bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Spinal Anesthesia in Geriatric Hip Fracture: A Propensity-Matched Study
Authors: Rodkey Daniel L. , Pezzi Alexandra , Hymes Robert 
Published: September 2021

Objectives:
To identify whether anesthesia type is associated with surgical outcomes in geriatric patients undergoing operative treatment for a hip fracture.

Design:
Retrospective database review of prospectively collected data.

Patients:
Patients included in the American College of Surgeons National Surgical Quality Improvement Program database. All included patients were 65–89 years of age and had a hip fracture treated with internal fixation, arthroplasty, or intramedullary device. Patients were excluded for open, pathologic, stress-related, or periprosthetic hip fractures.

Intervention:
Use of spinal anesthesia (SA) or general anesthesia (GA).

Main Outcome Measurements:
Complications, mortality, and discharge destination.

Results:
A total of 23,649 cases met inclusion and exclusion criteria and were successfully matched using propensity score matching: 15,766 GA and 7883 SA. The odds of sustaining a complication were 21% lower in the SA group compared with those in the GA group (odds ratio SA/GA 0.791; 95% confidence interval, 0.747–0.838). The 30-day mortality rate was not correlated with SA or GA choice. Patients who underwent SA were significantly more likely to be discharged to home (odds ratio SA/GA 1.65; 95% confidence interval, 1.531–1.773).

Conclusions:
No mortality difference exists between patients undergoing SA and those undergoing GA for hip fracture surgery. For patients undergoing hip fracture surgery with SA, there is lower 30-day complication profile and higher discharge to home rate compared with those undergoing GA. Both anesthesia modalities may be acceptable.

Level of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Accounting for Preinvasive Conditions in Analysis of Invasive Cancer Risk
Authors: Kim Jung In , Fine Jason P. , Sandler Dale P. , Zhao Shanshan 
Published: September 2021

Background:
Preinvasive cancer conditions are often actively treated to minimize progression to life-threatening invasive cancers, but this creates challenges for analysis of invasive cancer risk. Conventional methods of treating preinvasive conditions as censoring events or targeting at the composite outcome could both lead to bias.

Methods:
We propose two solutions: one that provides exact estimates of risk based on distributional assumptions about progression, and one that provides risk bounds corresponding to extreme cases of no or complete progression. We compare these approaches through simulations and an analysis of the Sister Study data in the context of ductal carcinoma in situ (DCIS) and invasive breast cancer.

Results:
Simulations suggested important biases with conventional approaches, whereas the proposed estimate is consistent when progression parameters are correctly specified, and the risk bounds are robust in all scenarios. With Sister Study, the estimated lifetime risks for invasive breast cancer are 0.220 and 0.269 with DCIS censored or combined. Without detailed progression information, a sensitivity analysis suggested lifetime risk falls between the bounds of 0.214 and 0.269 across assumptions of 10%–95% of DCIS patients progressing to invasive cancer in an average of 1–10 years.

Conclusions:
When estimating invasive cancer risk while preinvasive conditions are actively treated, it is important to consider the implied assumptions and potential biases of conventional approaches. Although still not perfect, we proposed two practical solutions that provide improved understanding of the underlying mechanism of invasive cancer.
The Association Between Concussion History and Increased Symptom Severity Reporting Is Independent of Common Medical Comorbidities, Personality Factors, and Sleep Quality in Collegiate Athletes
Authors: Brett Benjamin L. , Nelson Lindsay D. , Meier Timothy B. 
Published: September 2021

Objective:
We investigated the degree to which the association between history of concussion with psychological distress and general symptom severity is independent of several factors commonly associated with elevated symptom severity. We also examined whether symptom severity endorsement was associated with concussion injury specifically or response to injury in general.

Setting:
Academic medical center.

Participants:
Collegiate athletes (N = 106; age: M = 21.37 ± 1.69 years; 33 female) were enrolled on the basis of strict medical/psychiatric exclusion criteria.

Design:
Cross-sectional single-visit study. Comprehensive assessment, including semistructured interviews to retrospectively diagnose the number of previous concussions, was completed. Single-predictor and stepwise regression models were fit to examine the predictive value of prior concussion and orthopedic injuries on symptom severity, both individually and controlling for confounding factors.

