bluuebunny/crossref_metadata_2025 huggingface dataset:
High Methotrexate Triglutamate Level Is an Independent Predictor of Adverse Effects in Asian Indian Rheumatoid Arthritis Patients—A Preliminary Study
Authors: Sandhu Amit , Dhir Varun , Bhatnagar Archana , Dhawan Veena , Kaur Jasbinder , Sood Ankita , Naidu Shankar , Ahmad Shabeer , Varma Neelam , Sharma Aman , Sharma Shefali
Published: January 2017

Background:

It is unclear whether erythrocyte methotrexate polyglutamate levels (MTX-glun) are associated with response or adverse effects to methotrexate in rheumatoid arthritis. This preliminary study evaluated their utility in Asian Indian patients over 24 weeks.

Methods:

Rheumatoid arthritis patients were started on oral methotrexate at a dose of 15 mg/wk, which was escalated to 25 mg by 12 weeks and continued till 24 weeks. Erythrocyte (RBC) MTX-glu1 to MTX-glu5 levels (nmol/L RBC) were determined at 4, 8, 16, and 24 weeks by using reverse-phase high-performance liquid chromatography. Area under the concentration curve (AUC) of MTX-glu1–5, MTX-glu3–5, and MTX-glu3 levels was compared between groups with regards to response and adverse effects.

Results:

This study included 117 patients with mean (SD) age of 42.7 (±11.9) years and disease duration of 2.0 (1.7) years. Mean (SD) RBC MTX-glu1–5 levels at 4, 8, 16, and 24 weeks were 93 (±29), 129 (±46), 143 (±49), and 159 (±65) nmol/L RBC; the highest individual polyglutamate was MTX-glu3 (40%). There was significant correlation between MTX-glu1–5 (r = 0.38, P < 0.001) and MTX-glu3 (r = 0.49, P < 0.001) with methotrexate dose. There was no significant difference of AUC MTX-glun between responders and nonresponders. However, AUC MTX-glu3 was significantly (P = 0.03) higher in patients with adverse effects. On logistic regression, AUC of MTX-glu3 [odds ratio = 1.004 (95% confidence interval 1.002–1.007)] and methotrexate dose at 24 weeks were independent predictors of adverse effects.

Conclusions:

In this preliminary study, higher levels of RBC MTX-glu3 were found to be the independent predictors for adverse effects in rheumatoid arthritis patients.
RISK FACTORS AND CLINICAL SIGNIFICANCE OF PRECHOROIDAL CLEFT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Kim Jong Min , Kang Se Woong , Son Dae yong , Bae Kunho
Published: January 2017

Purpose:

To investigate the risk factors associated with prechoroidal cleft occurrence after treatment for neovascular age-related macular degeneration (nAMD) and to elucidate its clinical significance.

Methods:

Two hundred thirty-four subjects who were treated for neovascular age-related macular degeneration were assessed to identify prechoroidal cleft on optical coherence tomography. Clinical variables were compared between patients manifesting a cleft (cleft group) and patients who did not (control group).

Results:

Prechoroidal cleft was detected in 29 of 234 patients (8.1%). Although the baseline visual acuity was not different between the 2 groups, logMAR visual acuity at final visit was 0.89 ± 0.74 (with approximate Snellen equivalent of 20/160) in the cleft group and 0.65 ± 0.69 (with approximate Snellen equivalent of 20/100) in controls (P < 0.05). Within cleft group, the early-onset (<6 months) subgroup had even worse visual outcomes than the late-onset subgroup (P < 0.05). Multiple logistic regression analyses revealed that the incidence of prechoroidal cleft was positively correlated with having received intravitreal gas injection to displace a submacular hemorrhage and a diagnosis of retinal angiomatous proliferation and typical neovascular age-related macular degeneration (P < 0.05).

Conclusion:

Diagnosis of retinal angiomatous proliferation and typical neovascular age-related macular degeneration, and a submacular hemorrhage treated by pneumatic displacement were the independent risk factors for development of prechoroidal cleft. Eyes with a cleft, especially clefts that develop early, generally had worse prognoses than eyes without clefts.
Right Internal Mammary Artery Use in 140 Robotic Totally Endoscopic Coronary Bypass Cases: Toward Multiarterial Grafting
Authors: Balkhy Husam H. , Nathan Sandeep , Arnsdorf Susan E. , Krienbring Dorothy J.
Published: January 2017

Objective

Benefits of adding a second arterial graft in coronary bypass are well documented. In patients requiring mulitvessel grafting robotic totally endoscopic coronary bypass (TECAB) has allowed for routine harvesting and use of the right internal mammary artery (RIMA). We retrospectively reviewed the technical considerations and target choice in 140 cases of beating heart TECAB where a RIMA graft was used.

Methods

In 2008, we introduced beating heart TECAB with anastomotic connectors into our practice, first with single IMA and then with bilateral internal mammary artery. A robotic stabilizer was used not only to facilitate exposure of the coronary targets but also to aid the RIMA harvest using a skeletonized approach. Flow measurements were obtained routinely. We reviewed the technical aspects, target choice, and intraoperative flows in our TECAB patients who underwent grafting with RIMA grafts.

