bluuebunny/crossref_metadata_2025 huggingface dataset:
The law applicable to third-party effects of assignment and the conflict rules for insolvency according to EU law
Authors: Heinze Christian , Warmuth Cara
Published: January 2020

In March 2018, the European Commission issued its proposal for a regulation on the law applicable to third-party effects of assignments of claims, aiming to put an end to the ongoing debate on this issue and the legal uncertainty associated with it. On the basis of the Commission’s decision in favour of the application of the law of the assignor’s habitual residence, this article discusses the consequences of the Proposal under European Union (EU) insolvency law. For that purpose, the coherence of the Proposal with the Insolvency Regulation will be examined, first in general and then in more detail. The analysis comes to the result that the Commission’s objective of aligning the Proposal with the legal framework of the Insolvency Regulation has predominantly been well achieved. The authors point out remaining minor inaccuracies that may be clarified in the further legislative process or by later case law. It is concluded that, from the perspective of international insolvency law, the proposed uniform conflict-of-laws rule at the EU level offers a good opportunity to promote legal certainty with regard to cross-border assignments of claims in the future.
James Robert Alfano, A Giant in Phytopathogenic Bacteria Effector Biology
Authors: Collmer Alan
Published: January 2020

The worldwide molecular plant-microbe interactions research community was significantly diminished in November 2019 by the death of James “Jim” Robert Alfano at age 56. Jim was a giant in our field, who gained key insights into plant pathogenesis using the model bacterial pathogen Pseudomonas syringae. As a mentor, collaborator, and, above all, a friend, I know Jim’s many dimensions and accomplishments and, sadly, the depth of loss being felt by the many people around the world who were touched by him. In tracing the path of Jim’s career, I will emphasize the historical context and impact of his advances and, finally, the essence of the person we will so miss.
An oral drug for chronic lymphocytic leukemia
Authors: Koehler Amber
Published: January 2020

Ibrutinib is a new first-line drug for treating chronic lymphocytic leukemia (CLL), and could change frontline treatment of CLL from traditional IV chemotherapy to oral targeted therapy. Lymphocytosis often worsens with initiation of ibrutinib, but typically resolves over 6 to 18 months. Though patients generally tolerate ibrutinib well, the drug can cause adverse reactions including hypertension, atrial fibrillation, bleeding, and infections such as fungal pneumonia.
A Cross-sectional Study of Group B Streptococcus–Associated Sepsis, Coinfections, and Antibiotic Susceptibility Profile in Neonates in Pakistan
Authors: Asghar Samra , Khan Junaid Ali , Mahmood Muhammad Shahid , Arshad Muhammad Imran
Published: January 2020

Background:

Neonatal sepsis is a leading cause of morbidity and early-life mortality worldwide, and previous data have reported the highest neonatal mortality rate in Pakistan.

Purpose:

The present study aimed to decipher the prevalence of group B Streptococcus (GBS)–associated sepsis, coinfections, and antibiotic susceptibility of isolated microbes in neonates.

Methods:

Blood samples of 100 cases of neonatal sepsis were subcultured on blood agar, GBS agar, and MacConkey agar for isolation of GBS and suspected microbes.

Results:

Of 100 neonatal blood samples, 85 blood samples were culture-positive, including mixed culture growth (n = 18), 25 samples as early-onset neonatal sepsis (EONS) and 60 as late-onset neonatal sepsis (LONS). Staphylococcus aureus showed high percent positivity (31.4%), followed by Candida sp (16.5%), GBS (14.1%), Klebsiella (14.1%), Staphylococcus epidermidis (11.8%), Pseudomonas (9.4%), Acinetobacter (9.4%), Esherichia coli (8.2%), and Enterococcus (5.9%). GBS was isolated more frequently from EONS than from LONS with 50% coinfections. Mode of delivery, gender, and respiratory distress in neonates were significantly associated with culture-positive sepsis. GBS isolates were highly (91.7%) susceptible to vancomycin, cefotaxime, and chloramphenicol, followed by penicillin (83.3%), ampicillin, and tetracycline (75%). GBS isolates were resistant to erythromycin, clindamycin, ciprofloxacin, and linezolid.

Implications for Practice:

Our findings evidenced GBS-associated risk factors and antibiotic susceptibility pattern of neonatal sepsis, which will help clinicians in management, control, and treatment of neonatal sepsis.

Implications for Research:

The epidemiological evidence of GBS-associated neonatal sepsis, demographic characteristics, risk factor data analysis, and drug resistance pattern has disease prevention implications in neonates in low-income countries including Pakistan.
Missed Diagnosis and Acute Management of Radial Head Dislocation With Plastic Deformation of Ulna in Children
Authors: Singh Vivek , Dey Sukalyan , Parikh Shital N.
Published: January 2020

Background:

Radial head dislocation with ulnar bowing (Monteggia type I equivalent injury) is a frequently missed injury. If not recognized acutely, these missed injuries can lead to serious long-term complications. The purpose of this study was to evaluate the rate of missed diagnosis and to report on the characteristics and early management of this specific injury pattern.

Methods:

A total of 112 patients with Monteggia fracture-dislocation were identified, of which 18 patients had sustained a Monteggia type I equivalent injury. The total duration between injury, diagnosis, and treatment was noted. Medical records were reviewed to identify cases with the initially missed diagnosis. The radiographic assessment included the direction of radial head dislocation and location/displacement of the apex of the ulnar bow. Clinical outcomes were evaluated using Kim elbow performance score.

