bluuebunny/crossref_metadata_2025 huggingface dataset:
1115. Reducing Broad-Spectrum Antibiotics for Uncomplicated Urinary Tract Infections: A Multimodal Stewardship Intervention
Authors: Laguio-Vila Maryrose R , Staicu Mary L , Lourdes Brundige Mary , Alcantara-Contreras Jose , Yang Hongmei , Lautenbach Ebbing , Dumyati Ghinwa
Published: October 2019

Background

Urinary tract infections (UTIs) are the second most common reason for antibiotics in hospitalized patients, with most receiving broad-spectrum antibiotics (BSA) regardless of infection severity. The antimicrobial stewardship program (ASP) conducted a multimodal stewardship intervention targeting reduction in one BSA, ceftriaxone, and promoted narrow-spectrum antibiotics (NSA) such as cefazolin and cephalexin for uncomplicated UTIs.

Methods

Phase 1: In February 2018, the ASP created a pocket card (Figure 1) containing (1) a urinary antibiogram outlining the most common urine pathogens and their local susceptibility to NSA and (2) NSA guidelines for UTIs with 0–1 systemic inflammatory response syndrome (SIRS) criteria. ASP performed a daily prospective audit with feedback on all new orders of ceftriaxone and promoted prescription of NSA. Phase 2: In August 2018, a Best Practice Alert (BPA) in the electronic medical record (EMR) was designed to interrupt providers ordering ceftriaxone with the indication of a UTI, and prompted NSA prescription instead. Quarterly didactic sessions on UTI antibiotic use and BPA functionality were done. We compared antibiotics usage rates across the 3 study phases (pre-intervention, phase I and phase II) by computing rate ratios (RRs) using Poisson regression.

Results

Compared with pre-intervention, phase 1 resulted in a significant decrease in ceftriaxone DOT (RR: 1.06, CI: 1.03–1.09, P < 0.001) and ceftriaxone orders for UTI (RR: 1.14, P < 0.001) and an increase in cefazolin DOT (RR: 0.89, P = 0.029) and orders for UTI (RR; 0.12, P < 0.001). It also resulted in a significant increase in cephalexin DOT (RR: 0.92, P = 0.002) and orders for UTI (RR: 0.58, P < 0.001). In phase 2, an additional significant reduction in ceftriaxone DOT (RR: 1.04, CI: 1.01–1.08, P = 0.018) and orders for UTI (RR: 1.62, P < 0.001) and an increase in cefazolin DOT (RR: 0.96, P < 0.001) and orders for UTI (RR; 0.56, P < 0.001) occurred, when comparing phase I to phase 2. It also resulted in a decrease in cephalexin DOT (RR: 0.83, P < 0.001) and orders for UTI (RR: 0.70, P < 0.001).

Conclusion

A multimodal stewardship intervention using a pocket card with guidelines and urine antibiogram, and an EMR BPA successfully reduced BSA and increased NSA for treatment of uncomplicated UTIs.

Disclosures

All authors: No reported disclosures.
LB2. TORC1 Inhibition with RTB101 as a Potential Pan-Antiviral Immunotherapy to Decrease the Incidence of Respiratory Tract Infections Due to Multiple Respiratory Viruses in Older Adults
Authors: Mannick Joan , Tomlinson Amelia , Shergill Sarb , Teo Grace , Klickstein Lloyd
Published: October 2019

Background

Respiratory tract infections (RTIs) are a leading cause of hospitalization and death in people age ≥65 years. RTIs are caused by multiple viruses, most of which lack effective treatments. An immunotherapy that enhances pan-antiviral innate immunity may reduce RTI incidence in older adults. Inhibition of targets downstream of target of rapamycin complex 1 (TORC1) was reported to upregulate pan-antiviral gene expression and protect mice from a viral RTI (York AG et al. Cell 2015). We evaluated whether TORC1 inhibition increased antiviral gene expression and decreased RTI incidence in older adults.

Methods

A randomized, double-blind, placebo, controlled study was conducted to determine whether the TORC1 inhibitor RTB101 alone or in combination with the TORC1 inhibitor everolimus reduced the incidence of laboratory-confirmed RTIs. The study enrolled 652 older adults at increased risk of RTI-related morbidity and mortality (defined as age ≥85 years, or age ≥65 years with asthma, COPD, type 2 diabetes mellitus, or current smokers). Subjects were treated for 16 weeks during winter cold and flu season with oral RTB101 5 mg or 10 mg once daily (QD), RTB101 10 mg twice daily, RTB101 10 mg + everolimus 0.1 mg QD, or matched placebo. The primary endpoint was the percentage of subjects with ≥1 laboratory-confirmed RTI through Week 16.

Results

RTB101 was well tolerated. In the intent-to-treat analysis, RTB101 10 mg QD was observed to: reduce the percentage of subjects with laboratory-confirmed RTIs by 30.6% compared with placebo (P = 0.025); reduce the incidence of RTIs caused by multiple different viruses; and upregulate interferon-stimulated pan-antiviral gene expression in whole blood (P = 0.00001 vs. placebo, Figure 1). Furthermore, RTB101 10 mg QD was observed to reduce the time to alleviation of moderate to severe RTI symptoms by 5 days, and to reduce the rate of all-cause hospitalization (rate ratio 0.439, 90% CI 0.196–0.983, P = 0.047).