Main Outcome Measures:
Psychological distress was operationalized as Brief Symptom Inventory-18 Global Severity Index (BSI-GSI) ratings; concussion-related symptom severity was measured using the Sport Concussion Assessment Tool.

Results:
Controlling for baseline factors associated with the symptom outcomes (agreeableness, neuroticism, negative emotionality, and sleep quality), concussion history was significantly associated with psychological distress (B = 1.25 [0.55]; P = .025, ΔR
2 = 0.034) and concussion-like symptom severity (B = 0.22 [0.08]; P = .005, ΔR
2 = 0.064) and accounted for a statistically significant amount of unique variance in symptom outcomes. Orthopedic injury history was not individually predictive of psychological distress (B = −0.06 [0.53]; P = .905) or general symptom severity (B = 0.06 [0.08]; P = .427) and did not explain the relationship between concussion history and symptom outcomes.

Conclusions:
Concussion history is associated with subtle elevations in symptom severity in collegiate-aged athletes; this relationship is independent of medical, lifestyle (ie, sleep), and personality factors. Furthermore, this relationship is associated with brain injury (ie, concussion) and is not a general response to injury history.
Adolescent and Parent Perceptions of the Impact of Concussion/mTBI on Family Functioning and Activity Levels in Recovery
Authors: Quatman-Yates Catherine C. , Miley Aimee E. , Morrison Paige , Hugentobler Jason , Wade Shari L. , Rhine Tara D. , Kurowski Brad G. 
Published: September 2021

Objective:
To explore adolescent and parent perceptions of the impact of a concussion/mild traumatic brain injury (mTBI) on family functioning and activity levels in the first 4 weeks of recovery.

Setting:
Outpatient research setting.

Participants:
Twenty-seven adolescents (aged of 13-17 years) within 1 week of a concussion/mTBI and a parent/guardian were enrolled in the study.

Design:
Prospective ecological study with qualitative, semistructured interviews.

Main Measures:
Adolescents reported symptoms electronically every 2 days for 28 days via the Post-Concussion Symptom Inventory. Semistructured interviews were completed with each adolescent-parent dyad at the end of the 28-day period. Interview questions focused on perceptions of recovery progress and study procedures.

Results:
Symptom trajectories were variable across participants. Three main themes emerged from thematic analysis, including: (1) disruption of routines and activities, (2) injury management considerations, and (3) positive and negative influential factors (eg, school and coach support, timing of injury, and recovery expectations). Results highlighted nuances of recovery challenges that families specifically face and help emphasize the potential benefits of shared decision-making and where more guidance would be appreciated such as more specific self-management of symptoms and physical activity reintegration strategies.

Conclusions:
Study findings support a shared decision-making approach with the identified themes as potential topics to help consider social and environmental influences on recovery. The themes presented in the results could be topics emphasized during intake and follow-up visit processes to help guide plans of care and return-to-activity decisions.
Management of Pediatric Thoracic Empyema in the North Queensland Region of Australia and Impact of a Local Evidence-based Treatment Guideline
Authors: Gautam Anil , Wiseman Gregory , Legg Robert , Lindsay Daniel , Puvvadi Ramaa , Rathnamma Bhanu Mariyappa , Stalewski Harry , Norton Robert , White Andrew Vernon 
Published: September 2021

Aim:
The North Queensland region of Australia has a high incidence of pediatric thoracic empyema (pTE). We describe the management of empyema at the Townsville University Hospital which is the regional referral center for these children. The impact of a newly developed institutional guideline is also discussed.

Methods:
This retrospective audit included children under the age of 16 years treated for empyema between 1 Jan 2007 and 31 December 2018. Demographic and management-related variables were correlated to outcomes. A local guideline was introduced at the beginning of 2017 and patient outcomes characteristics pre, and post introduction of this guideline are compared.

Results:
There were 153 children with pTE (123 before and 30 after the introduction of a local guideline). Nonsurgical management was associated with a higher treatment failure rate. Median length of stay (LOS) was 11.8 (IQR 9.3–16) days. Longer hospital LOS was associated with younger age (r2 −0.16, P = 0.04), Aboriginal and/or Torres Strait (ATSI) ancestry (13.8 vs. 10.5 days, P = 0.002) and concomitant respiratory viral infections (14.4 vs. 10.9 days, P = 0.003). The introduction of local guideline was associated with significant decrease in the use of empirical chest CT scans (54.4% before vs. 6.7% after, P < 0.001) and duration of intravenous antibiotics (14 days before vs. 10 days after, P = 0.02). There was no significant change in the hospital LOS (12.1 days pre and 11.7 post, P = 0.8).