Results:

Thirteen of 18 cases with Monteggia equivalent injury were missed at the initial presentation. The diagnosis was established when the patients followed up in the orthopaedic clinic. Of these 18 patients, 11 were treated by closed reduction/cast and 7 patients required surgery. Significant differences were found between the closed reduction/cast and operative group for the mean time from injury to treatment (3.2±2.6 vs. 12.7±13.6 d). For each day of delay in treatment, the odds for surgical intervention increased by a factor of 1.126 (12.6%). There were no significant differences between the location and magnitude of the apex of the ulnar deformity between the 2 groups. Kim elbow score was excellent in all cases at the latest follow-up.

Conclusions:

Clinical suspicion and careful radiographic assessment are of utmost importance for every child with forearm and elbow injury without an apparent fracture, as there is a high rate of missed diagnosis for this specific Monteggia injury pattern. Prompt treatment would allow for successful closed reduction while even minor delays would increase the need for surgical intervention.

Level of Evidence:

Therapeutic, level III.
Perceived eHealth Literacy and Learning Experiences Among Japanese Undergraduate Nursing Students
Authors: Tanaka Junichi , Kuroda Hiromi , Igawa Nana , Sakurai Takayoshi , Ohnishi Mayumi
Published: January 2020

This study aimed to describe undergraduate nursing students' perceived eHealth literacy and learning experiences of eHealth literacy in Japan and to clarify the relationship between these factors. We conducted a self-administered online questionnaire survey using a convenience sample of 353 Japanese undergraduate nursing students selected from three universities. Participants completed the eHealth Literacy Scale and questionnaires on learning experiences of eHealth literacy and some demographic factors. Participants had moderate perceived eHealth (mean [SD], 24.52 [5.20]). More than half the participants responded that they had no learning experiences of health or science literacy. We observed a positive correlation between the total mean eHealth literacy and learning experiences scores. Undergraduate nursing students in Japan had slightly lower perceived eHealth literacy than nursing students in other countries, hospital nurses, and even patients. Of the 353 participants in this study, 69.4% did not know “where to find helpful health resources on the Internet,” 80.2% of those lacked the skills “to evaluate health resources,” and 68.9% could not “differentiate the quality of health resources on the Internet”; few of the participants perceived themselves as having any experience in learning the six domains of eHealth literacy. Very few reported learning about health (43.3%) and scientific (21.8%) literacy. The low perceived eHealth literacy among participants might reflect lack of knowledge and confidence in eHealth literacy as well as their own low level of health-promoting behaviors; this might influence the quality of health education of clients and their families. Nursing educators should address the lack of eHealth literacy among undergraduate nursing students.
Histopathological Features of Riehl Melanosis
Authors: Kim So Min , Lee Eun-So , Sohn Seonghyang , Kim You Chan
Published: January 2020

Histological features of Riehl melanosis have rarely been compared between lesional and perilesional normal skin and have not been precisely described using quantitative or immunohistochemical analysis or electron microscopic findings. To investigate the histopathological and immunohistochemical features of lesional and perilesional normal skin of patients with Riehl melanosis, we retrospectively evaluated the electronic medical records and skin biopsy specimens of 48 patients with Riehl melanosis. In addition, electron microscopy was performed on 1 case. Fontana–Masson staining for melanin and immunohistochemical staining for Melan-A, NKI/beteb, tyrosinase, and microphthalmia-associated transcription factor were performed. Although the difference was statistically insignificant, melanin pigment was increased in the epidermis of lesional skin compared with that of perilesional normal skin in patients. The number of melanocytes and their activity were significantly increased in lesional epidermal skin. Melanin pigment was also significantly increased in the lesional dermis. Pigmentary incontinence, basal cell liquefaction, dilated vessels, epidermal spongiosis, and colloid bodies were found in the lesional skin as well as in the perilesional normal skin to a lesser extent. Under electron microscopy of 1 randomly selected subject, many fibrocytes contained numerous melanosome particles in the cytoplasm of the lesional dermis. In perilesional normal skin, fibroblasts also contained melanosome particles; however, the number of melanosome-containing cells was less than that in lesional skin. Riehl melanosis is characterized by increased epidermal melanocytes and pigmentation, primarily involving the dermis, with histologically typical changes at the interface. Unlike that in other pigmentary diseases, most perilesional normal-appearing skin in Riehl melanosis also shows typical histopathological changes, although to a lesser extent.
Seasonal variation in blood pressure: Evidence, consensus and recommendations for clinical practice. Consensus statement by the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability
Authors: Stergiou George S. , Palatini Paolo , Modesti Pietro A. , Asayama Kei , Asmar Roland , Bilo Grzegorz , de la Sierra Alejandro , Dolan Eamon , Head Geoffrey , Kario Kazuomi , Kollias Anastasios , Manios Efstathios , Mihailidou Anastasia S. , Myers Martin , Niiranen Teemu , Ohkubo Takayoshi , Protogerou Athanasios , Wang Jiguang , O’Brien Eoin , Parati Gianfranco
Published: January 2020

