bluuebunny/crossref_metadata_2025 huggingface dataset:
P14 A case of myositis in patient with atypical bacterial pneumonia
Authors: Smrity Smrity , Lawson Cathy , Marsh Sarah
Published: October 2021

Case report - Introduction

Bacterial community-acquired atypical pneumonia is sometimes complicated by myositis or by renal parenchymal disease. They can present with myositis and present with muscle weakness, pain or swelling, and elevated muscle enzymes. We present the case of a patient with lower limb weakness and raised creatinine kinase with atypical pneumonia caused by Legionella pneumophila.

Case report - Case description

A 76-year-old Caucasian man, who was previously fit and independent and walked 3 miles every day presented with a 1-week history of progressive leg weakness, and inability to mobilize. He had a fall and was on the floor for 2 hours. He had a background history of hypercholesterolemia and was on atorvastatin for 15 years. On his vital observation, he was found tachypnoeic, tachycardic, and hypoxic. He had a right upper lobe crackle but he didn’t have respiratory symptoms. His muscle power in his leg was 3/5 with carpet burns on knees and elbow.

Initial investigation showed raised inflammatory marker CRP 412mg/L, AKI stage 1, and CK 43400 IU/L. His CXR showed dense right upper lobe consolidation. Legionella urinary antigen was positive. Myositis myoblot, ANA, ANCA negative. COVID-19 swab negative.

Treated with IV antibiotic, supplemental oxygen, and IV fluid. Transferred to ITU due to worsening of hypoxia and kidney function. Interestingly, the CK level had improved significantly within 48 hours along with clinical improvement in his symptoms. There was no role of steroid or immunosuppressant due to his significant clinical improvement. On day 7 he was off oxygen, kidney function improved, had physiotherapy, and transferred to ward and on day 10 he was ambulant and discharged home.

Case report - Discussion

To date, very few case reports of myositis in a patient with atypical pneumonia have been reported. The mechanism underlying acute myositis in atypical pneumonia is still unknown. The present analysis points out that the organism underlying atypical bacterial pneumonia may occasionally invade the muscle tissue thereby inducing both myositis and secondary kidney damage.

Case report - Key learning points

We should be aware of this rare complication of atypical pneumonia and the resolution of symptoms that occur with the treatment of pneumonia. This would avoid unnecessary investigation and use of steroid.
Chronotype as self-regulation: morning preference is associated with better working memory strategy independent of sleep
Authors: Heimola Mikko , Paulanto Kaisu , Alakuijala Anniina , Tuisku Katinka , Simola Petteri , Ämmälä Antti-Jussi , Räisänen Pekka , Parkkola Kai , Paunio Tiina
Published: October 2021

Study Objectives

We set out to examine how chronotype (diurnal preference) is connected to ability to function in natural conditions where individuals cannot choose their sleep schedule. We conducted a cross-sectional study in military conscript service to test the hypothesis that sleep deprivation mediates the adverse effects of chronotype on cognitive functioning. We also examined the effects of time of day.

Methods

One hundred forty participants (ages 18–24 years) completed an online survey, including the Morningness-Eveningness Questionnaire and a Cambridge Neuropsychological Test Automated Battery. Most (n = 106) underwent an actigraphy recording. After bivariate analyses, we created a mediation model (self-reported sleepiness and sleep deprivation mediating effect of chronotype on cognition) and a moderation model (synchrony between most alert time and testing time).

Results

Reaction times in inhibition task correlated negatively with sleep efficiency and positively with sleep latency in actigraphy. There was no relation to ability to inhibit responses. More significantly, spatial working memory performance (especially strategicness of performance) correlated positively with morning preference and negatively with sleep deprivation before service. Synchrony with most alert time of the day did not moderate these connections. No other cognitive task correlated with morningness or sleep variables.

Conclusions

In line with previous research, inhibitory control is maintained after insufficient sleep but with a tradeoff of slower performance. The connection between morning preference and working memory strategy is a novel finding. We suggest that diurnal preference could be seen as an adaptive strategy, as morningness has consistently been associated with better academic and health outcomes.
Diagnosed or prescribed only? A national analysis of initial evaluation and management of insomnia among older adult Medicare beneficiaries
Authors: Wickwire Emerson M , Jobe Sophia L , Martin Jennifer L , Williams Scott G , Capaldi Vincent F , Collen Jacob , Doyinsola Bailey M , Scharf Steven M , Johnson Abree , Albrecht Jennifer S
Published: October 2021

Study Objectives

To describe initial insomnia-related encounters among a national sample of Medicare beneficiaries, and to identify older adults at risk for potentially inappropriate prescription insomnia medication usage.

Methods

Our data source was a random 5% sample of Medicare administrative claims data (2006–2013). Insomnia was operationalized as International Classification of Disease, Ninth Revision, Clinical Modification diagnostic codes. Insomnia medications included FDA-approved insomnia-related medication classes and drugs. Logistic regression was employed to identify predictors of being “prescribed only” (i.e., being prescribed an insomnia medication without a corresponding insomnia diagnosis).

