bluuebunny/crossref_metadata_2025 huggingface dataset:
Pseudomonas cichorii (bacterial blight of endive).
Authors: Osdaghi Ebrahim
Published: April 2021

Under environmental conditions favourable to the pathogen, diseases incited by P. cichorii cause severe damage to the host and can result in outbreaks. Outbreaks in the nursery or in the field during warm winters in Florida, USA, can lead to widespread disease affecting thousands of plants (Jones et al., 1983; Chase and Brunk, 1984; Uddin and McCarter, 1996). Diseases caused by P. cichorii can appear sporadically over a number of years then cause severe outbreaks such as the outbreak of 'varnish spot of lettuce' in California (Grogan et al. 1977) and 'brown stem of celery' in Florida, USA (Pernezny et al., 1994). Severe disease outbreaks on lettuce leading to losses of up to 100% have been reported in California (Grogan et al., 1977), Italy (Bazzi and Mazzucchi, 1979) and Portugal (Ferreira-Pinto and Oliveira, 1993). In Italy and France, P. cichorii is a recurring problem on endive and lettuce (Allex and Rat 1990; D'Ascenzo et al., 1997). In Florida, brown stem of chrysanthemum only occurs about every 5 to 6 years whereas leaf spot occurs annually (Pernezny et al., 1994).
Causation and the Problem of Disagreement
Authors: Fischer Enno
Published: April 2021

This article presents a new argument for incorporating a distinction between default and deviant values into the formalism of causal models. The argument is based on considerations about how causal reasoners should represent disagreement over causes, and it is defended against an objection that has been raised against earlier arguments for defaults.
Helium ion beam lithography and liftoff
Authors: Rashid Sabaa , Walia Jaspreet , Northfield Howard , Hahn Choloong , Olivieri Anthony , Lesina Antonio Calà , Variola Fabio , Weck Arnaud , Ramunno Lora , Berini Pierre
Published: April 2021

We introduce a helium ion beam lithography and liftoff process to fabricate arbitrary nanostructures. Exploiting existing high-resolution positive tone resists such as poly (methyl methacrylate) (PMMA), the process offers three significant advantages over electron beam lithography: (a) the exposing helium ion beam produces a high secondary electron yield leading to fast patterning, (b) proximity effects are negligible due to the low count of backscattered helium ions from the substrate, and (c) the process is transferrable with minimal alteration among different types of substrates (e.g. silicon, fused silica). The process can be used to pattern any material compatible with liftoff such as evaporated metals or dielectrics, and allows overlay of nanostructures precision-aligned to microstructures realised beforehand on the same substrate. The process is demonstrated for several PMMA thicknesses to liftoff different thicknesses of deposited material. Resolution trials are conducted to determine the limits of the process for each PMMA thickness. Isolated lines as narrow as 14 nm, and line-space gratings of 40 nm pitch (50% duty cycle), are produced as resolution tests by lifting off a 20 nm thick Au film. Nanostructures of aspect ratio up to ∼3:1 have been realised. Plasmonic nanoantenna arrays overlaid to microscale contacts are produced as device demonstrators, for which optical measurements are in excellent agreement with theory.
Strategic Resource Mobilisation amongst Founder-CEOs of Social Work Organisations in Mainland China
Authors: Wu Juan , Chen Juan
Published: April 2021

Drawing on data from in-depth interviews with twenty-one founder-CEOs of social work organisations (SWOs) in Mainland China, this article develops the concept of ‘strategic resource mobilisation’ and investigates how founder-CEOs’ professional backgrounds influence their mobilisation of resources in three areas—funding, human resources and government relations. We find that founder-CEOs adopt different strategies in mobilising resources, presenting distinct advantages and disadvantages according to their professional background. In particular, founder-CEOs affiliated with universities are viewed with trust and respect by the government and have social work students as human resources but report a lack of management skills; founder-CEOs from a business background have wider access to financial support and make good use of their management experiences and skills but are challenged by frontline social workers; and founder-CEOs with prior government experience rely on connections with officials to secure funding but face greater administrative constraints. The findings provide valuable insights for SWO executives to better assess their organisational capacity, leadership and management. The research further suggests that, to ensure the sustainable development of SWOs in Mainland China, government policies could be introduced to help diversify the funding sources, and efforts should be made to improve the partnership between the government and SWOs.
Influenza Vaccination in Health Centers During the Coronavirus Disease 2019 Pandemic—United States, 7–27 November 2020
Authors: Marks Suzanne M , Clara Alexey , Fiebelkorn Amy Parker , Le Xuan , Armstrong Paige A , Campbell Stephanie , Van Alstyne Judith Mendel , Price Sarah , Bolton Joshua , Sandhu Paramjit K , Bombard Jennifer M , Strona F V
Published: April 2021

Background

Influenza vaccination is the most effective way to prevent influenza and influenza-associated complications including those leading to hospitalization. Resources otherwise used for influenza could support caring for patients with coronavirus disease 2019 (COVID-19). The Health Resources and Services Administration (HRSA) Health Center Program serves 30 million people annually by providing comprehensive primary healthcare, including influenza vaccination, to demographically diverse and historically underserved communities. Because racial and ethnic minority groups have been disproportionately affected by COVID-19, the objective of this analysis was to assess disparities in influenza vaccination at HRSA-funded health centers during the COVID-19 pandemic.

Methods

The Centers for Disease Control and Prevention and HRSA analyzed cross-sectional data on influenza vaccinations from a weekly, voluntary health center COVID-19 survey after addition of an influenza-related question covering 7–11 November 2020.