Conclusion

RTB101 10 mg QD was associated with a significant reduction in laboratory-confirmed RTIs due to multiple viral pathogens that lack effective medicines for treatment or prevention. RTB101 was observed to upregulate interferon-stimulated pan-antiviral gene expression, which may underlie the reduction in RTI incidence.

Disclosures

Joan Mannick, MD, resTORbio (Employee, Shareholder), Amelia Tomlinson, PhD, resTORbio (Employee), Sarb Shergill, PhD, resTORbio (Employee), Grace Teo, PhD, resTORbio (Employee), Lloyd Klickstein, MD, PhD, resTORbio (Employee).
LB4. Efficacy and Safety of Cefiderocol vs. High-Dose Meropenem in Patients with Nosocomial Pneumonia—Results of a Phase 3, Randomized, Multicenter, Double-Blind, Non-Inferiority Study
Authors: Wunderink Richard G , Wunderink Richard G , Matsunaga Yuko , Ari Mari , Ariyasu Mari , Echols Roger , Echols Roger , Menon Anju , Den Nagata Tsutae , Den Nagata Tsutae
Published: October 2019

Background

Cefiderocol (CFDC) is a novel siderophore cephalosporin with activity against a broad range of Gram-negative bacteria. In this study, Day 14 all-cause mortality (ACM) rates were compared between CFDC and meropenem (MEM) in patients with nosocomial Gram-negative pneumonia.

Methods

The study (NCT03032380) was a Phase 3, international, double-blind, randomized, non-inferiority study in hospitalized patients with ventilator-associated, hospital-acquired, or healthcare-associated pneumonia caused by suspected Gram-negative bacteria. Patients were treated with CFDC (2 g, q8h) or MEM (2 g, q8h), both infused for 3 hours, for 7–14 days. Adjunctive linezolid (600 mg, q12h, ≥5 days) was given in both arms to cover Gram-positive bacteria. The primary endpoint was non-inferiority of CFDC to MEM for Day 14 ACM rate in the modified intent-to-treat population (mITT; non-inferiority margin: –12.5%). Key secondary endpoints were clinical and microbiological outcomes at test of cure (TOC), and Day 28 mortality. Safety was investigated up to 28 days after the end of treatment.

Results

In the ITT population, 148 patients were randomized to CFDC and 150 to MEM: 59.7% were ventilated, 32.6% had failure of prior therapy, the median APACHE II score was 15, and 6.0% had concomitant Gram-negative bacteremia at baseline. In the mITT population, non-inferiority of CFDC to MEM for Day 14 ACM was demonstrated; CFDC: 12.4% (18 out of 145 patients) vs. MEM: 11.6% (17 out of 146 patients); treatment difference: 0.8; 95% confidence interval: –6.6; 8.2. Comparable Day 28 ACM (CFDC: 21.0% vs. MEM: 20.5%), clinical cure (CFDC: 64.8% vs. MEM: 66.7%), and microbiological eradication (CFDC: 47.6% vs. MEM: 48.0%) rates were demonstrated in the mITT population at TOC. Clinical cure rates for major target pathogens at TOC were similar between CFDC and MEM arms (figure). The rates of treatment-emergent adverse events (TEAEs), drug-related TEAEs, serious AEs, discontinuation due to TEAEs, and deaths were similar between treatment arms (table).

Conclusion

This study demonstrated the non-inferiority of CFDC to high-dose MEM for the pre-specified endpoint of Day 14 ACM. No unexpected safety signals were observed in the study.

Disclosures

Richard G. Wunderink, MD, Merck (Consultant, Grant/Research Support), Shionogi Inc. (Consultant), Yuko Matsunaga, MD, Shionogi Inc. (Employee), Mari Ariyasu, BPharm, Shionogi & Co., Ltd. (Employee), Roger Echols, MD, Shionogi Inc. (Consultant), Anju Menon, PhD, Shionogi Inc. (Employee), Tsutae Den Nagata, MD, Shionogi & Co., Ltd. (Employee).
LB10. A Randomized, Double-Blind, Placebo-Controlled Efficacy Trial of a Vaccine to Prevent Chronic Hepatitis C Virus Infection in an at-Risk Population
Authors: Cox Andrea L , Page Kimberly , Melia Michael , Veenhuis Rebecca , Massaccesi Guido , Osburn William , Wagner Katherine , Giudice Linda , Stein Ellen , Asher Alice K , Vassilev Ventzislav , Lin Lan , Nicosia Alfredo , Capone Stefania , Scarselli Elisa , Folgori Antonella , Gorman Richard , Chang Soju , Wolff Peter , Liang T Jake , Ghany Marc , Wierzbicki Michael , Lum Paula
Published: October 2019

Background

The development of a safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of elimination efforts, providing the rationale for the first HCV vaccine efficacy trial.

Methods

In a randomized, multicenter, double-blind, placebo-controlled efficacy trial (NCT01436357), we evaluated a recombinant chimpanzee adenovirus 3 vector vaccine prime followed by a recombinant modified vaccinia Ankara boost, both encoding nonstructural proteins of HCV. HCV-uninfected adults 18–45 years old at-risk for HCV infection due to injection drug use were randomized to receive the prime-boost regimen or placebo at Days 0 and 56. Trial participants were monitored for vaccine reactogenicity, adverse events, and HCV viremia. Vaccine safety, immunogenicity, and efficacy against progression to chronic HCV infection were assessed.