Results

From February 2008 to January 2015, a total of 404 patients underwent beating heart TECAB with anastomotic connectors, of which 194 (48%) were mulitvessel procedures. One hundred forty patients (35%) had a RIMA graft and constitute the patient population for this review. One hundred thirty-one RIMA grafts were harvested via left-sided ports and grafted to left coronary targets, and nine RIMA grafts were harvested via right-sided ports and grafted to the right coronary artery. Flow was greater than 25 mL/min (pulsatility index < 2) in 95% of grafts. Perioperative mortality was 0.7% and mean ± standard deviation length of hospital stay was 3.1(1.5) days. The RIMA was used as an in situ graft in 124 cases (84%) and as a free T-graft in 24 cases (16%) cases. Right internal mammary artery graft use in all TECABS increased from 23% in the first 5 years to 53% in the last 2 years.

Conclusions

Robotic TECAB allows the routine harvesting and use of the RIMA graft in a safe and reproducible manner. Skeletonization and sternal sparing allow the RIMA to reach various coronary targets. Further studies are needed for this approach to impact the adaption of multiarterial grafting.
Video-Assisted Thoracic Surgery in Patients with Previous Sternotomy and Cardiac Surgery
Authors: Serna-Gallegos Derek R. , Merry Heather E. , McKenna Robert J.
Published: January 2017

Objective

Although video-assisted thoracic surgery (VATS) lobectomy has become a standard approach for early-stage 1 lung cancer, concerns exist regarding potential damage to the heart or bypass grafts when VATS is performed after cardiac surgery via median sternotomy. We could find only case reports regarding VATS lobectomy after sternotomy for cardiac surgery. Therefore, we reviewed our series of patients who underwent VATS anatomic resections after sternotomy for cardiac surgery.

Methods

Between 1996 and 2010, there were 87 patients who underwent 88 pulmonary resections after sternotomy for coronary artery bypass grafting (64), valve replacement or repair (12), coronary artery bypass graft and valve replacement (6), and transplant (5). There were 10 women (11.5%) and 77 men (88.5%) with a mean age of 76.2 years. Diagnoses included lung cancer (83), pulmonary metastases (4), and benign disease (1).

Results

Dense adhesions between the lung and the mediastinum sometimes occur after cardiac surgery. Compared with the total series of 2684 VATS lobectomies, operations after sternotomy are associated with greater mortality (12, 0.4% vs 5, 5.7%), myocardial infarction (13, 0.5% vs 2, 2.3%), transfusion (45, 1.7% vs 12, 13.6), conversion to thoracotomy (188, 7% vs 14, 15.9%). Injury occurred to the left main pulmonary artery (1, 1%) and internal mammary artery graft (1, 1%). There were no intraoperative deaths.

Conclusions

Previous sternotomy for cardiac surgery does increase the risk for VATS lobectomy. Conversion to thoracotomy should be considered if dense adhesions are found. Techniques to reduce the risk for the heart are discussed.
Chronic Eosinophilic Meningoencephalitis by Prototheca Wickerhamii in an Immunocompetent Boy
Authors: Ahn Ari , Choe Yong-Joon , Chang Jeonghyun , Kim Duckhee , Sung Heungsup , Kim Mi-Na , Hong Seok Ho , Lee Jina , Yum Mi-Sun , Ko Tae-Sung
Published: January 2017

Human protothecosis is mainly a cutaneous infection caused by the Prototheca species. Prototheca wickerhamii is an established pathogen of eosinophilic meningoencephalitis in dogs, but no eosinophilic pleocytosis of the cerebrospinal fluid has been reported in human cases of meningitis. Herein, we report a case of chronic protothecosis manifesting eosinophilic meningoencephalitis in an immunocompetent boy.
Evaluating the impact of trigeminal neuralgia
Authors: Zakrzewska Joanna M. , Wu Jianhua , Mon-Williams Mark , Phillips Nicholas , Pavitt Sue H.
Published: January 2017

Patients with idiopathic trigeminal neuralgia (TN) were categorised into 3 subtypes (n = 225). Group 1 (n = 155, 68.9%) had TN without concomitant pain, group 2 (n = 32, 14.2%) had TN with intermittent concomitant pain, and group 3 (n = 39, 16.9%) had TN with autonomic symptoms. We tested 2 hypotheses: (1) that different pain profiles would be associated with the different groups; (2) that the severe pain associated with TN would impact negatively on activities of daily living and thereby result in disability as defined by the World Health Organisation. A different pain profile was found across the groups. We obtained unequivocal evidence that TN causes disability with up to 45% of patients being absent from usual daily activities 15 days or more in the past 6 months. On the Hospital Anxiety and Depression Scale, 35.7% patients had mild-to-severe depression and over 50% were anxious. The Pain Catastrophizing Scale showed that 78% of patients had considerable negative thoughts with scores >20 and a mean score of 36.4. Prior to referral, only 54% had been prescribed carbamazepine while opioids had been prescribed in 14.6% of the patients. Prior to referral, over 80% had already been to 1 specialist centre which had not provided appropriate management. Patients with TN report varied characteristics but all result in some degree of psychosocial disability especially before adequate therapy is attained.
Subdural Hematoma: A Rare Adverse Complication From Bone-Anchored Hearing Aid Placement
Authors: Amin Nikul , Aymat-Torrente Antonio
Published: January 2017

Objective:

Bone-anchored hearing aids (BAHA) are bone conduction hearing aids commonly implantated by Ear, Nose, and Throat surgeons. We present the first documented case of a subdural hematoma secondary to primary fixation of a BAHA.