Conclusions:
Younger age, concomitant viral respiratory infections and ATSI ancestry were identified as potential risk factors for increase LOS. Hospital LOS following the adoption of an institutional guideline was unchanged. However, such a guideline may identify populations at risk for an unfavorable course and avoid unnecessary antibiotic treatment and radiation exposure.
A New Surgical Technique for Postoperative Trachomatous Trichiasis
Authors: Merbs Shannath L. , Talero Sandra L. , Tadesse Demissie , Sisay Alemayehu , Bayissasse Belay , Weaver Jerusha U. , Gower Emily W. 
Published: September 2021

Introduction:
The World Health Organization has identified management of postoperative trichiasis (PTT) as one of the key remaining areas of focus needed to eliminate blinding trachoma as a public health problem. We developed the Bevel-Rotation Advancement Procedure (B-RAP) to treat individuals who need repeat trichiasis surgery.

Methods:
Scarring caused by trichiasis surgery can cause the eyelid to become thick and distorted, making repeat surgery more difficult. To minimize eyelid thickness following B-RAP, a beveled incision of the tarsus is made allowing a marginal rotation of the eyelash fragment. Dissection between the anterior and posterior lamellae above the beveled incision and removal of scar tissue allows the marginal rotation to be combined with a posterior lamellar advancement to treat severely scarred eyelids with PTT and eyelid contour abnormalities (ECAs).

Results:
Two surgeons performed B-RAP on 44 eyelids of 30 patients with PTT. The number of prior trachomatous trichiasis (TT) surgeries ranged from 2 to more than 4. At the 3–6 months postoperative visit, 37 eyelids (84%) had no recurrence of PTT. Three eyelids had central lashes touching; the remaining eyelids with recurrent PTT had nasal and temporal lashes touching. Fifteen eyelids (34%) had ECAs, but only 1 was severe.

Conclusions:
B-RAP was developed considering the altered eyelid anatomy found in the postsurgical eyelid with TT. Thinning of the eyelash fragment and removal of postoperative scar tissue improves the ability to advance and stabilize the eyelash fragment after external rotation. B-RAP shows promise as a procedure for improving outcomes of repeat trichiasis surgery.
Use of apheresis in the age of new therapies for familial hypercholesterolaemia
Authors: Thompson Gilbert R. 
Published: September 2021

Purpose of review
Lipoprotein apheresis has been first line therapy for homozygous familial hypercholesterolaemia (FH) and other severe and refractory forms of dyslpidaemia for over 40 years but the recent advent of novel and potent LDL-lowering compounds necessitates a reappraisal of its role.

Recent findings
During the past decade a substantial amount of evidence has accumulated describing the effect of LDL-lowering with apheresis and conventional drug therapy upon the cardiovascular outcomes associated with homozygous and statin-refractory heterozygous FH. This has necessitated re-defining the target levels of LDL cholesterol needed to arrest progression of atherosclerosis in these situations. At the same time, evidence has accrued regarding the pathogenicity of raised levels of lipoprotein (a) and the promising role of apheresis in mitigating the adverse effects of the latter. The latest advance in treatment has been the introduction of three classes of novel and potent LDL-lowering compounds in the shape of inhibitors of Propertin convertase subtilisin kexin 9 (PCSK9), microsomal triglyceride transfer protein and angiopoietin-like 3.

