bluuebunny/crossref_metadata_2025 huggingface dataset:
Description and Early Outcomes of a Comprehensive Curriculum Redesign at the Northwestern University Feinberg School of Medicine
Authors: Heiman Heather L. , O’Brien Celia L. , Curry Raymond H. , Green Marianne M. , Baker James F. , Kushner Robert F. , Thomas John X. , Corbridge Thomas C. , Corcoran Julia F. , Hauser Joshua M. , Garcia Patricia M.
Published: September 2017

In 2012, the Northwestern University Feinberg School of Medicine launched a redesigned curriculum addressing the four primary recommendations in the 2010 Carnegie Foundation for the Advancement of Teaching report on reforming medical education. This new curriculum provides a more standardized evaluation of students’ competency achievement through a robust portfolio review process coupled with standard evaluations of medical knowledge and clinical skills. It individualizes learning processes through curriculum flexibility, enabling students to take electives earlier and complete clerkships in their preferred order. The new curriculum is integrated both horizontally and vertically, combining disciplines within organ-based modules and deliberately linking elements (science in medicine, clinical medicine, health and society, professional development) and threads (medical decision making, quality and safety, teamwork and leadership, lifestyle medicine, advocacy and equity) across the three phases that replaced the traditional four-year timeline. It encourages students to conduct research in an area of interest and commit to lifelong learning and self-improvement. The curriculum formalizes the process of professional identity formation and requires students to reflect on their experiences with the informal and hidden curricula, which strongly shape their identities.

The authors describe the new curriculum structure, explain their approach to each Carnegie report recommendation, describe early outcomes and challenges, and propose areas for further work. Early data from the first cohort to progress through the curriculum show unchanged United States Medical Licensing Examination Step 1 and 2 scores, enhanced student research engagement and career exploration, and improved student confidence in the patient care and professional development domains.
Resident Empowerment as a Driving Theme of Graduate Medical Education Reform
Authors: Thibault George E.
Published: September 2017

Through a series of six recent conferences, the Josiah Macy Jr. Foundation wanted to try to change the discussion about graduate medical education (GME) reform to one that is about the innovations needed to better prepare residents for the changing world of practice they will be entering and for meeting the needs of the patient population they will serve. These conferences featured some of the encouraging innovations in GME that are occurring at local and regional levels. An ongoing theme from many of these reforms is the empowerment of residents. The author examines what it would mean for health care systems, residency programs, and residents themselves to pursue empowerment for this significant portion of the health care workforce. Residents should be seen as a valuable component of the health care workforce with the ability to contribute to institutional and societal goals. The author highlights examples of existing programs that use residents in this way, but to accomplish this more broadly will require culture change and greater flexibility on the part of GME and institutional leadership.
The Association Between Learning Climate and Adverse Obstetrical Outcomes in 16 Nontertiary Obstetrics–Gynecology Departments in the Netherlands
Authors: Smirnova Alina , Ravelli Anita C.J. , Stalmeijer Renée E. , Arah Onyebuchi A. , Heineman Maas Jan , van der Vleuten Cees P.M. , van der Post Joris A.M. , Lombarts Kiki M.J.M.H.
Published: September 2017

Purpose

To investigate the association between learning climate and adverse perinatal and maternal outcomes in obstetrics–gynecology departments.

Method

The authors analyzed 23,629 births and 103 learning climate evaluations from 16 nontertiary obstetrics–gynecology departments in the Netherlands in 2013. Multilevel logistic regressions were used to calculate the odds of adverse perinatal and maternal outcomes, by learning climate score tertile, adjusting for maternal and department characteristics. Adverse perinatal outcomes included fetal or early neonatal mortality, five-minute Apgar score < 7, or neonatal intensive care unit admission for ≥ 24 hours. Adverse maternal outcomes included postpartum hemorrhage and/or transfusion, death, uterine rupture, or third- or fourth-degree perineal laceration. Bias analyses were conducted to quantify the sensitivity of the results to uncontrolled confounding and selection bias.

Results

Learning climate scores were significantly associated with increased odds of adverse perinatal outcomes (aOR 2.06, 95% CI 1.14–3.72). Compared with the lowest tertile, departments in the middle tertile had 46% greater odds of adverse perinatal outcomes (aOR 1.46, 95% CI 1.09–1.94); departments in the highest tertile had 69% greater odds (aOR 1.69, 95% CI 1.24–2.30). Learning climate was not associated with adverse maternal outcomes (middle vs. lowest tertile: OR 1.04, 95% CI 0.93–1.16; highest vs. lowest tertile: OR 0.98, 95% CI 0.88–1.10).

Conclusions

Learning climate was associated with significantly increased odds of adverse perinatal, but not maternal, outcomes. Research in similar clinical contexts is needed to replicate these findings and explore potential mechanisms behind these associations.
Prediction of Bispectral Index during Target-controlled Infusion of Propofol and Remifentanil
Authors: Lee Hyung-Chul , Ryu Ho-Geol , Chung Eun-Jin , Jung Chul-Woo
Published: September 2017

Background

The discrepancy between predicted effect-site concentration and measured bispectral index is problematic during intravenous anesthesia with target-controlled infusion of propofol and remifentanil. We hypothesized that bispectral index during total intravenous anesthesia would be more accurately predicted by a deep learning approach.

