bluuebunny/crossref_metadata_2025 huggingface dataset:
1050. Impact of Weekend Infectious Diseases and Antimicrobial Stewardship Pharmacy Services
Authors: Bohn Brian C , Neuner Elizabeth A , Athans Vasilios , Rivard Kaitlyn R , Riffle Allison R , Richter Sandra S , Fraser Thomas G , Gordon Steven M
Published: October 2019

Background

In September 2018, pharmacy antimicrobial stewardship services were expanded to include weekends at Cleveland Clinic. Activities performed by antimicrobial stewardship (AMS) pharmacists on the weekend include blood culture rapid diagnostic (RDT) review, antiretroviral therapy (ART) review, prospective audit and feedback (PAF) utilizing clinical decision support, vancomycin dosing, and operational support. The purpose of this study was to assess the operational and clinical impact of these expanded AMS services.

Methods

This single-center, the quasi-experimental study included data from 13 weekends before (9/2017 – November 2017) and after (9/2018 – November 2018) implementation of weekend services. The primary outcome was the number of reviews relating to each stewardship activity. Secondary outcomes were time to AMS opportunity resolution, time to escalation or de-escalation following PAF or RDT alert, time to resolution of other AMS-related opportunities, length of stay (LOS), and antimicrobial use outcomes. Patients were included in time to resolution outcomes if they had an RDT, ART, or select PAF review requiring intervention. Time to opportunity resolution was defined as the time from AMS alert to implementation of the recommendation in the electronic health record.

Results

During the post-intervention period 1261 reviews were conducted, averaging 97/weekend. This included 187 RDT, 432 PAF, 124 ART, 331 vancomycin dosing notes and 187 other. Inclusion criteria for time to resolution outcomes were met by 72 patients pre-intervention compared with 59 patients post. No significant differences were seen in baseline characteristics between groups with 43% of patients requiring ID consultation and 58% requiring ICU admission. The median time to opportunity resolution improved significantly overall (P < 0.01), with de-escalation (P = 0.03), and with time to other AMS opportunity (P = 0.01) (Figure 1). A numerical reduction was seen with time to escalation (P = 0.1). LOS was a median of 13 and 14 days pre- and post-intervention, respectively (P = 0.4). No differences were seen in antimicrobial use outcomes.

Conclusion

Presence of pharmacist-driven weekend AMS services significantly reduced time to resolution of AMS interventions. These data support the value of weekend AMS services.

Disclosures

All authors: No reported disclosures.
1062. Provider-Based Survey to Determine the Relative Importance of Clinical Factors Used to Make Empiric Antibiotic Decisions
Authors: Kim Casey J , Szymczak Julia E , Herman David J , Kennedy Leigh A , Talati Naasha J , Akhter Shafinaz N , Schnellinger Erin M , Hamilton Keith W
Published: October 2019

Background

Despite advances in rapid organism identification, clinicians must make empiric antibiotic decisions prior to knowing the causative organism. Though many risk factors and patient characteristics have been studied and incorporated into predictive clinical decision support tools for empiric antibiotic prescription, little evidence exists on the relative importance of these factors in clinician judgment. The purpose of this study was to establish how providers evaluate patient and clinical risk factors when making empiric antimicrobial decisions.

Methods

An anonymous survey tool was distributed in February 2019 to medical providers who routinely prescribe antibiotics in 4 acute care hospitals throughout the University of Pennsylvania Health System. Providers were asked to rank the importance of 12 clinical factors using a 5-point scale from not important at all (1) to extremely important (5) in 3 unique clinical scenarios: uncomplicated cystitis, septic shock of unknown etiology, and uncomplicated pneumonia.

Results

Response rate was 30% (217/732). The importance of each factor varied among different clinical scenarios except for prior antibiotic exposure, local resistance patterns, drug-drug interactions, and treatment guidelines. However, the absolute difference varied by the factor and clinical scenario. Presence of indwelling catheter(s) had the largest absolute variation (median difference of 2 between septic shock and pneumonia, P < 0.001), and it was one of the top 5 most important factors for septic shock, but the least important factor for pneumonia.

Conclusion

The importance of clinicians place on clinical factors varies in different clinical scenarios. A better understanding of clinical decision-making in empiric antibiotic prescribing has the potential to guide stewardship efforts and clinical decision support.

Disclosures

All authors: No reported disclosures.
1067. Variation of Antimicrobial Stewardship Programs’ Membership and Organization Within a Single Health System
Authors: Bariola J Ryan , Khadem Tina
Published: October 2019

Background

Antimicrobial stewardship programs (ASPs) vary in terms of members and administrative (admin) structure. Joint Commission (TJC) has member requirements, but little is known about adherence or how ASP’s fit into hospitals’ admin structures. We reviewed the makeup and organization of ASP’s within a single healthcare system.

Methods

Survey of pharmacy directors or ASP pharmacists at 14 system hospitals in January 2019.

Results

All hospitals responded. All are TJC accredited. Thirteen (92%) had a local stewardship committee. Of these 13, 6 (42%) met quarterly, 4 (30%) monthly, and 3 (21%) every other month. 9 (69%) were a subcommittee of Pharmacy and Therapeutics, and 1 (11%) was a separate committee. 3 (23%) had no clearly defined reporting structure. Figure 1 shows ASP committee compositions. 9 (69%) had all TJC required members, if ID physician is considered a required member. All had pharmacy representation but only 4 (30%) had a pharmacist with ID training. Most had representation from ID physicians (10), Infection Prevention (12), other practitioners (11), and microbiology lab (9). Less than half had hospital admin members, and only 2 had nursing members. None had Information Technology (IT) representation. 12 (92%) created minutes, but only 4 (30%) forwarded minutes for review by hospital admin. Tables 1–3 describe relationships between hospitals based on bed size, if they submitted minutes for review, and if they had both an ID pharmacist and ID physician as members. No hospital indicated citations during a TJC visit about membership or organization.

