bluuebunny/crossref_metadata_2025_split huggingface dataset:
Itraconazole Dosing and Drug Monitoring at a Tertiary Children’s Hospital
Authors: Leong Ying Hua , Boast Alison , Cranswick Noel , Curtis Nigel , Gwee Amanda 
Published: March 2018

Background:
Itraconazole is a broad-spectrum antifungal agent used for prophylaxis and treatment of fungal infections in immunocompromised children. Achieving the recommended target serum itraconazole trough concentration of ≥0.5 mg/L is challenging in children because of variation in itraconazole pharmacokinetics with age. We studied itraconazole use and treatment outcomes in a tertiary children’s hospital.

Methods:
We did a 10-year retrospective review of medical records of children at the Royal Children’s Hospital Melbourne who received oral itraconazole and had therapeutic drug monitoring (TDM).

Results:
Overall, 81 children received 92 courses of oral itraconazole and had TDM. Of 222 TDM samples, 183 (82.4%) were taken at the appropriate time (trough level at steady state). Patients ≤12 and >12 years of age required median doses of 6.2 and 3.9 mg/kg/d, respectively, to attain target trough levels (P < 0.001). Of children ≤12 years of age, 71.4% required doses above the recommended dose of 5 mg/kg/d to achieve therapeutic levels, compared with 17.4% of those >12 years of age. At least 1 subtherapeutic trough concentration was reported in 63 (76.8%) courses; in only 18 (28.6%) of these was the dose adjusted. Gastrointestinal symptoms [14/92 (15.2%) courses] and hepatotoxicity [6/92 (6.5%)] were the most frequent adverse events. Neither was associated with elevated trough levels.

Conclusions:
The poor attainment of target levels with current recommended dosing in children <12 years of age suggests that higher empiric doses are needed in this age group. The poor compliance with TDM guidelines highlights the need for better education about appropriate timing of sampling and dose adjustment.
Analysis of Treatment Outcomes for Recurrent Clostridium difficile Infections and Fecal Microbiota Transplantation in a Pediatric Hospital
Authors: Aldrich Aileen M. , Argo Taylor , Koehler Tracy J. , Olivero Rosemary 
Published: March 2018

Background:

Clostridium difficile infection (CDI) is one of the most common nosocomial infections in the United States, with an increasing incidence in children. Approximately 20% of pediatric patients develop recurrent infections. It’s imperative to further analyze the incidence of recurrent CDI in the pediatric population and determine the most effective treatments. The primary goal of this study is to characterize children with recurrent CDI at our institution, including both hospital-acquired CDI (HA-CDI) and community-acquired CDI (CA-CDI) cases, summarize the various treatments utilized, including fecal microbiota transplant (FMT) and compare their success rates.

Methods:
A retrospective cohort study of pediatric patients 1–21 years of age treated for CDI at a single institution from January 2010 to December 2014 was performed.

Results:
There were 175 subjects with 215 separate episodes of CDI. Oral metronidazole was the most common initial treatment (145/207, 70%) followed by oral vancomycin (30/207, 15%), with recurrence rates of 30% (42/145) and 37% (11/30), respectively. Twenty-nine percent (63/215) of all initial CDI cases had at least 1 documented recurrence. Using multivariate analysis, subjects with HA-CDI were 2.6 times less likely to recur than those with CA-CDI (odds ratio: 0.39; 95% confidence interval: 0.18–0.85; P = 0.018). The overall success rate for FMT at our institution was 10/12 (83%).

Conclusions:
Our data show that cases of HA-CDI were less likely to recur compared with CA-CDI. Although currently reserved for multiply-recurrent cases, FMT was highly successful in our small cohort. More studies on FMT should be conducted to further evaluate its usefulness in the treatment of recurrent CDI in children.
Spinal manipulation and exercise for low back pain in adolescents: a randomized trial
Authors: Evans Roni , Haas Mitchell , Schulz Craig , Leininger Brent , Hanson Linda , Bronfort Gert 
Published: March 2018