Patient:

We present a 65-year-old male patient undergoing a left sided BAHA for bilateral chronic ear infections and difficulty wearing conventional hearing aids. The procedure was uneventful, however, the patient developed a postoperative large acute left temporoparietal intracerebral hematoma associated with an ipsilateral acute subdural hematoma. This required emergency transfer to the local tertiary neurosurgical center for a left decompressive craniotomy and evacuation of the hematoma.

Results:

The patient required a prolonged stay on an intensive care unit and was eventually discharged to the community for on-going neurological rehabilitation.

Conclusion:

This is a rare and devastating complication BAHA surgery. Otologist, general ENT surgeons, and neurosurgeons should be aware of this life-threatening complication of BAHA surgery.
FDA Benchmark Medical Device Flow Models for CFD Validation
Authors: Malinauskas Richard A. , Hariharan Prasanna , Day Steven W. , Herbertson Luke H. , Buesen Martin , Steinseifer Ulrich , Aycock Kenneth I. , Good Bryan C. , Deutsch Steven , Manning Keefe B. , Craven Brent A.
Published: January 2017

Computational fluid dynamics (CFD) is increasingly being used to develop blood-contacting medical devices. However, the lack of standardized methods for validating CFD simulations and blood damage predictions limits its use in the safety evaluation of devices. Through a U.S. Food and Drug Administration (FDA) initiative, two benchmark models of typical device flow geometries (nozzle and centrifugal blood pump) were tested in multiple laboratories to provide experimental velocities, pressures, and hemolysis data to support CFD validation. In addition, computational simulations were performed by more than 20 independent groups to assess current CFD techniques. The primary goal of this article is to summarize the FDA initiative and to report recent findings from the benchmark blood pump model study. Discrepancies between CFD predicted velocities and those measured using particle image velocimetry most often occurred in regions of flow separation (e.g., downstream of the nozzle throat, and in the pump exit diffuser). For the six pump test conditions, 57% of the CFD predictions of pressure head were within one standard deviation of the mean measured values. Notably, only 37% of all CFD submissions contained hemolysis predictions. This project aided in the development of an FDA Guidance Document on factors to consider when reporting computational studies in medical device regulatory submissions. There is an accompanying podcast available for this article. Please visit the journal’s Web site (www.asaiojournal.com) to listen.
Early Gains in Renal Function Following Implantation of HeartMate II Left Ventricular Assist Devices May Not Persist to One Year
Authors: Hasin Tal , Grupper Avishay , Dillon John J. , Maleszewski Joseph J. , Li Zhuo , Topilsky Yan , Frantz Robert P. , Edwards Brooks S. , Pereira Naveen L. , Maltais Simon , Stulak John M. , Joyce Lyle , Daly Richard , Park Soon J. , Kushwaha Sudhir S.
Published: January 2017

Renal function improves early after left ventricular assist device (LVAD) implantation but later decline has been observed. We sought to determine the occurrence and evaluate possible causes for this decline. In 62 consecutive patients with HeartMateII LVAD with available calculated glomerular filtration rate (GFR, ml/min/1.73 m2) 1 year after implant, GFR was assessed repeatedly and possible predictors for decline from 3 to 12 months were investigated. Post-mortem renal specimens for patients supported with an LVAD were evaluated. GFR 54.5 ± 19.5 at admission increased to 66.4 ± 22.3 preoperatively and to 79.2 ± 30.1 ~1 month after implantation. Subsequently at ~3 months GFR declined to 74.7 ± 25.4, at ~6 months to 68.8 ± 23.1, and ~1 year after implant to 63.9 ± 17.7. Glomerular filtration rate at 1 year was significantly lower (p < 0.0001, p < 0.0001, p = 0.005) than GFR 1, 3, and 6 months after implant. Early rise in GFR after surgery was not associated with late decline. Shorter bypass time (β = −0.09, p = 0.048) and higher albumin 3 months after LVAD (β = 14.4, p = 0.025) were significantly associated with less later decline in GFR. Arteriosclerosis was identified in autopsy renal specimens. In conclusion, early gains in renal function after LVAD implant are not sustained in many patients. Patient, device, and operative factors may influence long-term renal function in these patients.
Myocardial Recovery Strategy with Decommissioning for the HeartWare Left Ventricular Assist Device
Authors: MacGowan Guy A. , Wrightson Neil , Robinson-Smith Nicola , Woods Andrew , Parry Gareth , Gould Kate , Schueler Stephan
Published: January 2017

To manage myocardial recovery in patients with the HeartWare left ventricular assist device (HVAD), we describe a minimally invasive approach (decommissioning) that involves disconnecting the driveline and occluding the outflow tract through a small left thoracotomy incision, leaving the device in situ, in conjunction with optimal medical therapies and comprehensive assessment of left ventricular recovery. Nine patients (all male, 37 ± 12 years, all nonischemic dilated cardiomyopathy) had an HVAD implanted for 766 ± 343 days. When left ventricular function improved to mild impairment by echocardiography, patients underwent assessment at reduced flow (2578 ± 148 to 1822 ± 67 rpm) with documentation of compensated right heart hemodynamics and ejection fraction 52 ± 8%. Eight of nine patients underwent decommissioning, and 1 patient had a hybrid procedure of percutaneous occlusion of outflow graft and surgical division of driveline. Two patients died postoperatively at 413 days (sepsis) and 810 days (heart failure). In conclusion, in selected patients with nonischemic dilated cardiomyopathy, a prolonged period of HVAD support in conjunction with heart failure medications can lead to recovery of left ventricular function. Surgical decommissioning is then an option to remove these patients from support. These patients are, however, not cured and remain at risk for future deterioration in ventricular function and infections.
Prevalence of hepatitis B and C and factors for infection and nonimmune in inflammatory bowel disease patients in China
Authors: Chen Dafan , Luo Shengzheng , Ben Qiwen , Lu Lungen , Wan Xinjian , Wu Jianjiong
Published: January 2017

Objective

The aims of this study were to investigate the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in inflammatory bowel disease (IBD) patients and the risk factors related to the infection and nonimmune status.