Results

During the 3-week period, 1126 of 1385 health centers (81%) responded to the survey. Most of the 811 738 influenza vaccinations took place in urban areas and in the Western US region. There were disproportionately more health center influenza vaccinations among racial and ethnic minorities in comparison with county demographics, except among non-Hispanic blacks and American Indian/Alaska Natives.

Conclusions

HRSA-funded health centers were able to quickly vaccinate large numbers of mostly racial or ethnic minority populations, disproportionately more than county demographics. However, additional efforts might be needed to reach specific racial populations and persons in rural areas. Success in influenza vaccination efforts can support success in severe acute respiratory syndrome coronavirus 2 vaccination efforts.
Notions of indifference for genericity: Union sets and subsequence sets
Authors: Bhojraj Tejas
Published: April 2021

A set $I$ is said to be a universal indifferent set for $1$-genericity if for every $1$-generic  $G$ and for all $X \subseteq I$, $G \varDelta X$ is also $1$-generic. Miller (2013, The Journal of Symbolic Logic, 78, 113–138) showed that there is no infinite universal indifferent set for $1$-genericity. We introduce two variants (union and subsequence sets for $1$-genericity) of the notion of universal indifference and prove that there are no non-trivial universal sets for $1$-genericity with respect to these notions. In contrast, we show that there is a non-computable subsequence set for weak-$1$-genericity.
Correlation of Aneurysmal Wall Enhancement of Unruptured Intracranial Aneurysms on High-Resolution Vessel-Wall Imaging With Clinical Indices and Surgical Findings
Authors: Bae Heejin , Suh Sang-il , Yoon Won Ki , Roh Haewon , Kim Chungyeul , Kwon Taek-Hyun
Published: April 2021

BACKGROUND

Many physicians consider aneurysmal wall enhancement (AWE) on high resolution-vessel wall imaging (HR-VWI) as an imaging biomarker of unstable unruptured intracranial aneurysms (UIAs).

OBJECTIVE

To evaluate the clinical value of different AWE signal intensities (SIs) by assessing the correlation between the AWE SIs and surgical findings and rupture risk assessment tools.

METHODS

Twenty-six patients with 34 aneurysms who underwent surgical clipping were included. The corrected AWE SI was calculated by comparing T1-weighted images with post-gadolinium enhanced T1-weighted images. The correlation of AWE with the population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage from another aneurysm, site of aneurysm (PHASES) and earlier subarachnoid hemorrhage, location of the aneurysm, age >60 years, population, size of the aneurysm, shape of the aneurysm (ELAPSS) scores was evaluated using correlation and linear regression analysis. To quantify the surgical findings, the average color value of the aneurysms expressed in the CIELCh system was measured. Δh, color difference from yellow, was used for statistical analysis.

RESULTS

The mean age of the patients and aneurysm size were 64.08 yr and 6.95 mm, respectively. The mean AWE SI, PHASES and ELAPSS scores, and Δh were 22.30, 8.41, 20.32, and 41.36, respectively. The coefficients of correlation of AWE SI with the PHASES and ELAPSS scores and Δh were 0.526, 0.563, and –0.431. We found that the AWE SI affected the PHASES (β = 0.430) and ELAPSS scores (β = 0.514) and Δh (β = –0.427) in simple linear regression analysis.

CONCLUSION

The AWE on HR-VWI was correlated with the PHASES and ELAPSS scores and the color. The stronger the AWE, the higher were the PHASES and ELAPSS scores and the more abnormal was the color. The AWE might indicate the degree of inflammation.
Maternal sepsis update
Authors: Abir Gillian , Bauer Melissa E.
Published: April 2021

Purpose of review

Maternal sepsis is the second leading cause of maternal death in the United States. A significant number of these deaths are preventable and the purpose of this review is to highlight causes such as delays in recognition and early treatment.

Recent findings

Maternal sepsis can be difficult to diagnose due to significant overlap of symptoms and signs of normal physiological changes of pregnancy, and current screening tools perform poorly to identify sepsis in pregnant women. Surveillance should not only include during pregnancy, but also throughout the postpartum period, up to 42 days postpartum. Education and awareness to highlight this importance are not only vital for obstetric healthcare provides, but also for nonobstetric healthcare providers, patients, and support persons.

Through education and continual review and analysis of evidence-based practice, a reduction in maternal morbidity and mortality secondary to maternal sepsis should be attainable with dedication from all disciplines that care for obstetric and postpartum patients. Education and vigilance also extend to patients and support persons who should be empowered to escalate care when needed.
Formal Patient Complaints and Malpractice Events Against Pediatric Orthopaedic Surgeons
Authors: Piper James P. , Barreto Rocha Daniela F. , Hayes Daniel S. , Grandizio Louis C.
Published: April 2021

Background:

Formal patient complaints are associated with increased malpractice litigation and can have adverse occupational consequences for surgeons. Our purpose was to define and categorize patient complaints within an academic pediatric orthopaedic surgery practice over a 10-year period. We further aimed to define risk factors associated with patient complaints.

Methods:

We reviewed all complaints within our institution’s patient advocacy service filed on behalf of a patient against 4 pediatric orthopaedic surgeons over a 10-year period. Complaints were categorized using the Patient Complaint Analysis System. A control group of all patients seen by the surgeons during the study period was created. We compared baseline demographics between the patients with a complaint and the control group and compared complaint rates between the surgeons. Any malpractice events (lawsuits and claims) associated with the surgeons were obtained. We queried our institutional MIDAS reporting system (which allows for anonymous reporting of potential patient-safety or “near-miss” events), to assess whether patients with a complaint had a reported event.

