bluuebunny/crossref_metadata_2025 huggingface dataset:
An interpretable low-complexity machine learning framework for robust exome-based in-silico diagnosis of Crohn’s disease patients
Authors: Raimondi Daniele , Simm Jaak , Arany Adam , Fariselli Piero , Cleynen Isabelle , Moreau Yves
Published: February 2020

Whole exome sequencing (WES) data are allowing researchers to pinpoint the causes of many Mendelian disorders. In time, sequencing data will be crucial to solve the genome interpretation puzzle, which aims at uncovering the genotype-to-phenotype relationship, but for the moment many conceptual and technical problems need to be addressed. In particular, very few attempts at the in-silico diagnosis of oligo-to-polygenic disorders have been made so far, due to the complexity of the challenge, the relative scarcity of the data and issues such as batch effects and data heterogeneity, which are confounder factors for machine learning (ML) methods. Here, we propose a method for the exome-based in-silico diagnosis of Crohn’s disease (CD) patients which addresses many of the current methodological issues. First, we devise a rational ML-friendly feature representation for WES data based on the gene mutational burden concept, which is suitable for small sample sizes datasets. Second, we propose a Neural Network (NN) with parameter tying and heavy regularization, in order to limit its complexity and thus the risk of over-fitting. We trained and tested our NN on 3 CD case-controls datasets, comparing the performance with the participants of previous CAGI challenges. We show that, notwithstanding the limited NN complexity, it outperforms the previous approaches. Moreover, we interpret the NN predictions by analyzing the learned patterns at the variant and gene level and investigating the decision process leading to each prediction.
What Variables Correlate With Different Clinical Outcomes of Abusive Head Injury?
Authors: Ajmera Sonia , Motiwala Mustafa , Weeks Matt , Oravec Chesney S , Hersh David S , Fraser Brittany D , Vaughn Brandy , Klimo Paul
Published: February 2020

BACKGROUND

The spectrum of injury severity for abusive head trauma (AHT) severity is broad, but outcomes are unequivocally worse than accidental trauma. There are few publications that analyze different outcomes of AHT.

OBJECTIVE

To determine variables associated with different outcomes of AHT.

METHODS

Patients were identified using our AHT database. Three different, but not mutually exclusive, outcomes of AHT were modeled: (1) death or hemispheric stroke (diffuse loss of grey-white differentiation); (2) stroke(s) of any size; and (3) need for a neurosurgical operation. Demographic and clinical variables were collected and correlations to the 3 outcomes of interest were identified using bivariate and multivariable analysis.

RESULTS

From January 2009 to December 2017, 305 children were identified through a prospectively maintained AHT database. These children were typically male (60%), African American (54%), and had public or no insurance (90%). A total of 29 children (9.5%) died or suffered a massive hemispheric stroke, 57 (18.7%) required a neurosurgical operation, and 91 (29.8%) sustained 1 or more stroke. Death or hemispheric stroke was statistically associated with the pupillary exam (odds ratio [OR] = 45.7) and admission international normalized ratio (INR) (OR = 17.3); stroke was associated with the pupillary exam (OR = 13.2), seizures (OR = 14.8), admission hematocrit (OR = 0.92), and INR (9.4), and need for surgery was associated with seizures (OR = 8.6).

CONCLUSION

We have identified several demographic and clinical variables that correlate with 3 clinically applicable outcomes of abusive head injury.
Adherence to national paediatric bronchiolitis management guidelines and impact on emergency department resource utilization
Authors: Maki Kate , Azizi Hawmid , Hans Prabhjas , Doan Quynh
Published: February 2020

Objective

To evaluate the association between the use of nonrecommended pharmacology (salbutamol and corticosteroids) per national bronchiolitis guidelines, either during the index visit or at discharge, and system utilization measures (frequency of return visits [RTED] and on paediatric emergency department [PED] length of stay [LOS]).

Study Design

We conducted a retrospective case control study of 185 infants (≤12 months old) who presented to the PED between December 2014 and April 2017 and discharged home with a clinical diagnosis of bronchiolitis. Inclusion criteria included ≥ 1 viral prodromal symptom and ≥ 1 physical exam finding of respiratory distress. Cases were defined as infants who had ≥ 1 RTED within 7 days of their index visit and controls were matched for age and acuity but without RTED. Logistic regression analysis and multivariable linear regression were used to assess the odds of RTED and PED LOS associated with nonadherence to pharmaceutical recommendations per AAP and CPS bronchiolitis guidelines.

Results

Use of nonrecommended pharmacology per national bronchiolitis guidelines was documented among 39% of the 185 study participants. Adjusting for acuity of index visit, age, severe tachypnea, oxygen desaturation, and dehydration, use of nonrecommended pharmacology was not associated with RTED (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.47 to 2.03). Use of salbutamol and corticosteroids, however, were each independently associated with increased PED LOS (58.3 minutes [P=0.01] and 116.7 minutes [P<0.001], respectively).

