bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiology and Outcomes of Hospitalized Children With Necrotizing Soft-Tissue Infections
Authors: Totapally Balagangadhar R. 
Published: December 2016

Objective:The purpose of this study was to evaluate the epidemiology and outcome of hospitalized children with a diagnosis of necrotizing soft-tissue infections (NSTIs).Methods:Demographic and outcome data of children 1 month to 18 years of age with a diagnosis of NSTI (International Classification of Diseases, 9th revision diagnosis codes 728.86 and 729.4) were extracted from the Kids’ Inpatient Database 2009 and 2012. Univariate and multivariate analyses were done to determine the factors affecting mortality. The sample data were weighted to get national estimates.Results:A total of 446 children with NSTI (prevalence of 1.12/10,000 discharges) were included. Males comprised 54%. The median age was 10 (interquartile range 4–16) years. The mortality rate was 6%. In addition, 29.3% of children with NSTI were discharged to either skilled nursing facilities or to home health care compared with 4.5% of children without NSTI (odds ratio 8.9; 95% confidence interval 7.3–10.9;P< 0001). A bacterial infection was reported in 72.1% of children. An infection withStaphylococcus,Streptococcus, Gram-negative bacteria, anaerobic bacteria, methicillin-resistantStaphylococcus areusand polymicrobia was present in 34.5%, 21.8%, 8.6%, 3.9%, 18.7% and 13.6% of cases, respectively. A compartment syndrome, severe sepsis/septic shock and toxic shock were documented in 4.4%, 22.2% and 3.2% of the cases, respectively. Severe sepsis/septic shock, the need for mechanical ventilation and Hispanic race were associated with increased mortality, whereas skin/muscle surgery was associated with lower mortality.Conclusions:NSTI in children is associated with high morbidity. The mortality is higher with the presence of severe sepsis/septic shock and among Hispanics and lower with surgical intervention.
Clinical and Bacterial Risk Factors for Mortality in Children With Carbapenem-resistant Enterobacteriaceae Bloodstream Infections in India
Authors: Nabarro Laura E. B. , Shankar Chaitra , Pragasam Agila K. , Mathew Georgekutty , Jeyaseelan Visali , Veeraraghavan Balaji , Verghese Valsan P. 
Published: December 2016

Background:
Carbapenem-resistant Enterobacteriaceae (CRE) are an increasing cause of nosocomial infection in hospitalized children worldwide. Few studies have investigated risk factors for mortality in children with CRE bloodstream infection (BSI). Data are particularly scarce in areas where NDM and OXA carbapenemases predominate. Here, we investigate mortality rates, clinical and microbiologic risk factors for mortality in 50 pediatric patients with CRE BSI in India.

Methods:
Children younger than 17 years old with meropenem-resistant Klebsiella pneumoniae or Escherichia coli isolated from blood culture in 2014 and 2015 were identified from laboratory records. Clinical records were systematically reviewed for each child to establish mortality at 30 days and clinical details. Bacterial isolates were subjected to meropenem E test and multiplex polymerase chain reaction to determine carbapenemase gene. Data were analyzed to establish clinical and bacterial risk factors for mortality.

Results:
All CRE BSI were hospital-acquired or associated with healthcare. A total of 84% of children had an underlying comorbidity and 46% had a malignancy. K. pneumoniae was the most common bacteria isolated; NDM was the most common carbapenemase gene detected. The mortality rate was 52%. Significant risk factors for mortality included intensive care admission, intubation, inotropic support and respiratory source. Failure to clear bacteremia and a minimum inhibitory concentration > 8 mg/L for the isolate was associated with a statistically significant increase in mortality. Mortality rates were significantly lower when two or more effective drugs were used in combination.

Conclusions:
CRE BSI affects children with multiple comorbidities and repeated admissions to hospital. The mortality rate is high; combination therapy may be beneficial.
Nasal Airway Microbiota Profile and Severe Bronchiolitis in Infants
Authors: Hasegawa Kohei , Linnemann Rachel W. , Mansbach Jonathan M. , Ajami Nadim J. , Espinola Janice A. , Petrosino Joseph F. , Piedra Pedro A. , Stevenson Michelle D. , Sullivan Ashley F. , Thompson Amy D. , Camargo Carlos A. 
Published: December 2016

Background:
Little is known about the relationship of airway microbiota with bronchiolitis in infants. We aimed to identify nasal airway microbiota profiles and to determine their association with the likelihood of bronchiolitis in infants.

