bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Efficacy of Ceftazidime–Avibactam in the Treatment of Children ≥3 Months to <18 Years With Complicated Urinary Tract Infection: Results from a Phase 2 Randomized, Controlled Trial
Authors: Bradley John S. , Roilides Emmanuel , Broadhurst Helen , Cheng Karen , Huang Li-Min , MasCasullo Veronica , Newell Paul , Stone Gregory G. , Tawadrous Margaret , Wajsbrot Dalia , Yates Katrina , Gardner Annie 
Published: July 2019

Background:
Ceftazidime–avibactam is effective and well tolerated in adults with complicated urinary tract infection (cUTI), but has not been evaluated in children with cUTI.

Methods:
This single-blind, multicenter, active-controlled, phase 2 study (NCT02497781) randomized children ≥3 months to <18 years with cUTI (3:1) to receive intravenous (IV) ceftazidime–avibactam or cefepime for ≥72 hours, with subsequent optional oral switch. Total treatment duration was 7–14 days. Primary objective was assessment of safety. Secondary objectives included descriptive efficacy and pharmacokinetics. A blinded observer determined adverse event (AE) causality and clinical outcomes up to the late follow-up visit (20–36 days after the last dose of IV/oral therapy).

Results:
In total, 95 children received ≥1 dose of IV study drug (ceftazidime–avibactam, n = 67; cefepime, n = 28). The predominant baseline Gram-negative uropathogen was Escherichia coli (92.2%). AEs occurred in 53.7% and 53.6% patients in the ceftazidime–avibactam and cefepime groups, respectively. Serious AEs occurred in 11.9% (ceftazidime–avibactam) and 7.1% (cefepime) patients. One serious AE (ceftazidime–avibactam group) was considered drug related. In the microbiologic intent-to-treat analysis set, favorable clinical response rates >95% were observed for both groups at end-of-IV and remained 88.9% (ceftazidime–avibactam) and 82.6% (cefepime) at test-of-cure. Favorable per-patient microbiologic response at test-of-cure was 79.6% (ceftazidime–avibactam) and 60.9% (cefepime).

Conclusions:
Ceftazidime–avibactam was well tolerated in children with cUTI, with a safety profile consistent with that of adults with cUTI and of ceftazidime alone, and appeared effective in children with cUTI due to Gram-negative pathogens.
Asymptomatic Pharyngeal Carriage of Kingella kingae Among Young Children in Vancouver, British Columbia, Canada
Authors: Masud Shazia , Greenman Janet , Mulpuri Kishore , Hasan Mohammad R. , Goldfarb David M. , Tilley Peter , Gadkar Vijay J. , Al-Rawahi Ghada N. 
Published: July 2019

Background:

Kingella kingae has emerged as a significant cause of osteoarticular infections in young children. Pharyngeal colonization is considered a prerequisite for invasive K. kingae infection. We conducted a prospective study to estimate the prevalence of pharyngeal carriage of K. kingae among healthy young children in Vancouver.

Methods:
From March 2016 to May 2017, children between 6 and 48 months of age visiting British Columbia Children’s Hospital outpatient clinics for noninfectious causes were included in the study. Another set of participants was enrolled from a day-care center located at British Columbia Children’s Hospital. A single-throat swab was collected after obtaining consent from parent/guardian. The samples were stored at −70°C and tested using an in-house developed real-time polymerase chain reaction assay. Epidemiologic characteristics and risk factors for K. kingae colonization were collected via a study questionnaire.

Results:
A total of 179 children were enrolled in the study, but only 174 samples were eligible for testing. Of the 174 samples, 5 had indeterminate results and the remaining 169 samples were negative by K. kingae polymerase chain reaction. The median age of participants was 23 months. About 36% of children were attending day care and had another sibling <5 years of age. Previous history of cold symptoms and antibiotic use was reported in 42% and 12%, respectively.

Conclusions:
The results of our study showed no prevalence of asymptomatic pharyngeal carriage of K. kingae in young children in Vancouver. Additional multicenter studies may help to understand the differences in pharyngeal carriage rate among healthy children.
A Randomized, Double-blind, Active-controlled Phase III Trial of a Cell Culture-derived Quadrivalent Inactivated Influenza Vaccine in Healthy South Korean Children and Adolescents 6 Months to 18 Years of Age
Authors: Eun Byung Wook , Lee Taek Jin , Lee Jina , Kim Ki Hwan , Kim Dong Ho , Jo Dae Sun , Shin Sun Hee , Kim Hun , Kim Kyung-Ho , Kim Yun-Kyung 
Published: July 2019

Background:
Cell culture-derived influenza vaccines have several important advantages over egg-based influenza vaccines. The quadrivalent influenza vaccine may offer broader protection against seasonal influenza than trivalent influenza vaccine by containing 1 more B strain. The purpose of this study was to evaluate the immunogenicity and safety of NBP607-QIV, a novel cell culture-derived inactivated quadrivalent influenza vaccine (cIIV4), in children and adolescents.