Abstract
Low back pain (LBP) is common in adolescence, but there is a paucity of high-quality research to inform care. We conducted a multicenter randomized trial comparing 12 weeks of spinal manipulative therapy (SMT) combined with exercise therapy (ET) to ET alone. Participants were 185 adolescents aged 12 to 18 years with chronic LBP. The primary outcome was LBP severity at 12, 26, and 52 weeks. Secondary outcomes included disability, quality of life, medication use, patient- and caregiver-rated improvement, and satisfaction. Outcomes were analyzed using longitudinal linear mixed effect models. An omnibus test assessing differences in individual outcomes over the entire year controlled for multiplicity. Of the 185 enrolled patients, 179 (97%) provided data at 12 weeks and 174 (94%) at 26 and 52 weeks. Adding SMT to ET resulted in a larger reduction in LBP severity over the course of 1 year (P = 0.007). The group difference in LBP severity (0-10 scale) was small at the end of treatment (mean difference = 0.5; P = 0.08) but was larger at weeks 26 (mean difference = 1.1; P = 0.001) and 52 (mean difference = 0.8; P = 0.009). At 26 weeks, SMT with ET performed better than ET alone for disability (P = 0.04) and improvement (P = 0.02). The SMT with ET group reported significantly greater satisfaction with care at all time points (P ≤ 0.02). There were no serious treatment-related adverse events. For adolescents with chronic LBP, spinal manipulation combined with exercise was more effective than exercise alone over a 1-year period, with the largest differences occurring at 6 months. These findings warrant replication and evaluation of cost effectiveness.
Machine-learned analysis of the association of next-generation sequencing–based human TRPV1 and TRPA1 genotypes with the sensitivity to heat stimuli and topically applied capsaicin
Authors: Kringel Dario , Geisslinger Gerd , Resch Eduard , Oertel Bruno G. , Thrun Michael C. , Heinemann Sarah , Lötsch Jörn 
Published: March 2018

Abstract
Heat pain and its modulation by capsaicin varies among subjects in experimental and clinical settings. A plausible cause is a genetic component, of which TRPV1 ion channels, by their response to both heat and capsaicin, are primary candidates. However, TRPA1 channels can heterodimerize with TRPV1 channels and carry genetic variants reported to modulate heat pain sensitivity. To address the role of these candidate genes in capsaicin-induced hypersensitization to heat, pain thresholds acquired before and after topical application of capsaicin and TRPA1/TRPV1 exomic sequences derived by next-generation sequencing were assessed in n = 75 healthy volunteers and the genetic information comprised 278 loci. Gaussian mixture modeling indicated 2 phenotype groups with high or low capsaicin-induced hypersensitization to heat. Unsupervised machine learning implemented as swarm-based clustering hinted at differences in the genetic pattern between these phenotype groups. Several methods of supervised machine learning implemented as random forests, adaptive boosting, k-nearest neighbors, naive Bayes, support vector machines, and for comparison, binary logistic regression predicted the phenotype group association consistently better when based on the observed genotypes than when using a random permutation of the exomic sequences. Of note, TRPA1 variants were more important for correct phenotype group association than TRPV1 variants. This indicates a role of the TRPA1 and TRPV1 next-generation sequencing–based genetic pattern in the modulation of the individual response to heat-related pain phenotypes. When considering earlier evidence that topical capsaicin can induce neuropathy-like quantitative sensory testing patterns in healthy subjects, implications for future analgesic treatments with transient receptor potential inhibitors arise.
Illness Uncertainty and Posttraumatic Stress in Young Adults With Congenital Heart Disease
Authors: Moreland Patricia , Santacroce Sheila Judge 
Published: March 2018

Background:
Young adults with congenital heart disease (CHD) are at risk for chronic illness uncertainty in 4 domains: ambiguity about the state of their illness; lack of information about the disease, its treatment, and comorbidities; complexity of the healthcare system and relationship with healthcare providers; and unpredictability of the illness course and outcome. Chronic uncertainty has been associated with posttraumatic stress symptoms (PTSS) and posttraumatic stress disorder (PTSD).

Objective:
The aims of this study were to explore how young adults with CHD experience uncertainty and to describe the relationship between PTSS and the appraisal and management process.

Methods:
An exploratory, mixed methods design was used. Data were collected in person and via Skype from 25 participants (19–35 years old), who were diagnosed with CHD during childhood and able to read and write English. In-depth interviews and the University of California at Los Angeles Posttraumatic Stress Disorder Reaction Index were used to collect data. Qualitative data were analyzed using the constant comparative method.