Results:

The 4 pediatric orthopaedic surgeons saw a total of 25,747 unique patients during the study period. Forty-one patients had a formal complaint, resulting in a complaint rate of 0.15%. Complaint rates varied from 0.08% to 0.30% between surgeons. Humanness was the most frequent complaint designation category (32%) followed by Care and Treatment (19%). Of the 41 patients with a complaint, 18 (44%) underwent surgical treatment. Only 1 patient with a complaint also had an entry within our institutional patient-safety reporting system.

Conclusions:

The rate of patient complaints within an academic pediatric orthopaedic surgery practice over a decade was 0.15%, or ~1 complaint for every 670 new patients seen. The majority of patient complaints involved communication; a potentially modifiable area that can be targeted for improvement. While complaint rates among surgeons can vary, patient demographic factors are not associated with increased complaints. Understanding patient complaints rates and types may allow surgeons to target areas for improvement and decrease exposure to malpractice litigation.

Level of Evidence:

Level II—prognostic.
Association Between Premorbid Beta-Blocker Exposure and Sepsis Outcomes—The Beta-Blockers in European and Australian/American Septic Patients (BEAST) Study
Authors: Tan Kaiquan , Harazim Martin , Simpson Andrew , Tan Yi Chern , Gunawan Gunawan , Robledo Kristy P. , Whitehead Christina , Tang Benjamin , Mclean Anthony , Nalos Marek
Published: April 2021

OBJECTIVES:

To examine the effect of premorbid β-blocker exposure on mortality and organ dysfunction in sepsis.

DESIGN:

Retrospective observational study.

SETTING:

ICUs in Australia, the Czech Republic, and the United States.

PATIENTS:

Total of 4,086 critical care patients above 18 years old with sepsis between January 2014 and December 2018.

INTERVENTION:

Premorbid beta-blocker exposure.

MEASUREMENTS AND MAIN RESULTS:

One thousand five hundred fifty-six patients (38%) with premorbid β-blocker exposure were identified. Overall ICU mortality rate was 15.1%. In adjusted models, premorbid β-blocker exposure was associated with decreased ICU (adjusted odds ratio, 0.80; 95% CI, 0.66–0.97; p = 0.025) and hospital (adjusted odds ratio, 0.83; 95% CI, 0.71–0.99; p = 0.033) mortality. The risk reduction in ICU mortality of 16% was significant (hazard ratio, 0.84, 95% CI, 0.71–0.99; p = 0.037). In particular, exposure to noncardioselective β-blocker before septic episode was associated with decreased mortality. Sequential Organ Failure Assessment score analysis showed that premorbid β-blocker exposure had potential benefits in reducing respiratory and neurologic dysfunction.

CONCLUSIONS:

This study suggests that β-blocker exposure prior to sepsis, especially to noncardioselective β blockers, may be associated with better outcome. The findings suggest prospective evaluation of β-blocker use in the management of sepsis.
Neuroprognostic Accuracy of Quantitative Versus Standard Pupillary Light Reflex for Adult Postcardiac Arrest Patients: A Systematic Review and Meta-Analysis*
Authors: Wang Chih-Hung , Wu Cheng-Yi , Liu Carolyn Chia-Yu , Hsu Tzu-Chun , Liu Michael A. , Wu Meng-Che , Tsai Min-Shan , Chang Wei-Tien , Huang Chien-Hua , Lee Chien-Chang , Chen Shyr-Chyr , Chen Wen-Jone
Published: April 2021

OBJECTIVES:

An automated infrared pupillometer measures quantitative pupillary light reflex using a calibrated light stimulus. We examined whether the timing of performing quantitative pupillary light reflex or standard pupillary light reflex may impact its neuroprognostic performance in postcardiac arrest comatose patients and whether quantitative pupillary light reflex may outperform standard pupillary light reflex in early postresuscitation phase.

DATA SOURCES:

PubMed and Embase databases from their inception to July 2020.

STUDY SELECTION:

We selected studies providing sufficient data of prognostic values of standard pupillary light reflex or quantitative pupillary light reflex to predict neurologic outcomes in adult postcardiac arrest comatose patients.

DATA EXTRACTION:

Quantitative data required for building a 2 × 2 contingency table were extracted, and study quality was assessed using standard criteria.

DATA SYNTHESIS:

We used the bivariate random-effects model to estimate the pooled sensitivity and specificity of standard pupillary light reflex or quantitative pupillary light reflex in predicting poor neurologic outcome during early (< 72 hr), middle (between 72 and 144 hr), and late (≧ 145 hr) postresuscitation periods, respectively. We included 39 studies involving 17,179 patients. For quantitative pupillary light reflex, the cut off points used in included studies to define absent pupillary light reflex ranged from 0% to 13% (median: 7%) and from zero to 2 (median: 2) for pupillary light reflex amplitude and Neurologic Pupil index, respectively. Late standard pupillary light reflex had the highest area under the receiver operating characteristic curve (0.98, 95% CI [CI], 0.97–0.99). For early standard pupillary light reflex, the area under the receiver operating characteristic curve was 0.80 (95% CI, 0.76–0.83), with a specificity of 0.91 (95% CI, 0.85–0.95). For early quantitative pupillary light reflex, the area under the receiver operating characteristic curve was 0.83 (95% CI, 0.79–0.86), with a specificity of 0.99 (95% CI, 0.91–1.00).

