bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antifungal Treatment and Outcome in Very Low Birth Weight Infants
Authors: Fortmann Ingmar , Hartz Annika , Paul Pia , Pulzer Ferdinand , Müller Andreas , Böttger Ralf , Proquitté Hans , Dawczynski Kristin , Simon Arne , Rupp Jan , Herting Egbert , Göpel Wolfgang , Härtel Christoph 
Published: March 2018

Background:
The diagnostic proof of fungal infection in preterm infants is difficult. Antifungal treatment (AFT) is often initiated empirically when infants with suspected infection do not improve despite broad-spectrum antibiotic therapy. It was the aim of our study to determine the rate of exposure to empirical AFT in a large cohort of very low birth weight infants (VLBWI) of the German Neonatal Network and to address associated risks and outcomes.

Methods:
The epidemiologic database consisted of n = 13,343 VLBWI born in 54 German Neonatal Network centers between 2009 and 2015. AFT was defined as number of neonates who got any dose of at least one of the following antifungal drugs: fluconazole, amphotericin B, voriconazole and caspofungin (denominator: number of infants enrolled in German Neonatal Network) for treatment (not prophylaxis) of (suspected) fungal infection. Univariate and logistic regression analyses were used to identify risk factors for exposure to AFT and associated short-term morbidities and long-term outcomes at 5-year follow-up.

Results:
In our cohort, 724 out of 13,343 (5.4%) VLBWI were exposed to empiric AFT and had a mean gestational age of 25.7 (±2.1) weeks. Forty-four out of 13,343 (0.3%) had proven bloodstream infection with Candida spp. The main risk factors for exposure to AFT were gestational age, postnatal steroid treatment, need for abdominal surgery and use of carbapenems. Notably, AFT was associated with adverse outcomes such as bronchopulmonary dysplasia [adjusted odds ratio (OR): 1.9; 95% confidence interval (CI): 1.6–2.3; P < 0.001) and retinopathy of prematurity requiring intervention (adjusted OR: 1.69; 95% CI: 1.3–2.3; P <0.001) but not mortality. In the subgroup of infants available for 5-year follow-up (n = 895), exposure to AFT was associated with a risk for cerebral palsy (adjusted OR: 2.79; 95% CI: 1.11–7.04; P = 0.04) and intelligence quotient < 85 (adjusted OR: 2.07; 95% CI: 1.01–4.28; P = 0.049).

Conclusions:
A significant proportion of VLBWI is exposed to AFT, specifically those born <26 weeks. Exposed infants were found to have a higher risk for adverse outcomes, which may reflect their significant vulnerability in general. Given the observational design of our study, it remains unclear whether potential side effects of empirical or target AFT itself contribute to adverse outcome. Future studies need to include risk-based strategies and stewardship programs to restrict the use of antifungal management in VLBWI.
Fusobacterium necrophorum as an Emerging Pathogen of Acute Mastoiditis
Authors: Gelbart Miri , Bilavsky Efraim , Chodick Gabriel , Raveh Eyal , Levy Itzhak , Ashkenazi-Hoffnung Liat 
Published: March 2018

Background:
Recent reports have reported an increase in the incidence of acute mastoiditis because of Fusobacterium necrophorum. However, the crude incidence and the specific clinical and laboratory characteristics of F. necrophorum mastoiditis in children have not been described. Our aim was to describe these features to identify high-risk patients.

Methods:
The electronic medical records of all children with acute mastoiditis at a tertiary medical center between July 2011 and December 2015 were analyzed. Using a stepwise logistic regression to identify independent risk factors for F. necrophorum, we formulated a predictive model.

Results:

F. necrophorum was identified in 13% (19/149) of mastoiditis cases with an identifiable agent. Its incidence increased 7-fold from 2.8% in 2012 to 20.4% in 2015 (P = 0.02). F. necrophorum infection had unique clinical, laboratory and prognostic features. The vast majority had complications and underwent surgical intervention. The predictive model used 4 parameters to define high-risk patients for F. necrophorum infection at admission: females, winter/spring season, prior antibiotic treatment and a C-reactive protein value >20 mg/dL (area under receiver operating characteristic curve 0.929).