Summary
These recent developments raise the question of whether these compounds will be used as adjuvants to bolster lipoprotein apheresis in FH homozygotes or whether they will render it obsolete, as is already occurring with PCSK9 inhibitors in FH heterozygotes.
Data on Safety of Intravaginal Boric Acid Use in Pregnant and Nonpregnant Women: A Narrative Review
Authors: Mittelstaedt Rachel , Kretz Alyssa , Levine Michael , Handa Victoria L. , Ghanem Khalil G. , Sobel Jack D. , Powell Anna , Tuddenham Susan 
Published: September 2021

Abstract
Intravaginal boric acid (IBA) represents one of the only options available to treat azole-resistant vulvovaginal candidiasis (VVC) and is included as part of multiple national guidelines (including the United Kingdom and the United States) for the treatment of VVC or recurrent bacterial vaginosis. Novel products using IBA are under development for treatment and suppression of VVC and bacterial vaginosis. Use of over-the-counter or clinician-prescribed IBA in reproductive-aged women is already widespread and may increase further if drug resistance in VVC rises. However, IBA is not a Food and Drug Administration–approved drug, and safety data are sparse. Given these factors, it is important to understand the currently available data on the safety of IBA use. Herein, we set out to synthesize human and animal data (converting, where appropriate, dose and serum values to standard units to facilitate comparison) to answer 2 key questions: (1) What are the data on the safety of IBA use for women? and (2) What are the data on the safety of IBA use in pregnancy? We find that, despite gaps, available data suggest IBA use is safe, at least when used in doses commonly described in the literature as being prescribed by clinicians. Information on harms in pregnancy is limited, and data remain insufficient to change current guidelines, which recommend IBA avoidance in pregnancy.
Prediction Model Performance With Different Imputation Strategies: A Simulation Study Using a North American ICU Registry
Authors: Steif Jonathan , Brant Rollin , Sreepada Rama Syamala , West Nicholas , Murthy Srinivas , Görges Matthias 
Published: September 2021

OBJECTIVES:
To evaluate the performance of pragmatic imputation approaches when estimating model coefficients using datasets with varying degrees of data missingness.

DESIGN:
Performance in predicting observed mortality in a registry dataset was evaluated using simulations of two simple logistic regression models with age-specific criteria for abnormal vital signs (mentation, systolic blood pressure, respiratory rate, WBC count, heart rate, and temperature). Starting with a dataset with complete information, increasing degrees of biased missingness of WBC and mentation were introduced, depending on the values of temperature and systolic blood pressure, respectively. Missing data approaches evaluated included analysis of complete cases only, assuming missing data are normal, and multiple imputation by chained equations. Percent bias and root mean square error, in relation to parameter estimates obtained from the original data, were evaluated as performance indicators.

SETTING:
Data were obtained from the Virtual Pediatric Systems, LLC, database (Los Angeles, CA), which provides clinical markers and outcomes in prospectively collected records from 117 PICUs in the United States and Canada.

PATIENTS:
Children admitted to a participating PICU in 2017, for whom all required data were available.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Simulations demonstrated that multiple imputation by chained equations is an effective strategy and that even a naive implementation of multiple imputation by chained equations significantly outperforms traditional approaches: the root mean square error for model coefficients was lower using multiple imputation by chained equations in 90 of 99 of all simulations (91%) compared with discarding cases with missing data and lower in 97 of 99 (98%) compared with models assuming missing values are in the normal range. Assuming missing data to be abnormal was inferior to all other approaches.

CONCLUSIONS:
Analyses of large observational studies are likely to encounter the issue of missing data, which are likely not missing at random. Researchers should always consider multiple imputation by chained equations (or similar imputation approaches) when encountering even only small proportions of missing data in their work.
Suicide and Self-Harm in Children and Adolescents Admitted to PICUs in the United States
Authors: McCluskey Casey K. , Klein Margaret J. , Steward Sarah C. , Rotta Alexandre T. 
Published: September 2021

OBJECTIVES:
To characterize the epidemiology of children and adolescents admitted for deliberate self-harm to PICUs in the United States by examining patient demographics, diagnoses, modes of self-harm, and outcomes.

DESIGN:
Descriptive analysis of a large, multicenter, quality-controlled database.

SETTING:
The 137 PICUs participating in the Virtual Pediatric Systems database during the study period.

