bluuebunny/crossref_metadata_2025 huggingface dataset:
Day at the Races: Comparing BioFire FilmArray Blood Culture ID Panels With Verigene Blood Culture Panel in Gram-Negative Bloodstream Infections Using DOOR-MAT Analysis
Authors: Claeys Kimberly C , Schlaffer Kathryn , Smith Richard , Hitchcock Stephanie , Jiang Yunyun , Evans Scott , Johnson J Kristie , Leekha Surbhi
Published: March 2021

Three rapid diagnostic test panels (Verigene BC-GN, BioFire BCID, and BCID 2 [RUO]) were compared using the Desirability of Outcome Ranking Management of Antimicrobial Therapy (DOOR-MAT) to evaluate potential downstream antimicrobial prescribing decisions resulting from the panels’ different organism and resistance detection. BioFire BCID 2 (RUO) had the best mean DOOR-MAT scores.
Viral Sequencing to Investigate Sources of SARS-CoV-2 Infection in US Healthcare Personnel
Authors: Braun Katarina M , Moreno Gage K , Buys Ashley , Somsen Elizabeth D , Bobholz Max , Accola Molly A , Anderson Laura , Rehrauer William M , Baker David A , Safdar Nasia , Lepak Alexander J , O’Connor David H , Friedrich Thomas C
Published: March 2021

Background

Healthcare personnel (HCP) are at increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We posit that current infection control guidelines generally protect HCP from SARS-CoV-2 infection in a healthcare setting.

Methods

In this retrospective case series, we used viral genomics to investigate the likely source of SARS-CoV-2 infection in HCP at a major academic medical institution in the Upper Midwest of the United States between 25 March and 27 December 2020. We obtained limited epidemiological data through informal interviews and review of the electronic health record and combined this information with healthcare-associated viral sequences and viral sequences collected in the broader community to infer the most likely source of infection in HCP.

Results

We investigated SARS-CoV-2 infection clusters involving 95 HCP and 137 possible patient contact sequences. The majority of HCP infections could not be linked to a patient or coworker (55 of 95 [57.9%]) and were genetically similar to viruses circulating concurrently in the community. We found that 10.5% of HCP infections (10 of 95) could be traced to a coworker. Strikingly, only 4.2% (4 of 95) could be traced to a patient source.

Conclusions

Infections among HCP add further strain to the healthcare system and put patients, HCP, and communities at risk. We found no evidence for healthcare-associated transmission in the majority of HCP infections evaluated. Although we cannot rule out the possibility of cryptic healthcare-associated transmission, it appears that HCP most commonly become infected with SARS-CoV-2 via community exposure. This emphasizes the ongoing importance of mask wearing, physical distancing, robust testing programs, and rapid distribution of vaccines.
Plasma proteomics of green turtles (Chelonia mydas) reveals pathway shifts and potential biomarker candidates associated with health and disease
Authors: Marancik David P , Perrault Justin R , Komoroske Lisa M , Stoll Jamie A , Kelley Kristina N , Manire Charles A
Published: March 2021

Evaluating sea turtle health can be challenging due to an incomplete understanding of pathophysiologic responses in these species. Proteome characterization of clinical plasma samples can provide insights into disease progression and prospective biomarker targets. A TMT-10-plex-LC–MS/MS platform was used to characterize the plasma proteome of five, juvenile, green turtles (Chelonia mydas) and compare qualitative and quantitative protein changes during moribund and recovered states. The 10 plasma samples yielded a total of 670 unique proteins. Using ≥1.2-fold change in protein abundance as a benchmark for physiologic upregulation or downregulation, 233 (34.8%) were differentially regulated in at least one turtle between moribund and recovered states. Forty-six proteins (6.9%) were differentially regulated in all five turtles with two proteins (0.3%) demonstrating a statistically significant change. A principle component analysis showed protein abundance loosely clustered between moribund samples or recovered samples and for turtles that presented with trauma (n = 3) or as intestinal floaters (n = 2). Gene Ontology terms demonstrated that moribund samples were represented by a higher number of proteins associated with blood coagulation, adaptive immune responses and acute phase response, while recovered turtle samples included a relatively higher number of proteins associated with metabolic processes and response to nutrients. Abundance levels of 48 proteins (7.2%) in moribund samples significantly correlated with total protein, albumin and/or globulin levels quantified by biochemical analysis. Differentially regulated proteins identified with immunologic and physiologic functions are discussed for their possible role in the green turtle pathophysiologic response and for their potential use as diagnostic biomarkers. These findings enhance our ability to interpret sea turtle health and further progress conservation, research and rehabilitation programs for these ecologically important species.
Vedolizumab and Anti-Tumour Necrosis Factor α Real-World Outcomes in Biologic-Naïve Inflammatory Bowel Disease Patients: Results from the EVOLVE Study
Authors: Bressler Brian , Yarur Andres , Silverberg Mark S , Bassel Marielle , Bellaguarda Emanuelle , Fourment Chris , Gatopoulou Anthie , Karatzas Pantelis , Kopylov Uri , Michalopoulos George , Michopoulos Spyridon , Navaneethan Udayakumar , Rubin David T , Siffledeen Jesse , Singh Andrew , Soufleris Konstantinos , Stein Dara , Demuth Dirk , Mantzaris Gerassimos J
Published: March 2021

Background and Aims

This study aimed to compare real-world clinical effectiveness and safety of vedolizumab, an α4β7-integrin inhibitor, and anti-tumour necrosis factor-α [anti-TNFα] agents in biologic-naïve ulcerative colitis [UC] and Crohn’s disease [CD] patients.