Conclusion

Nonadherence to the pharmaceutical recommendations of national bronchiolitis guidelines was not associated with RTED but salbutamol and corticosteroid use increased PED LOS.
Passion and Melancholy: Julian of Norwich’s Medical Hermeneutic
Authors: Lucas Hannah
Published: February 2020

This paper examines Julian of Norwich’s representation of the Passion of Christ in her Revelation of Love, proposing that Julian reads the body of Christ through a medical hermeneutic which echoes vernacular texts of the spiritual ‘remedy’ genre. The essay’s overarching argument is that Julian’s engagement with humoral theory positions her as a participant in an emerging collective imaginary of vernacular medicine, related to the translation and transmission of medical texts in the late fourteenth and early fifteenth centuries. Comparing the Latin and Middle English versions of William Flete’s Remedies Against Temptations and related works, I examine how this spiritual-medical discourse is expressed in vernacular texts contemporary to Julian’s life. I then consider Julian’s own sophisticated invocation of medical theory and practice in her description of the Passion, where she deploys diagnostic markers to depict an ‘ex-sanguination’ of Christ’s perfect disposition. These markers serve to reify the traditional figure of the ‘Man of Sorrows’ with a portrayal of Christ’s body as melancholic, a humoral affliction which reiterates both his suffering and his ‘love-longing’ for humanity. Finally, I show how this medical account functions in Julian’s optimistic theology, offering a reminder of the eternal presence of God’s love even in times of pain and disease.
Ending the HIV Epidemic in the United States
Authors: Demeke Hanna B. , McCray Eugene , Dean Hazel D.
Published: February 2020

A new initiative aims to reduce new infections by 75% within five years.
The Medical Treatment of Botulism
Authors: Scruth Elizabeth , Schoenlein Max
Published: February 2020

Editor's note: The mission of Cochrane Nursing is to provide an international evidence base for nurses involved in delivering, leading, or researching nursing care. Cochrane Corner provides summaries of recent systematic reviews from the Cochrane Library. For more information, see https://nursing.cochrane.org.
New Treatment for Partial-Onset Seizures in Adults
Authors: Aschenbrenner Diane S.
Published: February 2020

Cenobamate (Xcopri) is now approved to treat partial-onset seizures in adults.

Serious adverse effects include drug reaction with eosinophilia and systemic symptoms (also called multiorgan hypersensitivity) and a shortened QT interval.
Population Genomic Screening of All Young Adults in a Health-Care System: A Cost-Effectiveness Analysis
Authors: Zhang Lei , Bao Yining , Riaz Moeen , Tiller Jane , Liew Danny , Zhuang Xun , Amor David J. , Huq Aamira , Petelin Lara , Nelson Mark , James Paul A. , Winship Ingrid , McNeil John J. , Lacaze Paul
Published: February 2020

(Abstracted from Genet Med 2019;21:1958–1968)

It is generally accepted that genetic screening has the potential to prevent disease through early identification. The authors suggest that one cost-effective way to implement genetic screening into a single-payer or state-funded health care system is a combined genetic screening approach—one that tests for multiple conditions concurrently—versus individual targeted testing.
What Does Context Have to Do With Anything? A Study of Professional Identity Formation in Physician-Trainees Considered Underrepresented in Medicine
Authors: Wyatt Tasha R. , Rockich-Winston Nicole , Taylor Taryn R. , White DeJuan
Published: February 2020

Purpose

Research on professional identity formation has largely ignored how race, ethnicity, and the larger sociohistorical context work to shape medical students’ professional identity. Researchers investigated how physician-trainees considered underrepresented in medicine (URM) negotiate their professional identity within the larger sociohistorical context that casts them in a negative light.

Method

In this qualitative study, 14 black/African American medical students were recruited from the Medical College of Georgia at Augusta University and Emory University College of Medicine between September 2018 and April 2019. Using constructive grounded theory and Swann’s model of identity negotiation, the authors analyzed interview data for how students negotiate their racial and professional identities within medical education.

Results

The results indicated that URM students were aware of the negative stereotypes ascribed to black individuals and the potential for the medical community to view them negatively. In response, students employed identity cues and strategies to bring the community’s perceptions in line with how they perceived themselves—black and a physician. Specifically, students actively worked to integrate their racial and professional identities by “giving back” to the African American community. Community-initiated mentoring from non-URM physicians helped to reify students’ hope that they could have a racialized professional identity.

Conclusions

Race, ethnicity, and the larger sociohistorical context is often overlooked in professional identity formation research, and this omission has resulted in an underappreciation of the challenges URM physicians’ experience as they develop a professional identity. Within the context of this study, findings demonstrated that black/African American physicians negotiated the formation of professional identity within a challenging sociohistorical context, which should be given greater consideration in related research.
Beyond High-Stakes Testing: Learner Trust, Educational Commodification, and the Loss of Medical School Professionalism
Authors: Hafferty Frederic W. , O’Brien Bridget C. , Tilburt Jon C.
Published: February 2020

With ever-growing emphasis on high-stakes testing in medical education, such as the Medical College Admission Test and the United States Medical Licensing Examination Step 1, there has been a recent surge of concerns on the rise of a “Step 1 climate” within U.S. medical schools. The authors propose an alternative source of the “climate problem” in current institutions of medical education. Drawing on the intertwined concepts of trust and professionalism as organizational constructs, the authors propose that the core problem is not hijacking-by-exam but rather a hijackable learning environment weakened by a pernicious and under-recognized tide of commodification within the U.S. medical education system. The authors discuss several factors contributing to this weakening of medicine’s control over its learning environments, including erosion of trust in medical school curricula as adequate preparation for entry into the profession, increasing reliance on external profit-driven sources of medical education, and the emergence of an internal medical education marketplace. They call attention to breaches in the core tenets of a profession—namely a logic that differentiates its work from market and managerial forces, along with related slippages in discretionary decision making. The authors suggest reducing reliance on external performance metrics (high-stakes exams and corporate rankings), identifying and investing in alternative metrics that matter, abandoning the marketization of medical education “products,” and attending to the language of educational praxis and its potential corruption by market and managerial lexicons. These steps might salvage some self-governing independence implied in the term “profession” and make possible (if not probable) a recovery of a public trust becoming of the term and its training institutions.
Experiential Learning in Project-Based Quality Improvement Education: Questioning Assumptions and Identifying Future Directions
Authors: Goldman Joanne , Kuper Ayelet , Baker G. Ross , Bulmer Beverly , Coffey Maitreya , Jeffs Lianne , Shea Christine , Whitehead Cynthia , Shojania Kaveh G. , Wong Brian
Published: February 2020