Results

A total of N = 60 362 beneficiaries received either an insomnia diagnosis or a prescription for an insomnia medication as their first sleep-related encounter during the study period. Of these, 55.1% (n = 33 245) were prescribed only, whereas 44.9% (n = 27 117) received a concurrent insomnia diagnosis. In a fully adjusted regression model, younger age (odds ratio (OR) 0.98; 95% confidence interval (CI) 0.98, 0.99), male sex (OR 1.15; 95% CI 1.11, 1.20), and several comorbid conditions (i.e., dementia [OR 1.21; 95% CI 1.15, 1.27] and anemia [OR 1.17; 95% CI 1.13, 1.22]) were positively associated with being prescribed only. Conversely, black individuals (OR 0.83; 95% CI 0.78, 0.89) and those of “other” race (OR 0.89; 95% CI 0.84, 0.94) were less likely to be prescribed only. Individuals who received care from a board-certified sleep medicine provider (BCSMP) were less likely to be prescribed only (OR 0.27; 95% CI 0.16, 0.46).

Conclusions

Fewer than half of Medicare beneficiaries prescribed insomnia medications ever received a formal sleep-related diagnosis.
Unfit Stewards: The Role of the Intensive Pet Parenting Ideology in Constructing Racialized Narratives
Authors: James Adilia E E
Published: October 2021

Scholars have found that privileged, white individuals in integrated neighborhoods construct narratives that people of color (POC) have relationships with pets that are culturally different and morally questionable. They use these narratives to justify surveilling, punishing, and excluding their POC neighbors. How do privileged white people come up with the pet-related narratives they use as part of racialization processes? The dual purposes in this paper are to identify the constitutive elements of the intensive pet parenting ideology and show how individuals rely on this ideology to construct pet-related, racialized narratives. I extend the current discussion about the use of pet-related, racialized narratives by taking a closer look at the white-dominated veterinary profession. I conducted 44 in-depth interviews with a racially-diverse group of employed veterinarians and veterinary college students to determine if and how they rely on the intensive pet parenting ideology to explain a broad racial/ethnic process such as occupational segregation. Respondents proposed that POC cultures do not promote a self-sacrificing love for common pet species that would engender a passion for veterinary medicine within individuals of color. In this manner, they drew on the intensive pet parenting ideology to both racialize people and naturalize POC exclusion from the veterinary profession.
The first comprehensive, multigene molecular phylogeny for big-headed flies (Diptera: Pipunculidae)
Authors: Motamedinia Behnam , Skevington Jeffrey H , Kelso Scott , Kehlmaier Christian
Published: October 2021

The first comprehensive molecular phylogeny of Pipunculidae (Diptera) is inferred from analyses of 6963 bp of DNA sequence data from the following five loci: cytochrome c oxidase subunit I (COI), cytochrome b (Cytb), 12S ribosomal DNA, carbamoyl phosphate synthetase region of CAD (CAD) and alanyl-tRNA synthetase (AATS). The monophyly of Pipunculidae and most known subfamilies, including Chalarinae, Nephrocerinae, Pipunculinae and Protonephrocerinae, are well supported, as are most existing generic concepts. Molecular analysis reveals that Nephrocerinae, either with or without Protonephrocerinae, depending on analytical method, is sister to the rest of the family. Within Pipunculinae, Cephalopsini is synonymized with Pipunculini (synon. nov.) and Eudorylini with Tomosvaryellini (synon. nov.), leaving Pipunculinae with three tribes: Microcephalopsini, Pipunculini and Tomosvaryellini. Jassidophaga is proposed as a synonym of Verrallia (synon. nov.). Beckerias, Cephalops s.s., Cephalosphaera s.s., Neocephalosphaera, Parabeckerias and Semicephalops are all raised to generic status (stat. nov.). Eudorylas fusculus and E. vineti are transferred to Clistoabdominalis (comb. nov.) and Clistoabdominalis ruralis and C. doczkali to Eudorylas (comb. nov.). We provide evidence for four new genera of Pipunculidae, one of which is described herein (Tricosus gen. nov.; Australia: New South Wales, contains two new combinations, Tricosus cyclohirtus and Tricosus anorhaebus).
Ask the question
Authors: Sheehy Susan , Schwartz Linda Spoonster
Published: October 2021

This article discusses health issues affecting US military members and veterans, and provides occupation-specific questions to guide civilian healthcare professionals in providing high-quality care to veterans and their families.
Establishing a Deaf and American Sign Language Inclusive Residency Program
Authors: Hill Colin , Deville Curtiland , Kiess Ana , Narang Amol , Ratnanather Tilak , Bienstock Jessica , Brinckerhoff Loring , Hodukavich Aaron , Anderson Roberta , Alcorn Sara , DeWeese Theodore , Viswanathan Akila , Page Brandi R.
Published: October 2021