Conclusion

ASPs within even a single health system vary as to membership and organizational structure. Some did not have all TJC required members. With few having admin representation or submitting minutes for admin review, it raises the concern of ASPs being ignored and possible noncompliance with TJC requirements regarding leadership support. ASP’s should actively work with hospital admins to ensure they have all needed representation and develop reporting mechanisms that keep hospital admins aware of their successes and needs. Lack of involvement from pharmacists with ID expertise, nursing, and IT are issues also. Larger evaluations are needed to determine whether membership and administrative structure can impact antimicrobial usage.

Disclosures

All authors: No reported disclosures.
1070. Handshake Antimicrobial Stewardship as a Model to Prevent Patient Safety Incidents and Recognize Diagnostic Errors
Authors: Searns Justin B , Williams Manon , MacBrayne Christine , Wirtz Ann , Parker Sarah , Grubenhoff Joseph A
Published: October 2019

Background

Patient safety incidents (PSIs), such as diagnostic errors, are common events that may lead to significant patient harm. Few studies describe the impact that antimicrobial stewardship programs (ASPs) have preventing PSIs and recognizing diagnostic errors. Handshake Stewardship has emerged as a specific ASP model that involves prospective review of hospital-wide antimicrobial ordering with a compressed “second look” of relevant clinical and historical patient data. In person recommendations are then provided directly to the medical team. The objective of this project was to evaluate the potential impact that Handshake Stewardship has on preventing PSIs and recognizing diagnostic errors.

Methods

Following Children’s Hospital Colorado (CHCO) ASP’s implementation of the Handshake Stewardship model in October 2013, the CHCO ASP team began prospectively self-labeling interventions as “Great Catches” (GCs). These GCs were defined as any ASP intervention that “notably changed the trajectory of patient care.” Patient charts for all GCs from October 2014 through May 2018 were retrospectively reviewed and each intervention was assigned one or more descriptive category labels including: administration error, de-escalation/escalation of therapy, bug-drug mismatch, inappropriate dose/duration, potential adverse effect, alternative diagnosis, additional testing, prevent hospital admission, and epidemiology alerts. In addition, each intervention was scored using the previously validated “Safer Dx Instrument” to determine which GCs intervened on a potential diagnostic error.

Results

From October 2014 through May 2018 there were 87,322 admissions to CHCO. Our ASP team intervened on 6,735/87,322 (7.7%) of these admissions. Of these, 174/6,735 (2.6%) were prospectively labeled by ASP providers as GCs, of which 44/174 (25%) resulted in new infectious disease consultations.

Conclusion

Given the frequency and significance of PSIs including diagnostic error, systems are needed to help recognize and prevent patient harm. The Handshake Stewardship model may help prevent PSIs and recognize diagnostic errors among hospitalized children.

Disclosures

All authors: No reported disclosures.
1071. Implementation and Impact of an Antimicrobial Tier Structure Along with Prospective Audit and Feedback at a Large Health System: Collaborations for Care Transformation
Authors: Minor Sarah Brooks , Rafferty Kelly D , Rutkowski Julia , Allison Steven , Herrera Victor
Published: October 2019

Background

Antibiotic overuse continues to be a challenge in the acute care setting. At AdventHealth Orlando (AHO), pharmacy-led prospective audit with feedback (PAAF) has been the primary stewardship tool. Despite PAAF and criteria for use, overall utilization of high-cost, broad-spectrum agents continues to increase. Recently, the Antimicrobial Stewardship Awareness Program (ASAP) employed transformation medical directors (TMDs) and, along with the pharmacy team, developed a novel concept using an antimicrobial tier structure, in addition to historical PAAF. The purpose was to assess the impact of the tier structure, along with PAAF performed by the pharmacists and TMDs, compared with PAAF alone.

Methods

This retrospective pre (March–August 2018)- and post (October 2018–March 2019) implementation study was conducted at AHO. The ASAP team developed a hospital-wide policy listing antimicrobials based on a tier system (Figure 1), with higher priority agents falling in tiers 3 (T3) and 4 (T4). Education was completed in September 2018 and the process was implemented in October 2018. Criteria for use was evaluated at the point of order entry, followed by PAAF by the pharmacist and TMD. The primary outcome was impact on T3 and T4 antimicrobial utilization, measured in days of therapy (DOT) per 1,000 days present (DP). Secondary outcomes included T3 and T4 antimicrobial cost/adjusted patient-days and rates of hospital-acquired C. difficile infections (CDI).

Results

During the post-implementation period, the average DOT per 1,000 DP for T3 and T4 agents decreased by 21.3% (89 vs. 70, P = 0.001) compared with the pre-implementation period (Figure 2). Average T3 and T4 antimicrobial costs decreased by 26% during the post-implementation period ($9.83 vs. $7.27, P < 0.001). Additionally, rates of hospital-acquired CDI decreased by 14% (P = 0.41) during the post-implementation period.