Results

A total of 455 subjects received the prime-boost regimen or two doses of placebo, with 202 and 199 in the respective groups included in the according-to-protocol efficacy cohort. Overall incidence of infection was 14.1 infections per 100 person-years. There were no differences in development of chronic infection between vaccine and placebo arms, with 14 chronically infected subjects in each group. Specifically, the vaccine efficacy in preventing chronic infection was −0.53 (95% confidence interval [CI], −2.5 to 0.34). Of vaccinated subjects, 78% generated T-cell responses to ≥1 vaccine-encoded HCV antigens. The vaccine was generally safe and well tolerated with no serious vaccine-related adverse events. There were more solicited reports of adverse events after either injection in the vaccine group (81%) than in the placebo group (59%), with the difference mainly due to injection-site reactions. Serious adverse events and deaths occurred with similar frequencies in the two groups.

Conclusion

A randomized, placebo controlled, Phase I/II trial of a prime-boost vaccine to prevent chronic HCV infection was completed in an at-risk population, demonstrating the feasibility of conducting rigorous vaccine research in people who inject drugs. The regimen elicited robust immune responses without evident safety concerns, but did not provide protection against chronic HCV infection.

Disclosures

Ventzislav Vassilev, PhD, GlaxoSmithKlein Vaccines (Employee), Lan Lin, MD, GlaxoSmithKlein Vaccines (Employee), Alfredo Nicosia, PhD, ReiThera (Employee, Shareholder), Antonella Folgori, PhD, ReiThera (Employee), ReiThera (Employee, Shareholder. Other Authors: No reported disclosures.
LB20. Valacyclovir to Prevent Vertical Transmission of Cytomegalovirus After Maternal Primary Infection During Pregnancy
Authors: Shahar-Nissan Keren , Pardo Joseph , Peled Orit , Krause Irit , Bilavsky Efraim , Bilavsky Efraim , Wiznitzer Arnon , Hadar Eran , Amir Jacob
Published: October 2019

Background

Cytomegalovirus (CMV) is the most common cause of congenital infection in humans. The highest risk of fetal injury follows a maternal primary infection early in pregnancy. Despite the potential for severe fetal injury, to date there are no proven means to prevent viral transmission. Valacyclovir is an antiviral drug proven effective in decreasing the risk for CMV infection among transplant recipients. Valacyclovir is safe for use in pregnancy, and concentrates in the amniotic fluid without accumulating. A dose of 8 g/day creates therapeutic drug levels in the amniotic fluid and fetal blood.

Methods

This is a randomized, double-blind, placebo-controlled study comprising pregnant women with serologic evidence of primary CMV infection during the periconceptional period and first trimester. After informed consent, patients were randomly assigned to a treatment group (8 g/day of Valacyclovir) or control group (placebo). Treatment was initiated at the time of serological detection, and continued until amniocentesis. The primary endpoint was the rate of vertical transmission of CMV—determined by amniotic fluid CMV PCR. Secondary endpoints included evidence of symptomatic congenital CMV infection—in utero or postnatally.

Results

One hundred women were recruited, 90 were included in the data analysis; 45 patients received Valacyclovir and 45 placebo. There were 2 twin pregnancies, and therefore 92 amniocentesis Amongst the Valacyclovir group, 5 (11.1%) amniocentesis were positive for CMV, compared with 14 (29.8%) in the placebo group (P GLMM = 0.03), corresponding with an odds ratio of 0.29 (95% CI: 0.09–0.90) for vertical CMV transmission. Amongst patients infected during the first trimester, a positive amniocentesis for CMV was significantly (P = 0.02) less likely in the Valacyclovir arm (2/19) compared with placebo (11/23). No significant differences (P = 0.91) in CMV-positive amniocentesis were observed between study arms amongst patients infected periconceptionally.

Conclusion

Valacyclovir at a dose of 8 g/day is effective in reducing the rate of fetal CMV infection following early maternal primary infection during pregnancy. The drug reduces the rate of fetal infection by 71%.

Disclosures

All authors: No reported disclosures.
Listeria Endophthalmitis cured with Linezolid in an Immunocompetent Farmer Woman: Hazard of a Sweep of a Cow Tail
Authors: Lécuyer Romain , Boutoille David , Khatchatourian Lydie , Ducloyer Jean-Baptiste , Gibaud Sophie , Raffi François , Gaborit Benjamin
Published: October 2019

We report the first case of an unexpected exogenous Listeria monocytogenes endophthalmitis in a previously healthy woman after a cow tail’s sweep, successfully treated with surgical and linezolid. It is the first case carried out with linezolid to treat Listeria endophthalmitis. Therefore, it may challenge the requirement for intravenous antibiotics for long-term treatment.
An Improved Question Format for Measuring Conspiracy Beliefs
Authors: Clifford Scott , Kim Yongkwang , Sullivan Brian W
Published: October 2019

In an era of increasing partisan polarization and media fragmentation, interest in the causes of conspiracy beliefs has been growing rapidly. However, there is little consensus on how to measure these beliefs. Researchers typically present respondents with a conspiratorial statement, then assess their endorsement of the statement using an agree-disagree scale, a true-false scale, or some other variant. Researchers sometimes include a no-opinion response option and sometimes do not. Yet, there is little evidence as to the best format. In this article, we argue that common measures not only are challenging for respondents to answer, but also inflate estimates of conspiracy belief among the mass public. We introduce an alternative measure that presents respondents with an explicit choice between a conspiratorial and a conventional explanation for an event. Across three studies, the explicit choice format reduces no-opinion responding and reduces estimates of conspiracy belief, particularly among those low in political knowledge or cognitive reflection. These results suggest that previous findings may be inflated due to measurement artifacts. This evidence suggests that researchers adopt the explicit choice format for measuring conspiracy beliefs and provide a no-opinion response option.
Cost reduction of the bond-swapping part in an anisotropic tensor renormalization group
Authors: Oba Hideaki
Published: October 2019