Purpose

Project-based experiential learning is a defining element of quality improvement (QI) education despite ongoing challenges and uncertainties. The authors examined stakeholders’ perceptions and experiences of QI project-based learning to increase understanding of factors that influence learning and project experiences.

Method

The authors used a case study approach to examine QI project-based learning in 3 advanced longitudinal QI programs, 2 at the University of Toronto and 1 at an academic tertiary-care hospital. From March 2016 to June 2017, they undertook 135 hours of education program observation and 58 interviews with learners, program directors, project coaches, and institutional leaders and reviewed relevant documents. They analyzed data using a conventional and directed data analysis approach.

Results

The findings provide insight into 5 key factors that influenced participants’ project-based learning experiences and outcomes: (1) variable emphasis on learning versus project objectives and resulting benefits, tensions, and consequences; (2) challenges integrating the QI project into the curriculum timeline; (3) project coaching factors (e.g., ability, capacity, role clarity); (4) participants’ differing access to resources and ability to direct a QI project given their professional roles; and (5) workplace environment influence on project success.

Conclusions

The findings contribute to an empirical basis toward more effective experiential learning in QI by identifying factors to target and optimize. Expanding conceptualizations of project-based learning for QI education beyond learner-initiated, time-bound projects, which are at the core of many QI educational initiatives, may be necessary to improve learning and project outcomes.
Online Forums and the “Step 1 Climate”: Perspectives From a Medical Student Reddit User
Authors: Ronner Lukas , Linkowski Lauren
Published: February 2020

Reddit is a popular content aggregator and discussion website that plays an important role in shaping medical student culture and study habits. The forum r/medicalschool, in particular, provides a distilled view into contemporary U.S. medical students’ attitudes and deteriorating relationship to their home institutions’ educators and curricula. As a national discussion on United States Medical Licensing Examination Step 1 reform emerges, the role of forums like r/medicalschool in shaping a “Step 1 climate” via the design and dissemination of prescriptive Step 1 study regimens based on commercially available resources and crowdsourced flash card decks goes largely unseen and undiscussed by medical educators. This Invited Commentary aims to introduce medical educators to these forums, highlight the common attitudes borne out of them, and contextualize one popular proposal for Step 1 reform—shifting to a pass/fail exam—within the author’s experience as an online forum insider.
Usefulness of Parasternal Intercostal Muscle Ultrasound during Weaning from Mechanical Ventilation
Authors: Dres Martin , Dubé Bruno-Pierre , Goligher Ewan , Vorona Stefannie , Demiri Suela , Morawiec Elise , Mayaux Julien , Brochard Laurent , Similowski Thomas , Demoule Alexandre
Published: February 2020

Background

The assessment of diaphragm function with diaphragm ultrasound seems to bring important clinical information to describe diaphragm work and weakness. When the diaphragm is weak, extradiaphragmatic muscles may play an important role, but whether ultrasound can also assess their activity and function is unknown. This study aimed to (1) evaluate the feasibility of measuring the thickening of the parasternal intercostal and investigate the responsiveness of this muscle to assisted ventilation; and (2) evaluate whether a combined evaluation of the parasternal and the diaphragm could predict failure of a spontaneous breathing trial.

Methods

First, an exploratory evaluation of the parasternal in 23 healthy subjects. Second, the responsiveness of parasternal to several pressure support levels were studied in 16 patients. Last, parasternal activity was compared in presence or absence of diaphragm dysfunction (assessed by magnetic stimulation of the phrenic nerves and ultrasound) and in case of success/failure of a spontaneous breathing trial in 54 patients.

Results

The parasternal was easily accessible in all patients. The interobserver reproducibility was good (intraclass correlation coefficient, 0.77 (95% CI, 0.53 to 0.89). There was a progressive decrease in parasternal muscle thickening fraction with increasing levels of pressure support (Spearman ρ = −0.61 [95% CI, −0.74 to −0.44]; P < 0.0001) and an inverse correlation between parasternal muscle thickening fraction and the pressure generating capacity of the diaphragm (Spearman ρ = −0.79 [95% CI, −0.87 to −0.66]; P < 0.0001). The parasternal muscle thickening fraction was higher in patients with diaphragm dysfunction: 17% (10 to 25) versus 5% (3 to 8), P < 0.0001. The pressure generating capacity of the diaphragm, the diaphragm thickening fraction and the parasternal thickening fraction similarly predicted failure or the spontaneous breathing trial.