Conclusions:
Clinicians should be aware of the increasing incidence of F. necrophorum mastoiditis and consider anaerobic cultures and specific anaerobic coverage in high-risk patients.
Bacterial Load and Molecular Markers Associated With Early-onset Group B Streptococcus
Authors: Seedat Farah , Brown Colin Stewart , Stinton Chris , Patterson Jacoby , Geppert Julia , Freeman Karoline , Tan Bee , Johnson Samantha Ann , Fraser Hannah , Uthman Olalekan A. , Robinson Esther R. , McCarthy Noel Denis , Clarke Aileen , Taylor-Phillips Sian 
Published: March 2018

Background:
The natural history of neonatal group B Streptococcus (GBS) is poorly understood. Little is known about the bacterial factors influencing the transmission of GBS from mother to neonate, or the development of invasive early-onset GBS disease (EOGBS) in colonized neonates. We reviewed whether bacterial load and molecular markers are associated with GBS vertical transmission and progression to EOGBS.

Methods:
We searched Medline, Embase, Cochrane and Web of Science from inception to October 10, 2016, for observational studies in English. We also hand-searched reference lists of relevant publications and experts cross-checked included studies. Two reviewers independently screened studies, extracted data and appraised the quality of included studies using the Quality in Prognosis Studies tool. We conducted random-effects meta-analyses where possible and narratively synthesized the evidence in text and tables.

Results:
Seventeen studies were included from 1107 records retrieved from electronic databases and publication references. Meta-analyses of 3 studies showed that neonates colonized by serotype III had a higher risk of developing EOGBS than serotype Ia (pooled risk ratio: 1.51, 95% confidence interval: 1.12–2.03) and serotype II (risk ratio: 1.95, 95% confidence interval: 1.10–3.45). Eleven studies showed that in heavily colonized mothers, 2–3 times more neonates were colonized, and in heavily colonized neonates, up to 15 times more neonates had EOGBS, compared with light colonization. Most evidence was published before 2000 and was at risk of bias.

Conclusions:
Acknowledging the difficulty of natural history studies, well-controlled studies are needed to assess the predictive value of pathogen subtype and heavy load; they may be useful for better-targeted prevention.
Hyperpolarization-activated cyclic nucleotide–gated channels contribute to spontaneous activity in L4 C-fiber nociceptors, but not Aβ-non-nociceptors, after axotomy of L5-spinal nerve in the rat in vivo
Authors: Djouhri Laiche , Smith Trevor , Ahmeda Ahmad , Alotaibi Mohammad , Weng Xiechuan 
Published: March 2018

Abstract
Peripheral neuropathic pain associated with partial nerve injury is believed to be driven partly by aberrant spontaneous activity (SA) in both injured and uninjured dorsal root ganglion (DRG) neurons. The underlying ionic mechanisms are not fully understood, but hyperpolarization-activated cyclic nucleotide–gated (HCN) channels which underlie the excitatory Ih current have been implicated in SA generation in axotomized A-fiber neurons after L5-spinal nerve ligation/axotomy (SNL/SNA). Here, using a modified model of SNA (mSNA) which involves, in addition to L5-SNA, loose ligation of the L4-spinal nerve with neuroinflammation-inducing chromic gut, we examined whether HCN channels also contribute to SA in the adjacent L4-neurons. Intracellular recordings from L4-DRG neurons in control rats, and L4-DRG neurons in mSNA rats were made using in vivo voltage- and current-clamp techniques. Compared with control, L4 C-nociceptors and Aβ-low-threshold mechanoreceptors (LTMs) exhibited SA 7 days after mSNA. This was accompanied, in C-nociceptors, by a significant increase in Ih amplitude, the percentage of Ih-expressing neurons, and Ih activation rate. Hyperpolarization-activated cyclic nucleotide–gated channel blockade with ZD7288 (10 mg/kg, intravenously) suppressed SA in C-nociceptors, but not Aβ-LTMs, and caused in C-nociceptors, membrane hyperpolarization and a decrease in Ih activation rate. Furthermore, intraplantar injection of ZD7288 (100 μM) was found to be as effective as gabapentin (positive control) in attenuating cold hypersensitivity in mSNA rats. These findings suggest that HCN channels contribute to nerve injury–induced SA in L4 C-nociceptors, but not Aβ-LTMs, and that ZD7288 exerts its analgesic effects by altering Ih activation properties and/or causing membrane hyperpolarization in L4 C-nociceptors.
Bivalent ligand MCC22 potently attenuates nociception in a murine model of sickle cell disease
Authors: Cataldo Giuseppe , Lunzer Mary M. , Olson Julie K. , Akgün Eyup , Belcher John D. , Vercellotti Gregory M. , Portoghese Philip S. , Simone Donald A. 
Published: March 2018