Methods

This was a 24-month retrospective medical chart study in adult UC and CD patients treated with vedolizumab or anti-TNFα in Canada, Greece and the USA. Inverse probability weighting was used to account for differences between groups. Primary outcomes were cumulative rates of clinical effectiveness [clinical response, clinical remission, mucosal healing] and incidence rates of serious adverse events [SAEs] and serious infections [SIs]. Secondary outcomes included cumulative rates of treatment persistence [patients who did not discontinue index treatment during follow-up] and dose escalation and incidence rates of disease exacerbations and disease-related surgeries. Adjusted analyses were performed using inverse probability weighting.

Results

A total of 1095 patients [604 UC, 491 CD] were included. By 24 months, rates of clinical effectiveness were similar between groups, but incidence rates of SAEs (hazard ratio [HR] = 0.42 [0.28–0.62]) and SIs (HR = 0.40 [0.19–0.85]) were significantly lower in vedolizumab vs anti-TNFα patients. Rates of treatment persistence [p < 0.01] by 24 months were higher in vedolizumab patients with UC. Incidence rates of disease exacerbations were lower in vedolizumab patients with UC (HR = 0.58 [0.45–0.76]). Other outcomes did not significantly differ between groups.

Conclusion

In this real-world setting, first-line biologic therapy in biologic-naïve patients with UC and CD demonstrated that vedolizumab and anti-TNFα treatments were equally effective at controlling disease symptoms, but vedolizumab has a more favourable safety profile.
How much healthcare is wasted? A cross-sectional study of outpatient overprovision in private-for-profit and faith-based health facilities in Tanzania
Authors: King Jessica J C , Powell-Jackson Timothy , Makungu Christina , Hargreaves James , Goodman Catherine
Published: March 2021

Overprovision—healthcare whose harm exceeds its benefit—is of increasing concern in low- and middle-income countries, where the growth of the private-for-profit sector may amplify incentives for providing unnecessary care, and achieving universal health coverage will require efficient resource use. Measurement of overprovision has conceptual and practical challenges. We present a framework to conceptualize and measure overprovision, comparing for-profit and not-for-profit private outpatient facilities across 18 of mainland Tanzania’s 22 regions. We developed a novel conceptualization of three harms of overprovision: economic (waste of resources), public health (unnecessary use of antimicrobial agents risking development of resistant organisms) and clinical (high risk of harm to individual patients). Standardized patients (SPs) visited 227 health facilities (99 for-profit and 128 not-for-profit) between May 3 and June 12, 2018, completing 909 visits and presenting 4 cases: asthma, non-malarial febrile illness, tuberculosis and upper respiratory tract infection. Tests and treatments prescribed were categorized as necessary or unnecessary, and unnecessary care was classified by type of harm(s). Fifty-three percent of 1995 drugs prescribed and 43% of 891 tests ordered were unnecessary. At the patient-visit level, 81% of SPs received unnecessary care, 67% received care harmful to public health (prescription of unnecessary antibiotics or antimalarials) and 6% received clinically harmful care. Thirteen percent of SPs were prescribed an antibiotic defined by WHO as ‘Watch’ (high priority for antimicrobial stewardship). Although overprovision was common in all sectors and geographical regions, clinically harmful care was more likely in for-profit than faith-based facilities and less common in urban than rural areas. Overprovision was widespread in both for-profit and not-for-profit facilities, suggesting considerable waste in the private sector, not solely driven by profit. Unnecessary antibiotic or antimalarial prescriptions are of concern for the development of antimicrobial resistance. Option for policymakers to address overprovision includes the use of strategic purchasing arrangements, provider training and patient education.
Laryngeal mask versus endotracheal tube for airway management in tracheal surgery: a case–control matching analysis and review of the current literature
Authors: Menna Cecilia , Fiorelli Silvia , Massullo Domenico , Ibrahim Mohsen , Rocco Monica , Rendina Erino Angelo
Published: March 2021

OBJECTIVES

The endotracheal tube (ETT) and the laryngeal mask airway (LMA) are possible strategies for airway management during tracheal resection and reconstruction for tracheal and laryngotracheal stenosis. The goal of the study was to analyse and compare outcomes in the LMA and ETT groups.

METHODS

Between 2003 and 2020, a total of 184 patients affected by postintubation, post-tracheostomy and idiopathic stenosis who had tracheal or laryngotracheal resections and reconstructions via a cervicotomy were retrospectively enrolled in this single-centre study. In 29 patients, airway management was achieved through LMA during tracheal surgery, whereas in 155 patients, it was achieved through ETT. A case–control matching analysis was performed with a 1:1 ratio, according to age, gender, body mass index, aetiology and length of stenosis (1–4 cm), resulting in 22 patients managed through LMA (LMA group) matched with 22 patients managed through ETT (ETT group).

RESULTS

No significant differences were found in the reintubation rate, 30-day mortality and postoperative length of stay. Operative time was shorter in patients with LMA (96.23 ± 34.72 min in the ETT group vs 76.14 ± 26.94 min in the LMA group; P = 0.043). Intensive care unit (ICU) admission rate and stay were lower in the LMA group [18 in the ETT group vs 8 in the LMA group, odds ratio = 10.17, confidence interval (CI) 95% 1.79–57.79; P = 0. 009; 22.77 ± 16.68 h in ETT group vs 9.23 ± 13.51 h in LMA group; P = 0.005]. Dysphonia was more frequent in the ETT group than in the LMA group (20 in the ETT group vs 11 in the LMA group, odds ratio = 13.79, CI 95% 1.86–102; P = 0.010).