Methods

A retrospective study was carried out at two clinical centers. The prevalence of viral markers and risk factors related to HBV and HCV infection and nonimmune status were analyzed in IBD patients. Age-matched and sex-matched healthy individuals were recruited as the controls.

Results

A total of 980 IBD patients were included in this study. Present and past HBV infection was detected in 41.21% of the IBD group, which was higher than that in the general population (P=0.003). Age older than 30 years (P=0.000), ulcerative colitis (P=0.002), and previous surgery (P=0.039) were found to be significant risk factors for HBV infection in the multivariate analysis. 36.43% of the patients in the IBD group had nonimmune status against HBV, and age less than 40 years (P=0.011) and Crohn’s disease (P=0.002) were identified as independent risk factors in the multivariate analysis. The prevalence of HCV infection was low and similar to that of the general population.

Conclusion

The prevalence of HBV infection in IBD patients in China was higher than that in Europe, USA, and the general population in China, but the prevalence of HCV infection in IBD patients was similar to that in the general population in this study. The frequency of nonimmune status against HBV was high, especially in young Crohn’s disease patients, and HBV vaccination should be intensified and have a targeted coverage.
Effects of introduction of an inflammatory bowel disease nurse position on the quality of delivered care
Authors: Coenen Sofie , Weyts Ellen , Vermeire Séverine , Ferrante Marc , Noman Maja , Ballet Vera , Vanhaecht Kris , Van Assche Gert
Published: January 2017

Background and aims

Inflammatory bowel diseases (IBDs) are chronic gastrointestinal conditions requiring long-term outpatient follow-up, ideally by a dedicated, multidisciplinary team. In this team, the IBD nurse is the key point of access for education, advice, and support. We investigated the effect of the introduction of an IBD nurse on the quality of care delivered.

Methods

In September 2014, an IBD nurse position was instituted in our tertiary referral center. All contacts and outcomes were prospectively recorded over a 12-month period using a logbook kept by the nurse.

Results

Between September 2014 and August 2015, 1313 patient contacts were recorded (42% men, median age: 38 years, 72% Crohn’s disease, 83% on immunosuppressive therapy). The contacts increased with time: Q1 (September–November 2014): 144, Q2: 322, Q3: 477, and Q4: 370. Most of the contacts were assigned to scheduling of follow-up (316/1420), start of new therapy (173/1420), therapy follow-up (313/1420), and providing disease information (227/1420). In addition, 134 patients contacted the IBD nurse for flare management and a smaller number for administrative support, psychosocial support, and questions about side effects. During the study period, 30 emergency room and 133 unscheduled outpatient visits could be avoided through the intervention of the IBD nurse. A faster access to procedures and other departments could be provided for 136 patients.

Conclusion

The role of IBD nurses as the first point of contact and counseling is evident from a high volume of nurse–patient interactions. Avoidance of emergency room and unscheduled clinic visits are associated with these contacts.
No more winter crisis? Forecasting daily bed requirements for emergency department admissions to hospital
Authors: Wargon Mathias , Brun-Ney Dominique , Beaujouan Laure , Casalino Enrique
Published: January 2017

Study hypothesis

We hypothesized that age, calendar variables, and clinical influenza epidemics may have an impact on the number of daily through-emergency department (ED) hospitalizations. The aim of our study was to elaborate a pragmatic tool to predict the daily number of through-ED hospitalizations.

Methods

We carried out a prospective-observational study including data from 18 ED located in the Paris metropolitan area. Daily through-ED hospitalizations numbers from 2007 to 2010 were modelized to forecast the year 2011 using a general linear model by age groups (<75-years; ≥75-years) using calendar variables and influenza epidemics as explanatory variables. Lower and higher limits forecast with the 95% confidence interval of each explanatory variable were calculated.

Results

2 741 974 ED visits and 518 857 through-ED hospitalizations were included. We found a negative trend (−2.7%) for hospitalization visits among patients less than 75 years of age and an increased trend (+6.2%) for patients of at least 75 years of age. Calendar variables were predictors for daily hospitalizations for both age groups. Influenza epidemic period was not a predictor for hospitalizations in patients less than 75 years of age; among patients of at least 75 years of age, significant value was found only in models excluding months. When forecasting hospitalizations, 70% for patients less than 75 years of age and 66.8% for patients of at least 75 years of age of daily predicted values were included in the forecast limits.