CONCLUSIONS:

Timing of pupillary light reflex examination may impact neuroprognostic accuracy. The highest prognostic performance was achieved with late standard pupillary light reflex. Early quantitative pupillary light reflex had a similar specificity to late standard pupillary light reflex and had better specificity than early standard pupillary light reflex. For postresuscitation comatose patients, early quantitative pupillary light reflex may substitute for early standard pupillary light reflex in the neurologic prognostication algorithm.
Identifying High-Risk Subphenotypes and Associated Harms From Delayed Antibiotic Orders and Delivery*
Authors: Han Xuan , Spicer Alexandra , Carey Kyle A. , Gilbert Emily R. , Laiteerapong Neda , Shah Nirav S. , Winslow Christopher , Afshar Majid , Kashiouris Markos G. , Churpek Matthew M.
Published: April 2021

OBJECTIVES:

Early antibiotic administration is a central component of sepsis guidelines, and delays may increase mortality. However, prior studies have examined the delay to first antibiotic administration as a single time period even though it contains two distinct processes: antibiotic ordering and antibiotic delivery, which can each be targeted for improvement through different interventions. The objective of this study was to characterize and compare patients who experienced order or delivery delays, investigate the association of each delay type with mortality, and identify novel patient subphenotypes with elevated risk of harm from delays.

DESIGN:

Retrospective analysis of multicenter inpatient data.

SETTING:

Two tertiary care medical centers (2008–2018, 2006–2017) and four community-based hospitals (2008–2017).

PATIENTS:

All patients admitted through the emergency department who met clinical criteria for infection.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Patient demographics, vitals, laboratory values, medication order and administration times, and in-hospital survival data were obtained from the electronic health record. Order and delivery delays were calculated for each admission. Adjusted logistic regression models were used to examine the relationship between each delay and in-hospital mortality. Causal forests, a machine learning method, was used to identify a high-risk subgroup. A total of 60,817 admissions were included, and delays occurred in 58% of patients. Each additional hour of order delay (odds ratio, 1.04; 95% CI, 1.03–1.05) and delivery delay (odds ratio, 1.05; 95% CI, 1.02–1.08) was associated with increased mortality. A patient subgroup identified by causal forests with higher comorbidity burden, greater organ dysfunction, and abnormal initial lactate measurements had a higher risk of death associated with delays (odds ratio, 1.07; 95% CI, 1.06–1.09 vs odds ratio, 1.02; 95% CI, 1.01–1.03).

CONCLUSIONS:

Delays in antibiotic ordering and drug delivery are both associated with a similar increase in mortality. A distinct subgroup of high-risk patients exist who could be targeted for more timely therapy.
Attitudes, Perceived Benefits, and Experiences of Engagement With Professional Competence Schemes for Doctors in Ireland: Findings From a National Survey
Authors: Hanlon Holly Rose , Prihodova Lucia , Hoey Hilary , Russell Thelma , Donegan Deirdre , O'Shaughnessy Ann
Published: April 2021

Introduction:

This study aimed to assess the attitudes, perceived benefits, and experiences of engaging with a formal system of continuing professional development (CPD) in the form of Professional Competence Schemes (PCSs) among doctors in Ireland.

Methods:

The study utilized an anonymous online survey measure with both open-ended and Likert-scale questions. The measure examined general attitudes, perceived impact, and experiences of engagement with PCS. This study examines the scale items only. All 4350 doctors enrolled on a PCS were invited through email to complete the survey. One thousand four hundred eight doctors participated, indicating a response rate of 32%.

Results:

Descriptive and inferential statistics (analysis of variance and Kruskal–Wallis) were performed on the scale items using IBM SPSS statistics, with group comparisons examining differences in responses according to gender and current primary role. A majority (80%) of respondents had positive overall attitudes to PCS. Most participants reported that CPD positively impacts their practice across a wide range of areas, particularly patient care. Most participants reported positive experiences engaging with PCS, although a minority reported difficulties, including lack of time to participate in and record CPD activities, difficulties obtaining evidence of participation, and feeling that their CPD activities are not easily captured by the PCS system. Significant differences in responses according to role were found for overall attitudes (confidence interval = 95%, P < .00) and overall experiences of PCS (confidence interval = 95%, P < .00) with nonconsultant hospital doctors emerging as a particularly vulnerable group with less positive attitudes and experiences.

Discussion:

Across the board overall attitudes, perceived impact and experiences of PCS were positive, and indicate that doctors feel that PCS is a valuable and beneficial activity. However, a minority of respondents reported experiencing difficulties with engagement, and these areas of difficulty represent targets for future improvement.
Fostering Mindfulness in Continuing Pharmacy Education Using a Board Game: Initial Experiences and Perceptions
Authors: Pogge Elizabeth K. , Davis Lindsay E.
Published: April 2021

Introduction:

Expansion of pharmacists' scope of practice creates a need to optimize learning within continuing professional development (CPD) that can simultaneously promote mindfulness and enhance clinical decision-making. An educational board game embracing the principles of situated learning was developed with the purpose of promoting clinical reasoning skills and mindfulness.

Methods:

Iter Vitae was used in a national pharmacy meeting CPD session. An evaluation was conducted by a voluntary survey to gather perceptions of game-based instruction.

Results:

Ninety of 115 session-attendees completed the anonymous survey. Participants strongly agreed that Iter Vitae is an effective learning tool of appropriate complexity for CPD sessions. Participant perceptions suggest that playing Iter Vitae may enhance clinical knowledge, foster critical thinking, and influence provider empathy. Open-ended responses revealed appreciation of collaborative learning within authentic case scenarios.