CONCLUSIONS

LMA is a feasible option for airway management in tracheal surgery, with lower operative time, ICU admission rate, ICU length of stay and postoperative dysphonia occurrence.
External fixation of airway stents for upper tracheal stenosis and tracheoesophageal fistula
Authors: Niwa Hideyuki , Oki Masahide , Saka Hideo , Torii Atsushi , Yamada Arisa , Shigematsu Fumie , Ishida Akane , Kogure Yoshihito
Published: March 2021

OBJECTIVES

Stent migration is a common complication of airway stent placement for upper tracheal stenosis and tracheoesophageal fistula. Although several researchers have reported that external fixation is effective in preventing stent migration, the usefulness and safety of external fixation have not been proved because their cohorts were small. We therefore investigated the efficacy and safety of external fixation during upper tracheal stenting.

METHODS

Records of patients who underwent airway stent placement from May 2007 to August 2018 in a single centre were retrospectively reviewed. We included only patients whose stent had been placed in the upper trachea with external fixation to the tracheal wall. The primary endpoint of this study was the rate of stent migration.

RESULTS

Altogether, 51 procedures were performed in 45 patients (32 males, 13 females; median age 60 years, range 14–91 years). The median follow-up period was 9 months (range 0.3–90 months). Among the procedures, 15 were performed for benign disease and 36 for malignancy. Stents were composed of either silicone (n = 42) or metal (n = 9). Stent migration occurred in 3 (6%) patients. The stents with migration were all composed of silicone. Other sequelae were granulation tissue formation in 10 (20%) patients, sputum obstruction in 6 (12%), cellulitis in 3 (6%) and pneumonia in 1 (2%).

CONCLUSIONS

External fixation was an effective method for preventing migration of airway stents placed for upper tracheal stenosis and tracheoesophageal fistula. The complications were acceptable in terms of safety.
High-risk-pattern lung adenocarcinoma with epidermal growth factor receptor mutation is associated with distant metastasis risk and may benefit from adjuvant targeted therapy
Authors: Wang Liang , Wang Xing , Huang Miao , Yan Shi , Li Shaolei , Lv Chao , Wu Nan , Yang Yue
Published: March 2021

OBJECTIVES

This study aimed to evaluate the value of the high-risk-pattern histology (micropapillary and solid components) for predicting distant metastasis in lung adenocarcinoma and to determine the survival benefit with adjuvant targeted therapy for resected non-small cell lung cancer with high-risk-pattern histology.

METHODS

Patients receiving surgery for non-small cell lung cancer were included in this retrospective study. Histological classification was performed according to 2015 World Health Organization classification. Tumours with micropapillary and solid components were defined as high-risk-pattern tumours. Univariable and multivariable Cox regression analyses were used for survival analysis. Adjuvant targeted therapy was alternative for patients with epidermal growth factor receptor (EGFR)-mutation and refusing adjuvant chemotherapy, and outcome was evaluated between 2 groups.

RESULTS

The 514 patients (78 in high-risk group and 436 in low-risk group) were followed up for a median of 64 months. High-risk-pattern adenocarcinoma was significantly more common in male patients (P < 0.001) and in smokers (P < 0.001). Among patients with EGFR mutation (n = 164), the high-risk pattern was significantly associated with distant metastasis (P = 0.028) including brain metastasis (P = 0.022). In the 42 patients with high-risk pattern plus EGFR mutation, survival was significantly better after treatment with adjuvant targeted therapy than with chemotherapy (5-year overall survival: 56.4 ± 2.6 vs 44.7 ± 3.7 months, P = 0.011; 5-year disease-free survival: 54.0 ± 3.3 vs 41.9 ± 4.5 months, P = 0.006).

CONCLUSIONS

High-risk pattern is associated with distant metastasis in non-small cell lung cancer after surgery. Adjuvant targeted therapy may be superior to chemotherapy for treatment of patients with high-risk pattern and EGFR mutation.
Endoscopic lung volume reduction coils for patients with severe emphysema—a single-centre retrospective analysis
Authors: Mang Sebastian , Huss Niklas , Schäfers Hans-Joachim , Wehrfritz Holger , Massmann Alexander , Lensch Christian , Langer Frank , Seiler Frederik , Bals Robert , Lepper Philipp M
Published: March 2021

OBJECTIVES

Patients with chronic obstructive pulmonary disease and lung emphysema may benefit from surgical or endoscopic lung volume reduction (ELVR). Previously reported outcomes of nitinol coil-based ELVR techniques have been ambiguous. The analysis was done to analyse outcomes of ELVR with nitinol coils in patients with severe pulmonary emphysema.

METHODS

From September 2013 to November 2014, our centre performed a total of 41 coil implantations on 29 patients with severe emphysema. Coils were bronchoscopically placed during general anaesthesia. Twelve out of 29 patients received staged contralateral treatments up to 112 days later to avoid bilateral pneumothorax. Lung function and 6-min walking distance were assessed 1 week prior, 1 week after as well as 6–12 months after the procedure. Patients were followed up to 48 months after ELVR and overall mortality was compared to a historic cohort.