Results:
The 4 domains of uncertainty were evident in the narratives. The PTSD mean (SD) score was 31.3 (7.7). Six participants met criteria for PTSD. Narrative analysis revealed a relationship between severity of PTSS and the appraisal and management of uncertainty. Participants with PTSD used management strategies that included avoidance, reexperiencing, and hyperarousal.

Conclusions:
Young adults with CHD may be at risk for the development of long-term psychological stress and PTSD in the setting of chronic uncertainty. Regular monitoring to identify PTSS/PTSD may be a means to promote treatment adherence and participation in healthcare.
A Survey on Sexual Counseling for Patients With Cardiac Disease Among Nurses in Jordan
Authors: Abu Ali Raeda M. , Abed Mona A. , Khalil Amani A. , Al-Kloub Manal I. , Ashour Ala F. , Alnsour Intesar A. 
Published: March 2018

Background:
Recovery among patients with cardiac disease also requires attention to their sexual health. However, cultural, religious, and social factors may make Arab Muslim patients reluctant to disclose their sexual concerns and nurses hesitant to discuss patients’ sexuality matters.

Objective:
The aim of this study was to explore sexual counseling (SC) among nurses in Jordan in terms of responsibility, confidence, and practice.

Method:
This was a descriptive, correlational study. Staff nurses were recruited from 10 hospitals in Jordan. Nurses completed the cardiac version of the Survey of Sexuality-Related Nursing Practice and reported their demographics.

Results:
The sample consisted of 379 nurses (female, 59%; mean age, 28.1 years). A significant proportion of nurses viewed assessment/discussion of patients’ sexuality matters as not within their responsibilities (39%), did not feel confident to address sexuality matters (50%), and rated themselves as not at all/not very knowledgeable about sexuality (60%). Few nurses were routinely integrating SC in clinical practice (9%). Sexual counseling was associated with nurses’ gender (male, higher confidence and practice) and previous training on sexuality in nursing practice.

Conclusions:
Nurses in Jordan, especially female nurses, are neither prepared nor competent to provide SC. Nurses need focused education on sexuality to optimize patients’ sexual health.
Decreased Quality of Life Due to Driving Restrictions After Cardioverter Defibrillator Implantation
Authors: Timmermans Ivy , Jongejan Niels , Meine Mathias , Doevendans Pieter , Tuinenburg Anton , Versteeg Henneke 
Published: March 2018

Background:
Driving restrictions for patients with an implantable cardioverter defibrillator (ICD) may require significant lifestyle adjustment and affect patients’ psychological well-being. This study explored the prevalence of, and factors associated with, patient-reported decrease in quality of life due to driving restrictions in the first 2 months postimplantation.

Methods:
Dutch ICD patients (N = 334; median age, 64 [interquartile range, 55–70) years; 81% male) completed questionnaires at the time of implantation and 4 months postimplantation, assessing their sociodemographic, psychological, and driving-related characteristics. Clinical baseline data were retrieved from patients’ medical records.

Results:
Nearly half of the patients (49%) reported decreased quality of life due to driving restrictions. Patient-reported reasons included dependency on others/public transport, (social) isolation, and inability to work. Patients reporting decreased quality of life were more likely to be younger (P = .01), to feel that the restriction lasts too long (P = .004), to have considered ICD refusal because of the restrictions (P = .03), and to have Type D personality (P = .02), anxiety (P = .05), depression (P = .003), and ICD-related concerns (P = .02). Multivariable analysis showed that being younger than 60 years (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.09–4.88; P = .03), feeling the driving restriction lasts too long (OR, 1.77; 95% CI, 1.23–2.55; P = .002), and depression (OR, 3.21; 95% CI, 1.09–9.47; P = .035) were independently associated with decreased quality of life due to driving restrictions.

Conclusions:
This study indicated that a significant group of ICD patients may experience decreased quality of life because of the driving restrictions postimplantation. The restrictions seem to particularly affect patients who are younger and distressed and patients who feel that the restriction lasts too long.
Predicting adverse hemodynamic events in critically ill patients
Authors: Yoon Joo H. , Pinsky Michael R. 
Published: March 2018

Purpose of review
The art of predicting future hemodynamic instability in the critically ill has rapidly become a science with the advent of advanced analytical processed based on computer-driven machine learning techniques. How these methods have progressed beyond severity scoring systems to interface with decision-support is summarized.