Conclusions

Ultrasound assessment of the parasternal intercostal muscle is feasible in the intensive care unit and provides novel information regarding the respiratory capacity load balance.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Open Reduction Is Associated With Greater Hazard of Early Reoperation After Internal Fixation of Displaced Femoral Neck Fractures in Adults 18–65 Years
Authors: Patterson Joseph T. , Ishii Keisuke , Tornetta Paul , Leighton Ross K. , Friess Darin M. , Jones Clifford B. , Levine Ari , Maclean Jeffrey J. , Miclau Theodore , Mullis Brian H. , Obremskey William T. , Ostrum Robert F. , Reid J. Spence , Ruder John A. , Saleh Anas , Schmidt Andrew H. , Teague David C. , Tsismenakis Antonios , Westberg Jerald R. , Morshed Saam
Published: February 2020

Objectives:

To determine (1) which factors are associated with the choice to perform an open reduction and (2) by adjusting for these factors, if the choice of reduction method is associated with reoperation.

Design:

Retrospective cohort study with radiograph and chart review.

Setting:

Twelve Level 1 North American trauma centers.

Patients:

Two hundred thirty-four adults 18–65 years of age with an isolated, displaced, OTA/AO type 31-B2 or type 31-B3 femoral neck fracture treated with internal fixation with minimum of 6-month follow-up or reoperation. Exclusion criteria were pathologic fractures, associated femoral head or shaft fractures, and primary arthroplasty.

Intervention:

Open or closed reduction technique during internal fixation.

Main outcome:

Cox proportional hazard of reoperation adjusting for propensity score for open reduction based on injury, demographic, and medical factors. Reduction quality was assessed by 3 senior orthopaedic traumatologists as “acceptable” or “unacceptable” on AP and lateral postoperative radiographs.

Results:

Median follow-up was 1.5 years. One hundred six (45%) patients underwent open reduction. Reduction quality was not significantly affected by open versus closed approach (71% vs. 69% acceptable, P = 0.378). The propensity to receive an open reduction was associated with study center; younger age; male sex; no history of injection drug use, osteoporosis, or cerebrovascular disease; transcervical fracture location; posterior fracture comminution; and surgery within 12 hours. A total of 35 (33%) versus 28 (22%) reoperations occurred after open versus closed reduction (P = 0.056). Open reduction was associated with a 2.4-fold greater propensity-adjusted hazard of reoperation (95% confidence interval 1.3–4.4, P = 0.004). A total of 35 (15%) patients underwent subsequent total hip arthroplasty or hemiarthroplasty.

Conclusions:

Open reduction of displaced femoral neck fractures in nonelderly adults is associated with a greater hazard of reoperation without significantly improving reduction. Prospective randomized trials are indicated to confirm a causative effect of open versus closed reduction on outcomes after femoral neck fracture.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
The Use of Tranexamic Acid (TXA) in Neuromuscular Hip Reconstruction: Can We Alter the Need for Blood Transfusion?
Authors: Lins Laura A.B. , Miller Patricia E. , Samineni Aneesh , Watkins Colyn J. , Matheney Travis H. , Snyder Brian D. , Shore Benjamin J.
Published: February 2020

Background:

Children with neuromuscular complex chronic conditions (NMCCC) frequently undergo hip reconstruction surgery requiring blood transfusion. The purpose of this study is to examine the efficacy of tranexamic acid (TXA) to reduce blood loss and transfusion requirement in NMCCC children undergoing hip reconstruction surgery.

Methods:

Children with NMCCC undergoing hip reconstruction surgery between 2013 and 2018 were identified. Two cohorts were identified: those who received TXA and those who did not. Patient and surgical characteristics between cohorts were used for propensity matching. Patients were matched on the basis of comorbid factors, bilateral involvement, pelvic osteotomy, open reduction, and surgeon. Comparative outcomes between cohorts were analyzed for intraoperative and postoperative blood loss and transfusion requirements and length of hospital stay (LOS).

Results:

A total of 166 patients underwent hip surgery at an average of 9.6 years (SD, 4.0). Propensity matching utilized 72% of the cohort including 47 TXA and 72 non-TXA subjects. There were no differences in patient or surgical characteristics across matched groups. Fifteen (15/47, 32%) TXA subjects required a postoperative blood transfusion compared with the 47% (34/72) of non-TXA subjects who required a transfusion and intraoperative transfusion rates were similar between the 2 groups. There was no significant difference in complication rate (TXA, 79%; non-TXA, 86%), reported estimated blood loss (median=200 mLfor both) or LOS (median=6 d for both). Hematocrit levels were slightly higher in TXA subjects intraoperatively (P=0.047), at the end of surgery (P=0.04), and for the overall lowest perioperative level (P=0.04). The overall percent loss of estimated blood volume was less for those who were given TXA compared with those who were not (P=0.001).

Conclusions:

The use of TXA during hip reconstruction surgery in NMCCC children significantly reduced the percent loss of estimated blood volume and postoperative transfusion rate. Further prospective multicenter studies are needed to verify the positive effects and safety of TXA in the setting of hip reconstruction surgery in NMCCC children.

Level of Evidence:

Level III—retrospective comparative study.
Effect of Antibiotic Discontinuation Strategies on Mortality and Infectious Complications in Critically Ill Septic Patients: A Meta-Analysis and Trial Sequential Analysis*
Authors: Arulkumaran Nishkantha , Khpal Muska , Tam Karen , Baheerathan Aravindhan , Corredor Carlos , Singer Mervyn
Published: February 2020

Objective:

To investigate methods of antibiotic duration minimization and their effect on mortality and infectious complications in critically ill patients.