Methods:
This phase III, randomized, double-blind, multicenter trial in children/adolescents (6 mo to 18 yr) was conducted in South Korea during 2014–2015 season. Subjects were randomized 4:1 to receive either NBP607-QIV or control inactivated trivalent influenza vaccine. Hemagglutination inhibition antibody titers were assessed in prevaccination and 28 days postvaccination sera. Safety data were collected for up to 6 months postvaccination.

Results:
A total of 454 participants completed the study. Three-hundred sixty-six subjects received cIIV4 and 88 subjects received inactivated trivalent influenza vaccine. Overall, NBP607-QIV met the immunogenicity criteria of Committee for Medicinal Products for Human Use for each of the 4 strains. Between the NBP607-QIV and control groups, immunogenicity endpoints were comparable. Participants younger than 3 years of age had lower immunologic responses to 2 influenza B strains in both NBP607-QIV and control group. No deaths, vaccine-related serious adverse events (AEs) or withdrawals because of AEs were reported. The solicited AEs reported were generally of mild intensity.

Conclusions:
NBP607-QIV, a novel cIIV4, showed good immunogenicity to all 4 influenza strains and had tolerable safety profiles in children and adolescents. Moreover, NBP607-QIV was more immunogenic against influenza B compared with the control, an egg-based subunit vaccine.
Linaclotide treatment reduces endometriosis-associated vaginal hyperalgesia and mechanical allodynia through viscerovisceral cross-talk
Authors: Ge Pei , Ren Jingmei , Harrington Andrea M. , Grundy Luke , Castro Joel , Brierley Stuart M. , Hannig Gerhard 
Published: July 2019

Abstract
Endometriosis, an estrogen-dependent chronic inflammatory disease, is the most common cause of chronic pelvic pain. Here, we investigated the effects of linaclotide, a Food and Drug Administration–approved treatment for IBS-C, in a rat model of endometriosis. Eight weeks after endometrium transplantation into the intestinal mesentery, rats developed endometrial lesions as well as vaginal hyperalgesia to distension and decreased mechanical hind paw withdrawal thresholds. Daily oral administration of linaclotide, a peripherally restricted guanylate cyclase-C (GC-C) agonist peptide acting locally within the gastrointestinal tract, increased pain thresholds to vaginal distension and mechanical hind paw withdrawal thresholds relative to vehicle treatment. Furthermore, using a cross-over design, administering linaclotide to rats previously administered vehicle resulted in increased hind paw withdrawal thresholds, whereas replacing linaclotide with vehicle treatment decreased hind paw withdrawal thresholds. Retrograde tracing of sensory afferent nerves from the ileum, colon, and vagina revealed that central terminals of these afferents lie in close apposition to one another within the dorsal horn of the spinal cord. We also identified dichotomizing dual-labelled ileal/colon innervating afferents as well as colon/vaginal dual-labelled neurons and a rare population of triple traced ileal/colon/vaginal neurons within thoracolumbar DRG. These observations provide potential sources of cross-organ interaction at the level of the DRG and spinal cord. GC-C expression is absent in the vagina and endometrial cysts suggesting that the actions of linaclotide are shared through nerve pathways between these organs. In summary, linaclotide may offer a novel therapeutic option not only for treatment of chronic endometriosis-associated pain, but also for concurrent treatment of comorbid chronic pelvic pain syndromes.
Preoperative breast volume evaluation of one-stage immediate breast reconstruction using three-dimensional surface imaging and a printed mold
Authors: Chen Keng , Feng Chin-Jung , Ma Hsu , Hsiao Fu-Yin , Tseng Ling-Ming , Tsai Yi-Fang , Lin Yen-Shu , Huang Li-Ying , Yu Wen-Chan , Perng Cherng-Kang 
Published: July 2019

Background:
Accurate assessment of breast volume is an essential component of preoperative planning in one-stage immediate breast reconstruction (IBR) for achieving breast symmetry and a satisfactory cosmetic outcome. In this study, we compared breast volume estimation using three-dimensional (3D) surface imaging with magnetic resonance imaging (MRI) to determine the accuracy of breast volume measurements. Further, a 3D printing mold for facilitating autologous breast reconstruction intraoperatively is described.