Improving diversity in residency programs has been increasingly emphasized as a means to address gender, racial, and ethnic disparities in medicine. However, limited attention has been given to the potential benefits of training physicians with differences other than gender or race and ethnicity. Americans with a disability represent about 27% of the U.S. population, whereas 1%–3% of physician trainees report having a disability. In 2013, a national survey identified only 86 physicians or trainees reporting deafness or hearing loss as a disability. To date, there are no published strategies on how to create an inclusive program for Deaf trainees. Herein, the authors report on the development of a Deaf and American Sign Language (ASL) inclusive residency program that can serve as an academic model for other programs, in any medical specialty, seeking to create an accessible training program for Deaf physicians and that can be adapted for trainees with other disabilities. In March 2017, the radiation oncology residency program at Johns Hopkins University matched an ASL-signing Deaf resident who would begin the program in July 2018. In preparation, department leadership engaged key stakeholders and leaders within the university’s health system and among the department faculty, residents, and staff as well as the incoming resident to create an ASL inclusive program. A 5-step transition process for the training program was ultimately developed and implemented. The authors focused on engaging the Deaf trainee and interpreters, engaging health system and departmental leadership, contracting a training consultant and developing oral and written training materials for faculty and staff, and optimizing the workspace via accommodations. Through collaborative preparation, a Deaf and ASL-signing resident was successfully integrated into the residency program. The proposed 5-step transition process provides an effective, engaging model to encourage other institutions that are seeking to employ similar inclusivity initiatives.
Intracranial Pressure Variability: A New Potential Metric of Cerebral Ischemia and Energy Metabolic Dysfunction in Aneurysmal Subarachnoid Hemorrhage?
Authors: Svedung Wettervik Teodor , Howells Timothy , Hånell Anders , Ronne-Engström Elisabeth , Lewén Anders , Enblad Per
Published: October 2021

Background:

It was recently reported that lower intracranial pressure variability (ICPV) is associated with delayed ischemic neurological deficits and unfavorable outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to determine whether lower ICPV also correlated with worse cerebral energy metabolism after aSAH.

Methods:

A total of 75 aSAH patients treated in the neurointensive care unit at Uppsala University Hospital, Sweden between 2008 and 2018 and with both intracranial pressure and cerebral microdialysis (MD) monitoring during the first 10 days after ictus were included in this retrospective study. ICPV was calculated with a bandpass filter limited to intracranial pressure slow waves with a wavelength of 55 to 15 seconds. Cerebral energy metabolites were measured hourly with MD. The monitoring period was divided into 3 phases; early (days 1 to 3), early vasospasm (days 4 to 6.5), and late vasospasm (days 6.5 to 10).

Results:

Lower ICPV was associated with lower MD-glucose in the late vasospasm phase, lower MD-pyruvate in the early vasospasm phases, and higher MD-lactate-pyruvate ratio (LPR) in the early and late vasospasm phases. Lower ICPV was associated with poor cerebral substrate supply (LPR >25 and pyruvate <120 µM) rather than mitochondrial failure (LPR >25 and pyruvate >120 µM). There was no association between ICPV and delayed ischemic neurological deficit, but lower ICPV in both vasospasm phases correlated with unfavorable outcomes.

Conclusion:

Lower ICPV was associated with an increased risk for disturbed cerebral energy metabolism and worse clinical outcomes in aSAH patients, possibly explained by a vasospasm-related decrease in cerebral blood volume dynamics and cerebral ischemia.
Failure of Hip Reconstruction in Children With Cerebral Palsy: What Are the Risk Factors?
Authors: Minaie Arya , Gordon J. Eric , Schoenecker Perry , Hosseinzadeh Pooya
Published: October 2021

Background:

The rates and risk factors contributing to failure after hip reconstruction among patients with cerebral palsy (CP) are not well established. In analyzing a large cohort of children with CP who underwent hip reconstruction, the objectives of this study are to establish (1) the failure rates and (2) associated risk factors.

Methods:

This retrospective study included chart and radiographic review of patients between the ages of 1 to 18, with a diagnosis of CP, who underwent a hip reconstructive procedure at a single children’s hospital over a 9-year period (2010 to 2018). Patients without at least 2 years of follow-up were excluded. Age at time of surgery, sex, Gross Motor Function Classification System (GMFCS), procedure(s) performed, preoperative migration percentage (MP), neck-shaft angle, and acetabular index (AI) were recorded. Failure was defined as need for revision surgery or a MP >50% on follow-up radiographs. Logistic regression and multiple-variable regression-type models were used to test for significance of risk factors.

Results:

Of the 291 hips in 179 patients (102 males, 77 females) that met inclusion criteria, 38 hips (13%) failed. Significant differences in the failure group were seen in age at time of surgery (6.2±3.2 vs. 8.1±3.2; P<0.001), preoperative MP (62.3±28.7 vs. 39.9±24.1%; P<0.001) and preoperative neck-shaft angle (164.9±8.2 vs. 157.3±15.6 degrees; P<0.001). Age below 6 at time of surgery significantly increased failure rate (26% vs. 6.3%, P<0.001) as did preoperative MP >70% (28.9% vs. 9.9%, P<0.001). Receiving an acetabular osteotomy was protective against failure (9.1% vs. 16.9%, P=0.048), particularly in patients with a preoperative AI >25° (odds ratio=0.236; confidence interval: 0.090-0.549).

Conclusions:

In this case series, failure after hip reconstruction for children with CP was determined to be 13.1%. There was a higher risk associated with age under 6 at time of surgery or a preoperative MP >70%. Correction of acetabular dysplasia when AI is more than 25 degrees with acetabular osteotomy at time of hip reconstruction, exerted a protective effect against subsequent failure.