Methods

Long short-term memory and the feed-forward neural network were sequenced to simulate the pharmacokinetic and pharmacodynamic parts of an empirical model, respectively, to predict intraoperative bispectral index during combined use of propofol and remifentanil. Inputs of long short-term memory were infusion histories of propofol and remifentanil, which were retrieved from target-controlled infusion pumps for 1,800 s at 10-s intervals. Inputs of the feed-forward network were the outputs of long short-term memory and demographic data such as age, sex, weight, and height. The final output of the feed-forward network was the bispectral index. The performance of bispectral index prediction was compared between the deep learning model and previously reported response surface model.

Results

The model hyperparameters comprised 8 memory cells in the long short-term memory layer and 16 nodes in the hidden layer of the feed-forward network. The model training and testing were performed with separate data sets of 131 and 100 cases. The concordance correlation coefficient (95% CI) were 0.561 (0.560 to 0.562) in the deep learning model, which was significantly larger than that in the response surface model (0.265 [0.263 to 0.266], P < 0.001).

Conclusions

The deep learning model–predicted bispectral index during target-controlled infusion of propofol and remifentanil more accurately compared to the traditional model. The deep learning approach in anesthetic pharmacology seems promising because of its excellent performance and extensibility.
Neostigmine Administration after Spontaneous Recovery to a Train-of-Four Ratio of 0.9 to 1.0
Authors: Murphy Glenn S. , Szokol Joseph W. , Avram Michael J. , Greenberg Steven B. , Shear Torin D. , Deshur Mark A. , Benson Jessica , Newmark Rebecca L. , Maher Colleen E.
Published: September 2017

Background

When a muscle relaxant is administered to facilitate intubation, the benefits of anticholinesterase reversal must be balanced with potential risks. The aim of this double-blinded, randomized noninferiority trial was to evaluate the effect of neostigmine administration on neuromuscular function when given to patients after spontaneous recovery to a train-of-four ratio of 0.9 or greater.

Methods

A total of 120 patients presenting for surgery requiring intubation were given a small dose of rocuronium. At the conclusion of surgery, 90 patients achieving a train-of-four ratio of 0.9 or greater were randomized to receive either neostigmine 40 μg/kg or saline (control). Train-of-four ratios were measured from the time of reversal until postanesthesia care unit admission. Patients were monitored for postextubation adverse respiratory events and assessed for muscle strength.

Results

Ninety patients achieved a train-of-four ratio of 0.9 or greater at the time of reversal. Mean train-of-four ratios in the control and neostigmine groups before reversal (1.02 vs. 1.03), 5 min postreversal (1.05 vs. 1.07), and at postanesthesia care unit admission (1.06 vs. 1.08) did not differ. The mean difference and corresponding 95% CI of the latter were −0.018 and −0.046 to 0.010. The incidences of postoperative hypoxemic events and episodes of airway obstruction were similar for the groups. The number of patients with postoperative signs and symptoms of muscle weakness did not differ between groups (except for double vision: 13 in the control group and 2 in the neostigmine group; P = 0.001).

Conclusions

Administration of neostigmine at neuromuscular recovery was not associated with clinical evidence of anticholinesterase-induced muscle weakness.
Learning Effects in Psychophysical Tests of Spectral and Temporal Resolution
Authors: de Jong Monique A. M. , Briaire Jeroen J. , Frijns Johan H. M.
Published: September 2017

Objectives:

Psychophysical tests of spectral and temporal resolution, such as the spectral-ripple discrimination task and the temporal modulation detection test, are valuable tools for the evaluation of cochlear implant performance. Both tests correlate with speech intelligibility and are reported to show no instantaneous learning effect. However, some of our previous trials have suggested that there is a learning effect over time. The aim of this study was to investigate the test-retest reliability of the two tests when measured over time.

Design:

Ten adult cochlear implant recipients, experienced with the HiResolution speech coding strategy, participated in this study. Spectral ripple discrimination and temporal modulation detection ability with the HiResolution strategy were assessed both before and after participation in a previous trial that evaluated two research speech coding strategies after 2 weeks of home-usage. Each test was repeated six times on each test day.

Results:

No improvement was observed for same-day testing. However, comparison of the mean spectral ripple discrimination scores before and after participation in the take-home trial showed improvement from 3.4 to 4.8 ripples per octave (p < 0.001). The mean temporal modulation detection thresholds improved from −15.2 to −17.4 dB (p = 0.035).

Conclusions:

There was a clear learning effect over time in the spectral and temporal resolution tasks, but not during same-day testing. Learning effects may stem from perceptual learning, task learning, or a combination of those two factors. These results highlight the importance of a proper research design for evaluation of novel speech coding strategies, where the baseline measurement is repeated at the end of the trial to avoid false-positive results as a consequence of learning effects.
Risk Factors for Dural Tears in Thoracic and Lumbar Burst Fractures Associated With Vertical Laminar Fractures
Authors: Xu Jian-Xiang , Zhou Cheng-Wei , Wang Cheng-Gui , Tang Qian , Li Jia-Wei , Zhang Li-Lian , Xu Hua-Zi , Tian Nai-Feng
Published: September 2017

Study Design.

Retrospective cohort study.

Objective.

To reveal the risk factors for dural tears in thoracic and lumbar (TL) burst fractures associated with vertical laminar fractures through multivariate analysis.