PATIENTS:
Children between 6 and 18 years old admitted to a participating PICU from January 1, 2009, to December 31, 2017, with a diagnosis involving deliberate self-harm or a suicide attempt.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Of 9,197 admissions for self-harm, females accounted for 6,740 (73.3%), whereas males incurred 174 of the 284 deaths (61.3%). Admissions for self-harm doubled over the study period (0.56% in 2009 vs 1.13% in 2017), with an increase observed across every age group. After PICU care, most patients were transferred to a general care floor (51.1%) or to a psychiatric rehabilitation facility (31.8%). Intentional drug ingestion (84%) was the most common mode of self-harm but was associated with less than 1% of the fatalities. Asphyxia/hanging or firearms were a factor in 411 (4.5%) and 106 (1.2%) of the admissions but were associated with 117 (28.5%) and 55 (51.9%) of the deaths, respectively.

CONCLUSIONS:
PICU admissions due to self-harm increased for all age groups during the study period. Females accounted for most of these admissions, whereas males accrued most of the in-hospital deaths. Intentional drug ingestion was the most common mode of self-harm and was rarely fatal, whereas asphyxia and firearms were the mechanisms associated with the highest mortality.
Circulating Biomarkers in Glioblastoma
Authors: Mathios Dimitrios , Phallen Jillian 
Published: September 2021

Abstract
Liquid biopsy approaches for detection of circulating biomarkers of cancer have been utilized in oncology in many clinical settings from early detection to disease monitoring. Recent approaches have focused on circulating tumor cells, circulating tumor DNA, and circulating RNAs in a variety of biofluids. However, very little progress has been made in implementing such approaches for detection of brain tumors, despite the tremendous clinical need for earlier and less invasive diagnosis, as well as more accurate assessment of disease status. In this review, we highlight the recent methodological improvements in the field of liquid biopsy technologies specifically for glioblastoma. Although many retrospective and few prospective studies have been conducted to assess the utility of circulating biomarkers for detection of brain tumors, none have yet moved forward to clinical implementation.
Clinical Targeting of Altered Metabolism in High-Grade Glioma
Authors: Scott Andrew J. , Lyssiotis Costas A. , Wahl Daniel R. 
Published: September 2021

Abstract
High-grade gliomas are among the deadliest of all cancers despite standard treatments, and new therapeutic strategies are needed to improve patient outcome. Targeting the altered metabolic state of tumors with traditional chemotherapeutic agents has a history of success, and our increased understanding of cellular metabolism in the past 2 decades has reinvigorated the concept of novel metabolic therapies in brain tumors. Here we highlight metabolic alterations in advanced gliomas and their translation into clinical trials using both novel agents and already established drugs repurposed for cancer treatment in an effort to improve outcome for these deadly diseases.
Improving Pediatric Drug Safety in Prehospital Emergency Care—10 Years on
Authors: Kaufmann Jost , Uhl Stefanie , Singer Eva , Eifinger Frank , Klein Tobias , Lechleuthner Alex , Engelhardt Thomas , Wappler Frank , Böhmer Andreas 
Published: September 2021

Objectives
The Pediatric Emergency Ruler (PaedER) is a height-based drug dose recommendation tool that was reported to reduce life-threatening medication errors by 90%. The PaedER was introduced into the Cologne Emergency Medical Service (EMS) in 2008 along with educational measures, publications, and lectures for pediatric drug safety. We reviewed the impact of these continuously ongoing measures on medication errors after 10 years.

Methods
The PaedER was introduced and distributed to all 14 emergency ambulances and 2 helicopters staffed with emergency physicians in the city of Cologne in November 2008. Electronic records and medical protocols of the Cologne EMS over two 20-month periods from March 2007 to October 2008 and March 2018 to October 2019 data sets were retrieved. The administered doses of either intravenous, intraosseous, intranasal, or buccal fentanyl, midazolam, ketamine, or epinephrine were recorded. Primary outcome measure was the rate of severe drug dosing errors with a deviation from the recommended dose of greater than 300%.

Results
A total of 59 and 443 drug administrations were analyzed for 2007/08 and 2018/19, respectively. The overall rate of drug dosing errors decreased from 22.0% to 9.9% (P = 0.014; relative risk reduction, 55%). Four of 5 severe dosing errors for epinephrine were avoided (P < 0.021; relative risk reduction, 78%). Documentation of patient’s weight increased from 3.2% in 2007/08 to 30.5% in 2018/19 (P < 0.001).

Conclusions
The distribution of the PaedER combined by educational measures significantly reduced the rates of life-threatening medication errors in a large EMS. Those results should motivate further initiatives on pediatric drug safety in prehospital emergency care.