The bottleneck part of an anisotropic tensor renormalization group (ATRG) is a bond-swapping part that consists of a contraction of two tensors and a partial singular value decomposition of a matrix, and their computational costs are $O(\chi^{2d+1})$, where $\chi$ is the maximum bond dimension and $d$ is the dimensionality of the system. We propose an alternative method for the bond-swapping part and it scales with $O(\chi^{\max(d+3,7)})$, though the total cost of ATRG with the method remains $O(\chi^{2d+1})$. Moreover, the memory cost of the whole algorithm can be reduced from $O(\chi^{2d})$ to $O(\chi^{\max(d+1,6)})$. We examine ATRG with or without the proposed method in the 4D Ising model and find that the free energy density of the proposed algorithm is consistent with that of the original ATRG while the elapsed time is significantly reduced. We also compare the proposed algorithm with a higher-order tensor renormalization group (HOTRG) and find that the value of the free energy density of the proposed algorithm is lower than that of HOTRG in the fixed elapsed time.
p38γ MAPK contributes to left ventricular remodeling after pathologic stress and disinhibits calpain through phosphorylation of calpastatin
Authors: Loonat Aminah A. , Martin E. Denise , Sarafraz‐Shekary Negin , Tilgner Katharina , Hertz Nicholas T. , Levin Rebecca , Shokat Kevan M. , Burlingame Alma L. , Arabacilar Pelin , Uddin Shahzan , Thomas Max , Marber Michael S. , Clark James E.
Published: October 2019

Despite the high and preferential expression of p38γ MAPK in the myocardium, little is known about its function in the heart. The aim of the current study was to elucidate the physiologic and biochemical roles of p38γ in the heart. Expression and subcellular localization of p38 isoforms was determined in mouse hearts. Comparisons of the cardiac function and structure of wild‐type and p38γ knockout (KO) mice at baseline and after abdominal aortic banding demonstrated that KO mice developed less ventricular hypertrophy and that contractile function is better preserved. To identify potential substrates of p38γ, we generated an analog‐sensitive mutant to affinity tag endogenous myocardial proteins. Among other proteins, this technique identified calpastatin as a direct p38γ substrate. Moreover, phosphorylation of calpastatin by p38γ impaired its ability to inhibit the protease, calpain. We have identified p38γ as an important determinant of the progression of pathologic cardiac hypertrophy after aortic banding in mice. In addition, we have identified calpastatin, among other substrates, as a novel direct target of p38γ that may contribute to the protection observed in p38γKO mice.—Loonat, A. A., Martin, E. D., Sarafraz‐Shekary, N., Tilgner, K., Hertz, N. T., Levin, R., Shokat, K. M., Burlingame, A. L., Arabacilar, P., Uddin, S., Thomas, M., Marber, M. S., Clark, J. E. p38γ MAPK contributes to left ventricular remodeling after pathologic stress and disinhibits calpain through phosphorylation of calpastatin. FASEB J. 33, 13131–13144 (2019). www.fasebj.org
Spicing up Scholarly Productivity: Impact of a Structured Resident Research Program
Authors: Guiahi Maryam , Alston Meredith , Metz Torri , Mazzoni Sara
Published: October 2019

PURPOSE:

To evaluate whether implementation of a structured resident research program improved scholarly productivity at an academic obstetrics and gynecology (OB-GYN) program.

BACKGROUND:

The Accreditation Council for Graduate Medical Education requires resident participation in scholarly activity. Since the 1970s, OB-GYN residents at University of Colorado (CU) have been required to complete a research project. Starting with the graduating class of 2016, the CU OB-GYN program appointed two Assistant Program Directors of Resident Research who instituted a formalized research program including didactics, timelines, detailed protocol review, an expectation of manuscript submission, and an internal grant funding mechanism.

METHODS:

We compared scholarly productivity related to the required resident research projects for the graduating classes of 2012-2014 (before program implementation) and 2016-2018 (after implementation). Two investigators independently searched for abstracts presented at national meetings, grants received, and publications using PubMed and Google search engines. We also confirmed with the resident or mentor. We compared the proportion of residents who had an accepted abstract or manuscript for their research projects using Fisher’s exact test.

RESULTS:

Fifty-four residents were included; 27 before and 27 after program implementation. The proportion of residents who had oral presentations at a national meeting remained the same (11%), whereas those with an accepted poster presentation increased from 44% to 89% (p=0.001). The proportion who had manuscript publication increased from 26% to 59% (p=0.03).