Data Sources:

A systematic search of PubMed, Embase (via Ovid), clinicaltrials.gov, and the Cochrane Central Register of Controlled Trials (via Wiley) (CENTRAL, Issue 2, 2015).

Study Selection:

Randomized clinical trials comparing strategies to minimize antibiotic duration (days) for patients with infections or sepsis in intensive care.

Data Extraction:

A systematic review with meta-analyses and trial sequential analyses of randomized clinical trials. Dichotomous data are presented as relative risk (95% CIs) and p value, and continuous data are presented as mean difference (CI) and p value.

Data Synthesis:

We included 22 randomized clinical trials (6,046 patients). Strategies to minimize antibiotic use included procalcitonin (14 randomized clinical trials), clinical algorithms (two randomized clinical trials), and fixed-antibiotic duration (six randomized clinical trials). Procalcitonin (–1.23 [–1.61 to –0.85]; p < 0.001), but not clinical algorithm–guided antibiotic therapy (–7.41 [–18.18 to 3.37]; p = 0.18), was associated with shorter duration of antibiotic therapy. The intended reduction in antibiotic duration ranged from 3 to 7 days in fixed-duration antibiotic therapy randomized clinical trials. Neither procalcitonin-guided antibiotic treatment (0.91 [0.82–1.01]; p = 0.09), clinical algorithm–guided antibiotic treatment (0.67 [0.30–1.54]; p = 0.35), nor fixed-duration antibiotics (1.21 [0.90–1.63]; p = 0.20) were associated with reduction in mortality. Z-curve for trial sequential analyses of mortality associated with procalcitonin-guided therapy did not reach the trial sequential monitoring boundaries for benefit, harm, or futility (adjusted CI, 0.72–1.10). Trial sequential analyses for mortality associated with clinical algorithm and fixed-duration treatment accumulated less than 5% of the required information size. Despite shorter antibiotic duration, neither procalcitonin-guided therapy (0.93 [0.84–1.03]; p = 0.15) nor fixed-duration antibiotic therapy (1.06 [0.74–1.53]; p = 0.75) was associated with treatment failure.

Conclusions:

Although the duration of antibiotic therapy is reduced with procalcitonin-guided therapy or prespecified limited duration, meta-analysis and trial sequential analyses are inconclusive for mortality benefit. Data on clinical algorithms to guide antibiotic cessation are limited.
Development and Feasibility of a Safety Plan Mobile Application for Adolescent Suicide Attempt Survivors
Authors: Jeong Yeo Won , Chang Hye Jung , Kim Jung A
Published: February 2020

Past suicide attempts are a powerful predictor of suicide. This study developed and evaluated the feasibility of a mobile application for creating safety plans, which include coping strategies that can be immediately accessed and used by suicide attempt survivors during a crisis. A safety plan mobile application, called Brake of My Mind, was developed (study 1). Heuristic evaluation (for experts) and user evaluations (for health professionals and adolescent suicide attempt survivors) were performed. A pilot test was then conducted based on the theory of planned behavior to evaluate the feasibility of Brake of My Mind (study 2). Three adolescent suicide attempt survivors used a pilot version of Brake of My Mind. Attitude toward suicide attempts, subjective norms, perceived behavioral control, and suicide intentions were assessed before, immediately after, and 1 week after using Brake of My Mind. Brake of My Mind showed very few low-priority usability problems, and it was considered a “good” and “acceptable” application. In study 2, median scores for attitudes toward suicide attempts, perceived behavioral control, and suicide intentions decreased over time after using Brake of My Mind. The subjective norm scores did not change. Brake of My Mind is an acceptable application for adolescent suicide attempt survivors that appears effective in decreasing their positive attitude toward suicide attempts.
Indications and Evidence for Dual Antiplatelet Therapy After Acute Ischemic Stroke
Authors: Ringler Jessica , Steck Mackenzie , Shah Samarth P. , Chester Katleen W.
Published: February 2020

The antiplatelet landscape for the secondary prevention of ischemic stroke has changed significantly over the past decade. Poststroke dual antiplatelet regimens are becoming increasingly routine as supported by recent literature and guideline recommendations. Dual antiplatelet therapy after stroke generally consists of aspirin and clopidogrel and is considered in the short term after stroke in select populations including those with mild stroke or transient ischemic attack and in patients with severe intracranial atherosclerosis. When initiating dual antiplatelet therapy, factors that may increase a patient's risk of bleeding must be weighed against the patient's risk of future ischemic events. This review focuses on antiplatelet medications available in the United States with the aim to provide a summary of the available literature on poststroke dual antiplatelet therapy, pharmacological nuances of the agents, and reversal of antiplatelets in the setting of intracerebral hemorrhage.
Pharmacologic Management of Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage
Authors: Smetana Keaton S. , Buschur Pamela L. , Owusu-Guha Jocelyn , May Casey C.
Published: February 2020