Conclusion

The tier concept, along with PAAF collaborations between the pharmacists and TMD, allowed for a greater impact on antimicrobial utilization, compared with pharmacist-led PAAF alone. In addition to significant decrease in antimicrobial utilization, substantial cost-savings were demonstrated. A nonsignificant declining trend in the incidence of hospital-acquired CDI was also noted during the post-implementation period.

Disclosures

All authors: No reported disclosures.
1111. Characterization of Antibiotic Ordering in Patients with Mental Status Changes and Presumed Urinary Tract Infection in Patients 65 and Older
Authors: Harrington Nicole , Leri Jessica , Shoop Scott
Published: October 2019

Background

Altered mental status (AMS) is the most common diagnosis among those 65 and older who present to the emergency department (ED). Urinary tract infections (UTIs) account for 15.5% of hospitalizations in this population. The purpose of this study was to determine the incidence of initiation of antibiotics in the ED in patients 65 years and older with mental status changes and asymptomatic bacteriuria or negative urine cultures.

Methods

A retrospective chart review was performed to evaluate patients aged 65 and older from January 2017 through June 2018 who presented to the ED from home with AMS, a urinalysis that reflexed to culture, and were admitted to an internal medicine unit. The primary outcome was defined as the percentage of patients with AMS who received antibiotics in the ED with asymptomatic bacteriuria or negative urine cultures. Secondary outcomes included adherence to the CCHS UTI antibiotic guideline, incidence of early discontinuation of antibiotics, culture sensitivity to ordered antibiotic, and disposition after discharge.

Results

A total of 91 patients were included in this study. Seventy-five patients had asymptomatic bacteriuria and antibiotics were started in the ED in 63 (84%) of these patients. Fourteen patients had no growth on culture and seven of these patients (50%) had antibiotics initiated in the ED. Of those who received antibiotics (n = 82), there was 81.7% adherence to the Christiana Care UTI antibiotic selection guideline. Sensitivities were available for 41 isolates and 65.9% were sensitive to the initial antibiotic administered. Antibiotics were discontinued early in 29/82 (35.4%) of patients. Thirty-one patients (33.7%) were discharged to a skilled nursing facility.

Conclusion

These results indicate that the majority of patients aged 65 and older who presented to the emergency department with altered mental status and no other UTI symptoms such as dysuria, urinary frequency, or urgency were treated with antibiotics. When antibiotics are initiated the majority of providers are adhering to organizational guidelines for antibiotic selection and duration. The results will be shared with Emergency Department and Internal Medicine leadership to foster practice change.

Disclosures

All authors: No reported disclosures.
1118. Trends of Paediatric Prescribing for Common Infections in British Columbia
Authors: Saatchi Ariana , Patrick David M , McCormack James , Morris Andrew , Marra Fawziah
Published: October 2019

Background

Antibiotic prescribing in pediatric care is highly prevalent, and quite often children are prescribed for conditions which are commonly self-limiting and viral in etiology. The purpose of this study was to examine the scope of pediatric antibiotic prescribing by indication, from 2013 to 2016, and identify potential new targets for provincial antimicrobial stewardship efforts.

Methods

Antibiotic prescription data for children were extracted from a provincial prescription database, and linked to physician billing data in order to obtain diagnostic information. Prescription rates were then calculated, and trends were examined by indication. Major categories included: upper respiratory tract infection, acute otitis media, lower respiratory tract, skin and soft tissue, and urinary tract infections.

Results

Our database included an average of 244,763 children per year, and 5,896,173 total antibiotic prescriptions. Increased indication-specific rates of prescribing were observed in children aged 0–2 years, for every category. Children aged 3–18 years experienced decreased prescribing across all indications, with the exception of urinary tract infections for those aged between 10–18 years. Urinary tract infections increased by 134% for children aged 0–2 years, and 75% for those aged 10–18 years, from 2013 to 2016. Although antibiotic use for upper respiratory tract infections decreased by 11% for all ages, these diagnoses continue to be prescribed for at rates 2 – 5 times higher than other conditions.

Conclusion

Although this study found a decrease in prescribing over time across all indications, antibiotic use continues to be a concern for upper respiratory tract infections in pediatric care. These diagnoses generally do not require antibiotics, and inappropriate prescribing is a major factor in antimicrobial resistance. The increased prescribing rates in the youngest age group (0–2 years) offers a new target for provincial stewardship efforts.

Disclosures

All authors: No reported disclosures.
1135. The 2018 Global Point Prevalence Survey of Antimicrobial Consumption and Resistance: Pediatric Results from 26 Canadian Hospitals
Authors: Lefebvre Marie-Astrid , Versporten Ann , Carrier Marie , Chang Sandra , Comeau Jeannette L , Emond Yannick , Frenette Charles , Khan Sarah , Landry Daniel L , MacLaggan Timothy D , Tien Nguyen Trong , Nguyen Tuyen , Valiquette Louis , Mertz Dominik , Pauwels Ines , Goossens Herman
Published: October 2019

Background

Inappropriate antimicrobial use (AMU) is strongly associated with antimicrobial resistance. The Global Point Prevalence Survey (Global-PPS) is a standardized tool that is used worldwide to characterize inpatient AMU. We report pediatric results from 26 Canadian hospitals that participated in the Global-PPS in 2018.