Conclusion

Daily number of emergency hospitalizations could be predicted on a regional basis using calendar variables with a low level of error. Forecasting through-ED hospitalizations requires to differentiate between elderly and younger patients, with a low impact of influenza epidemic periods in elders and absent in youngest patients.
Characteristics of children with microbiologically confirmed invasive bacterial infections in the emergency department
Authors: Gangoiti Iker , Valle Juan R. , Sota Mercedes , Martinez-Indart Lorea , Benito Javier , Mintegi Santiago
Published: January 2017

Background

Determination of the characteristics of paediatric invasive bacterial infections (IBI) is essential for early identification of children requiring immediate antibiotic therapy. The main objective is to characterize the emergency presentation of the IBI among children aged younger than 14 years.

Patients and methods

A prospective registry-based cohort study including all patients aged younger than 14 years diagnosed with confirmed IBI (culture or genomic detection using the polymerase chain reaction) was carried out in a paediatric emergency department between 2008 and 2015. Severity criteria were as follows: death, sequelae or admission to the ICU.

Results

Of the 223 IBIs reported, 187 (83.9%) corresponded to previously healthy patients (median age=19 months) and 165 (74%) were well appearing. The most common diagnoses were occult bacteraemia [60 (26.9%)] and sepsis [56 (25.1%)]. The most frequent pathogens were Streptococcus pneumoniae [68 (30.5%)] and Neisseria meningitidis [42 (18.8%)]. Four (1.8) patients died (S. pneumoniae, 2) and eight (3.5%) had sequelae (S. pneumoniae, 5). The diagnoses and clinical characteristics of the children varied significantly depending on the isolated pathogen. Duration of fever less than 24 h, symptoms other than fever and not being well-appearing upon arrival to the emergency department were independent risk factors for greater severity (area under the receiver operating characteristics curve=0.805; 95% confidence interval: 0.741–0.868).

Conclusion

IBIs are commonly diagnosed in previously healthy and well-appearing young children. S. pneumoniae was responsible for the majority of deaths or sequelae. Short duration of fever, symptoms other than fever and not being stable on arrival are associated with greater severity.
Acute hepatic and erythropoietic porphyrias: from ALA synthases 1 and 2 to new molecular bases and treatments
Authors: Manceau Hana , Gouya Laurent , Puy Hervé
Published: January 2017

Purpose of review

Many studies over the past decade have together identified new genes including modifier genes and new regulation and pathophysiological mechanisms in inherited inborn diseases of the heme biosynthetic pathway. A new porphyria has been characterized: X-linked protoporphyria and the perspective to have innovative treatment at very short-term became a reality. We will summarize how recent data on both ALAS1 and ALAS2 have informed our understanding of disease pathogenesis with an emphasis on how this information may contribute to new therapeutic strategies.

Recent findings

The development of clinical and biological porphyria networks improved the long-term follow up of cohorts. The ageing of patients have allowed for the identification of novel recurrently mutated genes, and highlighted long-term complications in acute hepatic porphyrias. The treatment of hepatic porphyrias by an RNAi-targeting hepatic ALAS1 is actually tested and may lead to improve the management of acute attacks.

In erythropoietic porphyrias, the key role of ALAS2 as a gate keeper of the heme and subsequently hemoglobin synthesis has been demonstrated. Its implication as a modifier gene in over erythroid disorders has also been documented.

The knowledge of both the genetic abnormalities and the regulation of heme biosynthesis has increased over the last 5 years and open new avenues in the management of erythropoietic and acute hepatic porphyrias.
Presymptomatic Diagnosis of Celiac Disease in Predisposed Children
Authors: Galatola Martina , Cielo Donatella , Panico Camilla , Stellato Pio , Malamisura Basilio , Carbone Lorenzo , Gianfrani Carmen , Troncone Riccardo , Greco Luigi , Auricchio Renata
Published: January 2017

Objective:

The prevalence of celiac disease (CD) has increased significantly in recent years, and risk prediction and early diagnosis have become imperative especially in at‐risk families. In a previous study, we identified individuals with CD based on the expression profile of a set of candidate genes in peripheral blood monocytes. Here we evaluated the expression of a panel of CD candidate genes in peripheral blood mononuclear cells from at‐risk infants long time before any symptom or production of antibodies.

Methods:

We analyzed the gene expression of a set of 9 candidate genes, associated with CD, in 22 human leukocyte antigen predisposed children from at‐risk families for CD, studied from birth to 6 years of age. Nine of them developed CD (patients) and 13 did not (controls). We analyzed gene expression at 3 different time points (age matched in the 2 groups): 4–19 months before diagnosis, at the time of CD diagnosis, and after at least 1 year of a gluten‐free diet. At similar age points, controls were also evaluated.

Results:

Three genes (KIAA, TAGAP [T‐cell Activation GTPase Activating Protein], and SH2B3 [SH2B Adaptor Protein 3]) were overexpressed in patients, compared with controls, at least 9 months before CD diagnosis. At a stepwise discriminant analysis, 4 genes (RGS1 [Regulator of G‐protein signaling 1], TAGAP, TNFSF14 [Tumor Necrosis Factor (Ligand) Superfamily member 14], and SH2B3) differentiate patients from controls before serum antibodies production and clinical symptoms. Multivariate equation correctly classified CD from non‐CD children in 95.5% of patients.