Methods:
A case-control study was conducted. As a part of a multicenter prospective study, we collected nasal airway samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 110 age-matched healthy controls. By applying 16S ribosomal RNA gene sequencing and an unbiased clustering approach to these 150 nasal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis.

Results:
Overall, the median age was 3 months and 56% were male. Unbiased clustering of airway microbiota identified 4 distinct profiles: Moraxella-dominant profile (37%), Corynebacterium/Dolosigranulum-dominant profile (27%), Staphylococcus-dominant profile (15%) and mixed profile (20%). Proportion of bronchiolitis was lowest in infants with Moraxella-dominant profile (14%) and highest in those with Staphylococcus-dominant profile (57%), corresponding to an odds ratio of 7.80 (95% confidence interval, 2.64–24.9; P < 0.001). In the multivariable model, the association between Staphylococcus-dominant profile and greater likelihood of bronchiolitis persisted (odds ratio for comparison with Moraxella-dominant profile, 5.16; 95% confidence interval, 1.26–22.9; P = 0.03). By contrast, Corynebacterium/Dolosigranulum-dominant profile group had low proportion of infants with bronchiolitis (17%); the likelihood of bronchiolitis in this group did not significantly differ from those with Moraxella-dominant profile in both unadjusted and adjusted analyses.

Conclusions:
In this case-control study, we identified 4 distinct nasal airway microbiota profiles in infants. Moraxella-dominant and Corynebacterium/Dolosigranulum-dominant profiles were associated with low likelihood of bronchiolitis, while Staphylococcus-dominant profile was associated with high likelihood of bronchiolitis.
Virologic Response to First-line Efavirenz- or Nevirapine-based Antiretroviral Therapy in HIV-infected African Children
Authors: Kekitiinwa Adeodata , Szubert Alexander J. , Spyer Moira , Katuramu Richard , Musiime Victor , Mhute Tawanda , Bakeera-Kitaka Sabrina , Senfuma Oscar , Walker Ann Sarah , Gibb Diana M. 
Published: December 2016

Background:
Poorer virologic response to nevirapine- versus efavirenz-based antiretroviral therapy (ART) has been reported in adult systematic reviews and pediatric studies.

Methods:
We compared drug discontinuation and viral load (VL) response in ART-naïve Ugandan/Zimbabwean children ≥3 years of age initiating ART with clinician-chosen nevirapine versus efavirenz in the ARROW trial. Predictors of suppression <80, <400 and <1000 copies/mL at 36, 48 and 144 weeks were identified using multivariable logistic regression with backwards elimination (P = 0.1).

Results:
A total of 445 (53%) children received efavirenz and 391 (47%) nevirapine. Children receiving efavirenz were older (median age, 8.6 vs. 7.5 years nevirapine, P < 0.001) and had higher CD4% (12% vs. 10%, P = 0.05), but similar pre-ART VL (P = 0.17). The initial non-nucleoside-reverse-transcriptase-inhibitor (NNRTI) was permanently discontinued for adverse events in 7 of 445 (2%) children initiating efavirenz versus 9 of 391 (2%) initiating nevirapine (P = 0.46); at switch to second line in 17 versus 23, for tuberculosis in 0 versus 26, for pregnancy in 6 versus 0 and for other reasons in 15 versus 5. Early (36–48 weeks) virologic suppression <80 copies/mL was superior with efavirenz, particularly in children with higher pre-ART VL (P = 0.0004); longer-term suppression was superior with nevirapine in older children (P = 0.05). Early suppression was poorer in the youngest and oldest children, regardless of NNRTI (P = 0.02); longer-term suppression was poorer in those with higher pre-ART VL regardless of NNRTI (P = 0.05). Results were broadly similar for <400 and <1000 copies/mL.

Conclusion:
Short-term VL suppression favored efavirenz, but long-term relative performance was age dependent, with better suppression in older children with nevirapine, supporting World Health Organization recommendation that nevirapine remains an alternative NNRTI.
Despite Access to Antiretrovirals for Prevention and Treatment, High Rates of Mortality Persist Among HIV-infected Infants and Young Children
Authors: Abrams Elaine J. , Woldesenbet Selamawit , Soares Silva Juliana , Coovadia Ashraf , Black Viviane , Technau Karl-Günter , Kuhn Louise 
Published: December 2016

Background:
Outcomes of HIV-infected children before widespread use of antiretroviral therapy (ART) for treatment and prevention of mother-to-child transmission (PMTCT) have been well characterized but less is known about children who acquire HIV infection in the context of good ART access.