Methods

The survey was completed by each site on the Global-PPS website for all patients aged 0–17 years hospitalized in a neonatal or pediatric ward on a chosen day between January and December 2018. Data collected included ward type, demographics, antimicrobials prescribed, diagnosis, type of indication (community-acquired [CA] vs. healthcare-associated [HA]) and type of therapy (empiric vs. targeted). Quality indicators included guideline compliance, medical record documentation of diagnosis, antimicrobial stop/review date, and surgical prophylaxis (SP) duration.

Results

Of the 26 sites, 23 were mixed and 3 were pediatric hospitals, with data on 767 inpatients. Overall, 25.8% (n = 198) of patients received at least one antimicrobial, and 21.9% (n = 168) were on at least one antibiotic. The highest AMU was found in Hematology-Oncology (84%), Pediatric Intensive Care (55.3%) and surgical (42.1%) units. Of the 330 antimicrobial prescriptions, 40.9% were for CA infections, 23% for medical prophylaxis, 20% for HA infections and 2.7% for SP. The most commonly treated infections were sepsis (16%) and lower respiratory tract infection (12.1%). The top five prescribed antibiotics were aminopenicillins (20.4%), aminoglycosides (16.1%), third-generation cephalosporins (15.4%), piperacillin–tazobactam (7.5%) and trimethoprim-sulfamethoxazole (7.5%). Diagnosis and stop/review date were documented for 88.1% and 65.1% of prescriptions, respectively. Compliance to local guidelines was found in 91.5% of therapies. SP exceeded 24 hours in 88.9% of courses.

Conclusion

The Global-PPS generated Canada-wide data on inpatient pediatric AMU, which will allow hospitals to benchmark and develop local quality improvement interventions to enhance appropriate AMU. Targets for improvement include suboptimal antimicrobial stop/review date documentation and prolonged SP.

Disclosures

All authors: No reported disclosures.
LB14. Cerebrospinal Fluid Profiling of the Human Host Response Reveals Species-Specific Enterovirus Biosignatures in Acute Flaccid Myelitis Cases
Authors: Briggs Benjamin J , Santos Yale , Ramesh Akshaya , Grabherr Manfred , Achari Asmeeta , Yu Guixia , Miller Steve , Miller Steve , Federman Scot , Arevalo Shaun , Sample Hannah , Zorn Kelsey , Harriman Kathleen , Messenger Sharon , Domingue Samuel , Dominguez Samuel , Glaser Carol , Wadford Debra , Messacar Kevin , Messacar Kevin , Wilson Michael , Chiu Charles , Chiu Charles
Published: October 2019

Background

Since 2014 there have been global biennial outbreaks of acute flaccid myelitis (AFM), a rare but severe “polio-like” illness of as yet-unknown etiology primarily affecting children. Enteroviruses (EVs),, especially EV-D68 and EV-A71, have been implicated in association with AFM cases, but proving causality has been difficult as EVs are rarely isolated from cerebrospinal fluid. In addition, early identification of EV-associated AFM is challenging given that the diagnosis is reliant on potentially subjective clinical and radiological criteria with no specific biomarkers described to date.

Methods

We leveraged existing and newly generated data from a clinical CSF metagenomic assay for pathogen identification at University of California, San Francisco (UCSF) to interrogate the host response at the transcriptome level by RNA sequencing (RNA-Seq). These transcriptome RNA-Seq data were used to create statistical classification models to discriminate among viral infections that have been linked to AFM, including EV-D68, EV-A71, West Nile virus, and Powassan virus. The dynamic range of CSF cellularity (0 to >106 cells/mL), resulting in varying trancriptome coverage, as well as technical variation across samples required the development and validation of novel normalization techniques. In total, we analyzed ~50 CSF samples split into independent training and test sets.

Results

We were able to demonstrate a distinct signature of AFM that was able to predict the virus associated with AFM in blinded test samples with >80% accuracy. The key transcriptional features that best discriminated EV-A71 from EV-D68-associated AFM involved protein targeting, viral transcription, viral gene expression, and translation initiation pathways.

Conclusion

Here we demonstrate a novel approach to diagnosis of AFM that relies on host transcriptional biomarkers from cerebrospinal fluid. In the future, this method might allow earlier diagnosis of AFM to drive appropriate therapies and vaccines and predict patient outcomes, as well as guide research studies on the pathophysiology of EV-associated AFM.

Disclosures

All authors: No reported disclosures.
Addressing the disease burden of vertically-acquired hepatitis C virus (HCV) infection among opioid-exposed infants
Authors: Protopapas Stella , Murrison Liza Bronner , Wexelblatt Scott L , Blackard Jason T , Hall Eric S
Published: October 2019

Purpose

This study aims to estimate the disease burden of vertically-acquired hepatitis C virus (HCV) in a large Midwestern hospital; and to identify factors associated with HCV diagnostic testing among high-risk infants.

Methods

Retrospective analysis of an infant cohort (n=58,427) born from 2014-2016 in the Greater Cincinnati region, where universal maternal urine testing is conducted at delivery to assess for intrauterine drug exposure (IUDE). Demographics and birth characteristics were analyzed among high-risk infants to identify factors associated with receiving HCV testing. A nested matched case-control analysis examined the association of pediatric HCV infection and IUDE.

Results

The HCV prevalence rate among high-risk infants who received testing was 3.6-5.2% of births. Approximately 66.7% of maternally-acquired HCV infections may be missed using current testing recommendations. Prenatal care had no significant effect (aOR 1.2 [95%CI 0.4-3.5]) on the odds of a high-risk infant receiving HCV testing. Opioid-exposed cases had an over 6-fold increase in the odds of HCV infection (aOR 6.2 [95%CI 2.3-16.6]) compared to non-opioid exposed infants.

