSION: Formation of a multicenter quality-improvement initiative exposed current limitations as to which medications are considered nephrotoxic in clinical and research settings and presented an opportunity to approach this problem using an evidence-based process. A consensus definition of nephrotoxic-medication exposure was achieved.

Clindamycin-susceptibility Rates of Methicillin-resistant Staphylococcus aureus Varies by Infection Type in Pediatric Patients.

Hospital-wide antibiograms provide general susceptibility patterns. Specific antibiograms were created for methicillin-resistant Staphylococcus aureus isolates based on infection process and epidemiology. Using clinical microbiology laboratory data and patient profiles, high clindamycin resistance rates were seen for nonskin and soft tissue infections and noncommunity-associated methicillin-resistant S. aureus isolates.

Preoperative Antibiotic Orders: Protocol-Initiated Pharmacist Order Entry.

OBJECTIVE: To evaluate the antibiotic selection of preoperative orders before and after a pharmacist order entry protocol for patients with methicillin-resistant Staphylococcus aureus (MRSA) colonization. METHODS: A retrospective chart review of orthopedic surgery procedures on patients with MRSA colonization at a free-standing, academic pediatric hospital, between February 2010 and February 2012. RESULTS: Procedures that were performed pre protocol (n = 27) implementation had a 63% rate of appropriate antibiotic selection compared to 81% in the postprotocol group (n = 32; p = 0.1155). The preprotocol group dose accuracy was 96% compared to 97% in the postprotocol group (p = 0.81). Two procedures, 1 in each group, were redosed appropriately for extended surgery duration. Correct timing of antibiotic administration occurred in 82% of cases pre protocol versus 68% post protocol (p = 0.42). CONCLUSIONS: Patients with MRSA colonization had a greater rate of appropriate drug selection after the implementation of a pharmacist-initiated preoperative protocol. Correct antibiotic dose and redose remained consistent between the study groups. Most of the orthopedic procedures performed included patients on antibiotic coverage at steady state for ongoing infections, which impacted the analysis of preoperative timing. Further studies should be conducted to assess whether the increase in the number of appropriate antibiotic selections decreases the rate of postoperative MRSA infections.

Comparison of genotypic and phenotypic HIV type 1 tropism assay: results from the screening samples of Cenicriviroc Study 202, a randomized phase II trial in treatment-naive subjects.

Cenicriviroc is a once-daily oral CCR5/CCR2 antagonist in development for treatment of HIV infection. CVC Study 202 (652-2-202; NCT01338883) excluded treatment-naive subjects demonstrated to harbor non-R5 (CXCR4-tropic or dual-mixed) tropic HIV-1 by either genotypic or phenotypic tropism testing. Here we compare the results of genotypic and phenotypic tropism testing in Study 202. A total of 304 subjects screened had paired genotypic and phenotypic results. Genotypic tropism testing (GTT) incorporated triplicate population sequencing using the geno2pheno algorithm and the PSSM algorithm, followed by ultradeep sequencing (UDS) for samples with R5 results. All samples were further evaluated with a phenotypic test, the enhanced-sensitivity Trofile assay (ESTA). Concordance between GTT and ESTA was 80% and increased to 84% when only geno2pheno was used for triplicate population sequencing. GTT (geno2pheno) classified 18% of the samples as non-R5 compared to 16% by ESTA. Only one-third of samples with non-R5 results by either test were classified as non-R5 by both tests. Median CD4((+)) cell counts were lower in patients with concordant non-R5 results by UDS and ESTA than in subjects with an R5 result by either assay (p=0.0004). UDS detected non-R5 virus in an additional 27/304 subjects (median 15% non-R5, interquartile range: 3.7-62%) with R5 results by ESTA. In conclusion, the geno2pheno algorithm improves concordance of GTT with a clinically validated phenotypic tropism assay as does the use of UDS. These findings provide support for recent guidelines indicating that genotypic tropism testing may be considered as an alternative to phenotypic testing.

Antibiotic Management of Animal Bites in Children During the Methicillin-Resistant Staphylococcus aureus Era.

Children presenting to an emergency department following an animal bite were found to be at risk for infection if they had puncture wounds, crush wounds, or were bitten by a cat. Of the infected wounds that were cultured, methicillin-resistant Staphylococcus aureus was not isolated as a pathogen.

The communicative functions of final rises in Finnish intonation.

This paper considers the communicative function of final rises in Finnish conversational talk between pairs of teenage girls. Final rises are fairly common, occurring approximately twice a minute, predominantly on declaratives and in narrative sequences. We briefly consider the interplay between voice quality (known to be a marker of transition relevance) and rising intonation in Finnish. We argue that in narrative sequences, rising terminals manage two main interactional tasks: they provide a place for a coparticipant to mark recipiency, and they project more talk by the current speaker. Using a methodology which combines phonetic observation with conversation analysis, we demonstrate participants' orientation to these functions.

A parametric approach to the phonetics of postvocalic /r/ in Dutch.

This paper describes the phonetic exponents of rhoticity in postvocalic position in the speech of 4 young adult speakers of Standard Dutch. In addition to describing aspects of the segmental realisation of /r/, the paper focusses on parametric differences between rhymes with and without postvocalic /r/ in the material under consideration, presenting both impressionistic observations and instrumental measurements. Results of the investigation suggest that parametric analysis is a crucial complement to segmental classification, in providing insights into the relation between segmental realisations and 'contextual effects' of /r/, the phonetics of /r/ deletion and similarities and differences between rhotics cross-linguistically.