Methods:
We enrolled newly diagnosed HIV-infected children ≤24 months of age at 3 hospitals and 2 clinics in Johannesburg, South Africa. We report ART initiation and mortality rates during 6 months from enrollment and factors associated with mortality.

Results:
Of 272 children enrolled, median age 6.1 months, 69.5% were diagnosed during hospitalization. By 6 months postenrollment, 53 (19.5%) died and 73 (26.8%) were lost-to-follow-up. Using Kaplan–Meier analysis, the probability of death by 6 months after enrollment was 23.5%. The median age of death was 9.1 months [95% confidence interval (CI): 8.6–12.0]. Overall, 226 (83%) children initiated ART which was associated with a 71% reduction in risk of death [hazard ratio (HR) = 0.29 (95% CI: 0.15–0.58)]. In multivariable analysis of infant factors, weight-for-age Z score < −2 standard deviation (SD) [HR = 2.43 (95% CI: 1.03–5.73)], CD4 <20% [HR = 3.29 (95% CI: 1.60–6.76)] and identification during hospitalization [HR = 2.89 (95% CI: 1.16–7.25)] were independently associated with mortality. In multivariable analysis of maternal factors, CD4 ≤350/no maternal ART was associated with increased mortality risk [HR = 2.57 (95% CI: 1.19–5.59)] versus CD4 >350/no maternal ART; exposure to maternal/infant antiretrovirals for PMTCT was associated with reduced mortality risk [HR = 0.53 (95% CI: 0.28–0.99)] versus no PMTCT.

Conclusions:
ART initiation is highly protective against death in young children. However, despite improved access to ART, young children remain at risk for early death; innovative approaches to rapidly diagnose and initiate treatment as early in life as possible are needed.
Highlights From the 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society on Management of Adults With Hospital-Acquired and Ventilator-Associated Pneumonia
Authors: File Thomas M. 
Published: December 2016

Abstract
Hospital-acquired pneumonia and ventilator-associated pneumonia are among the most serious hospital-associated infections. The Infectious Diseases Society of America and the American Thoracic Society have published an update of guidelines for these infections. This updated guideline provides new recommendations for appropriate management. Important highlights include elimination of health care–associated pneumonia; continued recommendation of a clinical diagnosis as compared with surveillance definition for decision to initiate antimicrobial therapy for suspected infection; specific antimicrobial recommendations for empiric and pathogen-directed therapy; use of pharmacodynamic dosing; and use of procalcitonin to assist with duration decision with 7 days as general recommendation for all pathogens.
Enhanced delivery of IL-1 receptor antagonist to the central nervous system as a novel anti–transferrin receptor-IL-1RA fusion reverses neuropathic mechanical hypersensitivity
Authors: Webster Carl I. , Hatcher Jon , Burrell Matthew , Thom George , Thornton Peter , Gurrell Ian , Chessell Iain 
Published: December 2016

Abstract
Neuropathic pain is a major unmet medical need, with only 30% to 35% of patients responding to the current standard of care. The discovery and development of novel therapeutics to address this unmet need have been hampered by poor target engagement, the selectivity of novel molecules, and limited access to the relevant compartments. Biological therapeutics, either monoclonal antibodies (mAbs) or peptides, offer a solution to the challenge of specificity as the intrinsic selectivity of these kinds of molecules is significantly higher than traditional medicinal chemistry–derived approaches. The interleukin-1 receptor system within the spinal cord has been implicated in the amplification of pain signals, and its central antagonism provides relief of neuropathic pain. Targeting the IL-1 system in the spinal cord with biological drugs, however, raises the even greater challenge of delivery to the central compartment. Targeting the transferrin receptor with monoclonal antibodies has proved successful in traversing the endothelial cell–derived blood–brain barrier and delivering proteins to the central nervous system. In this study, we describe a novel construct exemplifying an engineered solution to overcome these challenges. We have generated a novel anti–transferrin receptor-interleukin-1 receptor antagonist fusion that transports to the central nervous system and delivers efficacy in a model of nerve ligation–induced hypersensitivity. Approaches such as these provide promise for novel and selective analgesics that target the central compartment.
Light-Driven Contact Hearing Aid for Broad-Spectrum Amplification: Safety and Effectiveness Pivotal Study
Authors: Gantz Bruce J. , Perkins Rodney , Murray Michael , Levy Suzanne Carr , Puria Sunil 
Published: December 2016

Objective:
Demonstrate safety and effectiveness of the light-driven contact hearing aid to support FDA clearance.

Study Design:
A single-arm, open-label investigational-device clinical trial.

Setting:
Two private-practice and one hospital-based ENT clinics.