Conclusions

IUDE was significantly associated with increased odds of pediatric HCV infection in this population. The gaps in pediatric HCV testing identified in this study, despite known risk level and maternal infection, suggest the need for increased focus on HCV identification in the pediatric population.
Corticosteroids for Posttransplant Immune Reconstitution Syndrome in Cryptococcus gattii Meningoencephalitis: Case Report and Literature Review
Authors: Canfield Gregory S , Henao-Martínez Andrés F , Franco-Paredes Carlos , Zhelnin Kristen , Wilson Michael L , Shihadeh Katherine C , Wyles David , Gardner Edward M
Published: October 2019

Cryptococcus gattii represents an emerging fungal pathogen of immunocompromised and immunocompetent hosts in the United States. To our knowledge, this is the first case of posttransplant immune reconstitution syndrome due to C. gattii meningoencephalitis successfully treated with corticosteroids. We also report successful maintenance phase treatment with isavuconazole, a novel triazole, following fluconazole-induced prolonged QT syndrome.
Teen vaping: There is no vapour without fire
Authors: Chadi Nicholas , Belanger Richard E
Published: October 2019

E-cigarettes have become the most important source of nicotine exposure among adolescents. While e-cigarettes may have the potential to help some adults quit smoking, there is a lack of reliable evidence that this would apply to adolescents. On the contrary, e-cigarette use is associated with subsequent use of cigarettes and other tobacco products in teens and is also associated with increased use of alcohol, marijuana, and other drugs. Research on the health effects of e-cigarettes is rapidly emerging suggesting that they carry several acute and long-term risks, particularly for adolescents’ still-developing bodies and brains. While several strategies to help youth quit smoking exist, much less is known about effective clinical interventions for adolescents presenting with an addiction to nicotine consumed through e-cigarettes. We discuss the latest research on e-cigarettes with a focus on health effects in youth and propose potential avenues for concerted action among paediatric providers and decision makers.
Obesity reduces the real-world effectiveness of cytokine-targeted but not cell-targeted disease-modifying agents in rheumatoid arthritis
Authors: Schäfer Martin , Meißner Yvette , Kekow Jörn , Berger Sylvia , Remstedt Sven , Manger Bernhard , Listing Joachim , Strangfeld Anja , Zink Angela
Published: October 2019

Objectives

The effectiveness of TNF inhibitors in RA has been shown to be affected by obesity. No such effect has been found for abatacept and rituximab, while for tocilizumab results are ambiguous. Additionally, it remains unresolved whether sex is an effect modifier for obesity. We investigated the impact of obesity on the drug effectiveness of conventional synthetic or biologic DMARDs, taking into account potential sex-specific differences.

Methods

Data from 10 593 RA patients included in the German observational cohort study Rheumatoid Arthritis: oBservation of BIologic Therapy (RABBIT) since 2009 were analysed. Patients had to have a BMI ≥18.5 kg/m2, at least one follow-up and 6 months of observation time. The influence of obesity on drug effectiveness was investigated by regression analysis, adjusting for potential confounders.

Results

Obesity had a negative impact on improvement in the DAS with 28 joints using ESR as an inflammation marker of –0.15 (95% CI: –0.26; –0.04) units for women receiving conventional synthetic DMARDs, –0.22 (95% CI: –0.31; –0.12) units for women receiving TNF inhibitors, –0.22 (95% CI: –0.42; –0.03) units for women receiving tocilizumab and –0.41 (95% CI: –0.74; –0.07) units for men receiving tocilizumab. Overall, no negative obesity effects on the effectiveness of rituximab and abatacept were found.

Conclusion

Obesity has a negative impact on the effectiveness of cytokine-targeted but not cell-targeted therapies in daily practice, affecting more outcomes and therapies in women than in men. Overall, no effects of obesity on treatment effectiveness were found for rituximab and abatacept.
Wearable technologies for developing sleep and circadian biomarkers: a summary of workshop discussions
Authors: Depner Christopher M , Cheng Philip C , Devine Jaime K , Khosla Seema , de Zambotti Massimiliano , Robillard Rébecca , Vakulin Andrew , Drummond Sean P A
Published: October 2019

The “International Biomarkers Workshop on Wearables in Sleep and Circadian Science” was held at the 2018 SLEEP Meeting of the Associated Professional Sleep Societies. The workshop brought together experts in consumer sleep technologies and medical devices, sleep and circadian physiology, clinical translational research, and clinical practice. The goals of the workshop were: (1) characterize the term “wearable” for use in sleep and circadian science and identify relevant sleep and circadian metrics for wearables to measure; (2) assess the current use of wearables in sleep and circadian science; (3) identify current barriers for applying wearables to sleep and circadian science; and (4) identify goals and opportunities for wearables to advance sleep and circadian science. For the purposes of biomarker development in the sleep and circadian fields, the workshop included the terms “wearables,” “nearables,” and “ingestibles.” Given the state of the current science and technology, the limited validation of wearable devices against gold standard measurements is the primary factor limiting large-scale use of wearable technologies for sleep and circadian research. As such, the workshop committee proposed a set of best practices for validation studies and guidelines regarding how to choose a wearable device for research and clinical use. To complement validation studies, the workshop committee recommends the development of a public data repository for wearable data. Finally, sleep and circadian scientists must actively engage in the development and use of wearable devices to maintain the rigor of scientific findings and public health messages based on wearable technology.
Sleep in children with Smith–Magenis syndrome: a case–control actigraphy study
Authors: Trickett Jayne , Oliver Chris , Heald Mary , Denyer Hayley , Surtees Andrew , Clarkson Emma , Gringras Paul , Richards Caroline
Published: October 2019

Study Objectives

The objectives of the study were (1) to compare both actigraphy and questionnaire-assessed sleep quality and timing in children with Smith–Magenis syndrome (SMS) to a chronologically age-matched typically developing (TD) group and (2) to explore associations between age, nocturnal and diurnal sleep quality, and daytime behavior.