RESULTS

While coil-based ELVR led to significant short-term improvement of vital capacity (VC, +0.14 ± 0.39 l, P = 0.032) and hyperinflation (Δ residual volume/total lung capacity −2.32% ± 6.24%, P = 0.022), no significant changes were observed in 6-min walking distance or forced expiratory volume in 1 s. Benefits were short-lived, with only 15.4% and 14.3% of patients showing sustained improvements in forced expiratory volume in 1 s or residual volume after 6 months. Adverse events included haemoptysis (40%) and pneumothorax (3.4%), major complications occurred in 6.9% of cases. Overall survival without lung transplant was 63.8% after 48 months following ELVR, differing insignificantly from what BODE indices of patients would have predicted as median 4-year survival (57%) at the time of ELVR treatment.

CONCLUSIONS

ELVR with coils can achieve small and short-lived benefits in lung function at the cost of major complications in a highly morbid cohort. Treatment failed to improve 4-year overall survival. ELVR coils are not worthwhile the risk for most patients with severe emphysema.
From assurance to coproduction: a century of improving the quality of health-care service
Authors: Batalden Paul , Foster Tina
Published: March 2021

Background

Over the last century, the invitation to improve health-care service quality has taken many different forms: questions, observations, methods, tools and actions have emerged and evolved to create relevant ‘improvement work.’ In this paper we present three phases of this work. The basic frameworks used in these phases have not supplanted each other, but they have been layered one upon the next over time. Each brought important new thinking, new change opportunities and a new set of limits. The important messages of each need to be carried together into the future, as must the sense of curiosity and possibility about the commonalities that has driven this evolution.

Methods

Literature, personal experience and other artifacts were reviewed to develop this description of how the focus on quality work has evolved (and continues to evolve) over the last century.

Results

We describe three phases. Quality 1.0 seeks to answer the question ‘How might we establish thresholds for good healthcare services?’ It described certain ‘basic’ standards that should be used to certify acceptable performance and capability. This led to the formation of formal processes for review, documentation and external audits and a system for public notice and recognition. Over time, the limits and risks of this approach also became more visible: a ‘micro-accounting compliance’ sometimes triumphed over what might be of even greater strategic importance in the development and operations of effective systems of disease prevention and management to improve outcomes for patients and families. Quality 2.0 asked ‘How might we use enterprise-wide systems for disease management?’ It added a focus on the processes and systems of production, reduction of unwanted variation, the intrinsic motivation to take pride in work, outcome measurement and collaborative work practices as ways to improve quality, modeled on experiences in other industries. Quality 3.0 asks ‘How might we improve the value of the contribution that healthcare service makes to health?’ It requires careful consideration of the meaning of ‘service’ and ‘value’, service-creating logic, and prompts us to consider both relationships and activities in the context of the coproduction of health-care services.

Conclusion

Efforts to improve the quality and value of health-care services have evolved over the last century. With each success have come new challenges and questions, requiring the addition of new frames and approaches.
Variation in approaches to antimicrobial use surveillance in high-income secondary care settings: a systematic review
Authors: Patel Selina , Jhass Arnoupe , Slee Ann , Hopkins Susan , Shallcross Laura
Published: March 2021

Introduction

In secondary care, antimicrobial use (AMU) must be monitored to reduce the risk of antimicrobial resistance and infection-related complications. However, there is variation in how hospitals address this challenge, partly driven by each site’s level of digital maturity, expertise and resources available. This systematic review investigated approaches to measuring AMU to explore how these structural differences may present barriers to engagement with AMU surveillance.

Methods

We searched four digital databases and the websites of relevant organizations for studies in high-income, inpatient hospital settings that estimated AMU in adults. Excluded studies focused exclusively on antiviral or antifungal therapies. Data were extracted data on 12 fields (study description, data sources, data extraction methods and professionals involved in surveillance). Proportions were estimated with 95% CIs.

Results

We identified 145 reports of antimicrobial surveillance from Europe (63), North America (53), Oceania (14), Asia (13) and across more than continent (2) between 1977 and 2018. Of 145 studies, 47 carried out surveillance based on digital data sources. In regions with access to electronic patient records, 26/47 studies employed manual methods to extract the data. The majority of identified professionals involved in these studies were clinically trained (87/93).

Conclusions

Even in regions with access to electronic datasets, hospitals rely on manual data extraction for this work. Data extraction is undertaken by healthcare professionals, who may have conflicting priorities. Reducing barriers to engagement in AMU surveillance requires investment in methods, resources and training so that hospitals can extract and analyse data already contained within electronic patient records.
Evaluation of the GENE-UP®Salmonella Method for the Detection of Salmonella Species in a Broad Range of Foods and Select Environmental Surfaces: Collaborative Study, First Action 2020.02
Authors: Johnson Ronald L , Mills John C , Taylor Nikki J , Bird Patrick M
Published: March 2021

Background

The GENE-UP®Salmonella assay (Performance Tested MethodSM [PTM] 121802) is a PCR detection method that utilizes fluorescence resonance energy transfer (FRET) hybridization probes for the rapid detection of Salmonella species in foods and on environmental surfaces.

Objective

The purpose of this validation was to evaluate the method’s interlaboratory performance for submission to AOAC INTERNATIONAL for adoption as First Action Official Method of AnalysisSM.