Aneurysmal subarachnoid hemorrhage (aSAH) is responsible for 5% to 10% of all strokes in the United States annually and is a neurologic emergency with considerable morbidity and mortality. A common complication of aSAH is cerebral vasospasm (CVS) or narrowing of the cerebral arteries. While nearly 70% of aSAH patients will develop CVS, approximately 30% of those patients will go on to develop delayed cerebral ischemia, defined as symptomatic vasospasm or cerebral infarction demonstrated on imaging. While the pathophysiology of CVS is unclear, the prevention and treatment of this complication are a focus of ongoing research. Despite continued efforts, only one medication, nimodipine, is Food and Drug Administration approved for the improvement of neurologic outcomes by reducing the incidence and severity of ischemic deficits in patients with CVS during aSAH. This review provides nurse practitioners and the bedside nursing staff with a summary of the available literature on the pharmacologic management of CVS. It focuses on oral, intravenous, intra-arterial, and intraventricular medications available in the United States that may be utilized in the management of CVS.
CAR T-Cell-Associated Neurotoxicity
Authors: Rivera Amanda M. , May Scott , Lei Matthew , Qualls Stephanie , Bushey Katelyn , Rubin Daniel B. , Barra Megan E.
Published: February 2020

Axicabtagene ciloleucel and tisagenlecleucel are 2 chimeric antigen receptor (CAR) T-cell immunotherapies targeting CD19 for the treatment of B-cell acute lymphoblastic leukemia and non-Hodgkin lymphoma. Two commonly recognized complications associated with CAR T-cell therapies are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS can occur in isolation or concomitantly with CRS following CAR T-cell therapy and may be due to disruption of the blood-brain barrier and the effects of elevated cytokine levels on the central nervous system. Presently, the optimum management of ICANS remains elusive, as there lacks consensus guidelines. The objective of this review is to provide a comprehensive summary of ICANS and strategies for prompt identification and management of patients presenting to the intensive care unit with this syndrome.
Control of Shivering During Targeted Temperature Management
Authors: Armahizer Michael J. , Strein Micheal , Pajoumand Mehrnaz
Published: February 2020

Targeted temperature management (TTM) is used frequently in patients with a variety of diseases, especially those who have experienced brain injury and/or cardiac arrest. Shivering is one of the main adverse effects of TTM that can often limit its implementation and efficacy. Shivering is the body's natural response to hypothermia and its deleterious effects can negate the benefits of TTM. The purpose of this article is to provide an overview of TTM strategies and shivering management.
Prognostic Significance of Preoperative Prognostic Nutritional Index in Patients Undergoing Nephrectomy for Nonmetastatic Renal Cell Carcinoma
Authors: Kim Se Joong , Kim Sun Il , Cho Dae Sung
Published: February 2020

Objective:

The objective of this study was to assess the value of a preoperative Prognostic Nutritional Index (PNI) for predicting the survival of patients with nonmetastatic renal cell carcinoma (RCC) treated with partial or radical nephrectomy.

Materials and Methods:

The medical records of 480 patients with RCC who underwent partial or radical nephrectomy at 2 institutions between June 1994 and July 2017 were retrospectively reviewed. After the exclusion of 21 patients with lymph node or distant metastasis, the data of 459 patients with nonmetastatic RCC were included. The PNI was calculated using a combination of serum albumin level and lymphocyte count in the peripheral blood, as described previously. The prognostic significance of various clinicopathologic variables, including the PNI, was assessed in univariate and multivariate analyses.

Results:

The univariate analysis identified anemia, PNI, tumor size, T stage, Fuhrman nuclear grade, sarcomatoid differentiation, and lymphovascular invasion as significant prognostic factors of recurrence-free survival (RFS) and cancer-specific survival (CSS). In the multivariate analysis, anemia (P=0.010), PNI (P<0.001), tumor size (P<0.001), T stage (P<0.001), Fuhrman nuclear grade (P=0.023), sarcomatoid differentiation (P=0.003), and lymphovascular invasion (P=0.005) were independent prognostic factors for RFS, versus anemia (P=0.020), PNI (P=0.002), tumor size (P<0.001), T stage (P<0.001), sarcomatoid differentiation (P<0.001), and lymphovascular invasion (P=0.018) for CSS.

Conclusions:

The PNI is an independent prognostic factor for RFS and CSS in patients with nonmetastatic RCC treated with partial or radical nephrectomy. It may, therefore, be a useful tool for predicting recurrence and survival in these patients.
Toward Credible Patient-centered Meta-analysis
Authors: Manski Charles F.
Published: February 2020

Meta-analysis is widely used to combine the findings of multiple disparate studies of health risks or treatment response. Meta-analysis often uses a random-effects model to express heterogeneity across studies. The model interprets a weighted average of study-specific estimates as an estimate of a mean parameter across a hypothetical population of studies. The relevance of this methodology to patient care is not evident. Clinicians need to assess risks and choose treatments for populations of patients, not for populations of studies. This article draws on econometric research on partial identification to propose principles for patient-centered meta-analysis. One specifies a patient prediction of concern and determines what each available study reveals. Given common imperfections in internal and external validity, studies typically yield credible set-valued rather than point predictions. Thus, a study may enable one to conclude that a probability of disease, or mean treatment response, lies within a range of possibilities. Patient-centered meta-analysis would combine the findings of multiple studies by computing the intersection of the set-valued predictions that they yield.
Cosmetic Tattooing and Early Onset Basal Cell Carcinoma: A Population-based Case–Control Study from New Hampshire
Authors: Barton Dorothea Torti , Zens Michael S. , Marmarelis Eleni L. , Gilbert-Diamond Diane , Karagas Margaret R.
Published: February 2020

Background:

Cosmetic tattoos use dyes with carcinogenic potential. Skin cancers arising in tattoos have been reported.