Methods

Seven nights of actigraphy data were collected from 20 children with SMS (mean age 8.70; SD 2.70) and 20 TD children. Daily parent/teacher ratings of behavior and sleepiness were obtained. Mixed linear modeling was used to explore associations between total sleep time and daytime naps and behavior.

Results

Sleep in children with SMS was characterized by shorter total sleep time (TST), extended night waking, shorter sleep onset, more daytime naps, and earlier morning waking compared to the TD group. Considerable inter-daily and inter-individual variability in sleep quality was found in the SMS group, so caution in generalizing results is required. An expected inverse association between age and TST was found in the TD group, but no significant association was found for the SMS group. No between-group differences in sleep hygiene practices were identified. A bidirectional negative association between TST and nap duration was found for the SMS group. In the SMS group, increased afternoon sleepiness was associated with increased irritability (p = .007) and overactivity (p = .005).

Conclusion

These findings evidence poor sleep quality in SMS and the need to implement evidence-based interventions in this population.
Inhibition of dengue virus infection by 1‐stearoyl‐2‐arachidonoyl‐phosphatidylinositol in vitro
Authors: Sanaki Takao , Wakabayashi Masato , Yoshioka Takeshi , Yoshida Ryu , Shishido Takao , Hall William W. , Sawa Hirofumi , Sato Akihiko
Published: October 2019

Dengue fever is an acute febrile infectious disease caused by dengue virus (DENV). Despite the significant public health concerns posed by DENV, there are currently no effective anti‐DENV therapeutic agents. To develop such drugs, a better understanding of the detailed mechanisms of DENV infection is needed. Both lipid metabolism and lipid synthesis are activated in DENV‐infected cells, so we used lipid screening to identify potential antiviral lipid molecules. We identified 1‐stearoyl‐2‐arachidonoyl‐phosphatidylinositol (SAPI), which is the most abundant endogenous phosphatidylinositol (PI) molecular species, as an anti‐DENV lipid molecule. SAPI suppressed the cytopathic effects induced by DENV2 infection as well as the replication of all DENV serotypes without inhibiting the entry of DENV2 into host cells. However, no other PI molecular species or PI metabolites, including lysophosphatidylinositols and phosphoinositides, displayed anti‐DENV2 activity. Furthermore, SAPI suppressed the production of DENV2 infection‐induced cytokines and chemokines, including C‐C motif chemokine ligand (CCL)5, CCL20, C‐X‐C chemokine ligand 8, IL‐6, and IFN‐β. SAPI also suppressed the TNF‐α production induced by LPS stimulation in macrophage cells differentiated from THP‐1 cells. Our results demonstrated that SAPI is an endogenous inhibitor of DENV and modulated inflammatory responses in DENV2‐infected cells, at least in part via TLR 4.—Sanaki, T., Wakabayashi, M., Yoshioka, T., Yoshida, R., Shishido, T., Hall, W. W., Sawa, H., Sato, A. Inhibition of dengue virus infection by 1‐stearoyl‐2‐arachidonoyl‐phosphatidylinositol in vitro. FASEB J. 33, 13866‐13881 (2019). www.fasebj.org
Parenthood and Medical Careers: The Challenges and Experiences of Physician Moms in the US
Authors: Gray Beverly , Weber Jeremy , Pieper Carl , Dotters-Katz Sarah
Published: October 2019

PURPOSE:

This survey study sought to gain a better understanding of the experiences and challenges physician moms face during training and as junior faculty.

BACKGROUND:

Balancing the demands of medical training and a career along with those of parenthood is challenging. Currently 46% of residents and fellows in training are women, with a rate as high as 83% in Obstetrics and Gynecology.

METHODS:

We surveyed 897 physician moms from January 2018-February 2018 about their experiences with child-bearing, breastfeeding and maternity leave. Participants completed an open-ended question “What is your biggest challenge as a physician mom?”, these answers were qualitatively coded.

RESULTS:

The majority of participants (40%) had their first child between 31 and 34 years old; 36% of participants had their first child as a resident, while 28% did as junior faculty. For those who had a child during residency, 38% breastfed for 1 year or more, 26% breastfed for 6 months or less. For women who delayed child-bearing, 55% delayed to complete training, 21% delayed for financial reasons, 20% delayed for infertility, 12% of participants delayed due to pressure from their training program. For women who had a child during training 44% described having inadequate leave, but 53% report support from program administration. The themes for biggest challenges for physician moms were coded as: time/hours (37%), balance (26%); over-expectation/guilt/shame (21%), work/working at home (21%), missing out (18%); logistics/child-care (11%).

DISCUSSION:

Based on our results, there are clear ways residency programs and departments can support physician moms with the challenges they face.
How to optimize neuromuscular blockade in ambulatory setting?
Authors: Meistelman Claude , Plaud Benoit , Debaene Bertrand
Published: October 2019

Purpose of review

The purpose of this review is to discuss the optimal use of neuromuscular blocking agents (NMBA) during ambulatory surgery, and to provide an update on the routine use of neuromuscular monitoring and the prevention of residual paralysis.