Methods:
Patients scheduled to therapeutic or prophylactic mastectomy with one-stage IBR, either by autologous tissue transfer or direct implant, from 2016 to 2019, were enrolled in this study. 3D surface image and MRI were performed to evaluate breast volume and shape. The results were validated by the water displacement volume of the mastectomy specimen. Finally, a 3D printing mold was designed for breast reconstruction with autologous tissue.

Results:
Nineteen women who were scheduled to have 20 mastectomies (18 unilateral and one bilateral) were included. There was a strong linear association between breast volume measured using the two different methods and water displacement of mastectomy specimens when a Pearson correlation was used (3D surface image: r = 0.925, p < 0.001; MRI: r = 0.915, p < 0.001). Bland-Altman plots demonstrated no proportional bias between the assessment methods. The coefficient of variation was 52.7% for 3D surface imaging and 59.9% for MRI. The volume of six breasts was evaluated by both measurements and the intraclass correlation coefficient was 0.689 for 3D surface image (p = 0.043) and 0.743 for MRI (p = 0.028).

Conclusion:
Using 3D surface image to evaluate breast shape and volume is a quick, effective, and convenient method. The accuracy, reproducibility, and reliability of 3D surface imaging were comparable with MRI in our study. In addition, 3D-printed molds can achieve better symmetry and aesthetic outcomes in immediate autologous breast reconstructions.
CD4+ T Cell Count, Sleep, Depression, and Anxiety in People Living With HIV: A Growth Curve Mixture Modeling
Authors: Shi Yirong , Yang Chongming , Xu Liumei , He Yun , Wang Hui , Cao Jing , Wen Min , Chen Weimei , Wu Baohong , Chen Suqing , Chen Huiwen 
Published: July 2019

Abstract
We investigated changes in CD4+ T cell counts related to sleep quality, depression, anxiety, and sociodemographic variables in heterogeneous groups of people living with HIV in a 6-month prospective study. Our longitudinal study involved 247 ambulatory patients living with HIV and using antiretroviral therapy. Sleep quality, anxiety, depression, and CD4+ T cell counts were assessed three times at 3-month intervals. Growth curve mixture modeling was conducted to explore changes over time. A two-class mixture model with logarithmic change pattern fit the data best. For the majority of the sample (89.1%), anxiety, depression, and sleep quality did not change when CD4+ T cells increased. For a small proportion of the sample (11.9%), sleep quality, anxiety, and depression deteriorated when CD4+ T cells decreased. Marital status and alcohol use affected the classification significantly. Health care professionals should provide relevant services to people living with HIV with decreasing CD4+ T cell counts.
Perspective of neo-adjuvant/conversion and adjuvant therapy for pancreatic neuroendocrine tumors
Authors: Chen Luohai , Chen Jie 
Published: July 2019

Abstract
The incidence rate of pancreatic neuroendocrine tumors (panNET) is increasing continuously. Curative resection was the primary treatment choice for panNET. However, till now, there were few studies concerning neo-adjuvant/conversion and adjuvant therapy for panNET. In this article, we reviewed the currently widely used medical treatments for advanced panNET. It seemed that peptide receptor radionuclide therapy (PRRT), chemotherapy (temozolomide-based or streptozocin-based) and sunitinib might be more effective to induce tumor shrinkage in panNET and therefore, these treatments could be tried in panNET when neo-adjuvant/conversion therapy was considered. As for adjuvant therapy, it was of great importance to identify patients with high risks of recurrence after curative surgery and previous studies found that high ki-67 index, large tumor size, lymphatic metastasis and perineural/vascular invasion, and so on, were correlated with early recurrence of panNET. Since PRRT and chemotherapy were more cytotoxic, these two kinds of therapies might be worth trying as adjuvant therapies in patients with high risks of recurrence after curative resection of panNET. Admittedly, no studies discussed in this review directly investigated neo-adjuvant/conversion and adjuvant therapy for panNET. Therefore, more prospective studies were still warranted.
Incidence and Risk of Various Disorders of the External Ear in Patients With Hearing Aids Treated in ENT Practices in Germany
Authors: Seidel David Ulrich , Park Jonas Jae-Hyun , Sesterhenn Andreas M. , Kostev Karel 
Published: July 2019