Blood pressure (BP) exhibits seasonal variation with lower levels at higher environmental temperatures and higher at lower temperatures. This is a global phenomenon affecting both sexes, all age groups, normotensive individuals, and hypertensive patients. In treated hypertensive patients it may result in excessive BP decline in summer, or rise in winter, possibly deserving treatment modification. This Consensus Statement by the European Society of Hypertension Working Group on BP Monitoring and Cardiovascular Variability provides a review of the evidence on the seasonal BP variation regarding its epidemiology, pathophysiology, relevance, magnitude, and the findings using different measurement methods. Consensus recommendations are provided for health professionals on how to evaluate the seasonal BP changes in treated hypertensive patients and when treatment modification might be justified. (i) In treated hypertensive patients symptoms appearing with temperature rise and suggesting overtreatment must be investigated for possible excessive BP drop due to seasonal variation. On the other hand, a BP rise during cold weather, might be due to seasonal variation. (ii) The seasonal BP changes should be confirmed by repeated office measurements; preferably with home or ambulatory BP monitoring. Other reasons for BP change must be excluded. (iii) Similar issues might appear in people traveling from cold to hot places, or the reverse. (iv) BP levels below the recommended treatment goal should be considered for possible down-titration, particularly if there are symptoms suggesting overtreatment. SBP less than 110 mmHg requires consideration for treatment down-titration, even in asymptomatic patients. Further research is needed on the optimal management of the seasonal BP changes.
ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY AFTER IMMUNIZATION WITH MULTIPLE VACCINES
Authors: Kraemer Laura S. , Montgomery Jay R. , Baker Katherine M. , Colyer Marcus H.
Published: January 2020

Purpose:

To report a case of acute posterior multifocal placoid pigment epitheliopathy occurring in temporal association with multiple immunizations in a previously healthy 25-year-old woman.

Methods:

Acute posterior multifocal placoid pigment epitheliopathy was diagnosed based on ophthalmological findings of bilateral placoid subretinal lesions complicated by a serous retinal detachment in the left eye.

Results:

Through HLA typing, the patient was found to possess the HLA-B*40 and HLA-DB1*15 alleles. She was treated with topical prednisolone acetate 1% and monitored for several months. The serous retinal detachment resolved, and visual acuity returned to normal.

Conclusion:

This case report adds to the body of knowledge regarding possible atypical interplay between vaccines and specific T-cell receptors of the host immune system and adds Polio and Tetanus to the growing list of vaccines potentially triggering acute posterior multifocal placoid pigment epitheliopathy. Increased awareness of the presentation of acute posterior multifocal placoid pigment epitheliopathy and that it may arise after immunization may also improve evaluation of acute changes in visual acuity.
Short-Term Clinical Outcomes of a Novel Corneal Prosthetic Device in a Rabbit Model
Authors: Akpek Esen K. , Van Court Shanna , Glass Spencer , Schmiedel Thomas , Troutman Mitchell
Published: January 2020

Purpose:

To evaluate the clinical performance and biocompatibility of a novel synthetic corneal device.

Methods:

Synthetic, single-piece, foldable, suturable, optic-and-skirt design prototype devices were fabricated using expanded polytetrafluoroethylene. A combination of intralamellar and full-thickness penetrating techniques was used for implantation. A topical antibiotic-steroid regimen was used postoperatively. Rabbits were examined weekly using penlight and at monthly intervals under an operating microscope with integrated optical coherence tomography. Optical quality, retention, and complication rates at 3 and 6 months were assessed.

Results:

Nineteen rabbits underwent surgery. There were no device-related intraoperative complications. Creation of lamellar pocket was problematic in 2 younger rabbits with inadequate chamber depth. Two rabbits had early postoperative infectious keratitis attributed to bandage contact lens wear, which was ceased. Rabbits were treated using fourth-generation fluoroquinolone drops and did well over a period of 6 months without device extrusion or further complications. Four other rabbits had late postoperative infectious keratitis because of exposed suture(s), which progressed to endophthalmitis. One rabbit had sterile keratolysis and retraction of the anterior corneal lamella. There was no retinal detachment, glaucoma, anterior or posterior synechiae, or cataract formation in any of the rabbits. All devices remained in situ with clear optics without spoliation. Light microscopic examination of the globes demonstrated intact epithelium overlying the skirt and new collagen integration into the porous structure of the skirt without significant inflammation.

Conclusion:

Our results demonstrated favorable short-term anatomical clinical outcomes of this novel synthetic corneal prosthesis. Further studies are warranted to characterize the biointegration of this device.
Development of Corneal Sensation With Remodeling of the Epithelium and the Palisades of Vogt After Corneal Neurotization
Authors: Lathrop Kira L. , Duncan Katherine , Yu Jennifer , Shah Parth R. , Goldstein Jessie , Nischal Ken K.
Published: January 2020

Purpose:

Neurotrophic keratopathy (NK) produces persistent epithelial erosion which is hard to treat effectively. Recently, corneal neurotization surgery has produced reinnervation of the cornea with resolving neurotrophic keratopathy. We hypothesized that the generation of corneal epithelial nerves after neurotization surgery would not only restore the integrity of corneal epithelium but also produce a change in the configuration of the palisades of Vogt (POV), which houses the corneal epithelial stem cells.

Methods:

We assessed a patient with unilateral congenital corneal anesthesia with optical coherence tomography pre-neurotization and post-neurotization.