Method

The GENE-UP method was evaluated in a multi-laboratory study using unpaired test portions for one food matrix, raw ground beef (80% lean). The candidate method was compared to the US Department of Agriculture (USDA), Food Safety Inspection Service, Microbiology Laboratory Guidebook (MLG) 4.10 reference method. An alternative confirmation procedure, using ASAP™ and CHROMID®Salmonella chromogenic agars, was included in the validation study. Fifteen collaborators from 14 laboratories participated. Three levels of contamination were evaluated: a non-inoculated control level (0 CFU/test portion), a low contamination level (∼0.7 CFU/test portion), and a high contamination level (∼2 CFU/test portion). Data were analyzed using the probability of detection (POD) statistical model.

Results

The dLPODC values with 95% confidence interval for the GENE-UP Salmonella method, with either alternative or traditional confirmation, were: 0.00 (–0.03, 0.03), –0.02 (–0.15, 0.12), and 0.02 (–0.03, 0.09) for the non-inoculated, low, and high contamination levels respectively.

Conclusions

The dLPODC results demonstrate no difference in performance between the candidate method and reference method for the matrix evaluated.

Highlights

The GENE-UP Salmonella method, with ASAP and CHROMID Salmonella, provides industry with a simplified, rapid, and accurate workflow for the detection of Salmonella in a broad range of foods and select environmental surfaces.
African Courts and Principles of International Environmental Law: A Kenyan and South African Case Study
Authors: Kotzé Louis J , Soyapi Caiphas B
Published: March 2021

Scholarship increasingly reveals the distinct interplay between international environmental law and domestic legal systems, and the important role of courts the world over in fleshing out this relationship. Africa, however, seems to be underrepresented in these discussions, despite its being a key stakeholder in the development of international environmental law. As a contribution to this debate, we offer here an analysis of the relationship between international environmental law and domestic African legal systems, by focusing on how domestic courts in Kenya and South Africa have been engaging with the precautionary principle, the principle of public participation and the principle of sustainable development. Our analysis of a range of judgments shows that these courts have been exceptionally innovative in their growing support of these principles that they seem to embrace in their efforts to strengthen domestic environmental protection and to contribute to a nascent transnational judicial dialogue.
The Potential for Computer Vision to Advance Accountability in the Syrian Crisis
Authors: Radeva Elena
Published: March 2021

This article explores a novel approach to technology-enabled review of evidentiary material implemented by the United Nations International, Independent and Impartial Mechanism – Syria ('IIIM – Syria’ or ‘the Mechanism’). The Mechanism’s objective in pursuing automation is to significantly accelerate the speed and improve the consistency of review and analysis of large, digitized documentary data sets used in the pursuit of accountability for crimes committed in Syria. This approach represents one of the first uses of Computer Vision applied to documentary evidence in the field of international criminal investigations and is a tangible example of public–private cooperation developing meaningful technology-based upon modern best practices. The article first discusses why technological innovation in investigative analysis is necessary in relation to the Syrian conflict. Next, the article reviews the approach adopted by IIIM – Syria towards applying existing and novel technology in the processing, preservation, and analysis of evidentiary material. Specifically, it explores how the organization executed a novel approach to technology-enabled review of evidentiary material through the application of Computer Vision techniques designed by forensic and eDiscovery experts. Finally, the article explores the wider investigative possibilities presented by the use of Computer Vision as a technique for analytical review.
Long-Term Risk of Ovarian Cancer and Borderline Tumors After Assisted Reproductive Technology
Authors: Spaan Mandy , van den Belt-Dusebout Alexandra W , Lambalk Cornelis B , van Boven Hester H , Schats Roel , Kortman Marian , Broekmans Frank J M , Laven Joop S E , van Santbrink Evert J P , Braat Didi D M , van der Westerlaken Lucette A J , Cohlen Ben J , Cantineau Astrid E P , Smeenk Jesper M J , van Rumste Minouche M , Goddijn Mariëtte , van Golde Ron J T , Meeuwissen Paul A M , Hamilton Carl J C M , Ouwens Gabriële M , Gerritsma Miranda A , Schaapveld Michael , Burger Curt W , van Leeuwen Flora E
Published: March 2021

Background

Long-term effects of assisted reproductive technology (ART) on ovarian tumor risk are unknown.

Methods

This nationwide cohort study comprises 30 625 women who received ovarian stimulation for ART in 1983-2000 and 9988 subfertile women not treated with ART. Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry until July 2018. Ovarian tumor risk in ART-treated women was compared with risks in the general population and the subfertile non-ART group. Statistical tests were 2-sided.

Results

After a median follow-up of 24 years, 158 invasive and 100 borderline ovarian tumors were observed. Ovarian cancer risk in the ART group was increased compared with the general population (standardized incidence ratio [SIR] = 1.43, 95% confidence interval [CI] = 1.18 to 1.71) but not when compared with the non-ART group (age- and parity-adjusted hazard ratio [HR] = 1.02, 95% CI = 0.70 to 1.50). Risk decreased with higher parity and with a larger number of successful ART cycles (resulting in childbirth, Ptrend = .001) but was not associated with the number of unsuccessful ART cycles. Borderline ovarian tumor risk was increased in ART-treated women compared with the general population (SIR = 2.20, 95% CI = 1.66 to 2.86) and with non-ART women (HR = 1.84, 95% CI = 1.08 to 3.14). Risk did not increase with more ART cycles or longer follow-up time.