Summary of Background Data.

Dural tears associated with laminar fractures in patients with TL burst fractures represents a special group requires distinct treatment with different surgical prognosis. It is still very difficult to predict dural tears in patients with vertical laminar fractures. The risk factors for dural tears have seldom been evaluated.

Methods.

Medical records of 113 patients of TL burst fractures with vertical laminar fractures were reviewed. The data were subdivided into two groups consisting of patients with and without dural tears. Demographic information, preoperative clinical, and radiological characteristics were compared between the groups. Multivariate logistic regression models were employed to determine the independent risk factors for dural tears.

Results.

The incidence of dural tear was 27.4% in this retrospective cohort. When compared with the dural intact group, the dural tear group had significantly worse preoperative neurological status, wider interpedicular distance, greater separation of laminar fractures, and larger encroachment of retropulsed fragment in the bony spinal canal. Multivariate stepwise logistic regression analysis showed that the ratio of interpedicular distance greater than 125% (odds ratio = 9.5; P < 0.001) and the ratio of encroachment of retropulsed fragment in the bony spinal canal of more than 50% (odds ratio = 61.2; P < 0.001) were independent risk factors for dural tears.

Conclusion.

Patients with wider interpedicular distance and larger encroachment of retropulsed fragment in the bony spinal canal were more likely to have dural tears in TL burst fractures with vertical laminar fractures.

Level of Evidence: 3
Quality of Life and Slip Progression in Degenerative Spondylolisthesis Treated Nonoperatively
Authors: Cushnie Duncan , Johnstone Ryan , Urquhart Jennifer C. , Gurr Kevin R. , Bailey Stewart I. , Bailey Christopher S.
Published: September 2017

Study Design.

A prospective cohort study of consecutive patients.

Objective.

Determination of the quality of life (QoL) and prevalence of slip progression in patients with degenerative lumbar spondylolisthesis managed nonoperatively.

Summary of Background Data.

Lumbar spinal stenosis secondary to degenerative lumbar spondylolisthesis is a common radiographic diagnosis associated with chronic back pain and radicular symptoms. There is limited evidence as to the clinical course in terms of validated QoL measures, and the extent of slip progression in patients with this condition treated nonoperatively.

Methods.

Validated disease-specific and generic QoL metrics including SF12 physical and mental scores [SF12-physical component summary (PCS) and SF12-mental component summary (MCS)], Oswestry Disability Index (ODI), and numeric scales for back and leg pain as well as radiographic assessment of slip extent were evaluated at initial consultation (baseline) and at a minimum of 5 years after the baseline assessment. Slip progression was defined by a >5% increase in slip percentage.

Results.

Thirty-nine of 160 (24.4%) patients elected to switch to operative management, despite no slip progression on preoperative radiographs. Seventy spondylolisthetic levels in 66 participants were assessed after a minimum of 5 years of nonoperative management. Twenty-one participants (31.8%) had slip progression. SF12-PCS, ODI, and leg pain improved similarly in both groups (P < 0.05). SF12-MCS did not change significantly in either group. Back pain improved only in the nonprogressing group.

Conclusion.

The majority of cases of low-grade spondylolisthesis do not progress over 5 years with nonoperative management. Regardless of whether there was progression or not, the mean PCS, ODI, and leg pain improved from baseline, although symptoms remained and a significant number elected to switch to surgical management before 5 years. Back pain improved with nonoperative treatment only in those without progression.

Level of Evidence: 2
Visualization of Immune Responses in the Cornea
Authors: Perez Victor L.
Published: September 2017

The eye has become a useful site for the investigation and understanding of local and systemic immune responses. The ease of access and transparency of the cornea permits direct visualization of ocular structures, blood vessels, and lymphatic vessels, allowing for the tracking of normal and pathological biological processes in real time. As a window to the immune system, we have used the eye to dissect the mechanisms of corneal inflammatory reactions that include innate and adaptive immune responses. We have identified that the ocular microenvironment regulates these immune responses by recruiting different populations of inflammatory cells to the cornea through local production of selected chemokines. Moreover, crosstalk between T cells and macrophages is a common and crucial step in the development of ocular immune responses to corneal alloantigens. This review summarizes the data generated by our group using intravital fluorescent confocal microscopy to capture the tempo, magnitude, and function of innate and adaptive corneal immune responses.
Evidence-Based Consensus Recommendations for Colposcopy Practice for Cervical Cancer Prevention in the United States
Authors: Wentzensen Nicolas , Massad L. Stewart , Mayeaux Edward J. , Khan Michelle J. , Waxman Alan G. , Einstein Mark H. , Conageski Christine , Schiffman Mark H. , Gold Michael A. , Apgar Barbara S. , Chelmow David , Choma Kim K. , Darragh Teresa M. , Gage Julia C. , Garcia Francisco A.R. , Guido Richard S. , Jeronimo Jose A. , Liu Angela , Mathews Cara A. , Mitchell Martha M. , Moscicki Anna-Barbara , Novetsky Akiva P. , Papasozomenos Theognosia , Perkins Rebecca B. , Silver Michelle I. , Smith Katie M. , Stier Elizabeth A. , Tedeschi Candice A. , Werner Claudia L. , Huh Warner K.
Published: September 2017