Results:

Over the course of 2 years, the patient gained corneal epithelial sensation and corneal and limbal epithelium was restored to normal thickness with corresponding changes in the POV.

Conclusions:

The intimate relationship between epithelium and sensory nerves of the cornea has been well documented; however, changes in the corneal epithelial stem cell niche in conjunction with development of innervation have not previously been reported. Considering the architecture of the corneal nerves in conjunction with the architecture of the POV may assist in developing treatments that can support the regeneration and maintenance of epithelium during nerve regeneration.
5-Year Outcomes of Descemet Stripping Only in Fuchs Dystrophy
Authors: Artaechevarria Artieda June , Wells Matthew , Devasahayam Raj N. , Moloney Gregory
Published: January 2020

Purpose:

To report the 5-year outcomes of the first reported case of bilateral Descemet stripping only (DSO) for Fuchs endothelial corneal dystrophy (FECD) at our center. Visual, biomicroscopic, and confocal microscopic findings are described.

Methods:

A retrospective case report.

Results:

A 55-year-old woman with bilateral FECD was referred with decreased visual acuity and blurred vision that interrupted activities of daily living. She underwent sequential 4-mm DSO procedures 6 months apart, with early postoperative results previously reported. Subjective visual symptoms, visual acuity, and corneal edema were analyzed at 1 month, 3 months, 6 months, 12 months, 2 years, 3 years, and 5 years postoperatively. Best corrected visual acuity of 0.0 (logarithm of the minimum angle of resolution) and corneal clearance were achieved in the third month after the procedure. These results have remained stable in the 5-year follow-up period.

Conclusions:

Early postoperative results from DSO surgery are encouraging, but questions remain regarding its longevity. Publication of longer-term outcomes such as this is necessary to establish the validity of this procedure as an intervention for FECD.
Does preoperative serum creatinine affect the early surgical outcomes of acute Stanford type A aortic dissection?
Authors: Wu Zi-Ning , Guan Xin-Liang , Xu Shi-Jun , Wang Xiao-Long , Li Hai-Yang , Gong Ming , Zhang Hong-Jia
Published: January 2020

Background:

Acute Stanford type A aortic dissection is a lethal disease requiring surgery. Evidence regarding the effects of preoperative creatinine in mortality is limited, and few studies have evaluated the effect of postoperative dialysis treatment on it.

Methods:

In this cohort study, we continuously recruited 632 surgical patients who were treated for acute type A aortic dissection in our hospital between January 2015 and May 2017. The preoperative level of serum creatinine was measured. All patients were followed up after surgery for 30 days to determine early mortality.

Results:

The 30-day mortality after surgery increased with elevated levels of preoperative serum creatinine. Median (interquartile range) serum creatinine levels in survivors were 9.61 μmol/dL (7.28-12.62 μmol/dL) versus 13.41 μmol/dL (10.28-20.63 μmol/dL) in death (p < 0.01). Adjusted odds ratios for increasing per μmol/dL serum creatinine were 1.09 (95% confidence interval, 1.03-1.15). We also found that the effect of preoperative creatinine on 30-day mortality was diminished by dialysis treatment after surgery.

Conclusion:

Preoperative serum creatinine predicts outcome in patients undergoing surgery for Stanford type A aortic dissection, and postoperative dialysis treatment can reduce its hazard.
Prolonged activated partial thromboplastin time with no clear explanation
Authors: Nakav Sigal , Blickstein Dorit , Raanani Pia , Rabizadeh Esther , Spectre Galia
Published: January 2020

Evaluation of bleeding risk before operation includes history of bleeding, complete blood count and basic coagulation tests, prothrombin time and activated partial thromboplatin time (aPTT). In this article, we present a patient with colon cancer who presented with asymptomatic prolonged aPTT of 72–100 s, while past a PTT values were within normal limits. aPTT was corrected in vitro by mixing with normal plasma. Further laboratory workup excluded coagulation factors deficiencies or an acquired inhibitor to coagulation factors. The patient underwent uncomplicated laparoscopic anterior resection of a recto-sigmoid carcinoma after receiving fresh frozen plasma and correction of aPTT. Further investigation revealed a rare disorder of an acquired prekallikrein deficiency. We describe the patient's clinical presentation, laboratory workup and review the literature of contact phase proteins deficiency.
Use of a Symptom Diary on Oncology Wards
Authors: IJzerman-Korevaar Margriet , de Graeff Alexander , Heijckmann Steffie , Zweers Daniëlle , Vos Bernard H. , Hirdes Marloes , Witteveen Petronella O. , Teunissen Saskia C.C.M.
Published: January 2020

Background

Management of symptoms is essential in reducing the symptom burden of cancer patients. The effect of symptom diaries on symptom management to date has been evaluated only in ambulatory settings.

Objective

The aims of this study were to identify the key facilitators for successful implementation of symptom diaries on oncology wards from patients’ and professionals’ perspectives and to evaluate implementation outcomes.

Methods

In 2 cycles of action research, the Utrecht Symptom Diary (USD) was implemented on 3 oncology wards and a daycare unit. Key facilitators for implementation were identified by thematic coding of interviews. The effect of the implementation was evaluated in cycle II in a pretest-posttest design. We performed statistical tests (Mann-Whitney/t test/χ
2) on Symptom Management Performance items in questionnaires and medical records.