Discussion:

This game-based CPD session gave participants an opportunity to develop elements of mindful practice embedded within authentic case scenarios. Further research on game-based instruction is needed to determine its effects on knowledge and skill acquisition, retention, and impact on clinical practice.
An Active-Learning Quality Improvement Curriculum for Faculty in Hospital Medicine
Authors: Muthukrishnan Preetika , Burnett Maria , DeVoe Stephen G. , Kennedy Amanda G. , Pasanen Mark E. , Tompkins Bradley , Repp Allen B.
Published: April 2021

Introduction:

Despite the growing importance of quality improvement (QI) training in medical education, there is a lack of faculty with expertise in QI at many academic medical centers. In this report, we describe the design, implementation, and evaluation of a QI training program for faculty in hospital medicine at an academic medical center aimed at increasing faculty capacity in QI.

Methods:

With input from an initial focus group of hospital medicine faculty, we developed a 12-session, active-learning curriculum incorporating core concepts in QI applied to a real-life QI problem. We used a survey instrument to assess changes in self-reported confidence, the Quality Improvement Knowledge Application Tool-Revised to assess changes in applied knowledge, and a second focus group to obtain qualitative feedback regarding the curriculum.

Results:

Self-reported confidence in numerous QI skills increased after completion of the curriculum; however, concurrent improvement in applied knowledge was not observed. Qualitatively, participants not only described improved understanding of QI methodology and greater confidence contributing to QI initiatives but also a sense they were not prepared to lead a QI project independently.

Discussion:

An active-learning faculty training program is feasible with limited resources and was associated with increased faculty confidence in QI skills.
The COVID-19 Online Learning Transition and the Plus/Delta Debriefing Model
Authors: Dzara Kristina , Heller Ayres , Kesselheim Jennifer
Published: April 2021

As a result of the COVID-19 pandemic, the Harvard Medical School Master of Medical Sciences in Medical Education program implemented the Plus/Delta debriefing model to collect real-time learner feedback and facilitate continuous quality improvement within our assessment and program evaluation module, which rapidly transitioned online. The model is grounded in quality improvement methodology and encourages bidirectional rather than top–down feedback. Learners identified specifically what went well with each module session (Plus) and how to improve for the next time (Delta). After each session, narrative responses were reviewed, aggregated into meaningful categories, and implemented when possible. Implemented improvements focused on increasing session interactivity and enhancing communication. Learners pointed to the uniqueness of the model and applauded efforts to embed them in the cocreation process. Asking learners to debrief their experience—especially during a module which is iteratively redesigned week-by-week—can offer a realistic view of what is working and what needs further refinement. As we continue to navigate the COVID-19 pandemic, rapid, continuous educational quality improvement deserves renewed emphasis. Implementing the Plus/Delta debriefing model into longitudinal online teaching sessions is a translatable, easily replicable, and free method of receiving immediate and valuable learner feedback.
Ozone Attenuated H9c2 Cell Injury Induced by Doxorubicin
Authors: Xu Lingshan , Wang Chenhao , Zou Zhiqing , Wu Zhouquan
Published: April 2021

Doxorubicin (DOX) is a commonly used drug in the treatment of cancers, whereas its application in the clinical stage is restricted because of side effects such as cardiomyocyte injury. Increasing studies indicated that ozone may protect cardiomyocytes from injuries. This study aimed to explore the effects of ozone on cardiotoxicity induced by DOX treatment. Rat heart myoblasts (H9c2) were treated with increasing concentrations of DOX (0.5, 1, 1.5, and 2 μM) to induce cell injury. 3-(4,5)-dimethylthiahiazo(-2)-3,5-diphenytetrazoliumromide assay and flow cytometry analysis were used to measure the viability and apoptosis of H9c2 cells. The mRNA and protein levels of proinflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-(IL)1β, and IL-6, matrix metalloproteinases (MMP-2 and MMP-9), and the key factors on the TLR4/NF-kB signaling (TLR4, p-p65, and p65) were measured by reverse transcription quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and western blot. The result showed that DOX promoted apoptosis and increased the expression of TNF-α (by 3.65-fold changes), IL-1β (by 4.98-fold changes), IL-6 (by 3.44-fold changes), MMP-2 (by 1.98-fold changes), and MMP-9 (by 1.98-fold changes) levels in H9c2 cells. Moreover, the introduction of ozone reversed these changes in gene expression and suppressed the activation of the TLR4/NF-kB signaling, which indicated that ozone may exert protective effects on H9c2 heart myoblasts by relieving the cardiotoxicity induced by DOX. Our study provides theoretical basis for the significance of ozone in managing doxorubicin-induced H9c2 heart myoblast injury.
Adverse Events of Sacubitril/Valsartan: A Meta-analysis of Randomized Controlled Trials
Authors: Huang Yun , Zhang YuYu , Ma Lili , Zhou Hua , Fang Chongbo , Chen Chaolin
Published: April 2021