Patients:
Forty-three subjects (86 ears) with mild-to-severe bilateral sensorineural hearing impairment.

Intervention:
Bilateral amplification delivered via a light-driven contact hearing aid comprising a Tympanic Lens (Lens) with a customized platform to directly drive the umbo and a behind-the-ear sound processor (Processor) that encodes sound into light pulses to wirelessly deliver signal and power to the Lens.

Main Outcome Measures:
The primary safety endpoint was a determination of “no change” (PTA4 < 10 dB) in residual unaided hearing at the 120-day measurement interval. The primary efficacy endpoint was improvement in word recognition using NU-6 at the 30-day measurement interval over the baseline unaided case. Secondary efficacy endpoints included functional gain from 2 to 10 kHz and speech-in-noise improvement over the baseline unaided case using both omnidirectional and directional microphones.

Results:
The results for the 86 ears in the study determined a mean change of −0.40 dB in PTA4, indicating no change in residual hearing (p < 0.0001). There were no serious device- or procedure-related adverse events, or unanticipated adverse events. Word recognition aided with the Earlens improved significantly (p < 0.0001) over the unaided performance, by 35% rationalized arcsine units on average. Mean functional gain was 31 dB across 2 to 10 kHz. The average speech-recognition threshold improvement over the unaided case for the Hearing in Noise Test was 0.75 dB (p = 0.028) and 3.14 dB (p < 0.0001) for the omnidirectional and directional microphone modes, respectively.

Conclusion:
The safety and effectiveness data supported a de novo 510(k) submission that received clearance from the FDA.
Within-Stool and Within-Day Sample Variability of Fecal Calprotectin in Patients With Inflammatory Bowel Disease
Authors: Du Lillian , Foshaug Rae , Huang Vivian W. , Kroeker Karen I. , Dieleman Levinus A. , Halloran Brendan P. , Wong Karen , Fedorak Richard N. 
Published: December 2016

Background and Goals:
The use of fecal calprotectin (FC) as a stool biomarker for differentiating inflammatory bowel disease (IBD) from IBS has been well validated, and there is a strong correlation between FC and the presence of endoscopic inflammatory lesions. However, recent studies have demonstrated intraindividual sample variability in patients with IBD, possibly limiting the reliability of using a single sample for monitoring disease activity. Our aim was to assess the within-stool and within-day sample variability of FC concentrations in patients with IBD.

Study:
We examined a cross-sectional cohort of 50 adult IBD patients. Eligible patients were instructed to collect 3 samples from different parts of the stool from their first bowel movement of the day and 3 samples from each of up to 2 additional bowel movements within 24 hours. FC concentrations were measured by a rapid, quantitative point-of-care test using lateral flow technology (Quantum Blue). Descriptive statistics were used to assess FC variability within a single bowel movement and between different movements at different FC positivity cutoffs.

Results:
Within a single bowel movement, there was clinically significant sample variability ranging from 8% to 23% depending on the time of the day or on the FC positivity cutoff value. Between bowel movements, there was clinically significant sample variability ranging from 13% to 26% depending on the FC positivity cutoff.

Conclusions:
Considering a single FC sample, the first sample of the day with an FC positivity cutoff of 250 μg/g provided the most reliable indication of disease activity.
There is Significant Practice Pattern Variability in the Management of the Hospitalized Ulcerative Colitis Patient at a Tertiary Care and IBD Referral Center
Authors: Shah Shailja C. , Naymagon Steven , Cohen Benjamin L. , Sands Bruce E. , Dubinsky Marla C. 
Published: December 2016

Background and Goals:
Despite published clinical guidelines, substantive data underlying the approach to the management of hospitalized ulcerative colitis (UC) patients failing outpatient therapy are lacking. Variability in practice is therefore not uncommon and may impact clinical outcomes. The degree of variability, however, is not well-studied. Our aim was to evaluate variability in management of the hospitalized UC patient to inform future efforts targeting care optimization for this high-risk population.

Study:
An internet survey was distributed among inflammatory bowel disease providers, which included: (1) nonvignette-based questions assessing provider demographics, experience, and practice setting; (2) diagnostic and therapeutic practice patterns based on a vignette of a hospitalized UC patient. Descriptive and univariate analyses were performed.