Results

We interviewed 25 patients, 8 doctors, and 25 nurses. Seven key facilitators for implementation emerged. After implementation of the USD in cycle II, Symptom Management Performance was significantly (P < .05) improved for patients (3/12 items, n = 33 pretest/26 posttest) and professionals (6/12 items, n = 21 pretest/19 posttest). Significantly more symptoms (P = .00), working hypotheses (P = .023), treatment plans (P = .00), and interventions (P = .00) were reported (n = 47 pretest/47 posttest).

Conclusions

Implementation of the USD significantly improved symptom management in oncology wards. We recommend (1) using a diagnosis-specific diary; (2) making clear, individualized working-arrangements; (3) training professionals; (4) using the plan-do-check-act cycle; (5) acting multidisciplinary; (6) providing guidelines and training; and (7) assuring adequate information communications technology (ICT).

Implications

Symptom diaries are increasingly used, but implementation is challenging. This study provides knowledge on their benefits and an evidence-based strategy for implementation with positive outcomes achieved in patient care.
Real-Time Measurement of Crowding in Pediatric Emergency Department
Authors: Noel Guilhem , Jouve Elisabeth , Fruscione Sophie , Minodier Philippe , Boiron Laurence , Viudes Gilles , Gentile Stéphanie
Published: January 2020

Our study aimed to develop and validate a real-time crowding composite scale for pediatric emergency department (PED). The study took place in one teaching PED for 2 months. The outcome was the perception of crowding evaluated by triage nurses and pediatricians on a 10-level Likert scale. Triage nurses evaluated crowding at each moment of a child's admission and pediatrician at each moment of a child's discharge. The outcome was the hourly mean of all evaluations of crowding (hourly crowding perception). For analysis, originally, we only selected hours during which more than 2 nurses and more than 2 pediatricians evaluated crowding and, moreover, during which evaluations were the most consensual. As predictors, we used hourly means of 10 objective crowding indicators previously selected as consensual in a published French national Delphi study and collected automatically in our software system. The model (SOTU-PED) was developed over a 1-month data set using a backward multivariable linear regression model. Then, we applied the SOTU-PED model on a 1-month validation data set. During the study period, 7341 children were admitted in the PED. The outcome was available for 1352/1392 hours, among which 639 were included in the analysis as “consensual hours.” Five indicators were included in the final model, the SOTU-PED (R2= 0.718). On the validation data set, the correlation between the outcome (perception of crowding) and the SOTU-PED was 0.824. To predict crowded hours (hourly crowding perception >5), the area under the curve was 0.957 (0.933–0.980). The positive and negative likelihood ratios were 8.16 (3.82–17.43) and 0.153 (0.111–0.223), respectively. Using a simple model, it is possible to estimate in real time how crowded a PED is.
Male Rhinoplasty: Update
Authors: Rohrich Rod J. , Mohan Raja
Published: January 2020

Male rhinoplasty is unique in that it requires precise preoperative planning to achieve a successful result. Better communication and clarity are paramount with male rhinoplasty patients because the patients may be less attentive. It is important for the surgeon to screen the patients for any psychosocial disorders. Through a series of cases, male rhinoplasty techniques are highlighted. Masculine features should be preserved, and the nose should not be feminized or oversculpted. Another key component in any rhinoplasty case is proper skin care, especially during the postoperative period.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
The Role of an Inflammatory Bowel Disease Nurse in the Follow-Up of Patients From a Latin American Inflammatory Bowel Disease Program
Authors: Simian Daniela , Flores Lilian , Quera Rodrigo , Ibáñez Patricio , Figueroa Carolina , Lubascher Jaime , Pizarro Gonzalo , Kronberg Udo
Published: January 2020

Inflammatory bowel disease requires long-term treatment to maintain disease control. Favorable follow-up of patients indicates attention from a multidisciplinary team, in which the nurse's responsibilities have great importance. The aim of this observational, descriptive study was to describe the role of an inflammatory bowel disease nurse in the management of patients in a tertiary center in Chile, including all patients in follow-up between January 2016 and April 2017. Inflammatory bowel disease nurse contacts were recorded and classified. Demographic data, clinical variables, and patient satisfaction were also analyzed. A total of 597 patients (51%) were in follow-up over the 16-month period; 63% had ulcerative colitis, with a median age of 35 years. The inflammatory bowel disease nurse performed 760 contacts in 253 patients (42% of the follow-up patients). The most frequent nurse interventions were reinforcement of medical indications (42%), assessment of laboratory results (17%), and disease follow-up (12%); 49% related to education. Nurse interventions were focused in more severely ill patients; flares during the follow-up, biological therapy, immunomodulators, and steroids were all statistically significant. Of a sample of 107 patients surveyed, 96% perceived the inflammatory bowel disease program as excellent/good. The inflammatory bowel disease nurse plays an important role in the follow-up and management, specifically in education, of more severely ill patients.
Intravesical Antibiotic Administration in the Treatment of Recurrent Urinary Tract Infections: Promising Results From a Case Series
Authors: Chernyak Sofiya , Salamon Charbel
Published: January 2020

Objective

Intravesical antibiotic administration for the treatment of recurrent urinary tract infections (UTIs) provides targeted therapy that may be a useful alternative to oral antibiotics. The objective of the study was to assess the rate of UTIs before and after intravesical antibiotic instillations in community-dwelling postmenopausal women with recurrent UTIs.