This review aimed to summarize the adverse events (AEs) reported during the use of sacubitril/valsartan versus angiotensin converting enzyme inhibitors (ACEI)/angiotensin II receptor blocker (ARB). Studies containing safety outcomes or AEs during the use of sacubitril/valsartan versus ACEI/ARB were retrieved from the MEDLINE, Embase, and Cochrane Library databases and clinical trials. From the selected studies, the pooled risk ratios with 95% confidence intervals of dichotomous outcomes were assessed by a random or fixed effects model in our meta-analysis. Fourteen studies involving 20,261 patients were included in this review. No significant differences were found in total AEs between the sacubitril/valsartan and ACEI/ARB groups. Compared with ACEI/ARB, sacubitril/valsartan decreased the risk of death, discontinuation due to AEs, and renal dysfunction, whereas it increased the risk of hypotension. Specifically, sacubitril/valsartan decreased the risk of death compared with ACEI/ARB, whereas it increased the risk of hypotension for patients with heart failure and decreased the risk of discontinuation due to AEs in White patients. It also increased the risk of dizziness in Asians and decreased the risk of hyperkalemia and renal dysfunction, whereas it increased the risk of hypotension when the study duration was ≥48 weeks. The available evidence showed that sacubitril/valsartan was associated with fewer side effects than ACEI/ARB, except for hypotension. Study duration, race, and patients with primary diseases affected the AEs of sacubitril/valsartan.
Review of the Preanalytical Errors That Impact Therapeutic Drug Monitoring
Authors: Peck Palmer Octavia M. , Dasgupta Amitava
Published: April 2021

Purpose:

Preanalytical errors comprise the majority of testing errors experienced by clinical laboratories and significantly impact the accuracy of therapeutic drug monitoring (TDM).

Methods:

Specific preanalytical factors in sample timing, collection, transport, processing, and storage that lead to errors in TDM were reviewed. We performed a literature search using several scientific databases including PubMed, ScienceDirect, Scopus, Web of Science, and ResearchGate for human studies published in the English language from January 1980 to February 2021, reporting on TDM and the preanalytical phase.

Results:

Blood collection errors (ie, wrong anticoagulant/clot activator used, via an intravenous line, incorrect time after dosing) delay testing, cause inaccurate results, and adversely impact patient care. Blood collected in lithium heparin tubes instead of heparin sodium tubes produce supertoxic lithium concentrations, which can compromise care. Specimens collected in serum separator gel tubes cause falsely decreased concentrations due to passive absorption into the gel when samples are not processed and analyzed quickly. Dried blood spots are popular for TDM as they are minimally invasive, allowing for self-sampling and direct shipping to a clinical laboratory using regular mail. However, blood collection techniques, such as trauma to the collection site, filter paper fragility, and hematocrit (Hct) bias, can adversely affect the accuracy of the results. Volumetric absorptive microsampling is a potential alternative to dried blood spot that offers fast, volume-fixed sampling, low pain tolerance, and is not susceptible to Hct concentrations.

Conclusions:

The identification of preanalytical factors that may negatively impact TDM is critical. Developing workflows that can standardize TDM practices, align appropriate timing and blood collection techniques, and specimen processing will eliminate errors.
Interactions of hypertension, obesity, left ventricular hypertrophy, and heart failure
Authors: daSilva-deAbreu Adrian , Alhafez Bader Aldeen , Lavie Carl J. , Milani Richard V. , Ventura Hector O.
Published: April 2021

Purpose of review

Hypertension (HTN) and obesity are major risk factors for cardiac remodeling and dysfunction, leading to left ventricular hypertrophy (LVH) and heart failure (HF). In this review, we discuss the complex mechanisms and effects of HTN and obesity, and their treatments in LVH, ventricular function, and HF.

Recent findings

Obesity and HTN impact the heart through overlapping neurohormonal pathways. However, the relationship between obesity and cardiomyopathy is more complex, and additional metabolic and hemodynamic pathways seem to contribute to cardiac dysfunction in these patients. Weight loss and blood pressure (BP) control help to prevent and reverse at least some of the damage caused by obesity and HTN even beyond what would be expected from solely the hemodynamic changes.

Obesity and HTN cause maladaptive changes in the heart that can lead to LVH and HF. Weight loss and BP control help to, at least partially, reverse some of these changes and improve clinical outcomes in patients with HF.
Pharmacological Inhibition of Insulin Growth Factor-1 Receptor (IGF-1R) Alone or in Combination With Ruxolitinib Shows Therapeutic Efficacy in Preclinical Myeloproliferative Neoplasm Models
Authors: Basu Titiksha , Bertrand Hannah , Karantzelis Nikolaos , Gründer Albert , Pahl Heike L.
Published: April 2021

Even after development of the JAK1/JAK2 inhibitor ruxolitinib, myeloproliferative neoplasm (MPN) patients require novel therapeutic options. While ruxolitinib can considerably improve quality of life and prolong survival, it does not modify the natural disease course in most patients. Moreover, resistance develops with prolonged use. Therefore, various combination treatments are currently being investigated. Published data provide a compelling rationale for the inhibition of insulin growth factor-1 receptor (IGF-1R) signaling in MPN. Here we report that genetic and pharmacological inhibition of IGF-1R selectively reduced Jak2V617F-driven cytokine-independent proliferation ex vivo. Two different structurally unrelated IGF-1R inhibitors ameliorated disease phenotype in a murine MPN model and significantly prolonged survival. Moreover, in mice, low-dose ruxolitinib synergized with IGF-1R inhibition to increase survival. Our data demonstrate preclinical efficacy of IGF-1R inhibition in a murine MPN model.
Outcomes of Descemet-Stripping Endothelial Keratoplasty in 52 Eyes With Iridocorneal Endothelial Syndrome
Authors: Mohamed Ashik , Chaurasia Sunita , Senthil Sirisha , Choudhari Nikhil S.
Published: April 2021

Purpose:

To evaluate the long-term outcomes of Descemet-stripping endothelial keratoplasty (DSEK) in 52 eyes with iridocorneal endothelial (ICE) syndrome.