Recent findings

The number of major surgical procedures performed in ambulatory patients is likely to increase in the coming years, following the development of laparoscopic and thoracoscopic procedures. To successfully complete these procedures, the proper use of NMBA is mandatory. The use of NMBA not only improves intubating conditions but also ventilation. Recent studies demonstrate that NMBA are much more the solution rather than the cause of airway problems. There is growing evidence that the paralysis of the diaphragm and the abdominal wall muscles, which are resistant to NMBA is of importance during laparoscopic surgery. Further studies are still required to determine when deep neuromuscular block [posttetanic count (PTC) < 5] is required perioperatively. There is now a consensus to use perioperatively neuromuscular monitoring and particularly objective neuromuscular monitoring in combination with reversal agents to avoid residual paralysis and its related morbidity (e.g. respiratory complications in the PACU).

Recent data suggest that it is now possible to obtain a tight control of neuromuscular block to maintain optimal relaxation tailored to the surgical requirements and to obtain a rapid and reliable recovery at the end of the procedure.
Resuscitation with Hydroxyethyl Starch Maintains Hemodynamic Coherence in Ovine Hemorrhagic Shock
Authors: Arnemann Philip-Helge , Hessler Michael , Kampmeier Tim , Seidel Laura , Malek Youssef , Van Aken Hugo , Morelli Andrea , Rehberg Sebastian , Ince Can , Ertmer Christian
Published: October 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Fluid resuscitation in hemorrhagic shock aims to restore hemodynamics and repair altered microcirculation. Hemodynamic coherence is the concordant performance of macro- and microcirculation. The present study on fluid therapy in hemorrhagic shock hypothesized that the choice of fluid (0.9% sodium chloride [saline group] or balanced 6% hydroxyethyl starch 130/0.4 [hydroxyethyl starch group]) impacts on hemodynamic coherence.

Methods

After instrumentation, 10 sheep were bled up to 30 ml/kg body weight of blood stopping at a mean arterial pressure of 30 mmHg to establish hemorrhagic shock. To reestablish baseline mean arterial pressure, they received either saline or hydroxyethyl starch (each n = 5). Hemodynamic coherence was assessed by comparison of changes in mean arterial pressure and both perfused vessel density and microvascular flow index.

Results

Bleeding of 23 ml/kg blood [21; 30] (median [25th; 75th percentile]) in the saline group and 24 ml/kg [22; 25] (P = 0.916) in the hydroxyethyl starch group led to hemorrhagic shock. Fluid resuscitation reestablished baseline mean arterial pressure in all sheep of the hydroxyethyl starch group and in one sheep of the saline group. In the saline group 4,980 ml [3,312; 5,700] and in the hydroxyethyl starch group 610 ml [489; 615] of fluid were needed (P = 0.009). In hemorrhagic shock perfused vessel density (saline from 100% to 83% [49; 86]; hydroxyethyl starch from 100% to 74% [61; 80]) and microvascular flow index (saline from 3.1 [2.5; 3.3] to 2.0 [1.6; 2.3]; hydroxyethyl starch from 2.9 [2.9; 3.1] to 2.5 [2.3; 2.7]) decreased in both groups. After resuscitation both variables improved in the hydroxyethyl starch group (perfused vessel density: 125% [120; 147]; microvascular flow index: 3.4 [3.2; 3.5]), whereas in the saline group perfused vessel density further decreased (64% [62; 79]) and microvascular flow index increased less than in the hydroxyethyl starch group (2.7 [2.4; 2.8]; both P < 0.001 for saline vs. hydroxyethyl starch).

Conclusions

Resuscitation with hydroxyethyl starch maintained coherence in hemorrhagic shock. In contrast, saline only improved macro- but not microcirculation. Hemodynamic coherence might be influenced by the choice of resuscitation fluid.
Evolving concepts of the pathogenesis of rheumatoid arthritis with focus on the early and late stages
Authors: Coutant Frédéric , Miossec Pierre
Published: October 2019

Purpose of review

To provide an overview of recently published work covering key mechanisms involved in the pathogenesis of rheumatoid arthritis (RA), with focus on the early and late stages.

Recent findings

Present understanding of RA pathogenesis has been mainly focused on the inflammatory process at the established phase of the disease, but recent work has shed light on important molecular and cellular mechanisms involved both at the early and late/refractory stages. In early RA, the involvement of anticitrullinated protein antibodies in RA induction has been identified with a critical role of the IL-23/Th17 axis in the control of their pathogenicity. At the late stage, RA may be viewed as a cell-autonomous genetic and epigenetic disease, characterized by altered cell death pathways in synoviocytes after long-term exposure to inflammation. An improved knowledge of these cell-intrinsic altered pathways is the basis for the targeting of pathogenic synoviocytes, as a new therapeutic alternative against resistance to current treatment targeting the immune system.

We summarize these pathological pathways, and their understanding will facilitate the design of new diagnostic tools and therapeutic strategies combining the targeting of pathogenic synoviocytes with current immune-targeted therapies.
Syndesmosis and Syndesmotic Equivalent Injuries in Tibial Plafond Fractures
Authors: Haller Justin M. , Githens Michael , Rothberg David , Higgins Thomas , Barei David , Nork Sean
Published: October 2019

Objectives:

To identify the incidence and fracture characteristics associated with syndesmotic injury in tibial plafond fractures and report the incidence of posttraumatic osteoarthrosis (PTOA).