Objective:The aim of the study was to investigate the relationship between the presence of a hearing aid (HA) and the occurrence of various disorders of the external ear, using data from ear, nose, and throat (ENT) practices in Germany from a nationwide, representative practice database.Methods:In the period between 2012 and 2016, the incidences of disorders of the external ear (ICD-10 groups H60 and H61) in patients with HA prescriptions were compared retrospectively with a control group without HA prescriptions (1:1 matching).Results:A total of 20,127 patients with HA prescriptions were compared with 20,127 controls. The highest 12-month incidences (HA vs. controls) were determined for “Impacted cerumen” (H61.2) (16.5% vs. 4.2%), “Unspecified otitis externa” (H60.9) (2.6% vs. 1.2%) and "Acute noninfective otitis externa" (H60.5) (2.3% vs. 0.7%). The most significant risk increases for HA wearers were found for “Abscess of external ear" (H60.0, OR 10.03), “Other otitis externa" (H60.8, OR 6.00), and “Impacted cerumen" (H61.2, OR 4.55). A smaller risk increase was found for “Cholesteatoma of external ear" (H60.4, OR 2.26), among others.Conclusion:In HA wearers, the risk of developing almost all of the diagnoses reviewed is significantly increased, especially for external auditory canal (EAC) furuncle, chronic otitis externa, and impacted cerumen. This study provides the first epidemiological evidence for HA as a risk factor for the rare EAC cholesteatoma.
Vestibular Schwannoma Tumor Size Is Associated With Acute Vestibular Symptoms After Gamma Knife Therapy
Authors: Lee Daniel Y. , Lerner David K. , Naples James G. , Brant Jason A. , Bigelow Douglas C. , Lee John Y. K. , Alonso-Basanta Michelle , Ruckenstein Michael J. 
Published: July 2019

Objective:
To assess how pretreatment vestibular schwannoma (VS) tumor characteristics are associated with vestibular symptoms after gamma knife (GK) surgery.

Study Design:
Retrospective chart review of patients undergoing GK treatment for VS at our institution from 2005 to 2018.

Setting:
Academic tertiary referral center.

Patients:
Patients receiving primary GK surgery for vestibular schwannomas with at least 6 months of follow up. Patients with neurofibromatosis 2 or previous surgery were excluded.

Main Outcome Measures:
The presence of posttreatment vestibular symptoms within 6 months after GK. Clinical records were assessed for pretreatment tumor, patient, and treatment characteristics that impacted posttreatment symptoms.

Results:
All patients received radiation doses between 12 and 13 Gy. Of 115 patients, the average age was 60. Thirty-seven (32%) patients developed vestibular symptoms within 6 months post-GK, and 18 patients were referred for vestibular rehabilitation. Ten of 13 patients undergoing vestibular rehabilitation reported improvement. Overall, 112 patients had tumor measurements. Pretreatment tumors were significantly smaller for patients with acute vestibular symptoms (mean 1.43 cm versus 1.71 cm, p = 0.007). On multivariate analysis, smaller tumor size (p = 0.009, odds ratio [OR] = 0.29, 95% confidence interval [CI] [0.12–0.73]) was significantly associated with vestibular symptoms within 6 months of GK. Patients with tumors less than 1.6 cm were more likely to receive referrals for vestibular rehabilitation within 6 months posttreatment (25% versus 9.4%, p = 0.026, OR = 3.22, 95% CI [1.00, 11.32]).

Conclusions:
Smaller vestibular schwannomas were significantly associated with higher rates of post-GK vestibular symptoms. Pretreatment tumor size may be used to counsel patients on the likelihood of post-GK vestibular symptoms and vestibular rehabilitation.
Density of Macrophages Immunostained With Anti-iba1 Antibody in the Vestibular Endorgans After Cochlear Implantation in the Human
Authors: Okayasu Tadao , O’Malley Jennifer T. , Nadol Joseph B. 
Published: July 2019

Hypothesis:
Cochlear implantation may result in an increase in the density of macrophages in vestibular endorgans in the human.

Background:
Vestibular symptoms are a common complication of cochlear implantation. In a previous study, we demonstrated histological evidence of a foreign-body response caused by silicon and platinum in the human cochlea following cochlear implantation. The objective of the current study was to seek evidence of a possible immune response in vestibular endorgans after cochlear implantation.

Methods:
The density of macrophages immunostained with anti-Iba1 antibody in the vestibular endorgans (lateral and posterior semicircular canals, utricle and saccule) in 10 human subjects who had undergone unilateral cochlear implantation was studied by light microscopy. The densities of macrophages in the neuroepithelium, subepithelial stroma, and among dendritic processes in the mid-stromal zone in four vestibular endorgans in the implanted and the opposite unimplanted ears were compared. The distributions of macrophage morphology (amoeboid, transitional and ramified) were also compared.