Level of Evidence:

Level III—retrospective case series.
Circular RNA circ_0073181 contributes to tumorigenesis by regulating protein tyrosine phosphatase receptor type E via miR-548p in hepatocellular carcinoma
Authors: Wang Yan , Wang Hongxia , Jia Yanlin , Wang Xiyuan , Yang Chao , Xue Tongtong
Published: October 2021

Hepatocellular carcinoma (HCC) is a major world public problem in the world, with high morbidity and mortality rates. Circular RNA (circRNA) circ_0073181 has been reported to be related to HCC development. However, the mechanism of circ_0073181 in HCC is far from being addressed. Circ_0073181, microRNA-548p (miR-548p) and protein tyrosine phosphatase receptor type E (PTPRE) level were detected by real-time quantitative PCR (RT-qPCR). Cell proliferation, migration, invasion and apoptosis were detected by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2’-deoxyuridine, wound healing, transwell and flow cytometry assay. Protein levels of proliferating cell nuclear antigen, Bcl-2 related X protein (Bax) and PTPRE were examined by western blot assay. The binding relationship between miR-548p and circ_0073181 or PTPRE was predicted by circular RNA interactome and targetScan and then verified by a dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The biologic role of circ_0073181 on HCC tumor growth was examined by the xenograft tumor model in vivo. Circ_0073181 and PTPRE were upregulated, and miR-548p was decreased in HCC tissues and cells. Furthermore, circ_0073181 knockdown could boost proliferation, migration, invasion and repress apoptosis of HCC cells in vitro. The mechanical analysis suggested that circ_0073181 could regulate PTPRE expression by sponging miR-548p. In addition, circ_0073181 knockdown suppressed cell growth of HCC in vivo. Circ_0073181 silencing could inhibit HCC cell growth and metastasis partly by regulating the miR-548p/ PTPRE axis, providing a promising therapeutic target for the HCC treatment.
A Trigger and Response System for Preventing Cardiac Arrest in the ICU
Authors: Moskowitz Ari , Berg Katherine M. , Cocchi Michael N. , Grossestreuer Anne V. , Issa Mahmoud , Balaji Lakshman , Chase Maureen , Yang Jesse X. , Sarge Jennifer , O’Donoghue Sharon , Sarge Todd , Donnino Michael W.
Published: October 2021

OBJECTIVES:

Although patients in the ICU are closely monitored, some ICU cardiac arrest events may be preventable. In this study, we sought to reduce the rate of cardiac arrests occurring in the ICU through a quality improvement initiative.

DESIGN:

Prospective, observational study.

SETTING:

ICUs of a single tertiary care center.

PATIENTS:

Patients hospitalized in the ICUs between August 2017 and November 2019.

INTERVENTIONS:

A comprehensive trigger and response tool.

MEASUREMENT AND MAIN RESULTS:

Forty-three patients experienced an ICU cardiac arrest in the preintervention epoch (6.79 arrests per 1,000 discharges), and 59 patients experienced an ICU cardiac arrest in the intervention epoch (7.91 arrests per 1,000 discharges). In the intervention epoch, the clinical trigger and response tool was activated 106 times over a 1-year period, most commonly due to unexpected new/worsening hypotension. There was no step change in arrest rate (2.24 arrests/1,000 patients; 95% CI, –1.82 to 6.28; p = 0.28) or slope change (–0.02 slope of arrest rate; 95% CI, –0.14 to 0.11; p = 0.79) comparing the preintervention and intervention time epochs. Cardiac arrests in the preintervention epoch were more likely to be “potentially preventable” than that in the intervention epoch (25.6% vs 12.3%, respectively; odds ratio, 0.58; 95% CI, 0.20–0.88; p < 0.01).

CONCLUSIONS:

A novel trigger-and-response tool did not reduce the frequency of ICU cardiac arrest. Additional investigation is needed into the optimal approach for ICU cardiac arrest prevention.
Alterations in the oral microbiome in HIV infection: causes, effects and potential interventions
Authors: Li Shuang , Su Bin , He Qiu-Shui , Wu Hao , Zhang Tong
Published: October 2021

A massive depletion of CD4+ T lymphocytes has been described in early and acute human immunodeficiency virus (HIV) infection, leading to an imbalance between the human microbiome and immune responses. In recent years, a growing interest in the alterations in gut microbiota in HIV infection has led to many studies; however, only few studies have been conducted to explore the importance of oral microbiome in HIV-infected individuals. Evidence has indicated the dysbiosis of oral microbiota in people living with HIV (PLWH). Potential mechanisms might be related to the immunodeficiency in the oral cavity of HIV-infected individuals, including changes in secretory components such as reduced levels of enzymes and proteins in saliva and altered cellular components involved in the reduction and dysfunction of innate and adaptive immune cells. As a result, disrupted oral immunity in HIV-infected individuals leads to an imbalance between the oral microbiome and local immune responses, which may contribute to the development of HIV-related diseases and HIV-associated non-acquired immunodeficiency syndrome comorbidities. Although the introduction of antiretroviral therapy (ART) has led to a significant decrease in occurrence of the opportunistic oral infections in HIV-infected individuals, the dysbiosis in oral microbiome persists. Furthermore, several studies with the aim to investigate the ability of probiotics to regulate the dysbiosis of oral microbiota in HIV-infected individuals are ongoing. However, the effects of ART and probiotics on oral microbiome in HIV-infected individuals remain unclear. In this article, we review the composition of the oral microbiome in healthy and HIV-infected individuals and the possible effect of oral microbiome on HIV-associated oral diseases. We also discuss how ART and probiotics influence the oral microbiome in HIV infection. We believe that a deeper understanding of composition and function of the oral microbiome is critical for the development of effective preventive and therapeutic strategies for HIV infection.
Suicide Risk Screening in Pediatric Outpatient Neurodevelopmental Disabilities Clinics
Authors: Rybczynski Suzanne , Ryan Taylor C. , Wilcox Holly C. , Van Eck Kathryn , Cwik Mary , Vasa Roma A. , Findling Robert L. , Slifer Keith , Kleiner Daniel , Lipkin Paul H.
Published: October 2021