DISCUSSION:

A formalized, structured research curriculum resulted in improved scholarly productivity. Our experience can guide other programs faced with the challenge of improving resident scholarly activity and output.
Pathologic Fractures: What the Radiologist Needs to Know
Authors: Shin Jane , Jarolimek Amanda Mignon , Sanhaji Latifa
Published: October 2019

A pathologic fracture is a fracture of an abnormal bone weakened by an underlying disease, thus it requires careful assessment. Pathologic fractures may occur in benign lesions, primary and secondary malignancies, and a variety of metabolic disorders. A nontraumatic fracture, a fracture with minor trauma, and multiple contiguous fractures suggest a pathologic nature. In these cases of pathologic fractures, evaluation by advanced imaging modalities, including CT, MRI, and PET-CT, often reveals more significant findings. Accurately identifying and characterizing pathologic fractures on imaging are paramount for guiding proper treatment and reducing potential complications.
Cannabinoid hyperemesis syndrome
Authors: Knowlton Mary C.
Published: October 2019

Cannabinoid hyperemesis syndrome (CHS) is characterized by severe cyclical nausea, vomiting, and abdominal pain relieved by compulsive hot water bathing in the setting of chronic cannabinoid use. This article reviews the characteristics, proposed pathophysiology, treatment modalities, and role of nurses caring for patients with CHS.
Taken Out of Context: Hazards in the Interpretation of Written Assessment Comments
Authors: Ginsburg Shiphra , Kogan Jennifer R. , Gingerich Andrea , Lynch Meghan , Watling Christopher J.
Published: October 2019

Purpose

Written comments are increasingly valued for assessment; however, a culture of politeness and the conflation of assessment with feedback lead to ambiguity. Interpretation requires reading between the lines, which is untenable with large volumes of qualitative data. For computer analytics to help with interpreting comments, the factors influencing interpretation must be understood.

Method

Using constructivist grounded theory, the authors interviewed 17 experienced internal medicine faculty at 4 institutions between March and July, 2017, asking them to interpret and comment on 2 sets of words: those that might be viewed as “red flags” (e.g., good, improving) and those that might be viewed as signaling feedback (e.g., should, try). Analysis focused on how participants ascribed meaning to words.

Results

Participants struggled to attach meaning to words presented acontextually. Four aspects of context were deemed necessary for interpretation: (1) the writer; (2) the intended and potential audiences; (3) the intended purpose(s) for the comments, including assessment, feedback, and the creation of a permanent record; and (4) the culture, including norms around assessment language. These contextual factors are not always apparent; readers must balance the inevitable need to interpret others’ language with the potential hazards of second-guessing intent.

Conclusions

Comments are written for a variety of intended purposes and audiences, sometimes simultaneously; this reality creates dilemmas for faculty attempting to interpret these comments, with or without computer assistance. Attention to context is essential to reduce interpretive uncertainty and ensure that written comments can achieve their potential to enhance both assessment and feedback.
Finding Greater Value in the Fourth Year of Medical School: Accelerating the Transition to Residency
Authors: Pellegrini Vincent D. , Franks Adam M. , Englander Robert
Published: October 2019

The recent focus on competency-based medical education has heralded a true change in U.S. medical education. Accelerating the transition from medical school to residency may reduce student debt, encourage competency-based educational advancement, and produce residency graduates better prepared for the independent and unsupervised practice of medicine. With some purposeful design considerations, innovative time-variable programs or fixed-time accelerated tracks can be implemented within current regulatory parameters and without major alteration of existing institutional regulatory guidelines, state licensing requirements, or specialty certification requirements. Conferring an MD degree in less than 4 full academic years provides opportunities to customize and find greater value in the fourth year of medical school as well as to redeploy time from undergraduate medical education to graduate medical education; this could shorten the overall time to completion of training and/or provide for customization of training in the final years of residency. In this article, the authors discuss the regulatory requirements for successful implementation; consider issues related to “off-cycle” graduates advancing to residency training outside of the Match; and share examples of 3 innovative accelerated programs in pediatrics, family medicine, and orthopaedics that have yielded advantages to individual learners, including reduced educational debt, as well as to the health care system.
Pharmacological and Psychosocial Treatment of Adults With Gambling Disorder: A Meta-Review
Authors: Di Nicola Marco , De Crescenzo Franco , D’Alò Gian Loreto , Remondi Chiara , Panaccione Isabella , Moccia Lorenzo , Molinaro Marzia , Dattoli Luigi , Lauriola Alessandro , Martinelli Silvia , Giuseppin Giulia , Maisto Francesco , Crosta Maria Luigia , Di Pietro Salvatore , Amato Laura , Janiri Luigi
Published: October 2019

Background and Objectives:

Gambling disorder (GD) leads to impaired socioeconomical functioning and increased social costs. Although the research on GD has been rising over the years, approved treatment guidelines are currently not available. The aim of this study was to systematically review the literature on the pharmacological and psychosocial treatment of adults with GD, and to identify possible agreed-upon standards of care.

Methods:

MEDLINE, PubMed, Cochrane, Web of Science, Embase, and CINAHL electronic databases were searched up to April 2019 for systematic reviews on pharmacological, psychosocial, and combined treatment of adults with GD. Twenty-six studies were eventually included in this meta-review.

Results:

Studies reported promising results of opioid antagonists and mood stabilizers in reducing GD-related symptomatology. Lithium was particularly effective in subjects with comorbid bipolar disorders. Cognitive behavioral therapy (CBT) was the most commonly used psychological intervention and reduced global severity, gambling frequency, and financial loss. Motivational interviewing (MI) seemed to improve several GD domains, alone or in combination with CBT. Self-help interventions (SHIs) showed some efficacy in promoting treatment-seeking, and in combination with other treatments.

Conclusions:

We found moderate evidence of effect for CBT, but weaker evidence for pharmacotherapy and SHIs. Results suggested some efficacy for MI in the short but not in the long term. It is likely that certain interventions might be more effective than others on specific features of GD. Further studies are needed to compare the efficacy and acceptability of individual and combined psychosocial and pharmacological interventions, to deliver patient-tailored treatments.
Using Simulation to Define the Learning Curve for the Digital Cervical Examination
Authors: Nitsche Joshua F. , Knupp Rubymel J. , Tooze Janet A. , Sun Chenchen H. , Jin Sha , Brost Brian C.
Published: October 2019

INTRODUCTION:

To assess how skill in the digital cervical examination is acquired in medical students.