Methods

Patients with recurrent UTI who underwent antibiotic bladder instillations were included. Instillation was performed in the office by trained nursing staff using either gentamycin or tobramycin. Every instillation was preceded by bladder irrigation with sterile water. Retrospective chart review was performed to compare rates of UTIs for 6 months before and after intervention. Descriptive and nonparametric statistics were used for data analysis.

Results

Twelve patients were evaluated. The average rate of UTIs decreased from a median of 2.5 to 1.5 infections (P = 0.025) after intravesical instillations. The number of pathogen types decreased from a median of 2.5 to 1.5 after therapy (P = 0.025). There was a reduction in bacterial antibiotic resistance after completion of instillations, with an estimated median difference of −5.250 (P = 0.065). There were no adverse effects reported during instillations.

Conclusions

Intravesical instillations offer a promising therapy for the treatment of recurrent UTIs in postmenopausal women who failed oral antibiotic therapy. Future prospective studies are needed to further elucidate the clinical utility and long-term benefits of antibiotic instillations.
The Stress Urinary Incontinence in CrossFit (SUCCeSS) Study
Authors: Elks Whitney , Jaramillo-Huff Ashley , Barnes K. Lauren , Petersen Timothy R. , Komesu Yuko M.
Published: January 2020

Objective

To evaluate the prevalence and severity of urinary incontinence (UI) in women who participate in CrossFit classes compared with women who participate in non-CrossFit group fitness classes.

Methods

The authors conducted a cross-sectional study of women who participate in either CrossFit or non-CrossFit group fitness classes using an online survey. Participants provided demographic information and completed the Incontinence Severity Index and Urinary Distress Inventory. Participants were recruited from local CrossFit and non-CrossFit gyms, online via social media, and an electronic CrossFit Newsletter. Associated comorbidities, exercises associated with UI, and coping mechanisms for urinary leakage were also assessed.

Results

Four hundred twenty-three women meeting inclusion criteria completed the survey, including 322 CrossFit participants and 101 non-CrossFit participants. We found that CrossFit participants were older than non-CrossFit participants and more likely to self-identify as non-Hispanic white. CrossFit participants more commonly reported UI (84% vs 48%, P = <0.001), higher severity of UI (Urinary Distress Inventory score: 20.8 vs 12.5, P < 0.001), and specifically more stress UI (73% vs 47%, P < 0.001). Weightlifting and jumping movements were the most common exercises associated with UI in CrossFit participants. Age and participation in CrossFit are significant and independent predictors of UI.

Conclusions

More than 80% of CrossFit participants reported UI and half of these reported moderate-severe UI, as compared with women who participate in non-CrossFit classes, less than half of whom reported UI with a small minority reporting moderate-severe UI. Exercises most associated with UI were jumping and weightlifting.
Implantation Time Has No Effect on the Morphology and Extent of Previously Reported “Degradation” of Prolene Pelvic Mesh
Authors: Thames Shelby F. , Blanton Michael D. , Williams Eric B. , White Joshua B. , Stoner Kirsten E. , Ong Kevin L.
Published: January 2020

Objectives

Prolene polypropylene (“Prolene”) meshes demonstrate no in vivo degradation, yet some claim degradation continues until no more Prolene polypropylene can be oxidized. We studied whether implantation time affects the morphology/extent of previously reported as cracking/degradation of completely cleaned Prolene explants.

Methods

Urogynecological explants (248 patients) were collected. After excluding non-Prolene/unknown meshes and those without known implantation times, completely cleaned explants (n = 205; 0.2–14.4 years implantation) were analyzed with light microscopy, scanning electron microscopy, and Fourier transform infrared spectroscopy. Based on implant times and storage (fixative or dry), representative specimens were randomly selected for comparison. Controls were unused (“exemplar”) TVT specimens with and without intentional oxidation via ultraviolet light exposure.

Results

Prolene explants included 31 dry (18 TVT; 7 Prolift; 4 Gynemesh; 2 others) and 174 wet (87 TVT; 47 Prolift; 10 Gynemesh; 30 others) specimens. Specimens had similar morphologies before cleaning. Progressive cleaning removed tissue and cracked tissue-related material exposing smooth, unoxidized, and nondegraded fibers, with no visible gradient-type/ductile damage. Fourier transform infrared spectroscopy of the explants confirmed progressive loss of proteins. Cleaning intentionally oxidized exemplars did not remove oxidized carbonyl frequencies and showed deep cracks and gross fiber rupture/embrittlement, unlike the explants and nonoxidized exemplars.

Conclusions

If in vivo Prolene degradation exists, there should be wide-ranging crack morphology and nonuniform crack penetration, as well as more cracking, degradation, and physical breakage for implants of longer implantation times, but this was not the case. There is no morphologic or spectral/chemical evidence of Prolene mesh degradation after up to 14.4 years in vivo.
Optical Vaginal Biopsy Using Optical Coherence Tomography
Authors: Sudol Neha Talreja , Miao Yusi , Li Yan , Chen Jason J. , Jing Joseph C. , Zhu Jiang , Tadir Yona , Chen Zhongping , Lane Felicia
Published: January 2020

Objective

Optical coherence tomography is a noninvasive technology that visualizes tissue microstructure with high spatial resolution. We designed a novel vaginal system that demonstrates a clear distinction between vaginal tissues planes. In this study, we sought to compare vaginal tomographic images of premenopausal, perimenopausal, and postmenopausal women, demonstrate feasibility of tracking vaginal tissue changes after treatment with fractional-pixel CO2 laser therapy, and obtain a histologic correlation of these findings.