Methods:

Retrospective study of 52 eyes of 52 patients who were diagnosed with ICE syndrome and underwent DSEK between January 2010 and December 2019 with a follow-up of at least 6 months.

Results:

The mean age was 48.8 ± 10.8 years. Female patients (n = 33) constituted 63.5%. The median duration of follow-up was 2.4 years (range, 0.5–9.1 yrs). The mean best-corrected visual acuity improved significantly after surgery and remained stable (∼20/50) through 5 years. The mean endothelial cell loss was 28%, 37.9%, 43.6%, and 56.9% at 6 months and at 1, 2, and 3 years, respectively. Graft rejection was noted in 5 eyes (9.6%). Postoperatively, increased intraocular pressure (IOP) was seen in 17 eyes (32.7%), and 10 eyes (19.2%) underwent glaucoma surgeries. Fourteen eyes (26.9%) had secondary graft failures. The estimates of graft success were 93.6% ± 3.6% at 1 year, 85.6% ± 5.5% at 2 years, 79.3% ± 6.7% at 3 years, 69.0% ± 8.9% at 4 years, and 59.1% ± 11.9% at 5 years. Postoperative increased IOP was found to be the only significant (P = 0.05) risk factor (hazard ratio 8.92) associated with graft failure. The clinical variant of ICE syndrome did not seem to influence the graft survival (P = 0.68).

Conclusions:

In this study, DSEK had a success rate of ∼60% at 5 years. Increased IOP post-DSEK is a significant risk factor for graft failure. Graft survival is not affected by the clinical variant of ICE syndrome.
Circumferential Assessment of Changes in Anterior Segment Characteristics and Baseline Predictors of Angle Widening After Laser Iridotomy in Caucasian Eyes
Authors: Tun Tin A. , Sawicki Andrzej , Wilkos-Kuc Agnieszka , Aung Tin , Zarnowski Tomasz
Published: April 2021

Précis:

Laser peripheral iridotomy (LPI) widened the iridocorneal angle and flattened the iris circumferentially in Caucasian eyes and baseline refractive error, lens vault, and iris volume play a significant role in the angle widening.

Purpose:

The purpose of this study was to investigate circumferential angle widening and iris changes after LPI using swept-source optical coherence tomography (SS-OCT) in Caucasian eyes with the use of novel anterior segment parameters.

Materials and Methods:

A total of 130 eyes (68 primary angle-closure suspect, 34 primary angle closure, and 28 primary angle-closure glaucoma eyes) of 66 subjects underwent 360-degree SS-OCT (SS-1000 CASIA) angle imaging and gonioscopy in the dark before and 7, 30, 90 days after LPI. For each eye, 16 frames (11.25 degree apart) were selected for analysis from 128 cross-sectional images, and novel 2-dimensional and 3-dimensional anterior segment parameters namely angle opening distance area (AODA) and the trabecular-iris space volume (TISV) 750 µm from the scleral spur, as well as iris parameters such as iris thickness (IT750 and IT2000), iris curvature, and iris curvature area were measured for each image.

Results:

AODA and TISV were significantly increased and the iris curvature and iris curvature area were significantly decreased at days 7, 30, and 90 after LPI when compared with their baseline (all P<0.001) but there was no significant change in the IT750 and IT2000 (all P>0.05). The multivariable linear regression model showed a significant association of ΔAODA with refractive error (β=−0.23, P=0.013), lens vault (β=2.8, P=0.007), and iris volume (β=−0.11, P=0.027) after adjusting for age and sex.

Conclusions:

LPI widened the iridocorneal angle and flattened the iris circumferentially in Caucasian eyes in this study. Baseline refractive error, lens vault, and iris volume play a significant role in the circumferential angle widening by LPI.
Eyelid–Cheek Junction Soft-Tissue Perineurioma: Case Report and Controversies
Authors: Zhao Lily D. , Jarrar Faisal S. , Hussain Ahsen A. , Hyrcza Martin D. , Harvey John T.
Published: April 2021

Perineurioma is a rare soft-tissue tumor with characteristic histologic and immunohistochemical features. The diagnosis; however, can be met with certain challenges. A 71-year-old woman presented with an enlarging painless mass in the right lower eyelid–cheek junction. The lesion presented as a raised overhanging trunk-shaped mass. An excisional biopsy and local reconstruction were performed. The overall morphology and immunohistochemical findings were most supportive of a cellular soft-tissue perineurioma, with differential diagnoses including dermatofibroma. To the authors’ knowledge, this is the first histopathologically reported case of a superficially occurring soft-tissue perineurioma in the eyelid–cheek junction. The authors discuss the presentation, relevant literature, and controversies associated with this diagnosis.
Conversion Rate of Web-based Versus Non-web-based Patient Referral Sources in a Facial Plastic Surgery Practice
Authors: Abdolalizadeh Parya , Kashkouli Mohsen Bahmani , Gandomi-Mohammadabadi Alireza , Jafarpour Soheila , Karimi Nasser , Abri Aghdam Kaveh
Published: April 2021

Purpose:

To compare the conversion rate (number of procedures/referrals) of web-based and non-web-based referrals to a facial plastic surgery practice (2012–2019).