Objective:

The purpose of this study was to describe the implementation of universal suicide risk screening in pediatric neurodevelopmental disabilities (NDD) medical clinics, analyze demographic and clinical characteristics of eligible patients, describe outcomes of positive screenings, and describe factors that influenced participation in screenings.

Methods:

A suicide risk screening protocol was developed and implemented for medical clinic patients aged 8 to 18 years. Registered nurses screened patients using the “Ask Suicide-Screening Questions” tool during triage. Positive screenings were referred for further assessment and mental health management. Demographics and clinical data were extracted from medical records using retrospective chart reviews.

Results:

During the 6-month study period, 2961 individual patients presented for 5260 screening eligible patient visits. In total, 3854 (73.3%) screenings were completed with 261 (6.8%) positive screenings noted. Screenings were declined in 1406 (26.7%) visits. Parents of children with cognitive impairments were more likely to decline screening. Clinics serving children with autism spectrum disorder had higher rates of positive screenings compared with all other clinic attendees. Seventy-two of 187 children (38.5%) with positive screenings were identified and referred to outpatient mental health referrals. Seven (2.5%) of these children required acute psychiatric treatment.

Conclusion:

Routine screening, identification of increased suicide risk, and referral to mental health care among children with NDD are feasible. It remains unclear whether variation in rates among youth with and without NDD may indicate true differences in suicide risk or cognitive impairments or reflect psychiatric comorbidities. High rates of declined participation may have influenced identification of children with NDD and suicide risk. Preliminary findings identified groups of children with NDD at heightened risk for suicidal ideation and behavior. Further research is needed to assess the validity of suicide risk screening tools in children with neurodevelopmental disorders.
Neighborhood Socioeconomic Disadvantage and Childhood Body Mass Index Trajectories From Birth to 7 Years of Age
Authors: Rautava Samuli , Turta Olli , Vahtera Jussi , Pentti Jaana , Kivimäki Mika , Pearce Jamie , Kawachi Ichiro , Rautava Päivi , Lagström Hanna
Published: October 2021

Background:

The epidemic of increasing childhood overweight and obesity is a major global health concern, with local contextual factors identified as possible contributors. Robust research is needed to establish an evidence base supporting health policy decisions to reverse the trend. We aimed to examine the association between neighborhood socioeconomic disadvantage and trajectories of body mass index (BMI) from birth to age 7.

Methods:

The present study included 11,023 children born within the Southwest Finland Birth Cohort who were free of severe conditions affecting growth with adequate exposure and growth data. We obtained child growth data until school age from municipal follow-up clinics. We based cumulative childhood neighborhood socioeconomic disadvantage on the average annual income, unemployment, and level of education in a residential area defined using a geographic grid at a spatial resolution of 250 m by 250 m.

Results:

Cumulative neighborhood socioeconomic disadvantage was associated with distinct childhood BMI z score trajectories from birth to age 7. Despite being born in the lowest BMI z scores, children growing up in disadvantaged neighborhoods subsequently exhibited a trajectory of increasing BMI z scores starting at 4 years of age, ending up with a higher risk of overweight at the end of the follow-up (30%) as compared with children living in more affluent neighborhoods (22%). The corresponding risk of obesity was 5 % for those in affluent neighborhoods and 9 % and those in disadvantaged neighborhoods.

Conclusion:

Cumulative exposure to neighborhood socioeconomic disadvantage is independently associated with unfavorable BMI development and obesity in childhood.
Trastuzumab-Induced Negative Chronotropic and Lusitropic Effects in Cynomolgus Monkeys
Authors: Ishizaka Tomomichi , Yoshimatsu Yu , Maeda Yu , Chiba Katsuyoshi , Mori Kazuhiko
Published: October 2021