Design:

Retrospective comparative study.

Setting:

Two level-1 academic trauma centers.

Patients/Participants:

Of the 735 tibial plafond fractures (OTA/AO 43-B3 and 43-C) treated from January 2006 through December 2015, 108 patients (108/735, 15%) were identified with syndesmosis injury.

Intervention:

Either acute or missed syndesmotic injury.

Main Outcome Measurement:

PTOA.

Results:

Fourteen fractures (14/735, 2%) had missed syndesmotic injury. Volkmann fragment of ≤10 mm (P = 0.04) and fibular avulsion fracture (P = 0.05) were significantly more common in missed syndesmosis. Ninety fractures (14/14 missed, 76/94 acute) had greater than 12-month follow-up (mean, 26 months; range, 12–102 months). Nearly all patients with missed syndesmosis injury developed arthrosis (13/14, 93%), and 45% (34/76 fractures) of plafond fractures with acute syndesmosis injury developed arthrosis (P < 0.001). Although controlling for malreduction, patients with missed syndesmosis had significantly more PTOA development (P = 0.018). Controlling for malreduction, patients with syndesmotic fixation and a ≤10-mm Chaput or Volkmann fragment or fibular avulsion fracture (8/31, 26%) were less likely to develop PTOA than if they had a similar fracture pattern without syndesmotic fixation (9/10, 90%) (P = 0.011).

Conclusions:

Fifteen percent of tibia plafond fractures have a syndesmosis or syndesmotic equivalent injury. Missed syndesmosis injury has a high rate of PTOA development. Patients with a ≤10-mm Chaput or Volkmann fragment and/or fibular avulsion fracture benefit from syndesmotic fixation.

Level of Evidence:

Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Miniplate Augmented Tension-Band Wiring for Comminuted Patella Fractures
Authors: Cho Jae-Woo , Kent William T. , Cho Won-Tae , Kim Jin-Kak , Moon Ki-Ho , Yeo Do-Hyun , Kim Beom-Soo , Oh Chang-Wug , Oh Jong-Keon
Published: October 2019

The aim of this study was to introduce various applications of miniplate augmented tension-band wiring (TBW) for comminuted patella fractures and to evaluate the clinical outcomes. Comminuted articular patella fractures were managed with anterior cortical miniplate fixation with a TBW technique from January 2014 to January 2016. The primary end point was radiographic union. Secondary end points were complications related to the procedure. Functional outcomes including range of motion were also evaluated. Thirty patients were followed up for a mean of 20 months (range, 12–28) postoperatively. The primary union rate was 96% (29 of 30 patients). Mean time to union was 3.2 months. One patient required additional surgery because of acute postoperative infection. Twenty-five patients recovered a full range of motion relative to the contralateral limb. The mean Bostman score at the last follow-up was 28.6 points (range, 26–30). In conclusion, miniplate augmented TBW is a versatile and useful technique for comminuted patella fracture fixation.
Tensioned Wire–Assisted Intramedullary Nail Treatment of Proximal Tibia Shaft Fractures: A Technical Trick
Authors: Nicolescu Razvan , Quinnan Stephen M. , Lawrie Charles M. , Hutson James J.
Published: October 2019

Proximal tibia shaft fractures are often challenging to manage because of their intrinsic tendency toward valgus and apex anterior deformity. In recent years, intramedullary nailing (IMN) has become more frequently used to treat these injuries, allowing for biologic advantages such as load-sharing, immediate weight-bearing, and avoidance of disruption of periosteal blood supply. Several adjunctive techniques, such as semiextended positioning, blocking screws, and external fixation, have been developed to assist with fracture reduction during IMN. We describe a new adjunctive reduction technique—tensioned wire–assisted IMN—for the treatment of proximal tibia shaft fractures. We have found that tensioned wire assistance facilitates fracture reduction during IMN, does not interfere with intraoperative image intensification, and is compatible with both standard nailing instrumentation and additional adjunctive techniques. We present tensioned wire nailing as a technical trick for anatomic and stable reduction of proximal tibia fractures and compare a cohort of proximal tibia shaft fractures managed with and without tensioned wire assistance.
Publication Rates of Posters From the Orthopaedic Trauma Association Annual Meeting 2011–2016: Posters Are Not Second Rate
Authors: Melvin Patricia R. , Cannada Lisa K.
Published: October 2019

Objective:

To determine the publication rate of posters presented at the OTA annual meeting from 2011 to 2016.

Methods:

All posters presented at the OTA annual meetings from 2011 to 2016 were identified from the OTA's official website and confirmed through review of the OTA official programs. This information was then used to direct a search, and if the presentation was associated with a publication, publishing information was entered into the database.

Results:

From 2011 to 2016, there were a total of 875 posters with 473 associated publications (54%). The highest rate of publication was 64.1% of posters published in 2012. The posters were published at an average of 19.4 months after presentation. One hundred sixty posters were published in the Journal of Orthopaedic Trauma (35%).

Conclusion:

Our research demonstrated a 54% publication rate over a 6-year period of posters presented at the OTA annual meetings. This rate is higher than other publication rates for podium presentations in other societies (eg, American Academy of Orthopaedic Surgeons and American Academy for Surgery of the Hand). This validates the quality of research presented in poster format at the OTA annual meeting.