The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of colposcopy and directed biopsy for cervical cancer prevention in the United States (US). The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. An extensive literature review was conducted and supplemented by a systematic review and meta-analysis of unpublished data. In addition, a survey of practicing colposcopists was conducted to assess current colposcopy practice in the US. Recommendations were approved by the working group members, and the final revisions were made based on comments received from the public. The recommendations cover terminology, risk-based colposcopy, colposcopy procedures, and colposcopy adjuncts. The ASCCP Colposcopy Standards recommendations are an important step toward raising the standard of colposcopy services delivered to women in the US. Because cervical cancer screening programs are currently undergoing important changes that may affect colposcopy performance, updates to some of the current recommendations may be necessary in the future.
Positive Correlation Between Clearance of High-Risk Human Papillomavirus and Lack of Residual Disease After Loop Excision of the Transformation Zone in Early Stage Cervical Cancer
Authors: Siegler Efraim , Goldberg Yael , Baruch-Finkel Tamar , Shaked-mishan Pninint , Segev Yakir , Machuli Lena , Siegler Yoav , Auslender Ron , Lavie Ofer
Published: September 2017

Objectives

In cervical cancer, a number of pathological parameters have been explored for their utility in tailoring a less aggressive approach for patients with low-risk early stage disease. We examined whether, in patients with cervical cancer stage IA1 to IB1, diagnosed by loop excision of the transformation zone (LLETZ), positive for high-risk human papillomavirus (hrHPV), clearance of hrHPV after LLETZ correlates with absence of residual disease at the final pathology after definitive or further surgery.

Materials and Methods

Data were collected from patients diagnosed with early stage invasive cervical cancer and positive hrHPV DNA, who had a repeat cervical HPV test 3 to 12 weeks after LLETZ and before final surgical treatment. We compared characteristics of patients with post-LLETZ negative and positive hrHPV.

Results

Of 28 patients, 13 were post-LLETZ negative hrHPV; of these, 11 did not have residual cancer in the final pathological specimen; two patients had cervical intraepithelial neoplasia 3. Of the 15 women who had post-LLETZ positive hrHPV, 10 had residual cancer in the final pathological specimen and 3 had cervical intraepithelial neoplasia or adenocarcinoma in situ; only 2 were negative for cancer. The post-LLETZ hrHPV test shows a sensitivity of 86.7% and specificity of 84.6%.

Conclusions

Clearance of hrHPV from the cervix after LLETZ was found to correlate with the absence of residual cancer in the final surgical specimen. Testing for hrHPV post-LLETZ might serve as a new parameter for risk assessment and tailoring of a less radical operation in women with early stage cervical cancer.
Large Loop Excision of the Transformation Zone Versus True Cone Biopsy Electrode Excision: A Randomized Trial
Authors: Hilal Ziad , Rezniczek Günther A. , El-Fizazi Nariman , Tempfer Clemens B.
Published: September 2017

Objectives

The aim of the study was to compare two conization techniques, large loop excision of the transformation zone (LLETZ), and true cone biopsy electrode excision (TCBEE) in women with cervical dysplasia.

Materials and Methods

In a randomized clinical trial, we compared LLETZ and TCBEE in women undergoing surgical treatment of cervical dysplasia in a 1:1 ratio. The primary endpoint was resection margin status (RMS), secondary endpoints were fragmentation of the surgical specimen, resection volume, operation time, time to complete hemostasis, blood loss, intraoperative and postoperative complications, surgeon's preference, and patient's postoperative pain, estimated by an 11-level visual analog scale (nVAS11), and a 5-level pictogram.

Results

One hundred seventy-two women were randomized. No difference in the primary outcome, resection margin status, was observed between LLETZ and TCBEE (involved margins: 12/91 [13%] vs 7/81 [9%], respectively; p = .4). However, fragmentation rate (1 vs >1 fragment: 85 [93%] and 6 [7%] for LLETZ vs 63 [78%] and 18 [22%] for TCBEE; p = .004) and surgeon preference (nVAS11: 1 [0–2] vs 3 [1–7]; p < .001) favored LLETZ. Postoperative pain, however, was lower after TCBEE (nVAS11: 1 [0–3] vs 0 [0–2]; p = .02). The secondary outcome parameters resection volume, operation time, time to complete hemostasis, blood loss, intraoperative complications, and postoperative complications were not different between the study groups. In a multivariate analysis, age, body mass index, and parity did not affect the primary and secondary outcome parameters.

Conclusions

LLETZ and TCBEE are equally safe and efficacious procedures, but specimen fragmentation and surgeon preference favor loop excision.
Frequency of Adequate Endometrial Biopsy in Evaluation of Postmenopausal Women With Benign Endometrial Cells on Pap Test
Authors: Hastings Jeffrey W. , Alston Meredith J. , Mazzoni Sara E. , Stickrath Elaine
Published: September 2017

Objective

The aim of the study was to determine the frequency that endometrial biopsies (EMBs) performed on postmenopausal (PMP) women with benign endometrial cells (BECs) on Pap test are adequate for assessing malignancy or hyperplasia.