Methods

Enrolled subjects underwent imaging and were divided into 3 groups based on menopausal status. Women with genitourinary syndrome of menopause who received fractional-pixel CO2 laser therapy were assessed before and after treatment. A cadaveric vagina was used to obtain tomographic and histologic images to assess for accuracy. Our primary outcome was mean vaginal epithelial thickness. Statistical analysis was performed using analysis of variance and t tests, respectively.

Results

Among 6 women, the mean vaginal epithelial thickness decreased with menopause (P < 0.01). Although change in epithelial thickness after fractional-pixel CO2 laser treatment varied between the 2 subjects evaluated, it increased significantly for the subject who reported improvement of vaginal symptoms (P < 0.01). Using a cadaveric specimen, optical biopsy was correlated to an hematoxylin and eosin–stained biopsy of the same vaginal site.

Conclusions

This study establishes feasibility of optical coherence tomography in providing an optical biopsy of the vaginal epithelium and lamina propria. In addition, it demonstrates vaginal changes as women enter menopause. This report is the initial phase of a longitudinal cohort study to evaluate changes in vaginal microstructure after energy-based treatment.
A reappraisal of polymyxin B dosing based on population pharmacokinetic model in patient with renal insufficiency
Authors: Yu Xuben , Zhang Chunhong , Pan Jingye , Dai Ying , Zhou Ziye , Yang Fan , Sun Ruolan , Wang Yexuan , Cao Yancheng , Sheng Changcheng , Jiao Zheng , Lin Guanyang
Published: January 2020

Background

Current FDA-approved label recommends polymyxin B dosing should be adjusted according to renal function, despite several studies proved poor correlation between polymyxin B PK and creatinine clearance. The study aims to assess the impact of renal function on polymyxin B metabolism and identify an alternate dosing strategy by population analysis.

Methods

Blood samples from adult patients were collected at steady state during routine therapeutic drug monitoring. Nonlinear mixed effects modeling was employed to build a population PK model of polymyxin B. Monte Carlo simulations were performed to design polymyxin B dosing regimens across various renal function.

Results

Pharmacokinetic analyses included 112 polymyxin B concentrations at steady state from 32 adult patients aged 37-93 received intravenous polymyxin B (100-200 mg/d). The creatinine clearance in patients was 5.91-244 mL/min. In the final population PK model, CrCL was the significant covariate on CL (typical value, 1.59 L/hr; between-subject variability, 13%). Mean (SD) individual empirical Bayesian estimates of CL was 1.75 (0.43) L/hr. A new dosing strategy combining the PK/PD targets and Monte Carlo simulation indicated that polymyxin B dose reductions improved the probability of achieving optimal exposures in simulated patients with renal insufficiency. For severe infections caused by organisms with MIC of ≥ 2 mg/L, though a high daily dose (e.g. 200mg/day) would possible for bacterial eradication, the risk of nephrotoxicity is significantly increased.

Conclusion

A population PK model was established to develop individualized polymyxin B dosage regimens that the dose of polymyxin B should be adjusted according to CrCL.
Lab-wide association scan of polygenic scores identifies biomarkers of complex disease
Authors: Dennis Jessica K , Sealock Julia M , Straub Peter , Hucks Donald , Actkins Ky’Era , Faucon Annika , Goleva Slavina B , Nirachou Maria , Singh Kritika , Morley Theodore , Ruderfer Douglas M. , Mosley Jonathan D , Chen Guanhua , Davis Lea K
Published: January 2020

Clinical laboratory (lab) tests are used in clinical practice to diagnose, treat, and monitor disease conditions. Test results are typically stored in electronic health records (EHRs), and a growing number of EHRs are linked to patient DNA, offering unprecedented opportunities to query relationships between clinical lab tests and genetics. Clinical lab data, however, are of uneven quality, and previous studies have focused on a small number of lab traits. We present two methods, QualityLab and LabWAS, to clean and analyze EHR labs at scale in a Lab-Wide Association Scan. In a proof of concept analysis focused on blood lipids and coronary artery disease, we found that heritability estimates of QualityLab lipid values were comparable to previous reports; polygenic scores for lipids were strongly associated with the referent lipid in a LabWAS; and a LabWAS of a polygenic score for coronary artery disease recapitulated known heart disease biomarker profiles and identified novel associations. Our methods extend previous EHR-based analysis tools and increase the amount of EHR data usable for discovery.
Connectome-wide search for functional connectivity locus associated with pathological rumination as a target for real-time fMRI neurofeedback intervention
Authors: Misaki Masaya , Tsuchiyagaito Aki , Zoubi Obada A , Paulus Martin , Bodurka Jerzy ,   Tulsa 1000 Investigators
Published: January 2020