Conclusions:

The expression of a small set of candidate genes in peripheral blood mononuclear cells can predict CD at least 9 months before the appearance of any clinical and serological signs of the disease.
Effects of Infant Formula With Human Milk Oligosaccharides on Growth and Morbidity
Authors: Puccio Giuseppe , Alliet Philippe , Cajozzo Cinzia , Janssens Elke , Corsello Giovanni , Sprenger Norbert , Wernimont Susan , Egli Delphine , Gosoniu Laura , Steenhout Philippe
Published: January 2017

Objectives:

The aim of the study was to evaluate the effects of infant formula supplemented with 2 human milk oligosaccharides (HMOs) on infant growth, tolerance, and morbidity.

Methods:

Healthy infants, 0 to 14 days old, were randomized to an intact‐protein, cow's milk–based infant formula (control, n = 87) or the same formula with 1.0 g/L 2′fucosyllactose (2′FL) and 0.5 g/L lacto‐N‐neotetraose (LNnT) (test, n = 88) from enrollment to 6 months; all infants received standard follow‐up formula without HMOs from 6 to 12 months. Primary endpoint was weight gain through 4 months. Secondary endpoints included additional anthropometric measures, gastrointestinal tolerance, behavioral patterns, and morbidity through age 12 months.

Results:

Weight gain was similar in both groups (mean difference [95% confidence interval] test vs control: −0.30 [−1.94, 1.34] g/day; lower bound of 95% confidence interval was above noninferiority margin [−3 g/day]). Digestive symptoms and behavioral patterns were similar between groups; exceptions included softer stool (P = 0.021) and fewer nighttime wake‐ups (P = 0.036) in the test group at 2 months. Infants receiving test (vs control) had significantly fewer parental reports (P = 0.004–0.047) of bronchitis through 4 (2.3% vs 12.6%), 6 (6.8% vs 21.8%), and 12 months (10.2% vs 27.6%); lower respiratory tract infection (adverse event cluster) through 12 months (19.3% vs 34.5%); antipyretics use through 4 months (15.9% vs 29.9%); and antibiotics use through 6 (34.1% vs 49.4%) and 12 months (42.0% vs 60.9%).

Conclusions:

Infant formula with 2′FL and LNnT is safe, well‐tolerated, and supports age‐appropriate growth. Secondary outcome findings showing associations between consuming HMO‐supplemented formula and lower parent‐reported morbidity (particularly bronchitis) and medication use (antipyretics and antibiotics) warrant confirmation in future studies.
Case Volume and Revisits in Children Undergoing Gastrostomy Tube Placement
Authors: Arca Marjorie J. , Rangel Shawn J. , Hall Matt , Rothstein David H. , Blakely Martin L. , Minneci Peter C. , Shah Samir S. , Heiss Kurt F. , Snyder Charles L. , Berman Loren , Browne Marybeth , Vinocur Charles D. , Raval Mehul V. , Goldin Adam B.
Published: January 2017

Objectives:

Emergency department (ED) visits and hospital readmissions are common after gastrostomy tube (GT) placement in children. We sought to characterize interhospital variation in revisit rates and explore the association between this outcome and hospital‐specific GT case volume.

Patients and Methods:

We conducted a retrospective cohort study from 38 hospitals using the Pediatric Health Information System database. Patients younger than 18 years who had a GT placed in 2010 to 2012 were assessed for a GT‐related (mechanical or infectious) ED visit or inpatient readmission at 30 and 90 days after discharge from GT placement. Risk‐adjusted rates were calculated using generalized linear mixed‐effects models accounting for hospital clustering and relevant demographic and clinical attributes, then compared across hospitals.

Results:

A total of 15,642 patients were included. A median of 468 GTs were placed in all the 38 hospitals during 3 years (range: 83–891), with a median of 11.4 GT placed per 1000 discharges (range: 2.4–16.7). Median ED visit for each hospital at 30 days after discharge was 8.2% (range: 3.7%–17.2%) and 14.8% at 90 days (range: 6.3%–26.1%). Median inpatient readmissions for each hospital at 30 days after discharge was 3.5% (range: 0.5%–10.5%) and 5.9% at 90 days (range: 1.0%–18.5%). Hospital‐specific GT placement per 1000 discharges (rate of GT placement) was inversely correlated with ED visit rates at 30 (P = 0.007) and 90 days (P = 0.020). The adjusted 30‐ and 90‐day readmission rate and the adjusted 30‐ and 90‐day ED return rates decreased with increasing GT insertion rate (P < 0.001).

Conclusion:

Higher hospital GT insertion rates are associated with lower ED revisit rates but not inpatient readmissions.
Utility of Gastric and Duodenal Biopsies During Follow‐up Endoscopy in Children With Eosinophilic Esophagitis
Authors: Kaur Sunpreet , Rosen John M. , Kriegermeier Alyssa A. , Wechsler Joshua B. , Kagalwalla Amir F. , Brown Jeffrey B.
Published: January 2017

Objectives:

Eosinophilic esophagitis (EoE) is a chronic antigen‐mediated immune disorder of the esophagus. Consensus guidelines recommend obtaining esophageal, gastric, and duodenal biopsies at diagnostic endoscopy when EoE is suspected. The utility of repeated gastric and duodenal biopsies during follow‐up endoscopy in patients previously diagnosed with EoE is not established. The aim of the present study was to explore the role of gastric and duodenal biopsies in children with an established diagnosis of EoE undergoing repeat endoscopy to assess histological response to treatment.