Methods

This is a case series including all PMP women older than 55 years at a single academic institution between January 2008 and September 2015 with a Pap test result including BEC. Patients were identified via an internal cytology database. Patient data, the ability to obtain an EMB, and the result of the EMB were collected. An adequate EMB was defined as the presence of glands and stroma sufficient to assess for endometrial hyperplasia and/or malignancy. Descriptive statistics were performed, and then univariable and logistic regression analyses were used to evaluate associations of patient factors and adequacy of EMB.

Results

One hundred sixteen women met inclusion criteria. One hundred seven had an EMB scheduled (92%) and of those 91 EMBs were obtained (85%). Of the obtained biopsies, 63 were inadequate to rule out the diagnosis of hyperplasia and/or malignancy (69%). Of these, 19 patients underwent pelvic ultrasound (30%), 12 followed up with repeat Pap test (19%), and 4 underwent dilation and curettage (6%). Of the adequate biopsies, 5 had a diagnosis of hyperplasia (18%) and 5 with malignancy (18%).

Conclusions

In PMP women with BEC on Pap test, adequate EMB was only obtained in 31% of patients. Most patients without an adequate biopsy had no further workup of their abnormal Pap test.
Cervical Excision Procedure: A Trend of Decreasing Length of Excision Observed in a Multicenter Survey
Authors: Ciavattini Andrea , Clemente Nicolò , Liverani Carlo Antonio , Cattani Paolo , Giannella Luca , Delli Carpini Giovanni , Morini Stefano , Buttignol Monica , Sopracordevole Francesco
Published: September 2017

Objectives

The aim of the present study was to observe the trend of length of cone excisions in women treated with cervical excision procedure in five institutions of Central and Northern Italy.

Materials and Methods

A multicenter retrospective cohort study was conducted on women who underwent a cervical excision procedure between January 2006 and December 2014. The pertinent clinical, histopathological, and sociodemographic characteristics of each woman were collected. In particular, the length of the cone specimen was evaluated and all of the factors that potentially influenced the length of excision were considered.

Results

A total of 1482 women who underwent a cervical excision procedure from January 2006 to December 2014 were included. A mean (SD) cone length of 12.9 (5.0) mm was reported, and mostly, a significant decrease during the whole study period emerged. Age (r = 0.1, p = .007) and preoperative diagnosis of glandular lesions (r = 0.1, p < .001) were significantly related to the length of cone excision on multivariate analysis. Compared with the carbon dioxide laser excisional procedure, loop electrosurgical excision procedure showed a negative correlation with the length of excision (r = −0.2, p < .001).

Conclusions

During the study period, a significant decrease in the length of cone excision was observed, probably reflecting the gynecologists' acquired awareness of the increased risk of adverse obstetric outcomes for future pregnancies in the case of wide cone excisions.
ASCCP Colposcopy Standards: Colposcopy Quality Improvement Recommendations for the United States
Authors: Mayeaux Edward J. , Novetsky Akiva P. , Chelmow David , Garcia Francisco , Choma Kim , Liu Angela H. , Papasozomenos Theognosia , Einstein Mark H. , Massad L. Stewart , Wentzensen Nicolas , Waxman Alan G. , Conageski Christine , Khan Michelle J. , Huh Warner K.
Published: September 2017

Objectives

The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of and approach to colposcopy and biopsy for cervical cancer prevention in the United States. The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. The ASCCP Quality Improvement Working Group developed evidence-based guidelines to promote best practices and reduce errors in colposcopy and recommended indicators to measure colposcopy quality.

Materials and Methods

The working group performed a systematic review of existing major society and national guidelines and quality indicators. An initial list of potential quality indicators was developed and refined through successive iterative discussions, and draft quality indicators were proposed. The draft recommendations were then reviewed and commented on by the entire Colposcopy Standards Committee, posted online for public comment, and presented at the International Federation for Cervical Pathology and Colposcopy 2017 World Congress for further comment. All comments were considered, additional adjustments made, and the final recommendations approved by the entire Task Force.

Results

Eleven quality indicators were selected spanning documentation, biopsy protocols, and time intervals between index screening tests and completion of diagnostic evaluation.

Conclusions

The proposed quality indicators are intended to serve as a starting point for quality improvement in colposcopy at a time when colposcopy volume is decreasing and individual procedures are becoming technically more difficult to perform.
Risks of CIN 2+, CIN 3+, and Cancer by Cytology and Human Papillomavirus Status: The Foundation of Risk-Based Cervical Screening Guidelines
Authors: Demarco Maria , Lorey Thomas S. , Fetterman Barbara , Cheung Li C. , Guido Richard S. , Wentzensen Nicolas , Kinney Walter K. , Poitras Nancy E. , Befano Brian , Castle Philip E. , Schiffman Mark
Published: September 2017

Objectives

The next round of the American Society for Colposcopy and Cervical Pathology (ASCCP)-sponsored cervical cancer screening and management guidelines will recommend clinical actions based on risk, rather than test-based algorithms. This article gives preliminary risk estimates for the screening setting, showing combinations of the 2 most important predictors, human papillomavirus (HPV) status and cytology result.

Materials and Methods

Among 1,262,713 women aged 25 to 77 years co-tested with HC2 (Qiagen) and cytology at Kaiser Permanente Northern California, we estimated 0–5-year cumulative risk of cervical intraepithelial neoplasia (CIN) 2+, CIN 3+, and cancer for combinations of cytology (negative for intraepithelial lesion or malignancy [NILM], atypical squamous cells of undetermined significance [ASC-US], low-grade squamous intraepithelial lesion [LSIL], atypical squamous cells cannot exclude HSIL [ASC-H], high-grade squamous intraepithelial lesion [HSIL], atypical glandular cells [AGC]) and HPV status.