Real-time fMRI neurofeedback (rtfMRI-nf) enables noninvasive targeted intervention in brain activation with high spatial specificity. To achieve this promise of rtfMRI-nf, we introduced and demonstrated a data-driven framework to design a rtfMRI-nf intervention through the discovery of precise target location associated with clinical symptoms and neurofeedback signal optimization. Specifically, we identified the functional connectivity locus associated with rumination symptoms, utilizing a connectome-wide search in resting-state fMRI data from a large cohort of mood and anxiety disorder individuals (N=223) and healthy controls (N=45). Then, we performed a rtfMRI simulation analysis to optimize the online functional connectivity neurofeedback signal for the identified functional connectivity. The connectome-wide search was performed in the medial prefrontal cortex and the posterior cingulate cortex/precuneus brain regions to identify the precise location of the functional connectivity associated with rumination severity as measured by the ruminative response style (RRS) scale. The analysis found that the functional connectivity between the loci in the precuneus (−6, −54, 48 mm in MNI) and the right temporo-parietal junction (RTPJ; 49, −49, 23 mm) was positively correlated with RRS scores (depressive,p< 0.001; brooding,p< 0.001; reflective,p= 0.002) in the mood and anxiety disorder group. We then performed a rtfMRI processing simulation to optimize the online computation of the precuneus-RTPJ connectivity. We determined that the two-point method without a control region was appropriate as a functional connectivity neurofeedback signal with less dependence on signal history and its accommodation of head motion. The present study offers a discovery framework for the precise location of functional connectivity targets for rtfMRI-nf intervention, which could help directly translate neuroimaging findings into clinical rtfMRI-nf interventions.
Two-stage biologically interpretable neural-network models for liver cancer prognosis prediction using histopathology and transcriptomic data
Authors: Zhan Zhucheng , Jing Zheng , He Bing , Hosseini Noshad , Westerhoff Maria , Choi Eun-Young , Garmire Lana X.
Published: January 2020

Purpose

Pathological images are easily accessible data with the potential as prognostic biomarkers. Moreover, integration of heterogeneous data types from multi-modality, such as pathological image and gene expression data, is invaluable to help predicting cancer patient survival. However, the analytical challenges are significant.

Experimental Design

Here we take the hepatocellular carcinoma (HCC) pathological image features extracted by CellProfiler, and apply them as the input for Cox-nnet, a neural network-based prognosis. We compare this model with conventional Cox-PH model, CoxBoost, Random Survival Forests and DeepSurv, using C-index and log ranked p-values on HCC testing samples. Further, to integrate pathological image and gene expression data of the same patients, we innovatively construct a two-stage Cox-nnet model, and compare it with another complex neural network model PAGE-Net.

Results

pathological image based prognosis prediction using Cox-nnet is significantly more accurate than Cox-PH and random survival forests models, and comparable with CoxBoost and DeepSurv methods. Additionally, the two-stage Cox-nnet complex model combining histopathology image and transcriptomics RNA-Seq data achieves better prognosis prediction, with a median C-index of 0.75 and log-rank p-value of 6e-7 in the testing datasets. The results are much more accurate than PAGE-Net, a CNN based complex model (median C-index of 0.68 and log-rank p-value of 0.03). Imaging features present additional predictive information to gene expression features, as the combined model is much more accurate than the model with gene expression alone (median C-index 0.70). Pathological image features are modestly correlated with gene expression. Genes having correlations to top imaging features have known associations with HCC patient survival and morphogenesis of liver tissue.

Conclusion

This work provides two-stage Cox-nnet, a new class of biologically relevant and relatively interpretable models, to integrate multi-modal and multiple types of data for survival prediction.
Machine learning to identify socio-behavioural predictors of HIV positivity in East and Southern Africa
Authors: Orel Erol , Esra Rachel , Estill Janne , Marchand-Maillet Stéphane , Merzouki Aziza , Keiser Olivia
Published: January 2020

Background

There is a need for high yield HIV testing strategies to reach epidemic control. We aimed to predict the HIV status of individuals based on socio-behavioural characteristics.

Methods

We analysed over 3,200 variables from the most recent Demographic Health Survey from 10 countries in East and Southern Africa. We trained four machine-learning algorithms and selected the best based on the f1 score. Training and validation were done on 80% of the data. The model was tested on the remaining 20% and on a left-out country which was rotated around. The best algorithm was retrained on the variables which were most predictive. We studied two scenarios: one aiming to identify 95% of people living with HIV (PLHIV) and one aiming to identify individuals with 95% or higher probability of being HIV positive.

Findings

Overall 55,151 males and 69,626 females were included. XGBoost performed best in predicting HIV with a mean f1 of 76·8% [95% confidence interval 76·0%-77·6%] for males and 78·8% [78·2%-79·4%] for females. Among the ten most predictive variables, nine were identical for both sexes: longitude, latitude and, altitude of place of residence, current age, age of most recent partner, total lifetime number of sexual partners, years lived in current place of residence, condom use during last intercourse and, wealth index. Model performance based on these variables decreased minimally. For the first scenario, 7 males and 5 females would need to be tested to identify one HIV positive person. For the second scenario, 4·2% of males and 6·2% of females would have been identified as high-risk population.

Interpretation

We were able to identify PLHIV and those at high risk of infection who may be offered pre-exposure prophylaxis and/or voluntary medical male circumcision. These findings can inform the implementation of HIV prevention and testing strategies.

Funding

Swiss National Science Foundation.