Conclusions

Increased ovarian cancer risk in ART-treated women compared with the general population is likely explained by nulliparity rather than ART treatment. The increased risk of borderline ovarian tumors after ART must be interpreted with caution because no dose-response relationship was observed.
Evaluating the Feasibility and Acceptability of the Lifestyle Enhancement for ADHD Program
Authors: Ola Cindy , Gonzalez Erin , Tran Nguyen , Sasser Tyler , Kuhn Michelle , LaCount Patrick A , Stein Mark A , Mendoza Jason A , Tandon Pooja S
Published: March 2021

Objective 

To evaluate the feasibility and acceptability of the Lifestyle Enhancement for Attention Deficit Hyperactivity Disorder (ADHD) Program (LEAP), a novel parent behavior management training program that promotes physical activity (PA) and positive health behaviors and is enhanced with mobile health technology (Garmin) and a social media (Facebook) curriculum for parents of children with ADHD.

Methods 

The study included parents of children ages 5–10 years diagnosed with ADHD who did not engage in the recommended >60 min/day of moderate to vigorous PA based on parent report at baseline. Parents participated in the 8-week LEAP group and joined a private Facebook group. Children and one parent wore wrist-worn Garmin activity trackers daily. Parents completed the Treatment Adherence Inventory, Client Satisfaction Questionnaire, and participated in a structured focus group about their experiences with various aspects of the program.

Results 

Of 31 children enrolled, 51.5% had ADHD combined presentation, 36.3% with ADHD, predominately inattentive presentation, and 12.1% had unspecified ADHD (age 5–10; M = 7.6; 48.4% female). Parents attended an average of 86% of group sessions. On average, parents wore their Garmins for 5.1 days/week (average step count 7,092 steps/day) and children for 6.0 days/week (average step count 9,823 steps/day). Overall, parents and children were adherent to intervention components and acceptability of the program was high.

Conclusions 

Findings indicate that the LEAP program is an acceptable and feasible intervention model for promoting PA among parents and their children with ADHD. Implications for improving ADHD symptoms and enhancing evidence-based parent training programs are discussed.
#9: Frequency and Antimicrobial Susceptibility of Gram-Negative Organisms Causing Bloodstream Infections in Pediatric Patients from United States (US) Medical Centers (2014–2018)
Authors: Sader H S , Castanheira M , Streit J M , Carvalhaes C G , Mendes R E
Published: March 2021

Background

Ceftazidime–avibactam is US FDA approved for the treatment of pneumonia and complicated intra-abdominal and urinary tract infections in adults, and it is in late-stage clinical development for the treatment of pediatric patients.

Methods

Organisms were consecutively collected from pediatric patients (≤17 years old) with bloodstream infections in 33 US medical centers in 2014–2018. Enterobacterales, P. aeruginosa, and H. influenzae isolates (n = 976) were susceptibility (S) tested against ceftazidime–avibactam and comparators by reference broth microdilution methods; 42.9% of isolates tested were from patients <1 year old, and 70.7% from patients ≤5 years old. Isolates with an ESBL–phenotype were screened for β-lactamase genes.

Results

Overall, 40.1% of organisms were Gram-negative bacteria (GNB), 57.0% Gram-positives, and 2.8% Candida spp. The five most common GNB were E. coli (32.4% of GNB), K. pneumoniae (17.3%), E. cloacae (9.8%), P. aeruginosa (9.2%), and S. marcescens (5.5%; Table). Enterobacterales, P. aeruginosa, and H. influenzae isolates combined represented 89% of GNB and all isolates (100.0%) were susceptible to ceftazidime–avibactam. Among Enterobacterales (n = 845; MIC50/90, 0.12/0.25 mg/L), the highest ceftazidime–avibactam MIC value was only 4 mg/L and 99.2% of isolates were inhibited at ≤1 mg/L. Enterobacterales susceptibility to ceftriaxone, piperacillin–tazobactam, ceftolozane–tazobactam, and meropenem were 88.2%, 93.1%, 97.5%, and 99.5%, respectively. Forty-four Enterobacterales isolates (5.2%) produced an ESBL, including CTX-M-type (n = 35 [79.5% of ESBL producers], 21 being CTX-M-15), SHV-type (12; 27.3%), and OXA-1/30 (9; 20.5%). Twelve isolates (27.3%) produced >1 ESBL. No carbapenemase gene was detected. Among ESBL producers, highest ceftazidime–avibactam MIC was 2 mg/L, and susceptibility rates for ceftolozane–tazobactam and meropenem were 92.9% and 100.0%, respectively. Ceftazidime–avibactam exhibited complete activity against P. aeruginosa (MIC50/90, 2/4 mg/L; 100.0% susceptible). P. aeruginosa susceptibility rates for meropenem, piperacillin–tazobactam, and ceftolozane–tazobactam were 82.5%, 85.6%, and 100.0%, respectively; and 10.3% of isolates exhibited multidrug-resistance phenotype (not susceptible to ≥3 classes). Ceftazidime–avibactam was highly active against H. influenzae (n = 34; MIC50/90, ≤0.015/0.03 mg/L; highest MIC, 0.06 m/L).

Conclusions

Ceftazidime–avibactam exhibited potent activity against a large collection of GNB isolated from pediatric patients with bacteremia and showed complete coverage (100.0% susceptibility) against P. aeruginosa, Enterobacterales, and H. influenzae.
#39: Streptococcus anginosus Group Infections in Children: A Retrospective Cohort Study, 2015–2019
Authors: Amin O , Smith O , Berkowitz F , Lyon T , Kao C , Shane A , Yildirim Ia , Gonzalez M
Published: March 2021

Background

Infections attributed to the Streptococcus anginosus group (SAG), which includes Streptococcus anginosus, Streptococcus constellatus, and Streptococcus intermedius, have varying clinical presentations. SAG infections are difficult to identify initially, and members of the group may require different management strategies.