Results:
Ninety-one percent of eligible individuals were included. Nearly 97% endorsed confidence in management of hospitalized UC patients. In general, 83% initiate intravenous corticosteroids (IVCS) as initial therapy, whereas 17% initiate infliximab (IFX) (+/−IVCS). At IVCS failure in the vignette, 74% initiated IFX, 15% increased IVCS dose, 7% initiated cyclosporine, and 4% chose colectomy. Of those choosing IFX, 65% chose 5 mg/kg as the initial dose, whereas the remainder chose 10 mg/kg. Twenty-eight percent gave an additional IFX 5 mg/kg and 7% gave an additional 10 mg/kg dose to the patient in the vignette not responding to 5 mg/kg.

Conclusions:
Even among experienced inflammatory bowel disease providers, there is significant practice pattern variability in the management of hospitalized UC patients. Future efforts should target this variability. Adjunctively, prospective trials are needed to guide appropriate therapeutic algorithms, especially with respect to positioning and optimally dosing IFX in this population.
Diabetes Mellitus is Associated With Mortality in Acute Pancreatitis
Authors: Huh Ji Hye , Jeon Hosung , Park Sun Min , Choi EunHee , Lee Geun Sook , Kim Jae Woo , Lee Kyong Joo 
Published: December 2016

Background and Aim:
Predicting severe pancreatitis is important for early aggressive management of patients with acute pancreatitis (AP). Despite the established role of diabetes mellitus (DM) in the risk of AP, the impact of DM on the clinical outcome in AP has not been fully elucidated. The objective of this study was to assess the risk of mortality and severity in AP among patients with type-2 DM.

Methods:
Patients diagnosed with first attacks of AP were enrolled from January 2013 to June 2015.

Results:
A total of 201 patients (63.2% male, mean age, 59.4 y) with AP were included. Etiologies included gallstones (51.2%), alcohol (37.3%), hypertriglyceridemia (2%), and idiopathic causes (9.5%). There were 54 AP patients (26.9%) with type-2 DM. Severity indices in AP, such as Atlanta Classification (severe), Ranson score, and Bedside Index of Severity in Acute Pancreatitis, were higher in subjects with DM than those without DM. Prevalence of intensive care unit admission and mortality were higher in AP patients with DM compared with those without DM. The association between DM and increased risk of mortality in AP remained statistically significant even after adjustments for confounding factors and Atlanta Classification (odds ratio, 7.76, 95% confidence interval, 1.26-47.63, P=0.027).

Conclusions:
Type-2 DM was associated with severity and increased mortality in patients with AP. Our findings provide evidence of the potential role of DM in the pathogenesis and management of severe AP.
EUS-guided Versus Percutaneous Gallbladder Drainage
Authors: Tyberg Amy , Saumoy Monica , Sequeiros Enrique V. , Giovannini Marc , Artifon Everson , Teoh Anthony , Nieto Jose , Desai Amit P. , Kumta Nikhil A. , Gaidhane Monica , Sharaiha Reem Z. , Kahaleh Michel 
Published: December 2016

Background and Aims:
Endoscopic ultrasound–guided drainage (EUS-GLB) is a minimally invasive option for patients with cholecystitis who are poor surgical candidates. Compared with percutaneous drainage (PC-GLB), earlier studies have demonstrated similar efficacy with improved quality of life. We present a multicenter, international experience comparing PC-GLB and EUS-GLB in nonsurgical patients with cholecystitis.

Methods:
All patients who underwent either PC-GLB drainage or EUS-GLB drainage from 7 centers between January 2010 and December 2015 were included. Technical success was defined as successful placement of a catheter or stent into the gallbladder. Clinical success was defined as resolution of clinical symptoms after intervention. Adverse events, length of stay, and the need for repeat interventions and/or hospitalizations were recorded for all patients.

Results:
A total of 155 patients were included (mean age 74±14.24 y; range, 31 to 96; 56% male). Forty-two patients underwent EUS-GLB and 113 patients underwent PC-GLB. Technical success was achieved in 40 patients (95%) in the EUS-GLB group and 112 patients (99%) in the PC-GLB group (P=0.179). Clinical success was achieved in 40 patients (95%) in the EUS-GLB group and 97 patients (86%) in the PC-GLB group (P=0.157). There was no difference in hospital readmission rates between the 2 groups (14% vs. 24%; P=0.194). However, there was significantly higher number of patients requiring repeat interventions in the PC-GLB group (n=28, 24%) compared with the EUS-GLB group (n=4, 10%) (P=0.037). There was no difference in adverse events between the 2 groups.

Conclusions:
EUS-GLB is safe and efficacious, with comparable technical and clinical success rates and no difference in adverse events. In addition, EUS-GLB offers a potential cost-saving benefit and morbidity benefit by demonstrating a decreased number of repeat interventions.