AbstractSickle cell disease (SCD) is a chronic inflammatory disorder accompanied by chronic pain. In addition to ongoing pain and hyperalgesia, vaso-occlusive crises–induced pain can be chronic or episodic. Because analgesics typically used to treat pain are not very effective in SCD, opioids, including morphine, are a primary treatment for managing pain in SCD but are associated with many serious side effects, including constipation, tolerance, addiction, and respiratory depression. Thus, there is a need for the development of novel treatments for pain in SCD. In this study, we used the Townes transgenic mouse model of SCD to investigate the antinociceptive efficacy of the bivalent ligand, MCC22, and compared its effectiveness with morphine. MCC22 consists of a mu-opioid receptor agonist and a chemokine receptor-5 (CCR5) antagonist that are linked through a 22-atom spacer. Our results show that intraperitoneal administration of MCC22 produced exceptionally potent dose-dependent antihyperalgesia as compared to morphine, dramatically decreased evoked responses of nociceptive dorsal horn neurons, and decreased expression of proinflammatory cytokines in the spinal cord. Moreover, tolerance did not develop to its analgesic effects after repeated administration. In view of the extraordinary potency of MCC22 without tolerance, MCC22 and similar compounds may vastly improve the management of pain associated with SCD.
Wind-up in lamina I spinoparabrachial neurons: a role for reverberatory circuits
Authors: Hachisuka Junichi , Omori Yu , Chiang Michael C. , Gold Michael S. , Koerber H. Richard , Ross Sarah E. 
Published: March 2018

Abstract
Wind-up is a frequency-dependent increase in the response of spinal cord neurons, which is believed to underlie temporal summation of nociceptive input. However, whether spinoparabrachial neurons, which likely contribute to the affective component of pain, undergo wind-up was unknown. Here, we addressed this question and investigated the underlying neural circuit. We show that one-fifth of lamina I spinoparabrachial neurons undergo wind-up, and provide evidence that wind-up in these cells is mediated in part by a network of spinal excitatory interneurons that show reverberating activity. These findings provide insight into a polysynaptic circuit of sensory augmentation that may contribute to the wind-up of pain's unpleasantness.
Factors Associated With Self-Reported Concussion History in Middle School Athletes
Authors: Terry Douglas P. , Wojtowicz Magdalena , Cook Nathan E. , Maxwell Bruce A. , Zafonte Ross , Seifert Tad , Silverberg Noah D. , Berkner Paul D. , Iverson Grant L. 
Published: March 2018

Objective:
Identifying personal characteristics associated with sustaining a concussion is of great interest, yet only a few have examined this in children. The purpose of this study was to examine the association between sex, neurodevelopmental disorders, health history, and lifetime history of self-reported concussion in 12- and 13-year-old athletes.

Design:
Cross-sectional study.

Setting:
Middle schools.

Participants:
Participants were 1744 twelve- and thirteen-year-old student athletes who completed preseason Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) testing, including a self-report questionnaire about previous concussions, developmental diagnoses, and previous medical treatment.

Independent Variables:
Age, sex, attention-deficit/hyperactivity disorder (ADHD), learning disabilities (LDs), and previous treatment for migraine.

Main Outcome Measures:
Self-reported history of concussion.

Results:
A minority of athletes (13.7%) reported previous concussions (1 concussion, n = 181; 2 concussions, n = 41; and 3+ concussions, n = 17). A small proportion reported a history of ADHD (4.4%), LD (2.8%) or migraine treatment (4.0%). Higher rates of self-reported previous concussions were associated with male sex [16.9% vs 9.1%; χ2(1) = 21.47, P < 0.001] and previous migraine treatment [31.9% vs 13.0%; χ2(1) = 20.08, P < 0.001]. There were no differences in self-reported concussion history between 12- and 13-year olds (P = 0.18) and those with/without ADHD (P = 0.41) or LDs (P = 0.06). The overall logistic regression model was statistically significant [χ2(5) = 42.01, P < 0.001] but explained only 4.3% of the variance. Previous treatment for migraine [P < 0.001, Exp(B) = 3.30] and male sex [P < 0.001, Exp(B) = 2.06] were independently associated with a self-reported concussion history, whereas age, LD, and ADHD were not (P's > 0.05).

Conclusions:
Male sex and previous migraine treatment were associated with higher rates of self-reported previous concussions in both independent and multivariate models in middle school athletes, whereas age, ADHD, and LDs were not.
Orthopedic Injuries in Professional Surfers: A Retrospective Study at a Single Orthopedic Center
Authors: Hohn Eric , Robinson Sean , Merriman Jarrad , Parrish Robin , Kramer Warren 
Published: March 2018

Background:
Literature regarding surfing injuries is scarce and most studies report a high number of minor injuries. Recent literature suggests that musculoskeletal injuries are more common than previously reported. In the mid 2000s, competitive surfing has seen an increase in aerial maneuvers, as they have become more highly rewarded by the judging panel, which may be contributing to a change in injury patterns. Our goal was to evaluate orthopedic injuries in professional surfers.