Method:

Data on demographics, referral source, patient’s concern, and their facial procedures were recorded. Web-based referral sources include website and Instagram. Non-web-based counterparts were the word-of-mouth, medical professionals, and others (TV, radio, printed media). Patient concerns were either cosmetic or noncosmetic (functional). Patients who underwent facial cosmetic surgery and injections (botulinum toxin A, filler, fat) were categorized in the cosmetic procedure group. Patients with functional procedures with or without facial injections were categorized in the noncosmetic procedure group. The conversion rate was defined as the ratio of the number of referrals with different facial procedures to the total number of referrals.

Results:

Included were 19,965 patients, majority of whom (63.3%) had cosmetic concern. Total, cosmetic, and noncosmetic conversion rates were 30.1%, 27.7%, and 2.4% for the web-based and 24.1%, 19.8%, and 4.3% for the non-web-based referrals, respectively (0.3 < p < 0.4). Cosmetic conversion rate grew from 6.7% in referrals ≤20 to more than 23% in >20 years of age (p = 0.03). It was also significantly (p < 0.001) higher in the referrals with cosmetic (28.3%) than noncosmetic (12.1%) concern. Gender and year of practice did not have a significant effect on the conversion rates.

Conclusion:

Conversion rates were not significantly different between the web-based and non-web-based referrals. A significantly higher cosmetic conversion rate was observed for the referrals with cosmetic concern and older than 20 years.
Occupations Associated With Poor Cardiovascular Health in Women
Authors: Nriagu Bede N. , Ako Ako A. , Wang Conglong , De Roos Anneclaire J. , Wallace Robert , Allison Matthew A. , Seguin Rebecca A. , Michael Yvonne L.
Published: April 2021

Introduction:

Research on the effect of occupation on cardiovascular health (CVH) among older women is limited.

Methods:

Each of the seven American Heart Association's CVH metrics was scored as ideal (1) or non-ideal (0) and summed. Multivariable logistic regression was used to estimate the odds of poor overall CVH (CVH score of 0 to 2) comparing women employed in each of the top 20 occupational categories to those not employed in that category, adjusting for age, marital status, and race/ethnicity.

Results:

(1) Bookkeeping, accounting, and auditing clerks; (2) first-line supervisors of sales workers; (3) first-line supervisors of office and administrative support workers; and (4) nursing, psychiatric, and home health aides were more likely to have poor overall CVH compared to women who did not work in these occupations.

Conclusions:

Several commonly held occupations among women were associated with poor CVH.
Left Ventricular End-Diastolic Dimension and Clinical Outcomes After Centrifugal Flow Left Ventricular Assist Device Implantation
Authors: Truong Vien T. , Shreenivas Satya , Mazur Wojciech , Egnaczyk Gregory F. , Palmer Cassady , Rao Sriram D. , Rame J. Eduardo , Chung Eugene S.
Published: April 2021

The impact of preoperative end-diastolic left ventricular dimension (preLVEDD) on long-term outcomes with centrifugal continuous-flow left ventricular assist device (CF-LVAD) is not well established. Accordingly, we performed an analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry to study this relationship. All patients with centrifugal CF-LVAD in the INTERMACS registry from June 2006 to December 2017 were screened. The final study group consisted of 3,304 patients. After a median follow-up of 9.0 months (interquartile range [IQR], 4.2–18.8 months), 2,596 (79%) patients were alive. After adjusting for significant covariates, increased preLVEDD was associated with lower mortality (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.84–0.98; p = 0.01), stroke (HR, 0.85; 95% CI, 0.77–0.93; p < 0.001), and gastrointestinal bleeding (HR, 0.88; 95% CI, 0.80–0.97; p = 0.01), although there were more arrhythmias (HR, 1.14; 95% CI, 1.05–1.24; p = 0.003). Our study suggests that preLVEDD is an independent predictor of mortality and adverse events in patients treated with centrifugal CF-LVAD. preLVEDD should be considered an important preimplant variable for risk stratification when considering a CF-LVAD.
Predicting occupational outcomes from neuropsychological test performance in older people with HIV
Authors: Brouillette Marie-Josée , Koski Lisa , Forcellino Laurence , Gasparri Joséphine , Brew Bruce J. , Fellows Lesley K. , Mayo Nancy E. , Cysique Lucette A.
Published: April 2021

Objective:

The ability to work is amongst the top concerns of people living with well treated HIV. Cognitive impairment has been reported in many otherwise asymptomatic persons living with HIV and even mild impairment is associated with higher rates of occupational difficulties. There are several classification algorithms for HIV-associated neurocognitive disorder (HAND) as well as overall scoring methods available to summarize neuropsychological performance. We asked which method best explained work status and productivity.

Design:

Participants (N = 263) drawn from a longitudinal Canadian cohort underwent neuropsychological testing.

Methods

: Several classification algorithms were applied to establish a HAND diagnosis and two summary measures (NPZ and Global Deficit Score) were computed. Self-reported work status and productivity was assessed at each study visit (four visits, 9 months apart). The association of work status with each diagnostic classification and summary measure was estimated using logistic regression. For those working, the value on the productivity scale was regressed within individuals over time, and the slopes were regressed on each neuropsychological outcome.

Results:

The application of different classification algorithms to the neuropsychological data resulted in rates of impairment that ranged from 28.5 to 78.7%. Being classified as impaired by any method was associated with a higher rate of unemployment. None of the diagnostic classifications or summary methods predicted productivity, at time of testing or over the following 36 months.

Conclusion:

Neuropsychological diagnostic classifications and summary scores identified participants who were more likely to be unemployed, but none explained productivity. New methods of assessing cognition are required to inform optimal workforce engagement.