Results

Ninety percent of screened women had HPV-negative NILM and an extremely low risk of subsequent cancer. Five-year risks of CIN 3+ were lower after HPV negativity (0.12%) than after NILM (0.25%). Among HPV-negative women, 5-year risks for CIN 3+ were 0.10% for NILM, 0.44% for ASC-US, 1.8% for LSIL, 3.0% for ASC-H, 1.2% for AGC, and 29% for HSIL+ cytology (which was very rare). Among HPV-positive women, 5-year risks were 4.0% for NILM, 6.8% for ASC-US, 6.1% for LSIL, 28% for ASC-H, 30% for AGC, and 50% for HSIL+ cytology.

Conclusions

As a foundation for the next guidelines revision, we confirmed with additional precision the risk estimates previously reported for combinations of HPV and cytology. Future analyses will estimate risks for women being followed in colposcopy clinic and posttreatment and will consider the role of risk modifiers such as age, HPV vaccine status, HPV type, and screening and treatment history.
Systematic Review of International Colposcopy Quality Improvement Guidelines
Authors: Mayeaux Edward J. , Novetsky Akiva P. , Chelmow David , Choma Kim , Garcia Francisco , Liu Angela H. , Papasozomenos Theognosia , Einstein Mark H.
Published: September 2017

Objectives

The American Society for Colposcopy and Cervical Pathology Colposcopy Standards Committee organized multiple working groups to draft colposcopy standards for the United States. As part of this project, international quality assurance and improvement measures were examined.

Materials and Methods

The quality improvement working group performed a systematic review of the literature to collate international guidelines related to quality improvement. Source guidelines were collected using searches in Medline, Google Scholar, the International Federation of Cervical Pathology and Colposcopy Web site, other regional colposcopy group's Web sites, and communications with International Federation of Cervical Pathology and Colposcopy board of directors' members and other expert members of various national groups. Once identified, the sources were reviewed by multiple workgroup members for potential guideline materials.

Results

Fifty-six unique documents were identified, of which 18 met inclusion criteria and contributed data to the analysis. Information was abstracted and grouped by related subject.

Conclusions

Wide variation exists in colposcopy guidance and quality indicators from regional and national colposcopy societies. Abstracted international guidelines are presented.
Development and Psychometric Testing of an Electronic Patient-Reported Outcome Tool for Vulval Disorders (ePAQ-Vulva)
Authors: Gray Thomas G. , Alexander Charlotte , Jones Georgina L. , Tidy John A. , Palmer Julia E. , Radley Stephen C.
Published: September 2017

Objective

Development of an electronic patient-reported outcome measure (PROM) specifically designed for vulval disorders. Psychometric testing of the components of the questionnaire, which assess vulval symptoms, sexual function, and quality of life (QoL).

Materials and Method

Development and programming of the instrument (ePAQ-Vulva) was informed by national guidelines for the assessment of vulval disorders, an expert panel, and a survey of 61 vulval clinic patients. The PROM assesses frequency and impact of vulval symptoms, sexual function, and QoL. It also records conditions and behaviors related to vulval disorders and patient concerns/goals.

Scale generation and psychometric testing were undertaken for the vulval symptoms, sexual function, and QoL components of the PROM with 91 participants; descriptive statistics, factor analysis and internal reliability of identified domains, and agreement between free-text and multiple-choice items to assess convergent validity and interrater reliability of picture items were assessed.

Results

Descriptive statistics showed high floor effects for seven questionnaire items. Factor analysis identified 5 principal components. These were reviewed and amended to provide a putative domain structure of 6 domains. Internal reliability of these domains was assessed using Cronbach α, producing values of 0.715 to 0.917. Interrater reliability of the picture items produced a κ statistic of 0.405. Spearman rank showed moderate correlation between multiple-choice answers and free-text concerns (r = 0.364–0.462) in 3 of the 6 domains (pain, sex, and dyspareunia).

Conclusions

ePAQ-Vulva offers the first patient-reported outcome tool, specifically designed for vulval disorders. The instrument requires further validation and testing, including evaluation of the stability, responsiveness, and reliability.
Validity Parameters of the Human Papillomavirus Detection Test Hybrid Capture 2 With and Without Cytology After Laser Destruction and Large Loop Excision of the Transformation Zone Treatment of High-Grade Cervical Intraepithelial Neoplasia Lesions
Authors: Hansen Johanna , Waibel Julia , Timme Sylvia , Gitsch Gerald , Bossart Michaela , Oehler Martin K. , Klar Maximilian
Published: September 2017

Objective

The aim of this study was to calculate the validity parameters of the Digene Hybrid Capture 2 (HC2) high-risk human papillomavirus DNA test with and without cytology in the follow-up examinations after laser treatment of the transformation zone or large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia (CIN).

Methods

We performed a standardized follow-up examination in 113 postlaser and 153 post-LLETZ patients in our colposcopy clinic. Routine cytology, HC2 tests, and colposcopically-guided cervical biopsies were performed and sensitivity, specificity, and positive and negative predictive values were calculated using the histological cervical biopsy result as the criterion standard.