Treatment with trastuzumab, an antihuman epidermal growth factor receptor type 2 humanized monoclonal antibody, has been associated with heart failure in certain patients with cancer; however, the mechanism underlying trastuzumab-induced cardiac dysfunction remains unclear. This study was conducted to clarify the cardiac effects of trastuzumab in cynomolgus monkeys, which are commonly used as cross-reactive species in preclinical safety evaluation. Monkeys were treated with trastuzumab weekly for 1 month (5 doses in total). At first and fifth doses for pressure–volume loop analysis, trastuzumab at 20 mg·kg−1·10 min−1, equivalent to the human therapeutic dose, was administered intravenously to isoflurane-anesthetized animals, followed by 60 mg·kg−1·10 min−1 at a 30-minute interval. The other doses were fixed at 80 mg·kg−1·10 min−1 under unanesthetized conditions. After the first dose, reduced heart rate, decreases in maximal rate of fall of left ventricular pressure, and prolonged time constant for isovolumic relaxation, which are predictors of drug-induced changes in lusitropy, were observed at 20 and 60 mg·kg−1. The changes after the fifth dose were comparable with those after the first dose, indicating trastuzumab did not show exacerbation of cardiac function during the 1-month trial. No significant changes in slope of preload recruitable stroke work, which is a load-independent inotropic parameter, were observed at either dose. In conclusion, trastuzumab-induced little inotropic effect but induced negative chronotropic or lusitropic effects in monkeys, which might be associated with impaired left ventricular diastolic function.
Review of Scavenged Sampling for Sustainable Therapeutic Drug Monitoring: Do More With Less
Authors: Schouwenburg Stef , van der Klip Robin F. J. , Smeets Tim J. L. , Hunfeld Nicole G. M. , Flint Robert B. , de Hoog Matthijs , Endeman Henrik , Koch Birgit C. P. , Wildschut Enno D. , Abdulla Alan
Published: October 2021

Purpose:

Innovative and sustainable sampling strategies for bioanalytical quantification of drugs and metabolites have gained considerable interest. Scavenging can be stratified as a sustainable sampling strategy using residual material because it aligns with the green principles of waste reduction and sampling optimization. Scavenged sampling includes all biological fluids' (eg, blood, liquor, and urine) leftover from standard clinical care. This review elaborates on the past and current landscape of sustainable sampling within therapeutic drug monitoring, with a focus on scavenged sampling.

Methods:

In February 2021, 4 databases were searched to assess the literature on the clinical use of innovative and sustainable sampling techniques without applying publication date restrictions. Studies reporting the clinical use of scavenged blood sampling and bridging studies of scavenged sampling and normal blood sampling were eligible for inclusion.

Results:

Overall, 19 eligible studies concerning scavenged sampling were identified from 1441 records. Scavenged sampling is mainly applied in the pediatric population, although other patient groups may benefit from this strategy. The infrastructure required for scavenged sampling encounters several challenges, including logistic hurdles, storage and handling conditions, and documentation errors. A workflow is proposed with identified opportunities that guide the implementation of scavenged sampling.

Conclusions:

This review presents current evidence on the clinical use of scavenged sampling strategies. Scavenged sampling can be a suitable approach for drug quantification to improve dosage regimens, perform pharmacokinetic studies, and explore the value of therapeutic drug monitoring without additional sample collection.
Brugada syndrome – minimizing overdiagnosis and over treatment in children
Authors: Corcia M. Cecilia Gonzalez
Published: October 2021

Purpose of review

Is to summarise the new contributions toward the understanding of the broad spectrum of manifestations of Brugada syndrome (BrS) during the first years of life. The review encompasses the screening of the asymptomatic patient referred due to family history in one extreme of the spectrum, and also the rare child with early clinical expression of the disease on the opposite side.

Recent findings

Involve specific features of pediatric BrS including the risk related to a positive family history of sudden cardiac death, the risk of presenting with syncope and the multiple diagnostic challenges of the disease. We included some of the most controversial aspects of the diagnosis and risk stratification, encompassing noninvasive studies (Holter monitors, exercise test, implantable loop recorders, and provocative tests), as well as invasive stratification during the first years of life. Finally, the role and concerns of genetic testing in this age group are commented upon.

The main key to minimize overdiagnosis and overtreatment in the young population with a personal and/or family diagnosis of BrS is to perform a systematic but also individualized assessment. Appropriate diagnostic guidelines need to be created and age-specific risk stratification algorithms built for the young patient both with suspected and confirmed BrS.
Association of parental and adolescent emotion-related factors with adolescent chronic pain behaviors
Authors: Koechlin Helen , Beeckman Melanie , Meier Andrea H. , Locher Cosima , Goubert Liesbet , Kossowsky Joe , Simons Laura E.
Published: October 2021

Chronic pain is a prevalent condition in youth, and the pain experience is strongly influenced by emotional processes. Studying emotion variability and regulation (ER) may help better understand pain behavior. As the development of emotion-related abilities predominantly takes place in the family context, examining ER within parent–adolescent dyads is important. We set out to test the association of parent and adolescent ER and adolescent emotional variability with adolescent pain behavior (ie, pain interference, activity avoidance, and activity engagement). A sample of 56 adolescents (Mage = 14.5, 85.7% women) with chronic pain and one of their parents (92.9% mothers) participated in this study. Adolescents completed baseline measures of average pain intensity, ER, and mean positive and negative affect. Furthermore, adolescents completed an electronic diary for 14 consecutive days, reporting on emotional state, activity avoidance, activity engagement, and pain interference. Parents completed measures of ER and their own history of pain. We performed a variable selection procedure, the least absolute shrinkage and selection operator method, to determine important predictors of adolescent pain behavior. Adolescent high positive affect was associated with more activity engagement, less pain interference, and less activity avoidance, indicating that positive affect might enhance the willingness to engage in activities in the presence of pain. Adolescent ER strategy emotional reappraisal and parents' own history of pain were predictors of less activity engagement. Parent ER was not related to adolescent ER. In conclusion, our results highlight the potential of enhancing positive affect as an intervention target for chronic pain.
Nutrient Intake of Wildland Firefighters During Arduous Wildfire Suppression
Authors: Brooks Samantha J. , West Molly R. , Domitrovich Joseph W. , Sol Joseph A. , Holubetz Heidi , Partridge Cassandra , Ruby Brent C. , Brown Ann F. , Roe Annie J.
Published: October 2021

Wildland firefighters (WLFFs) perform in adverse environments making rapid adjustments to dietary needs. The National Mobile Food Services (NMFS) contract details WLFF dietary provisions on wildfire incidents.