Methods:

We investigated whether risk of early onset basal cell carcinoma was related to the site and colors of cosmetic tattoos as part of a population-based case–control study of cases (ages 25–50 years), identified from a state-wide surveillance system, and age- and gender-matched controls, selected from driver’s license records, randomly assigned an anatomic site of the cases.

Results:

One hundred fifty-six cases (17%) with early onset basal cell carcinoma and 213 controls (26%) reported cosmetic tattoos. Among those with tattoos, the adjusted odds ratio of basal cell carcinoma at the tattoo site compared to another site was 1.8 (95% confidence interval = 1.0, 3.2). We observed the strongest associations for yellow and green tattoo colors.

Conclusion:

Our preliminary findings support the possibility of an enhanced risk of early onset basal cell carcinomas at the site of cosmetic tattoos.
The Tenons’ Layer Reposition Approach of Trabeculectomy: A Longitudinal Case Series of a Mixed Group of Glaucoma Patients
Authors: Chan Poemen P. , Wong Liam Y.N. , Chan Tommy C.Y. , Lai Gilda , Baig Nafees
Published: February 2020

Synopsis:

This 1-year prospective study demonstrated that the Tenon’s layer reposition approach of trabeculectomy could achieve zero leakage rate, minimal rate of transient hypotony without compromising the surgical outcome.

Purpose:

The purpose of this study was to investigate the effectiveness and safety of a Tenon’s layer reposition approach of trabeculectomy.

Methods:

A prospective, noncomparative case series of 30 eyes of 30 Chinese patients with mixed types of glaucoma who underwent fornix-based trabeculectomy combined with intraoperative mitomycin C application. During the conjunctival flap closure, the Tenons’ layer was identified, separated, and anchored on to the sclera surface with 8/0 vicryl, followed by conjunctival closure with 10/0 nylon as a separate layer. All patients were followed up for 1 year. Assessment including intraocular pressure (IOP), vertical cup-disc ratio measurement, best-corrected visual acuity, and visual field examination were performed before and after the operation. Qualified and complete success was defined as IOP of ≤21 mm Hg in 2 consecutive visits with or without medication, respectively. Outcomes were evaluated using scattered plot and Kaplan-Meier survival curve.

Results:

Twenty-one eyes (70%) and 28 eyes (93.3%) achieved complete and partial success at 1 year, respectively. There was a significant reduction of IOP (28.5±9.6 to 15.5±2.6 mm Hg, P<0.001) and medication use (4.4±0.9 to 0.8±1.2 bottles/eye, P<0.001). There were no significant changes in best-corrected visual acuity, vertical cup-disc ratio, and visual field indices. No wound leak was identified throughout the study. The procedure did not induce significant astigmatic change. Other postoperative complications, including 2 eyes (6.7%) with transient hypotony and 1 eye (3.3%) required cataract surgery, were of relatively low rate.

Conclusion:

The Tenon’s layer reposition approach of performing trabeculectomy is a safe and efficacious procedure for Chinese subjects with different types of glaucoma.
Tear Meniscus Imaging by Anterior Segment-Optical Coherence Tomography in Medically Controlled Glaucoma
Authors: Agnifili Luca , Brescia Lorenza , Scatena Barbara , Oddone Francesco , Figus Michele , Perna Fabiana , Doronzo Emanuele , D’Ugo Erminia , Mastropasqua Leonardo
Published: February 2020

Purpose:

The purpose of this study was to investigate the tear meniscus in medically controlled glaucoma patients (MCGP) using anterior segment-optical coherence tomography (AS-OCT).

Materials and Methods:

Fifty-six MCGP, 24 patients with evaporative dry eye (EDE), and 30 healthy subjects (controls), were enrolled. MCGP were divided into group 1 (14 eyes): β-blockers; group 2 (14 eyes): prostaglandin analogs; group 3 (28 eyes) ≥2 drugs. Ocular Surface Disease Index (OSDI) questionnaire, tear film break-up time, corneal fluorescein staining, Schirmer Test I, and tear meniscus height (lower and upper: L-TMH, U-TMH) and area (L-TMA, U-TMA) using AS-OCT, were performed.

Results:

OSDI score was higher (P<0.05) in patients with EDE and in group 3 compared with groups 1, 2, and controls. No significant differences were found between group 3 and patients with EDE for all clinical parameters. L-TMA was significantly lower in groups 1 to 3 (P<0.05) and in EDE patients (P<0.001) compared with controls, and it was lower in group 3 and in EDE patients compared with groups 1 and 2 (P<0.05). L-TMH was lower in groups 1 to 3 and in EDE patients compared with controls (P<0.001), and in EDE patients and in group 3 compared with groups 1 and 2 (P<0.05). U-TMA was lower in EDE and MCGP groups compared with controls (P<0.05). L-TMA and L-TMH negatively correlated with OSDI score (P<0.01, r=−0.379 and P<0.01, r=−0.352, respectively).