Methods:

Retrospective chart review of children diagnosed with EoE at a tertiary care center was conducted. A total of 160 patients with EoE with demographic clinical, endoscopic, and histological data at diagnosis and follow‐up endoscopy were included. The frequency of gastric and duodenal biopsies at follow‐up endoscopy with abnormal histology and their correlation to endoscopic findings was determined.

Results:

At follow‐up endoscopy, 83% (132/160) of patients had gastric and 74% (118/160) had duodenal biopsies. Histology was normal in 81% of gastric and 92% of duodenal biopsies. The most frequent gastric abnormalities were chemical and inactive chronic gastritis. The most frequent duodenal abnormality was villous blunting with increased intraepithelial lymphocytes. Two patients with normal gastric and duodenal histology progressed to eosinophilic gastroenteritis at follow‐up endoscopy.

Conclusions:

Gastric and duodenal biopsies obtained in EoE patients during follow‐up endoscopy show pathology in a minority of patients, increase costs, and may add potential risk of adverse events. Large multicenter, prospective studies of endoscopic practice during follow‐up of EoE are warranted to provide evidence supporting best practices.
Refinement of a Conceptual Model for Adolescent Readiness to Engage in End-of-Life Discussions
Authors: Bell Cynthia J. , Zimet Gregory D. , Hinds Pamela S. , Broome Marion E. , McDaniel Anna M. , Mays Rose M. , Champion Victoria L.
Published: January 2017

Background:

Adolescents living with incurable cancer require ongoing support to process grief, emotions, and information as disease progresses including treatment options (phase 1 clinical trials and/or hospice/palliative care). Little is known about how adolescents become ready for such discussions.

Objective:

The purpose of this study was to explore the process of adolescent readiness for end-of-life preparedness discussions, generating a theoretical understanding for guiding clinical conversations when curative options are limited.

Methods:

We explored 2 in-depth cases across time using case-study methodology. An à priori conceptual model based on current end-of-life research guided data collection and analysis. Multiple sources including in-depth adolescent interviews generated data collection on model constructs. Analysis followed a logical sequence establishing a chain of evidence linking raw data to study conclusions. Synthesis and data triangulation across cases and time led to theoretical generalizations. Initially, we proposed a linear process of readiness with 3 domains: a cognitive domain (awareness), an emotional domain (acceptance), and a behavioral domain (willingness), which preceded preparedness.

Results:

Findings led to conceptual model refinement showing readiness is a dynamic internal process that interacts with preparedness. Current awareness context facilitates the type of preparedness discussions (cognitive or emotional). Furthermore, social constraint inhibits discussions.

Conclusions:

Data support theoretical understanding of the dynamism of readiness. Future research that validates adolescent conceptualization will ensure age-appropriate readiness representation.

Implications for Practice:

Understanding the dynamic process of readiness for engaging in end-of-life preparedness provides clinician insight for guiding discussions that facilitate shared decision making and promote quality of life for adolescents and their families.
Symptom Characteristics Among Hospitalized Children and Adolescents With Cancer
Authors: Linder Lauri A. , Al-Qaaydeh Sharifa , Donaldson Gary
Published: January 2017

Background:

Studies addressing physical and psychosocial symptoms among hospitalized children and adolescents with cancer are limited. Understanding commonly occurring symptoms and their associated characteristics across the hospitalization is needed to guide symptom management strategies.

Objective:

This study described the symptom experience of hospitalized children and adolescents with cancer. The study explored the frequencies of individual symptoms and the severity, duration, and associated distress of symptoms during the course of the hospitalization.

Methods:

Participants completed the Memorial Symptom Assessment Scale 7–12 during each 12-hour shift of the 3-day/3-night data collection period.

Results:

Participants were 50 children and adolescents (mean age, 12.6 years; range, 7.1–18.6 years) receiving inpatient chemotherapy. Participants reported a mean of 2.75 symptoms at each assessment point and a mean of 5.42 different symptoms during their hospitalization. Mixed model analyses identified a significant fixed effect for study day, with participants reporting fewer symptoms (F = 8.4, P < .01), less symptom severity (F = 5.81, P < .01), and shorter duration (F = 6.67, P < .01) on day 3 relative to days 1 and 2. A fixed effect for study day was not present for symptom distress.

Conclusions:

Children and adolescents receiving inpatient chemotherapy experience multiple physical and psychosocial symptoms of moderate or greater severity and duration throughout the course of their hospitalization. Symptoms of greatest severity may not be those that are most distressing to the patient.

Implications for Practice:

Ongoing assessment that incorporates the multidimensional nature of symptoms is needed. Prioritizing interventions for symptoms that are most distressing to the patient may support a more meaningful, patient-centric approach to care.
Actualization of a Seamless Nursing Program
Authors: Wallen Andrea , McKay Linda , Santos Ellen , LaFrance Holly , Veith Rose M.
Published: January 2017

Upward educational mobility of licensed practical nurses (LPNs) is important for their professional development. For the nursing profession, this upward mobility increases workforce diversity. To address the paucity of programs accepting the LPN’s education, a team of 6 BSN and LPN nurse educators, backed by 2 universities, developed a seamless LPN-BSN program. This article documents the process, including a needs assessment, curriculum development, admission criteria, implementation, lessons learned, and outcomes.
Implementation of a Pediatric Orthopaedic Bundle to Reduce Surgical Site Infections
Authors: Schriefer Jan , Sanders James , Michels Julie , Wolcott Kori , Ruddy Connor , Hanson Jenna
Published: January 2017