Objective:

Determine the nutrient content of food and drink provided to and consumed by WLFFs under the NMFS contract.

Methods:

Individual (n = 122) dietary provisions and consumption was recorded during 1 workday. Nutritional analysis of items provided was compared with consumption and the recommended dietary allowance (RDA).

Results:

WLFFs consumed significantly (P < 0.05) fewer macronutrients than provided for calories, protein, and fat. Provided and consumed micronutrients were below the RDA for vitamins D and E, magnesium, and manganese.

Conclusion:

Most dietary recommendations were met by NMFS provisions. Next steps include WLFF nutrition education to improve consumption and contract revisions to meet micronutrient recommendations.
Risk Factors for Pneumothorax Development Following CT-Guided Core Lung Nodule Biopsy
Authors: Sargent Tyler , Kolderman Nathan , Nair Girish B. , Jankowski Michelle , Al-Katib Sayf
Published: October 2021

Background:

This study aims to correlate nodule, patient, and technical risk factors less commonly investigated in the literature with pneumothorax development during computed tomography-guided core needle lung nodule biopsy.

Patients and Methods:

Retrospective data on 671 computed tomography-guided percutaneous core needle lung biopsies from 671 patients at a tertiary care center between March 2014 and August 2016. Univariate and multivariable logistic regression analyses were used to identify pneumothorax risk factors.

Results:

The overall incidence of pneumothorax was 26.7% (n=179). Risk factors identified on univariate analysis include anterior [odds ratio (OR)=1.98; P<0.001] and lateral (OR=2.17; P=0.002) pleural surface puncture relative to posterior puncture, traversing more than one pleural surface with the biopsy needle (OR=2.35; P=0.06), patient positioning in supine (OR=2.01; P<0.001) and decubitus nodule side up (OR=2.54; P=0.001) orientation relative to decubitus nodule side down positioning, and presence of emphysema in the path of the biopsy needle (OR=3.32; P<0.001). In the multivariable analysis, the presence of emphysematous parenchyma in the path of the biopsy needle was correlated most strongly with increased odds of pneumothorax development (OR=3.03; P=0.0004). Increased body mass index (OR=0.95; P=0.001) and larger nodule width (cm; OR=0.74; P=0.02) were protective factors most strongly correlated with decreased odds of pneumothorax development.

Conclusion:

Emphysema in the needle biopsy path is most strongly associated with pneumothorax development. Increases in patient body mass index and width of the target lung nodule are most strongly associated with decreased odds of pneumothorax.
Diagnosing rare bleeding disorders
Authors: Rodríguez María Falcón
Published: October 2021

Rare bleeding disorders (RBDs) comprise the inherited deficiencies of coagulation factors such as fibrinogen, factor (F)II, FV, FV fl FVIII, FVII, FX, FXI, and FXIII, and are usually transmitted as autosomal recessive disorders. Given the low prevalence of these coagulopathies, information about their genetic, clinical and laboratory characteristics is limited. The clinical symptoms of RCDs are extremely diverse in terms of bleeding type, site, severity, age at onset, and duration. The weak association between residual coagulant activity and clinical bleeding severity, or at times inexistent, correlation between the factor's residual levels and clinical manifestations in some RBDs makes it difficult to use a single criterion to classify such conditions. Standardization and customization of coagulation assays, full genome sequencing, and global clotting assays will significantly improve diagnosis of patients with RBDs.
Clinical and metabolic parameters for predicting disease progression of gallbladder adenocarcinoma
Authors: Han Yeon-Hee , Jeong Hwan-Jeong , Lim Seok Tae
Published: October 2021

Objective

This study aimed to identify reliable predictors of disease progression in patients with gallbladder (GB) adenocarcinoma.

Patients and methods

A total of 54 patients with GB adenocarcinoma underwent preoperative F-18 fluorodeoxyglucose (FDG) PET/CT. Age, sex, clinical stage, and pathologic differentiation were collected. Tumor size and PET parameters such as SUVmax, SUVmean, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis were measured. Univariate and multivariate logistic regression analyses were performed to determine the utility of clinical values and PET parameters. Pearson bivariate correlation was used to evaluate the association between progression-free survival (PFS) and various parameters.

Results

No recurrence was found in 15 of 54 patients, while six showed recurrence and another 33 manifested disease progression. There were significant differences in size, stage, pathologic differentiation, and PET parameters between the groups with and without recurrence/progression. However, there was no difference in those parameters between the groups with recurrence and progression. The average PFS of the groups with no recurrence, recurrence, and progression groups was 33.1, 17.1, and 5.0 months, respectively. In univariate analysis, age, sex, clinical stage, pathologic differentiation, size, and PET parameters were correlated with PFS. In multivariate analysis, only clinical stage and MTV were statistically significant and MTV showed the highest odds ratio. Pearson correlation coefficients showed moderate negative correlations between PFS and clinical stage or MTV.