METHODS:

In a longitudinal study, medical students completed 200 simulated cervical examinations. We performed regressions of each student's cumulative accuracy using the linear, power, and sigmoidal models to determine best fit. We also constructed multilevel models to determine the influence of dilation and effacement on accuracy and to determine whether the starting level and rate of learning varied between individuals. To assess skill decay, we assessed accuracy at 1, 2, and 5 months after training. We defined the amount of sustained accuracy needed to achieve competence using cumulative summation analyses and determined the amount of practice needed to reach this level of skill.

RESULTS:

Twenty-five medical students participated. The median (interquartile range) of cumulative accuracy at the end of the study was 69% (65–78) for dilation and 80% (76–91) for effacement. The sigmoidal model had the best fit. All students achieved competence during the study. The multilevel models showed that accuracy decreased with higher dilation and lower effacement and found that starting level and rate of learning varied between individuals. Maximal accuracy in both dilation and effacement was seen after 150 repetitions. Accuracy of the medical students persisted for 1 month for dilation and 2 months for effacement. The average±SD number of repetitions needed to achieve competence was 89±46 (range 35–195) for dilation and 48±38 (range 11–174) for effacement.

DISCUSSION:

Based on the variability in skill between individuals and the rate of skill acquisition and decay, we feel that a competence-based rather than time-based approach is most appropriate, that trainee performance should be monitored both during and after training, and that 150 repetitions, or more, should be included in any digital cervical examination simulation regimen.
Tracking—A Flexible Obstetrics and Gynecology Residency Curriculum
Authors: Reed Vicki R. , Emery Jonathan , Farrell Ruth M. , Jelovsek J. Eric
Published: October 2019

Residency programs across the United States are searching for ways to improve surgical skills and operative experiences in obstetrics and gynecology residencies. We developed an obstetrics and gynecology residency program that offers a flexible curriculum, referred to as tracking, to address these needs. Curriculum content was developed using a modified Delphi method, using input from experts in medical education and obstetrics and gynecology. Outcome data were collected on trainees who graduated between 2016 and 2019, including postgraduate fellowship placement and our residents' achievement of surgical minimum requirements based on procedure logs. Trainees from this program have consistently exceeded minimal surgical requirements in all areas, regardless of tracking preference. Since the beginning of the program in 2012, more than 60% of graduates have matriculated into fellowships. Flexible curricula, such as tracking, offer one approach to a changing climate of medicine. The ability to offer flexible, focused, and individualized training is an approach with great potential to produce graduates who excel in all areas of obstetrics and gynecology while sharpening skills specific to their areas of interest.
Morphology of the Posterior Malleolar Fracture Associated With a Spiral Distal Tibia Fracture
Authors: Mitchell Phillip M. , Harms Kelly A. , Lee Adam K. , Collinge Cory A.
Published: October 2019

Objective:

To define the pathoanatomy of the posterior malleolus fracture associated with a spiral distal tibia fracture to guide clamp and implant placement when treating these common injuries.

Design:

Retrospective cohort.

Setting:

Level I trauma center.

Patients/Participants:

One hundred twenty-two spiral infraisthmal tibia fractures identified from a cohort of 922 tibia fractures undergoing intramedullary nailing over a 7-year period.

Main Outcome Measurements:

We collected instances of intra-articular extension seen on preoperative, intraoperative, or postoperative imaging. For patients with a posterior malleolus fracture and computed tomography imaging, we used an axial image 2–3 mm above the articular surface to create a fracture map.

Results:

Intra-articular extension was present in 84 patients (68.9%), with posterior malleolus fractures occurring most commonly (n = 59, 48.4%). Other fractures included plafond fractures (n = 8), medial malleolus fractures (n = 7), anterior–inferior tibiofibular ligament avulsions (n = 5), and other anterior fractures (n = 5). Forty-one of 44 (93%) posterior malleolus fractures with cross-sectional imaging were Haraguchi type I (posterolateral-oblique type) with an average angle of 24 degrees off the bimalleolar axis. The remaining 3 were type II (transverse-medial extension type) fractures. Posterior malleolus fractures were visible 61% of the time on preoperative radiographs.

Discussion:

Posterior malleolus fractures occur in approximately half of spiral distal tibia fractures and are consistently posterolateral in their morphology. This study can be used to enhance evaluation of the posterior malleolus intraoperatively (eg, ∼25 degrees external rotation view), and if the typical variant of posterior malleolus is identified, clamps and lag screws might be applied accordingly.
A New Fastener With Improved Bone-To-Implant Interface Shows Superior Torque Stripping Resistance Compared With the Standard Buttress Screw
Authors: Alfonso Nicholas A. , Baldini Todd , Stahel Philip F.
Published: October 2019

Objective:

The conventional AO buttress screw used for fracture fixation relies on a historic buttress thread design, which is prone to stripping at the bone–implant interface. We hypothesized that a new Bone-Screw-Fastener with an innovative interlocking thread design demonstrates increased resistance to torque stripping forces compared with the buttress screw, without compromising pullout strength.