Hypothesis:
Orthopedic injuries in professional surfers are diverse and have evolved with skill and technology.

Study Design:
Retrospective observational study.

Level of Evidence:
Level 4 Case Series.

Methods:
Medical records of professional surfers from a single orthopedic center between 1991 and 2016 were reviewed. Injuries sustained while surfing and chronic injuries related to surfing were included. Site of injury, diagnosis, and treatment were recorded along with demographic data.

Results:
In total, 163 injuries in 86 athletes were recorded. The median injury age was 28.5 years (range 12-62 years) and 92.6% of patients were male. The most frequently injured body parts were the knee (28.2%), ankle (22.1%), and shoulder (19%). Most knee injuries were of the medial collateral ligament at 49%, with 75% of ankle injuries being sprains, and in shoulder, 48% had instability, 42% had a rotator cuff tear, and 35% had a superior anterior–posterior labral tear. Lower extremity injuries primarily affected the surfers' back leg (72.5%). In all, 34.6% of all injuries required surgical intervention and involved shoulder injuries most the time.

Conclusions:
The most common orthopedic injuries in professional surfers involve the knee, ankle, shoulder, hip, and back. Surfers' rear extremities were preferentially injured which is the extremity responsible for power and torque. Shoulder injuries increased the probability of an operative intervention. Last, overuse injuries (femoral-acetabular impingement, rotator cuffs) occurred in the older surf population compared with more acute injuries (ankle sprains/fractures, anterior cruciate ligament tears) which is also consistent with time to surgery.
p16 Immunohistochemistry Is Not Always Required For Accurate Diagnosis of Grade 2 Squamous Intraepithelial Lesions
Authors: Sun Lulu , Zhang Lingxin , Krigman Hannah R. , Hagemann Ian S. 
Published: March 2018

ObjectivesPreinvasive squamous neoplasms of the lower genital tract are currently classified using a two-tier system (high- or low-grade squamous intraepithelial lesion) as directed by the Lower Anogenital Squamous Terminology (LAST) guidelines but may also be subclassified as intraepithelial neoplasia grade 1 (−IN1), −IN2, or −IN3. The LAST recommended that all diagnoses of −IN2 be supported by immunohistochemistry (IHC) for p16. We examined whether p16 and Ki-67 IHC are necessary to diagnose −IN2 when the lesion has obvious high-grade histology.Materials and Methodsp16 and Ki-67 IHC were performed prospectively and retrospectively on vulvar, vaginal, and cervical specimens with an initial diagnosis of −IN2 based on hematoxylin and eosin morphology, and a final diagnosis was made after consensus review.ResultsFive of 46 prospective and four of 38 retrospective cases were p16 negative. The diagnosis of −IN2 was maintained in eight of these nine cases because of compelling high-grade squamous intraepithelial lesion histology. Overall, p16 and Ki-67 IHC altered the −IN2 diagnosis to a lower grade in only one of 84 cases (1.2%, <0.01%–7.1%). Moreover, p16 was positive in all cases where the preanalytic impression was of −IN2/3 (13/13).Conclusionsp16 IHC lacks utility in cases of morphologically obvious −IN2, because the stain is positive in most cases. The LAST recommendation to use p16 IHC to support all diagnoses of −IN2 will result in performing the immunostain in many circumstances where it is not medically necessary. Among cases that are p16 negative, many have compelling high-grade morphology. The LAST perspective that the stain trumps histology may allow false-negative IHC results to prevail.
The aVOR App Increases Medical Students’ Competence in Treating Benign Paroxysmal Positional Vertigo (BPPV)
Authors: Dlugaiczyk Julia , Thiemer Michael , Neubert Christian , Schorn Bianca Anna , Schick Bernhard 
Published: March 2018

Hypothesis:
Implementation of the “aVOR app” into teaching courses at medical school enhances students’ satisfaction with the course and increases their competence in treating benign paroxysmal positional vertigo (BPPV).

Background:
BPPV is often underdiagnosed and left untreated. One problem in teaching the management of BPPV to health care professionals is the lack of simulation-based training tools. The aVOR app (aVOR = angular vestibulo-ocular reflex) works as a bionic labyrinth that simulates the activation of the semicircular canals by rotational acceleration and the resulting vestibular evoked eye movements.