Methods

A retrospective review of SAG-positive cultures from January 2015, to September 2019, was conducted to describe the demographic, clinical, and laboratory features including the site of infection, antibiotic susceptibility, management, and clinical outcome.

Results

We identified 561 patients [median age 11.3, interquartile range (IQR) 7.1–14.9 years, male:female ratio 3:2, non-Hispanic–non-Latino 454 (81%), White 279 (49%)]. Thirty-nine (7%) had at least one underlying condition. Of these, inflammatory bowel disease 15 (39%), diabetes 7 (18%), immunodeficiency 5 (13%). SAG was found in exudate, fluid, or aspirate (537/561, 96%), blood (11/561, 2%), and tissue (11/561, 2%) samples; 388 (69%) were polymicrobial infections. The most common site of infection was intra-abdominal (175, 31%), followed by neck/odontogenic (114. 20%) and genitourinary tract (66, 12%). The median length of stay was 6 days (IQR 3–10 days) and was statistically significantly longer for patients with blood, central nervous system, and pulmonary infections compared with soft tissue and upper respiratory tract infections (P < 0.001). Beta-lactams were the most commonly used antibiotics (38%), followed by clindamycin (30 %) (see Figure for antibiotic susceptibility results) and 33 (56%) patients received combination therapy. We did not observe any SAG attributed to mortality.

Conclusions

In our retrospective cohort, SAG infections were more commonly identified in males, were associated with abscess formation, and presented as polymicrobial infections. Children with underlying comorbidities are more likely to present with systemic SAG infections. SAG-associated infections can be variable in presentation site and severity and should be considered as pathogens when managing patients.
#82: Osteomyelitis with Panton-Valentine Leukocidin Producing Staphylococcus aureus Strains, Experience in a Tertiary Pediatric Hospital in Mexico City
Authors: Aguilar Nancy , Aquino Alejandra , Vázquez Guillermo , Mérida Jocelin , Isunza-Alonso Oscar , Tamez Oscar , de Colsa Agustín
Published: March 2021

Background

S. aureus is the most common cause of osteomyelitis in children. Panton-Valentine leucocidin (PVL) is an exotoxin produced by certain S. aureus strains, which can be detected in both methicillin-sensitive and -resistant strains of staphylococci. Pediatric osteomyelitis by PVL producing S. aureus constitute a rare, but highly critical event. They are characterized by a rapid course of marked inflammation, worsening under conservative therapy, and a high rate of recurrence. No information is available on osteomyelitis and Panton-Valentine leukocidin producing S. aureus in Mexico.

Objective

The aim of this study was to determine the molecular characterization of S. aureus strains isolated in pediatric patients with osteomyelitis and their clinical features in a tertiary hospital in Mexico City.

Methods

We conducted a prospective study of children admitted for osteomyelitis, between December 2018 and November 2019, at Instituto Nacional de Pediatría. We obtained an informed consent in children under 12 years of age and an informed assent in children over 12. The confirmation of the S. aureus isolates was performed by amplification and analysis of 16S rRNA and nuc genes. The mecA and pvl genes were detected by PCR, the clinical features were obtained at the admission.

Results

Fifty patients were included and 26 cases of osteomyelitis were diagnosed, 13 were due to staphylococcus aureus genus and 6 due to S. aureus; all of them were methicillin susceptible and two were PVL producers. Both patients had a severe initial presentation, with extensive local abscesses, and one required three surgical procedures and developed septic pulmonary embolism. The two patients received double antimicrobial treatment and required a long therapy interval.

Conclusions

Osteomyelitis with Panton-Valentine Leukocidin producing S. aureus seems to be more severe. In patients with severe osteomyelitis, it is essential to detect the PVL toxin because they require early surgical intervention and prolonged intravenous therapy. Our findings suggest that the severity of the osteomyelitis is linked with PVL production more than with methicillin resistance due to that all our isolates were methicillin susceptible.
#99: Streptococcus pyogenes Utilizes the Peptide-Based Rgg 2/3 Quorum Sensing System During Oropharyngeal Colonization
Authors: Gogos Artemis , Federle Michael J
Published: March 2021

Background

Streptococcus pyogenes is a human-restricted pathogen most often found in the human nasopharynx. Multiple bacterial factors have been found to contribute to persistent colonization of this niche, and many of these factors are important in mucosal immunity and vaccine development. In this work, we infected mice intranasally with transcriptional regulator mutants of the Rgg2/3 quorum sensing (QS) system—a peptide-based signaling system conserved in all sequenced isolates of S. pyogenes.

Methods

Three-week-old CD1 mice were intranasally infected with ~107 CFU of S. pyogenes strain MGAS315. Calcium alginate throat swabs were used to monitor nasopharyngeal colonization by the bacteria over time. Luciferase reporters used alongside an IVIS camera were able to show quorum sensing activity levels after inoculation into the mouse nose. Bacterial RNA was isolated from the throat of the mice and quantitative RT–PCR was performed on the samples to corroborate the luciferase reporter data. The nasal-associated lymphoid tissue (NALT) was excised and its supernatants were subjected to 32-plex murine cytokine and chemokine analysis (Millipore).