Methods:

A biomechanical model was established in 6 matched pairs of adult human cadaveric tibiae to test torque resistance between the 3.5 mm Bone-Screw-Fastener and the 3.5 mm cortical AO buttress screw until failure. Uniaxial pullout testing of both screw types was performed as an internal control experiment.

Results:

The 3.5 mm Bone-Screw-Fastener had a significantly increased resistance to torque failure compared with the standard 3.5 mm AO buttress screw (P = 0.0145). In contrast to the buttress screws, none of the Bone-Screw-Fasteners stripped from the bone but rather failed at the screwdriver–implant interface in terms of a metal-on-metal failure. The internal control experiments revealed no significant difference in axial pullout strength between the 2 implants (P = 0.47).

Conclusions:

These data demonstrate the superiority of the new Bone-Screw-Fastener over the conventional AO buttress screw regarding protection from torque stripping forces. In addition, the new thread design that interlocks to the bone does not sacrifice axial pullout resistance conveyed by the buttress screw. Future controlled trials will have to validate the in vivo relevance of these findings in a clinical setting.
Early Immunologic Response in Multiply Injured Patients With Orthopaedic Injuries Is Associated With Organ Dysfunction
Authors: Gaski Greg E. , Metzger Cameron , McCarroll Tyler , Wessel Robert , Adler Jeremy , Cutshall Andrew , Brown Krista , Vodovotz Yoram , Billiar Timothy R. , McKinley Todd O.
Published: October 2019

Objectives:

To quantify the acute immunologic biomarker response in multiply injured patients with axial and lower extremity fractures and to explore associations with adverse short-term outcomes including organ dysfunction and nosocomial infection (NI).

Design:

Prospective cohort study.

Setting:

Level 1 academic trauma center.

Patients:

Consecutive multiply injured patients, 18–55 years of age, with major pelvic and lower extremity orthopaedic injuries (all pelvic/acetabular fractures, operative femur and tibia fractures) that presented as a trauma activation and admitted to the intensive care unit from April 2015 through October 2016. Sixty-one patients met inclusion criteria.

Intervention:

Blood was collected upon presentation to the hospital and at the following time points: 8, 24, 48 hours, and daily during intensive care unit admission. Blood was processed by centrifugation, separation into 1.0-mL plasma aliquots, and cryopreserved within 2 hours of collection.

Main Outcome Measurements:

Plasma analyses of protein levels of cytokines/chemokines were performed using a Luminex panel Bioassay of 20 immunologic mediators. Organ dysfunction was measured by the Marshall Multiple Organ Dysfunction score (MODScore) and nosocomial infection (NI) was recorded. Patients were stratified into low (MODS ≤ 4; n = 34) and high (MODS > 4; n = 27) organ dysfunction groups.

Results:

The MODS >4 group had higher circulating levels of interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1), IL-1 receptor antagonist (IL-1RA), and monokine induced by interferon gamma (MIG) compared with the MODS ≤4 group at nearly all time points. MODS >4 exhibited lower levels of IL-21 and IL-22 compared with MODS ≤4. Patients who developed NI (n = 24) had higher circulating concentrations of IL-10, MIG, and high mobility group box 1 (HMGB1) compared with patients who did not develop NI (n = 37).

Conclusions:

Temporal quantification of immune mediators identified 8 biomarkers associated with greater levels of organ dysfunction in polytrauma patients with major orthopaedic injuries.

Level of Evidence:

Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Medial Epicondyle Fractures: Current Practices and Preferences Between SLAOTI Members (Sociedad Latinoamericana de Ortopedia y Traumatología Infantil)
Authors: Masquijo J. Javier , Ferreyra Andrés , Torres-Gomez Armando , Allende Victoria
Published: October 2019

Background:

Medial epicondyle fractures represent up to 20% of elbow fractures in children and adolescents. There is a growing body of literature to support surgical fixation for displaced fractures. However, controversy regarding imaging modality for displacement measurement and surgical indications remain controversial. The purpose of this survey was to gauge Latin American surgeons’ practices and preferences for the evaluation and treatment of medial epicondyle fractures.

Methods:

A web-based survey containing 19 questions was distributed to active members of SLAOTI (Sociedad Latinoamericana de Ortopedia y Traumatología Infantil) in November 2018. The survey elicited information regarding surgeon demographics, evaluation methods, the factors involved in the decision to perform surgery, and their experience in cases of symptomatic nonunion. Categorical variables were summarized using frequencies and proportions. Analysis of associations between surgeon demographics and treatment preferences were carried out.

Results:

A total of 193 out of 354 completed questionnaires were returned (54% response rate). In total, 74% of the participants (142/193) favored radiographs for the evaluation of the fracture displacement, and 25.4% (49/193) added a computed tomography scan for a more detailed evaluation. The majority of respondents (48.2%) would consider a 5 mm displacement as the cutoff for surgical treatment, 21.8% 2 mm, 20.7% 10 mm, and 9.3% 15 mm. There were no differences between the experience of the participants, academic versus private setting, or training regarding surgical/nonsurgical management.

Conclusions:

There are significant differences in opinions between SLAOTI members as to the optimal management of medial epicondyle fractures. Implications of disagreement in evaluation and treatment support the need for multicenter prospective studies to develop evidence-based guidelines for the management of this fracture.

Level of evidence:

Level V—expert opinion. Cross-sectional electronic survey.
Clinical Level of Evidence Presented at the Cervical Spine Research Society (CSRS) Annual Meeting Over 10 Years (2008–2017)
Authors: Eyrich Nicholas W. , Liesman Daniel , Pescatore Nicole A. , Aleem Ilyas S.
Published: October 2019

Study Design.