Methods:
In this prospective, randomized, controlled study, medical students at a university hospital were randomly assigned to two kinds of small instructional groups. Students of the control group (n = 67) practiced diagnostic and therapeutic maneuvers for BPPV on each other, while the participants of the study group (n = 46) used the aVOR app as a virtual patient in addition. At the end of the term, students were asked to arrange the steps of the canalith repositioning procedure in the correct order in a written test.

Results:
Quality of the teaching media was rated significantly better in the aVOR group (two-sided Mann–Whitney test: P < 0.00001). Significantly more students of the aVOR group than the control group arranged the steps of the canalith repositioning procedure correctly in the final exam (56.3% versus 25.9%, Fisher's exact test: P = 0.006).

Conclusion:
Implementation of the aVOR app as a virtual patient into small instructional courses is well adopted by medical students and increases their competence in treating BPPV.
The relationship between urinary genistein levels and serum alanine aminotransferase levels in adults in the USA: National Health and Nutrition Examination Survey 1999–2010
Authors: Marcelo Carolyn , Warwick Melissa , Marcelo Catherine , Malik Manpreet , Qayyum Rehan 
Published: March 2018

Background
Genistein, a phytoestrogen with similarities to female sex hormones, has been shown to protect against oxidative stress and fibrosis in nonalcoholic fatty liver injury in animal studies. However, few studies have examined genistein’s effects on liver function in humans.

Participants and methods
We analyzed data from the National Health and Nutrition Examination Survey from 1999 to 2010. Individuals younger than 21 years, with viral hepatitis, or with serum alanine aminotransferase (ALT) at the extremes of distribution (5% on each extreme) were excluded. Urinary genistein was normalized by urinary creatinine levels. The relationship between normalized urinary genistein (nUG) and serum ALT was examined using linear regression models with and without adjustment for potential confounders, and the differential effect of sex was examined using an interaction term.

Results
Of the 9864 participants, 52% were female, 50% were White, 24% were elderly, 36% had hypertension, 12% had diabetes, and 8.1% were heavy alcohol drinkers. Serum ALT was significantly lower in the highest quartile compared with the lowest quartile of nUG (22.3 vs. 23.5 U/l; P<0.001). In adjusted models, individuals in the highest quartile had 0.75 U/l lower ALT levels than those in the lowest quartile (P=0.02). We found a significant difference in ALT levels between the lowest and highest quartiles of nUG in males, but not in females (difference in differences=1.77 U/l, interaction P=0.04).

Conclusion
We found a statistically significant association between higher nUG and lower serum ALT in males, but not in females. The sex-specific role of genistein in mitigating liver disease merits further study.
Oregon Medicaid Expenditures After the 2014 Affordable Care Act Medicaid Expansion: Over-time Differences Among New, Returning, and Continuously Insured Enrollees
Authors: Springer Rachel , Marino Miguel , O’Malley Jean P. , Lindner Stephan , Huguet Nathalie , DeVoe Jennifer E. 
Published: March 2018

Background:
There is interest in assessing health care utilization and expenditures among new Medicaid enrollees after the 2014 Medicaid expansion. Recent studies have not differentiated between newly enrolled individuals and those returning after coverage gaps.

Objectives:
To assess health care expenditures among Medicaid enrollees in the 24 months after Oregon’s 2014 Medicaid expansions and examine whether expenditure patterns were different among the newly, returning, and continuously insured (CI).

Research Design:
Retrospective cohort study using inverse-propensity weights to adjust for differences between groups.

Subjects:
Oregon adult Medicaid beneficiaries insured continuously from 2014 to 2015 who were either newly, returning, or CI.

Measures:
Monthly expenditures for inpatient care, prescription drugs, total outpatient care, and subdivisions of outpatient care: emergency department, dental, mental and behavioral health, primary care, and specialist care.

Results:
After initial increases, newly and returning insured (RI) outpatient expenditures dropped below CI. Expenditures for emergency department and dental services among the RI remained higher than among the newly insured. Newly insured mental and behavioral health, primary care, and specialist expenditures plateaued higher than RI. Prescription drug expenditures increased over time for all groups, with CI highest and RI lowest. All groups had similar inpatient expenditures over 24 months post-Medicaid expansion.

Conclusions:
Our findings reveal that outpatient expenditures for new nonpregnant, non–dual-eligible Oregon Medicaid recipients stabilized over time after meeting pent-up demand, and prior insurance history affected the mix of services that individuals received. Policy evaluations should consider expenditures over at least 24 months and should account for enrollees’ prior insurance histories.