Results

After a median follow-up time of 25.5 months, the overall posttreatment recurrence/persistence rate of CIN 2 or higher (CIN 2+) was 24% after laser and 12.4% after Post-LLETZ treatment. Hybrid Capture 2 alone had a sensitivity/NPV of 70/88% in post-laser and 70/93% in post-LLETZ patients. Cytology alone had a sensitivity/NPV for CIN 2+ of 48/84% in post-laser and 58/91% in post-LLETZ patients. Combined testing of HC2 with cytology had a sensitivity/NPV of 81/92% in postlaser and 88/95% in post-LLETZ patients.

Discussion

In this test of cure study, combined testing of cytology with HC2 resulted in a high sensitivity and NPV. Hybrid Capture 2 and cytology-negative women may safely return to routine recall. Cytology alone is not an adequate follow-up strategy in postlaser patients.
An Analysis of Safety and Adverse Events Following Cochlear Implantation in Children Under 12 Months of Age
Authors: Kim Yesul , Patel Vijay A. , Isildak Huseyin , Carr Michele M.
Published: September 2017

Objective:

To determine perioperative morbidity of children ≤12 months undergoing cochlear implantation (CI).

Study Design:

Retrospective analysis using the American College of Surgeons National Surgical Quality Improvement Program Pediatric Database (ACS-NSQIP-P).

Setting:

General acute care children's hospitals, children's hospitals within larger hospitals, specialty children's hospitals, and general acute care hospitals with a pediatric wing.

Patients:

Children who underwent CI were queried using the ACS-NSQIP-P from 2012 to 2015.

Intervention:

Cochlear implantation.

Main Outcome Measures:

Risk factors analyzed include age, prematurity, and presence of congenital disorders. Outcomes analyzed include operative time, length of stay, general surgical complications, readmissions, and related reoperations.

Results:

Over the database accrual period, the percentage of children ≤12 months at the time of surgery increased from 2012 to 2015 (6.08–7.78%, p = 0.0752). Total operative time, length of stay (≥1 d), and readmissions for those ≤12 months were significantly greater compared with those >12 months at the time of surgery (p < 0.001, p = 0.0037, and p < 0.0001, respectively). There were no statistically significant differences in general surgical complications (i.e., superficial incisional surgical site infections, organ/space surgical site infections, and/or unplanned reoperations) in cases ≤12 months. Complications specific to CI such as facial nerve paralysis, cerebrospinal fluid leak, and mastoiditis were not recorded in the ACS-NSQIP-P.

Conclusion:

Infants had no more general surgical complications in the immediate postoperative period compared with older children, although total operative time, length of stay, and readmissions were found to be significantly greater in frequency.
Uncontrolled bleeding of the gastrointestinal tract
Authors: D’Hondt Alain , Haentjens Lionel , Brassart Nicolas , Flamme Frédéric , Preiser Jean-Charles
Published: September 2017

Purpose of review

Acute gastrointestinal bleeding is a frequent emergency situation, whose incidence will likely rise as a result of the increasing use of direct anticoagulants and of the medical progresses resulting in longer life expectancy with underlying comorbidities. Updated guidelines and improvements in the diagnostic and therapeutic tools are now available and will likely improve the management of massive gastrointestinal bleeding in the near future.

Recent findings

The assessment of severity has been improved by validated scores useable upon admission. Massive blood transfusion protocols and specific care in case of bleeding of patients treated with direct anticoagulants, including concentrates of coagulation factors and monoclonal antibodies are now available. The endoscopic management has been facilitated by the use of hemostatic powders and by the use of self-expanding metal stents in case of variceal hemorrhage. New diagnostic tools include emergency video-capsule endoscopy, multiphasic computed tomography angiography and enterography.

The implementation of multidisciplinary diagnostic and therapeutic algorithms for the management of massive bleeding requires a close collaboration between emergency physicians, intensivists, endoscopists, radiologists and surgeons. A sequential strategy involving each of these specialists is desirable for a successful management of acute and massive gastrointestinal bleeding.
Real-time measurement of glomerular filtration rate
Authors: Solomon Richard , Goldstein Stuart
Published: September 2017

Purpose of review

Measurement of glomerular filtration rate is an essential tool for determining the health or dysfunction of the kidney. The glomerular filtration rate is a dynamic function that can change almost instantaneously in response to stressors. Despite its central role in nephrology, there are no techniques available to the clinician for monitoring glomerular filtration rate in real time. Recent advances in technology to measure fluorescent compounds through the skin are providing a new approach for real-time monitoring of glomerular filtration rate. This review frames these technologies within how such measurements might be used in clinical medicine.

Recent findings

Fluorescent molecules that act as ideal filtration markers are now available. Using transdermal sensors, the plasma disappearance rate of these exogenous markers can be measured rather than their steady state concentration. This eliminates the delay inherent in using an endogenous marker of filtration and permits continuous monitoring of GFR.