Results:
The densities of macrophages in implanted ears in four vestibular endorgans were significantly greater than that in opposite unimplanted ears except in the subepithelial zone of the utricle and posterior semicircular canal. In contrast to the neuroepithelium, the subepithelial distribution of amoeboid macrophages in implanted ears was significantly less than in unimplanted ears.

Conclusion:
An increase in the density of macrophages in four vestibular endorgans after implantation was demonstrated. The transition among phenotype of macrophages suggested possible migration of amoeboid macrophages from the subepithelial stroma into the neuroepithelium.
Hearing and Quality of Life Over Time in Vestibular Schwannoma Patients: Observation Compared to Stereotactic Radiosurgery
Authors: Miller Lauren E. , Brant Jason A. , Chen Jinbo , Kaufman Adam C. , Ruckenstein Michael J. 
Published: July 2019

Objective:
To examine quality of life changes for patients with vestibular schwannoma (VS) undergoing observation or stereotactic radiosurgery (SRS).

Study Design:
Retrospective review.

Setting:
Academic medical center.

Patients:
Patients with VS who underwent observation or SRS and had at least two audiograms and Penn Acoustic Neuroma Quality of Life (PANQOL) surveys, a quality of life survey for patients with VS.

Interventions:
SRS or observation.

Main Outcome Measures:
Pure-tone average (PTA), speech discrimination score (SDS), PANQOL score; controlling for tumor size, baseline hearing, and other factors.

Results:
One hundred twenty-three patients met inclusion criteria: 89 underwent observation and 34 SRS. There was no significant difference in the rate of decline measured by PTA (PTA worsened at a rate of 0.25 dB/yr more in the observation group compared with the SRS group, p = 0.77) and SDS (SDS worsened at a rate of 2.1%/yr more in the SRS group compared with the observation group, p = 0.82). Kaplan–Meier analysis demonstrated the SRS group had a higher probability to progress to class D hearing over observation (hazard ratio 7.1, p = 0.005). The rate of change of the SRS PANQOL scores was significantly improved in the total (p = 0.005) and hearing (p = 0.04) domain score compared with observation. However, both groups regress to a similar PANQOL total and hearing domain score over time.

Conclusion:
PANQOL scores were higher at baseline in the observation group than in the SRS group. However, over time, PANQOL scores in the observation group decreased while PANQOL scores in the SRS group increased, resulting in PANQOL scores that were equivalent by the end of follow-up.
The Influence of Metabolic Syndrome on the Prognosis of Idiopathic Sudden Sensorineural Hearing Loss
Authors: Zhang Yanni , Jiang Qian , Wu Xuewen , Xie Shaobing , Feng Yong , Sun Hong 
Published: July 2019

Objectives:
We aimed to verify the hypothesis that metabolic syndrome (MetS) and its components affect the prognosis of idiopathic sudden sensorineural hearing loss (ISNNHL).

Study Design:
A retrospective cohort study.

Setting:
Tertiary otology referral center.

Patients:
We divided patients who were diagnosed with ISSNHL between January 2015 and January 2018 into a MetS group and a Non-MetS group according to the diagnostic criteria of MetS.

Interventions:
We diagnosed ISSNHL patients by using pure-tone audiometry and treated them with oral steroids, blood flow promoting agents, and hyperbaric oxygen therapy.

Main Outcome Measures:
We used multivariate logistic analysis to identify prognostic factors of ISSNHL.

Results:
The MetS group comprised 94 patients, and the Non-MetS group comprised 162 subjects. Despite the rate of hypertension, diabetes mellitus, hyperlipidemia, and BMI, no significant difference was observed between the two groups (p > 0.05). The rates of complete recovery and partial recovery of the MetS group were significantly lower than those of the Non-MetS group (p < 0.05). According to the multivariate analysis, MetS was significantly correlated with a poor prognosis (OR = 2.912, p = 0.008), and the OR increased with an increase in the number of MetS components. Late onset of treatment, high initial hearing threshold, and presence of diabetes mellitus and hyperlipidemia were associated with a poor prognosis (p < 0.05).

Conclusions:
The presence of MetS may negatively affect the recovery of Chinese patients with ISSNHL, and the prognosis was poorer with an increase in the number of MetS components. Early onset of treatment, low initial hearing threshold and absence of diabetes mellitus, and hyperlipidemia are associated with favorable hearing recovery.