Conclusions:

AS-OCT permits a noninvasive and reliable tear meniscus imaging in medically controlled glaucoma, depicting the glaucoma-related ocular surface disease as a dry eye disease–like condition. Thus, reduced values of TMH and TMA can be proposed as structural indicators of glaucoma therapy–related ocular surface disease.
Detection of Respiratory Viruses in the Clinical Outcome of Children With Fever and Neutropenia
Authors: Cerdeira Barreiro Natalia , Santiago-García Begoña , Casas Inmaculada , Pozo Francisco , Santos Sebastián Mar , Navarro Marisa , Mata Cristina , Garrido-Colino Carmen , Catalán Pilar , Hernández-Rupérez Belén , Huerta Jorge , Rincón-López Elena , Beléndez Cristina , García-Morín Marina , Cela Elena , Hernández-Sampelayo Teresa , Saavedra-Lozano Jesús
Published: February 2020

Background:

Several evidence-based guidelines for the management of children with febrile neutropenia (FN) have been published, with special focus in bacterial and fungal infections. However, the role of acute respiratory infections caused by respiratory viruses (RV) has not been clearly established. The aim of this study was to evaluate the epidemiology, clinical presentation and outcome of acute respiratory infections in children with FN.

Methods:

Patients, <18 years of age admitted to the Pediatric Oncology-Hematology Unit after developing FN between November 2010 and December 2013, were prospectively included in the study. Children were evaluated by clinical examination and laboratory tests. Nasopharyngeal sample was obtained for detection of RV.

Results:

There was a total of 112 episodes of FN in 73 children admitted to the hospital during a 32-month period. According to disease severity, 33% of the episodes were considered moderate or severe. Rhinovirus was the most frequently detected RV (66.6%; 24/36), followed by parainfluenza. On regard to clinical outcome, RV-infected children developed fewer episodes of moderate or severe FN compared with non-RV infected children (16.7% vs. 33.3%; P = 0.08).

Conclusions:

A great proportion of children with FN admitted to a tertiary hospital had a RV isolation. The rate of this RV isolation was significantly higher when a rapid molecular test was used compared with conventional microbiologic methods. Rhinovirus was the most frequently isolated, although its role as an active agent of acute infection was not clear. Children with FN and a RV isolate had a lower rate of severe disease.
The Incidence of Tuberculosis in Infants, Siaya District, Western Kenya
Authors: Nduba Videlis , Kaguthi Grace , van’t Hoog Anna H. , Mitchell Ellen M. H. , Borgdorff Martien
Published: February 2020

Background:

Infants are a target population for new tuberculosis (TB) vaccines. TB incidence estimates are needed to guide the design of trials. To determine the TB incidence and cohort retention among young children using comprehensive diagnostic methods in a high burden area.

Methods:

Infants 0–42 days were enrolled. Through 4 monthly follow-up and unscheduled (sick) visits up to the age of 2 years, infants with presumptive TB based on a history of contact, TB symptoms or pre-determined hospitalization criteria were admitted to a case verification ward. Two induced sputa and gastric aspirates were collected for culture and GeneXpert. Mantoux and HIV tests were done. Clinical management was based on the Keith Edwards score. Cases were classified into microbiologically confirmed or radiologic, diagnosed by blinded expert assessment. Cox regression was used to identify risk factors for incident TB and study retention.

Results:

Of 2900 infants enrolled, 927 (32%) developed presumptive TB, 737/927 (80%) were investigated. Sixty-nine TB cases were diagnosed (bacteriologic and radiologic). All TB incidence was 2/100 person-years of observation (pyo) (95% CI: 1.65–2.65). Nine were bacteriologic cases, incidence 0.3/100 pyo. The radiologic TB incidence was 1.82/100 pyo. Bacteriologic TB was associated with infant HIV infection, higher Keith Edwards scores. Completeness of 4-month vaccinations and HIV infection were positively associated with retention.

Conclusions:

TB incidence was high. An all TB endpoint would require a sample size of a few thousand children, but tens of thousands, when limited to bacteriologic TB.
The Influence of Caregiver Preparedness on Caregiver Contributions to Self-care in Heart Failure and the Mediating Role of Caregiver Confidence
Authors: Vellone Ercole , Biagioli Valentina , Durante Angela , Buck Harleah G. , Iovino Paolo , Tomietto Marco , Colaceci Sofia , Alvaro Rosaria , Petruzzo Antonio
Published: February 2020

Background

Caregiver contributions (CC) to heart failure (HF) self-care maintenance (ie, CC to maintaining HF stability) and management (ie, CC to dealing with HF signs and symptoms) improve patient outcomes, but it is unknown whether caregiver preparedness influences CC to self-care and whether caregiver confidence mediates this process.

Objectives

We evaluated the influence of caregiver preparedness on CC to HF self-care maintenance and management and the mediating role of caregiver confidence.

Methods

This is a secondary analysis of the MOTIVATE-HF study. Patients were 18 years or older, with a diagnosis of HF in New York Heart Association classes II to IV, who had insufficient self-care and did not have severe cognitive impairment. Patients' informal caregivers were those people inside or outside the family who gave most of the informal care to the patients. We used the Caregiver Preparedness Scale and the Caregiver Contribution to Self-Care of HF Index. We tested a path analysis model and the indirect effects.

Results

Caregivers (n = 323) were 55 (SD, 15) years old on average and predominantly female (77%). The path analysis showed that higher scores in caregiver preparedness were associated with higher scores in caregiver confidence. In turn, higher caregiver confidence was associated with higher CC to self-care maintenance and management. Caregiver confidence mediated the association between caregiver preparedness and CC to self-care maintenance and management.

Conclusions

Caregiver confidence may play a role in CC to self-care. Interventions to improve CC to HF self-care should not only be focused on improving caregiver preparedness but also should consider the role of caregiver confidence.