Systematic review.

Objective.

We systematically reviewed the level of clinical evidence presented at Cervical Spine Research Society annual meetings from 2008 through 2017.

Summary of Background Data.

The Cervical Spine Research Society is dedicated to advancing knowledge of the cervical spine to promote evidence-based care. Research presented at these meetings impacts clinical practice.

Methods.

A total of 774 paper abstracts presented at Cervical Spine Research Society (CSRS) annual meetings were independently assessed by two reviewers. Reviewers designated a clinical level of evidence (LOE) to each included abstract from level I to level IV based on criteria set forth by the Oxford Centre for Evidence-Based Medicine. Reviewer agreement was assessed using Cohens Kappa coefficient (k) and disagreements were discussed until a consensus was reached. Wilcoxon rank sum test was used to assess for differences in LOE grades. Chi-squared testing was used to assess nonrandom changes in level of evidence and in excluded studies.

Results.

A total of 583 abstracts were included. Over the last 10 CSRS meetings, 5.15% of presentations were level I, 27.8% level II, 27.4% level III, and 39.6% level IV. The average LOE from 2008 to 2017 was 3.02 (median = 3). Additionally, 49.7% were therapeutic studies, 37.6% prognostic studies, and 12.7% diagnostic studies. When comparing the first 5 years (2008–2012) to the last 5 years (2013–2017), we observed a significant increase in Level II (P = 0.007) evidence and a corresponding decrease in level IV evidence (P < 0.001). The average LOE improved from 3.14 (2008–2012) to 2.91 (2013–2017); there was a significant improvement in LOE between the two periods (P = 0.001).

Conclusion.

Emphasis on evidence-based medicine within cervical spine research has positively influenced the clinical level of evidence disseminated at CSRS annual meetings between 2008 and 2017. Continued focus on higher quality Level I studies is warranted.

Level of Evidence: 4
Does Patient Frailty Status Influence Recovery Following Spinal Fusion for Adult Spinal Deformity?
Authors: Pierce Katherine E. , Passias Peter G. , Alas Haddy , Brown Avery E. , Bortz Cole A. , Lafage Renaud , Lafage Virginie , Ames Christopher , Burton Douglas C , Hart Robert , Hamilton Kojo , Kelly Michael , Hostin Richard , Bess Shay , Klineberg Eric , Line Breton , Shaffrey Christopher , Mummaneni Praveen , Smith Justin S , Schwab Frank A.
Published: October 2019

Study Design.

Retrospective review of a prospective database.

Objective.

The aim of this study was to evaluate postop clinical recovery among adult spinal deformity (ASD) patients between frailty states undergoing primary procedures

Summary of Background Data.

Frailty severity may be an important determinant for impaired recovery after corrective surgery.

Methods.

It included ASD patients with health-related quality of life (HRQLs) at baseline (BL), 1 year (1Y), and 3 years (3Y). Patients stratified by frailty by ASD-frailty index scale 0-1(no frailty: <0.3 [NF], mild: 0.3–0.5 [MF], severe: >0.5 [SF]). Demographics, alignment, and SRS-Schwab modifiers were assessed with χ
2/paired t tests to compare HRQLs: Scoliosis Research Society 22-question Questionnaire (SRS-22), Numeric Rating Scale (NRS) Back/Leg Pain, Oswestry Disability Index (ODI). Area-under-the-curve (AUC) method generated normalized HRQL scores at baseline (BL) and f/u intervals (1Y, 3Y). AUC was calculated for each f/u, and total area was divided by cumulative f/u, generating one number describing recovery (Integrated Health State [IHS]).

Results.

A total of 191 patients were included (59 years, 80% females). Breakdown of patients by frailty status: 43.6% NF, 40.8% MF, 15.6% SF. SF patients were older (P = 0.003), >body mass index (P = 0.002). MF and SF were significantly (P < 0.001) more malaligned at BL: pelvic tilt (NF: 21.6°; MF: 27.3°; SF: 22.1°), pelvic incidence and lumbar lordosis (7.4°, 21.2°, 19.7°), sagittal vertical axis (31 mm, 87 mm, 82 mm). By SRS-Schwab, NF were mostly minor (40%), and MF and SF markedly deformed (64%, 57%). Frailty groups exhibited BL to 3Y improvement in SRS-22, ODI, NRS Back/Leg (P < 0.001). After HRQL normalization, SF had improvement in SRS-22 at year 1 and year 3 (P < 0.001), and NRS Back at 1Y. 3Y IHS showed a significant difference in SRS-22 (NF: 1.2 vs. MF: 1.32 vs. SF: 1.69, P < 0.001) and NRS Back Pain (NF: 0.52, MF: 0.66, SF: 0.6, P = 0.025) between frailty groups. SF had more complications (79%). SF/marked deformity had larger invasiveness score (112) compared to MF/moderate deformity (86.2). Controlling for baseline deformity and invasiveness, SF showed more improvement in SRS-22 IHS (NF: 1.21, MF: 1.32, SF: 1.66, P < 0.001).

Conclusion.

Although all frailty groups exhibited improved postop disability/pain scores, SF patients recovered better in SRS-22 and NRS Back. Despite SF patients having more complications and larger invasiveness scores, they had overall better patient-reported outcomes, signifying that with frailty severity, patients have more room for improvement postop compared to BL quality of life.

Level of Evidence: 3