Conclusion

In GB adenocarcinoma, clinical stage and MTV are the most powerful parameters for predicting recurrence and disease progression. Based on clinical stage, MTV will represent a strong prognostic predictor.
Why antibiotics should not be used to treat Shiga toxin-producing Escherichia coli infections
Authors: Tarr Phillip I. , Freedman Stephen B.
Published: October 2021

Purpose of review

There has been much debate about treating Shiga toxin-producing Escherichia coli (STEC) infections with antibiotics. No data convincingly demonstrate that antibiotics are better than no antibiotic treatment at all, and many studies suggest antibiotics increase the risk of developing the hemolytic uremic syndrome (HUS). This topic is timely, because emerging technology enables rapid identification of STEC-infected patients, and we anticipate questions about management will increase. This review is designed to familiarize readers with the series of observations that underlie our recommendations.

Recent findings

The long debate over antibiotics in STEC infections appears resolved by gradually accruing information that show that antibiotics do not benefit infected patients. In fact, they are associated with an increased likelihood of developing HUS. A meta-analysis published in 2016 demonstrated that low risk of bias studies find a clear association between antibiotic use and development of HUS. Subsequent publications do not refute these findings.

In high-income countries, antibiotics should not routinely be given to patients with acute diarrhea unless testing demonstrates a pathogen for which antibiotics are indicated, and STEC infection has been excluded. Future work to prevent HUS should focus on preventing primary infections, and mitigating extraintestinal consequences of STEC gut infections.
Effect of a Smart Pill Bottle Reminder Intervention on Medication Adherence, Self-efficacy, and Depression in Breast Cancer Survivors
Authors: Park Hyang Rang , Kang Hee Sun , Kim Soo Hyun , Singh-Carlson Savitri
Published: October 2021

Background

Globally, breast cancer has been identified as the most common cancer among women. The clinical efficacy of adjuvant oral antiestrogen therapy—including tamoxifen and aromatase inhibitors—has been proven to be clinically efficacious for breast cancer survivors. However, medication adherence for these therapies remains suboptimal among breast cancer survivors.

Objective

The aim of this study was to evaluate the effect of a reminder intervention—a smart pill bottle paired with the Pillsy mobile application—on medication adherence, medication self-efficacy, and depression, among breast cancer survivors who were undergoing oral antiestrogen therapy.

Methods

This study is a randomized controlled trial. Sixty-one women were allocated to an experimental group (n = 31) and the control group (n = 30). The experimental group received the reminder intervention of a smart pill bottle for 4 weeks. Study outcomes were identified as medication adherence, medication self-efficacy, and depression.

Results

Fifty-seven women completed the follow-up measurement. Significant differences in favor of the experimental group were noted for medication adherence (P = .004) and medication self-efficacy (P = .004). There was no statistically significant difference between the 2 groups with regard to depression (P = .057).

Conclusions

Reminder intervention using smart pill bottles was effective in improving medication adherence and medication self-efficacy among breast cancer survivors undergoing oral antiestrogen therapy.

Implications for Practice

A smart pill bottle method of intervention can be a useful reminder strategy to improve medication adherence among breast cancer survivors.
Tranexamic acid administration and pulmonary embolism in combat casualties with orthopaedic injuries
Authors: Hoyt Benjamin W. , Baird Michael D. , Schobel Seth , Robertson Henry , Sanka Ravi , Potter Benjamin K. , Bradley Matthew , Oh John , Elster Eric A.
Published: October 2021

Objectives:

In combat casualty care, tranexamic acid (TXA) is administered as part of initial resuscitation effort; however, conflicting data exist as to whether TXA contributes to increased risk of venous thromboembolism (VTE). The purpose of this study is to determine what factors increase risk of pulmonary embolism after combat-related orthopaedic trauma and whether administration of TXA is an independent risk factor for major thromboembolic events.

Setting:

United States Military Trauma Centers.

Patients:

Combat casualties with orthopaedic injuries treated at any US military trauma center for traumatic injuries sustained from January 2011 through December 2015. In total, 493 patients were identified.

Intervention:

None.

Main Outcome Measures:

Occurrence of major thromboembolic events, defined as segmental or greater pulmonary embolism or thromboembolism-associated pulseless electrical activity.

Results:

Regression analysis revealed TXA administration, traumatic amputation, acute kidney failure, and hypertension to be associated with the development of a major thromboembolic event for all models. Injury characteristics independently associated with risk of major VTE were Injury Severity Score 23 or greater, traumatic amputation, and vertebral fracture. The best performing model utilized had an area under curve  = 0.84, a sensitivity=0.72, and a specificity=0.84.

Conclusions:

TXA is an independent risk factor for major VTE after combat-related Orthopaedic injury. Injury factors including severe trauma, major extremity amputation, and vertebral fracture should prompt suspicion for increased risk of major thromboembolic events and increased threshold for TXA use if no major hemorrhage is present.

Level of evidence:

III, Prognostic Study