Surgical site infections (SSIs) cost an estimated $27,288 per case. An analysis of the National Surgical Quality Improvement Program data at the University of Rochester Medical Center suggested that rates of SSIs could be lowered in comparison with both peers and baseline. The aim of this study was to reduce the number of SSIs to zero through the implementation of a “bundle” or a combination of practices. Meetings were held with the multidisciplinary care team that includes surgeons and staff from pediatric pharmacy, pediatric infectious diseases, anesthesia, and nursing to create a care bundle for all pediatric orthopaedic surgery patients. Bundle elements included use of chlorhexidine gluconate wipes the night before surgery and the day of surgery, use of preoperative nutrition screens, development and use of a prophylactic antibiotic dosing chart, use of methicillin-resistant Staphylococcus aureus screening, maintenance of normal patient temperature, and use of nasal swabs in the operating room. The SSI rate dropped from a baseline figure of 4% in 2013 (n = 154) and 3.2% in 2014 (n = 189) to 0.0% (n = 198) in 2015 after the bundles were implemented. Both compliance with the bundle and SSI rates must be monitored monthly. Staff and providers should be offered monthly feedback on SSI rates and care bundle compliance. If an SSI does occur, a root–cause analysis is performed with the multidisciplinary care team using a standardized review form.
Early Fluid Overload Prolongs Mechanical Ventilation in Children With Viral-Lower Respiratory Tract Disease*
Authors: Ingelse Sarah A. , Wiegers Hanke M. G. , Calis Job C. , van Woensel Job B. , Bem Reinout A.
Published: January 2017

Objectives:

Viral-lower respiratory tract disease is common in young children worldwide and is associated with high morbidity. Acute respiratory failure due to viral-lower respiratory tract disease necessitates PICU admission for mechanical ventilation. In critically ill patients in PICU settings, early fluid overload is common and associated with adverse outcomes such as prolonged mechanical ventilation and increased mortality. It is unclear, however, if this also applies to young children with viral-lower respiratory tract disease induced acute respiratory failure. In this study, we aimed to investigate the relation of early fluid overload with adverse outcomes in mechanically ventilated children with viral-lower respiratory tract disease in a retrospective dataset.

Design:

Retrospective cohort study.

Setting:

Single, tertiary referral PICU.

Patients:

One hundred thirty-five children (< 2 yr old) with viral-lower respiratory tract disease requiring mechanical ventilation admitted to the PICU of the Academic Medical Center, Amsterdam between 2008 and 2014.

Interventions:

None.

Measurements and Main Results:

The cumulative fluid balance on day 3 of mechanical ventilation was compared against duration of mechanical ventilation (primary outcome) and daily mean oxygen saturation index (secondary outcome), using uni- and multivariable linear regression. In 132 children, the mean cumulative fluid balance on day 3 was + 97.9 (49.2) mL/kg. Higher cumulative fluid balance on day 3 was associated with a longer duration of mechanical ventilation in multivariable linear regression (β = 0.166; p = 0.048). No association was found between the fluid status and oxygen saturation index during the period of mechanical ventilation.

Conclusions:

Early fluid overload is an independent predictor of prolonged mechanical ventilation in young children with viral-lower respiratory tract disease. This study suggests that avoiding early fluid overload is a potential target to reduce duration of mechanical ventilation in these children. Prospective testing in a clinical trial is warranted to support this hypothesis.
Readmission and Late Mortality After Critical Illness in Childhood*
Authors: Hartman Mary E. , Saeed Mohammed J. , Bennett Tellen , Typpo Katri , Matos Renee , Olsen Margaret A.
Published: January 2017

Objectives:

Little is known about the ongoing mortality risk and healthcare utilization among U.S. children after discharge from a hospitalization involving ICU care. We sought to understand risks for hospital readmission and trends in mortality during the year following ICU discharge.

Design:

Retrospective observational cohort study.

Setting:

This study was performed using administrative claims data from 2006-2013 obtained from the Truven Health Analytics MarketScan Database.

Subjects:

We included all children in the dataset admitted to a U.S. ICU less than or equal to 18 years old.

Interventions:

The primary outcome was nonelective readmission in the year following discharge. Risk of rehospitalization was determined using a Cox proportional hazards model.

Measurements and Main Results:

We identified 109,130 children with at least one ICU admission in the dataset. Over three quarters of the index ICU admissions (78.6%) had an ICU length of stay less than or equal to 3 days, and the overall index hospitalization mortality rate was 1.4%. In multivariate analysis, risk of nonelective readmission for children without cancer was higher with longer index ICU admission length of stay, younger age, and several chronic and acute conditions. By the end of the 1-year observation period, 36.0% of children with an index ICU length of stay greater than or equal to 14 days had been readmitted, compared with only 13.9% of children who had an index ICU length of stay equals to 1 day. Mortality in the year after ICU discharge was low overall (106 deaths per 10,000 person-years of observation) but was high among children with an initial index ICU admission length of stay greater than or equal to 14 days (599 deaths per 10,000 person-years).

Conclusions:

Readmission after ICU care is common. Further research is needed to investigate the potentially modifiable factors affecting likelihood of readmissions after discharge from the ICU. Although late mortality was relatively uncommon overall, it was 10-fold higher in the year after ICU discharge than in the general U.S. pediatric population.