These new technologies provide enhanced opportunities for diagnosis of kidney dysfunction and therapeutic monitoring. Accurate assessment of measured GFR will eliminate the erroneous diagnosis of chronic kidney disease (CKD) from many patients. Assessment of renal reserve will provide a new risk factor for progression of CKD. Real-time monitoring of GFR in critically ill patients will allow for earlier diagnosis of acute kidney injury and a dynamic metric to guide therapeutics. These are but a few of the many opportunities that this new technology will provide in both the clinical and research arenas.
Lichtenstein Versus Total Extraperitoneal Patch Plasty Versus Transabdominal Patch Plasty Technique for Primary Unilateral Inguinal Hernia Repair
Authors: Köckerling Ferdinand , Bittner Reinhard , Kofler Michael , Mayer Franz , Adolf Daniela , Kuthe Andreas , Weyhe Dirk
Published: September 2017

Objective:

Outcome comparison of the Lichtenstein, total extraperitoneal patch plasty (TEP), and transabdominal patch plasty (TAPP) techniques for primary unilateral inguinal hernia repair.

Background:

For comparison of these techniques the number of cases included in meta-analyses of randomized controlled trials is limited. There is therefore an urgent need for more comparative data.

Methods:

In total, 57,906 patients with a primary unilateral inguinal hernia and 1-year follow up from the Herniamed Registry were selected between September 1, 2009 and February 1, 2015. Using propensity score matching, 12,564 matched pairs were formed for comparison of Lichtenstein versus TEP, 16,375 for Lichtenstein versus TAPP, and 14,426 for TEP versus TAPP.

Results:

Comparison of Lichtenstein versus TEP revealed disadvantages for the Lichtenstein operation with regard to the postoperative complications (3.4% vs 1.7%; P < 0.001), complication-related reoperations (1.1% vs 0.8%; P = 0.008), pain at rest (5.2% vs 4.3%; P = 0.003), and pain on exertion (10.6% vs 7.7%; P < 0.001). TEP had disadvantages in terms of the intraoperative complications (0.9% vs 1.2%; P = 0.035). Likewise, comparison of Lichtenstein versus TAPP showed disadvantages for the Lichtenstein operation with regard to the postoperative complications (3.8% vs 3.3%; P = 0.029), complication-related reoperations (1.2% vs 0.9%; P = 0.019), pain at rest (5% vs 4.5%; P = 0.029), and on exertion (10.2% vs 7.8%; P < 0.001).

Conclusions:

TEP and TAPP were found to have advantages over the Lichtenstein operation.
Time-lagged effect of predators on tadpole behaviour and parasite infection
Authors: Koprivnikar Janet , Urichuk Theresa M. Y.
Published: September 2017

Prey should adjust their defences against natural enemies to match their current level of risk and balance other needs. This is particularly important when optimal defences represent trade-offs, as is the case with many predator-induced trait-mediated indirect effects (TMIEs) that are antagonistic to those promoting host resistance to parasites and pathogens. However, trade-offs may depend on whether different natural enemies are present simultaneously or represent temporally discrete threats. We found that larval amphibians (
Anaxyrus americanus
) previously exposed to predator cues did not engage in anti-parasite behaviours (activity increases) in response to a current risk of infection by a pathogenic trematode parasite compared to controls, resulting in higher infection intensities. This suggests that the memory of the likely more lethal threat (predation) had greater influence, maladaptively dampening tadpole activity. Incorporating complexity inherent in natural systems, including spatial and temporal overlap, is necessary to better understand natural enemy ecology and how TMIEs relate to infectious diseases.
Extinction rates in tumour public goods games
Authors: Gerlee Philip , Altrock Philipp M.
Published: September 2017

Cancer evolution and progression are shaped by cellular interactions and Darwinian selection. Evolutionary game theory incorporates both of these principles, and has been proposed as a framework to understand tumour cell population dynamics. A cornerstone of evolutionary dynamics is the replicator equation, which describes changes in the relative abundance of different cell types, and is able to predict evolutionary equilibria. Typically, the replicator equation focuses on differences in relative fitness. We here show that this framework might not be sufficient under all circumstances, as it neglects important aspects of population growth. Standard replicator dynamics might miss critical differences in the time it takes to reach an equilibrium, as this time also depends on cellular turnover in growing but bounded populations. As the system reaches a stable manifold, the time to reach equilibrium depends on cellular death and birth rates. These rates shape the time scales, in particular, in coevolutionary dynamics of growth factor producers and free-riders. Replicator dynamics might be an appropriate framework only when birth and death rates are of similar magnitude. Otherwise, population growth effects cannot be neglected when predicting the time to reach an equilibrium, and cell-type-specific rates have to be accounted for explicitly.
A geometric method for eigenvalue problems with low-rank perturbations
Authors: Anastasio Thomas J. , Barreiro Andrea K. , Bronski Jared C.
Published: September 2017

We consider the problem of finding the spectrum of an operator taking the form of a low-rank (rank one or two) non-normal perturbation of a well-understood operator, motivated by a number of problems of applied interest which take this form. We use the fact that the system is a low-rank perturbation of a solved problem, together with a simple idea of classical differential geometry (the envelope of a family of curves) to completely analyse the spectrum. We use these techniques to analyse three problems of this form: a model of the oculomotor integrator due to Anastasio & Gad (2007J. Comput. Neurosci.22, 239–254. (doi:10.1007/s10827-006-0010-x)), a continuum integrator model, and a non-local model of phase separation due to Rubinstein & Sternberg (1992IMA J. Appl. Math.48, 249–264. (doi:10.1093/imamat/48.3.249)).