Recent findings
Data mining of large multidimensional clinical time-series databases using a variety of machine learning tools has led to our ability to identify alert artifact and filter it from bedside alarms, display real-time risk stratification at the bedside to aid in clinical decision-making and predict the subsequent development of cardiorespiratory insufficiency hours before these events occur. This fast evolving filed is primarily limited by linkage of high-quality granular to physiologic rationale across heterogeneous clinical care domains.

Summary
Using advanced analytic tools to glean knowledge from clinical data streams is rapidly becoming a reality whose clinical impact potential is great.
Reduction in postpercutaneous coronary intervention angina in addition to gastrointestinal events in patients on combined proton pump inhibitors and dual antiplatelet therapy: a systematic review and meta-analysis
Authors: Khan Muhammad Y. , Siddiqui Waqas J. , Alvarez Chikezie , Aggarwal Sandeep , Hasni Syed F. , Ahmad Asyia , Eisen Howard 
Published: March 2018

Background
Primary percutaneous coronary intervention (PCI) is a standard treatment in patients with acute coronary syndrome. Studies have shown that proton pump inhibitors (PPIs) can potentially attenuate the antiplatelet effects of P2Y12 inhibitors with associated adverse cardiovascular outcomes.

Materials and methods
Medline was searched using Pubmed from inception to 8 November 2017 for randomized control trials studying the effect of PPIs on coronary artery disease with concomitant use of dual antiplatelet therapy (DAPT). Overall, 692 studies were identified of which five randomized control trials were included. Statistical analysis was done using RevMan, version 5.3.

Results
Five studies with 6239 patients (3113 on PPI with DAPT and 3126 with only DAPT) were included. Our analysis showed that PPI significantly reduced the incidence of gastrointestinal (GI) bleed [22 vs. 66, odds ratio (OR)=0.37, confidence interval (CI)=0.23–0.61, P≤0.0001, I
2=0%], GI ulcers and GI erosions (7 vs. 18, OR=0.39, CI=0.16–0.94, P=0.04, I
2=0%), and the incidence of post-PCI unstable angina in patients treated with PPI and P2Y12 agents (46 vs. 67, OR=0.67, CI=0.45–0.99, P=0.05, I
2=0%). There was an insignificant difference in myocardial infarction, stroke, and cardiovascular cause of mortality. A trend toward decreased all-cause mortality with PPIs was noted. Heterogeneity was calculated using I
2.

Conclusion
Concomitantly administered PPIs with P2Y12 inhibitors have a protective effect on the GI events. It also decreases the post-PCI angina without increased adverse cardiovascular outcomes.
Myeloid cells regulate plasma LDL-cholesterol levels
Authors: Bazioti Venetia , La Rose Anouk M. , Westerterp Marit 
Published: March 2018

Purpose of review
Leukocytosis, elevated blood leukocyte levels, is associated with enhanced cardiovascular risk in humans. Hematopoietic stem and progenitor cells (HSPCs) drive leukocyte production in a process called hematopoiesis, which mainly occurs in the bone marrow, and under certain conditions also in other organs such as the spleen. Cholesterol accumulation in HSPCs enhances hematopoiesis, increasing levels of blood monocytes that infiltrate into atherosclerotic plaques. Although HSPC proliferation and monocytosis enhance atherogenesis in several studies, concomitant decreases in LDL-cholesterol levels have also been reported, associated with anti-atherogenic effects. This review focuses on the link between HSPC proliferation, leukocytosis, plasma LDL-cholesterol levels, and atherogenesis.

Recent findings
Recent studies have shown that an acute infection enhances cholesterol accumulation in HSPCs, driving HSPC proliferation, and leading to the expansion of myeloid cells (monocytes, neutrophils, and macrophages). Enhanced hematopoiesis is associated with low plasma LDL-cholesterol levels in animal models and humans, probably because of the increased number of myeloid cells that take up LDL-cholesterol. Despite low-plasma LDL-cholesterol levels, specific patient populations with enhanced hematopoiesis show increased cardiovascular risk.