Results

Deletion of the QS system’s transcriptional activator (Δrgg2) dramatically diminished the percentage of colonized mice. Deletion of the transcriptional repressor (Δrgg3) increased the percentage of colonized mice compared with wild type. Stimulation of the QS system using synthetic pheromones prior to inoculation did not significantly increase the percentage of animals colonized, indicating that activity of the QS system is responsive to conditions of the host nasopharynx. Mice inoculated with QS-dependent luciferase reporters were subjected to in vivo imaging and showed activation within 1 hour. Bacterial RNA extracted directly from oropharyngeal swabs and evaluated by quantitative RT–PCR subsequently confirmed QS upregulation within 1 hour of inoculation. In the nasal-associated lymphoid tissue (NALT), a muted inflammatory response to the Δrgg2 bacteria suggests that their rapid elimination fails to elicit the previously characterized response to intranasal inoculation of GAS.

Conclusions

Deletion of the Rgg2 transcriptional activator of the Rgg 2/3 quorum sensing system eliminates colonization of the murine nasopharynx and changes the transcriptional profile of the bacteria in this niche. An existing small-molecule inhibitor of the Rgg2/3 system was unable to inhibit QS activation in vivo, likely due to the suboptimal achievable doses; however, results of our study indicate inhibition of QS may diminish the oropharyngeal colonization of S. pyogenes and argue for further development.
#84: Evolutionary Pressure from APOBEC Causes an Underrepresentation of TC Motifs in Human Polyomavirus
Authors: Shapiro Kate , Shapiro Maxwell , MacCarthy Thomas
Published: March 2021

Background

Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) is a family of enzymes found in mammals that deaminate cytidine to uridine on ssDNA, facilitating a C-to-T mutation. Less commonly, APOBEC effectively mutates C-to-G as well. APOBEC has the potential to mutate the viral genome, rendering the virus nonproductive. The enzyme targets certain mutational motifs, also known as hotspots: most APOBECs deaminate at TC motifs. We hypothesize that human polyomaviruses (hPyV) have an under-representation of TC hotspots in their genomes to avoid APOBEC targeting. Specifically, we analyzed the degree of TC motif under-representation in five conserved genes of hPyV, each of which is expressed in either the early or late phase of the viral life cycle.

Methods

We utilized a statistical tool, the Cytidine Deaminase Under-representation Reporter (CDUR) that can be used to analyze sequences and determine whether these sequences have mutated under the evolutionary pressure of APOBEC based on the targeted hotspot. This tool uses a permutation test to determine whether the number of hotspots at a given coding sequence is significantly more or significantly less than expected under pseudo-random biological sequence evolution. The same analysis was used to determine whether the number of nonsynonymous mutations that might occur at those hotspots is significantly more or significantly less than expected by chance.

Results

TC motifs in early genes were more underrepresented compared with late genes in most hPyV species. Most early genes were susceptible to nonsynonymous mutations at the TC motifs. Those species which did not fit into this paradigm showed a similar degree of under-representation and susceptibility to nonsynonymous mutations at AC motifs. We also find a large over-representation of TG hotspots, but not TT hotspots.

Conclusions

hPyV may have evolved a reduced number of hotspots to subvert APOBEC and evade host immune defenses. Under-representation of TC motifs is more prevalent in early genes. Early genes include the small T and large T antigens, essential for viral proliferation. In addition, the large T antigen was particularly susceptible to mutation at TC motifs. This underscores the evolutionary pressure imposed on hPyV by APOBEC to evade host immunity. It is possible that the over-representation of TG motifs in hPyV is due to specific host DNA-repair mechanisms, but this requires further investigation.
#10: Fever and neutropenia. 10 years surveillance in a pediatric Mexican hospital
Authors: Sánchez-Medina E , Reyes-Hernández A , Severiano-Tellez A
Published: March 2021

Background

Fever and neutropenia, is a very common complication of chemotherapy in the treatment of cancer. It could happen in 10–50% of patients with solid tumors and more than 80% of patients with blood cancer. During leukemia treatment is very important first defense mechanisms integrity, such as skin, mucous membranes, Tlaxcala Children’s Hospital is a pediatric general hospital, located in the center of Mexico and is where the pediatric cancer patients are treated, with almost 30 new cases by year, treatment with chemotherapy and as an adverse event fever and neutropenia, which increases morbidity and mortality

Methods

We conducted an observational, descriptive, and analytic study aiming to identify fever and neutropenic events in ALL patients, their epidemiologic characteristics, antibiotic use, isolation and antibiogram, and outcome.

Results

We reviewed 124 files from ALL patients between 2007–2017, we found 204 cases, 70 (33.8%) at induction, 18.6% consolidation, reinduction 17.6%, maintenance 14.2%. Out of 204 cases, we documented 177 with fever and neutropenia, 15 events of septic shock and 12 with fever and neutropenia with an identifiable source; the first-line antibiotic for fever and neutropenia was ceftazidime/amikacin, and for septic shock cefepime with an aminoglycoside, we found 3.39%, 20%, and 0% deaths from each group. Patients with fever and neutropenia with or without identifiable source had a length-stay average of 9.8 days compared with 30 days in patients with septic shock, CRP average was 12.47 mg/dL in the patients who survived and 8.23 mg/dL in those who did not. We found a very low positivity in cultures, and in most cases, those cultures did not meet criteria for diagnosis, the most common bacteria identified were E. coli, P. aeruginosa.

Conclusions

This is the first approach to get a better knowledge about infectious complications in patients with ALL, these findings could lead to identifying opportunities to improve diagnosis and treatment which lead to reducing cost, morbidity, healthcare-associated infections.