Summary
Enhanced hematopoiesis and monocytosis may accelerate atherogenesis. Studies on these processes may lead to the identification of new therapeutic targets for cardiovascular diseases.
Evolving understanding of neonatal necrotizing enterocolitis
Authors: Isani Mubina A. , Delaplain Patrick T. , Grishin Anatoly , Ford Henri R. 
Published: March 2018

Purpose of review
Necrotizing enterocolitis (NEC) is a devastating disease that predominately affects premature neonates. The pathogenesis of NEC is multifactorial and poorly understood. Risk factors include low birth weight, formula-feeding, hypoxic/ischemic insults, and microbial dysbiosis. This review focuses on our current understanding of the diagnosis, management, and pathogenesis of NEC.

Recent findings
Recent findings identify specific mucosal cell types as potential therapeutic targets in NEC. Despite a broadly accepted view that bacterial colonization plays a key role in NEC, characteristics of bacterial populations associated with this disease remain elusive. The use of probiotics such as lactobacilli and bifidobacteria has been studied in numerous trials, but there is a lack of consensus regarding specific strains and dosing. Although growth factors found in breast milk such as epidermal growth factor and heparin-binding epidermal growth factor may be useful in disease prevention, developing new therapeutic interventions in NEC critically depends on better understanding of its pathogenesis.

Summary
NEC is a leading cause of morbidity and mortality in premature neonates. Recent data confirm that growth factors and certain bacteria may offer protection against NEC. Further studies are needed to better understand the complex pathogenesis of NEC.
Chapter 8. 50 Years of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)
Authors: Auricchio Salvatore , Cadranel Samy , Guandalini Stefano , Kelly Deirdre , Koletzko Berthold , Lentze Michael J. , McNeish Alexander S. , Milla Peter J. , Rey Jean , Schmitz Jacques , Shamir Raanan , Strandvik Birgitta , Troncone Riccardo , Visakorpi Jarmo 
Published: March 2018

ABSTRACTSince the conception of an idea of a few paediatric gastroenterologists in Europe to create a society for Paediatric Gastroenterology in 1967, and its foundation in 1968, half a century has passed. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) now celebrates its 50th anniversary and its utmost success in combining clinical and scientific expertise in the fields of paediatric gastroenterology, haepatology, and nutrition. To describe this success story 14 of the still living presidents of ESPGHAN recount their impressions of the steady growth of ESPGHAN with all the historical facets from their own points of view. This historical view of ESPGHAN over the last 5 decades provides personal accounts of the development of all activities and creations of this great European Society. The Society started as a small family of experts in the field into a global working open society involved in a large variety of activities within the subspecialties, becoming a leading organisation in Europe and beyond. This unique view gives also a wonderful insight into the famous clinicians and researchers from all over Europe who have helped in the growth and development of ESPGHAN. By describing all these activities and collaborations it becomes clear that this astonishing pan‐European enterprise was achieved by people who put considerable effort and time into the development of this society. Their statements serve as a historical source and reference for future evaluation of the first 50 years of ESPGHAN. In depicting different time episodes, and by assembling all the historical pieces of a puzzle together, the statements help to illustrate how a highly structured society such as ESPGHAN has evolved over the last 50 years, for what it stands for today and what is to be expected in the future.
Chapter 9. Words From Partner Societies
Authors: Golden Barbara , Stiris Tom , Panés Julián , Namazova‐Baranova Leyla , Van Gossum André , Boeing Heiner , Bhutta Zulfiqar A. , Madrazo Armando , Heubi James E. , Mouane Nezha , Fockens Paul , Koletzko Berthold 
Published: March 2018

ABSTRACTOn the occasion of the 50th anniversary of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), its close partner associations submitted comments and felicitations which are presented here. These include words from the Latin American (LASPGHAN), North American (NASPGHAN) and Panarabian Societies (PASPGHAN) and the Commonwealth Association (CAPGHAN) of Paediatric Gastroenterology, Hepatology and Nutrition, the Federation of International Societies of Paediatric Gastroenterology, Hepatology and Nutrition (FISPGHAN), the European Academy of Pediatrics (EAP), the European Pediatric Association/Union of National Pediatric Societies (EPA‐UNEPSA), the International Pediatric Association (IPA), the European Crohn's and Colitis Organisation (ECCO), European Society for Clinical Nutrition and Metabolism (ESPEN) , the Federation of European Nutrition Societies (FENS), and United European Gastroenterology (UEG).