bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexibility unbound: understanding the heterogeneity of preferences among food delivery platform workers
Authors: Piasna Agnieszka , Drahokoupil Jan
Published: May 2021

This article investigates the preferences of food delivery platform workers regarding their employment status and working hours. We focus on the relationship between flexibility and protection, both of which can be understood—from a worker’s perspective—as a means towards increased autonomy and control. The analysis is based on a case study of Deliveroo in Belgium, which hired riders as employees through an intermediary, SMart. Despite their flexible working lives, most riders preferred employee status to self-employment. However, riders were divided in their preferences regarding working time flexibility, with many in favour of more regular working time patterns. To explain this divergence, we develop an embeddedness framework that relates worker preferences to the degree of their dependency as shaped by labour market and institutional factors. We thus link divergence in preferences concerning flexibility to workers’ scope for exercising control, their labour market vulnerability and economic attachment to the platform.
Characterization of Fungi Associated with Olive Fruit Rot and Olive Oil Degradation in Crete, Southern Greece
Authors: Markakis Emmanouil A. , Roditakis Emmanouil N. , Kalantzakis Georgios S. , Chatzaki Anastasia , Soultatos Stefanos K. , Stavrakaki Marianna , Tavlaki Georgia I. , Koubouris Georgios C. , Bagkis Nikolaos , Goumas Dimitrios E.
Published: May 2021

In November 2019, a severe outbreak of fruit rot was observed in olive orchards in Crete, southern Greece. Symptoms appeared primarily on fruits and stalks, resembling those caused by anthracnose. Typical symptoms were fruit rot, shrinkage, and mummification, associated commonly with stalk discoloration and fruit drop. Disease incidence was estimated at up to 100% in some cases, and an unprecedented increase in olive oil acidity reaching up to 8% (percentage of oleic acid) in severely affected olive groves was recorded. Thirty-two olive groves were then surveyed, and samples of fruit, stalk, leaf, and shoot were collected. Visual, stereoscopic, and microscopic observations revealed several fungi belonging to the genera Alternaria, Botryosphaeria, Capnodium, Colletotrichum, Fusarium, and Pseudocercospora. Fungal infection in fruits was commonly associated with concomitant infestation by the olive fruit fly Bactrocera oleae along with increased air temperature and relative humidity conditions that prevailed in October and November 2019. Twenty representative fungal strains isolated from symptomatic fruits and stalks were characterized by morphological, physiological, and molecular analyses. By internal transcribed spacer regions of ribosomal DNA region and translation elongation factor 1-α gene sequencing analysis, these isolates were identified as Alternaria spp., A. infectoria, Botryosphaeria dothidea, Colletotrichum boninense sensu lato, Fusarium lateritium, F. solani species complex and Stemphylium amaranthi. Pathogenicity tests on punctured fruits revealed that all isolates were pathogenic; however, F. solani isolates along with B. dothidea were the most virulent, and wounds were necessary for efficient fungal infection. Moreover, as few as 10 spores of F. solani were sufficient to cause significant infection in punctured fruits. F. solani was also capable of infecting olive fruits in the presence of B. oleae, with no additional wounding, in artificial inoculation experiments. Moreover, it was capable of colonizing and affecting olive blossoms. Further analyses of olive oil extracted from fruits artificially inoculated with F. solani indicated a significant increase in oil acidity, K232, K270, and peroxide value, whereas total phenol content was significantly decreased. To the best of our knowledge, this is the first report of F. solani associated with olive fruit rot and olive oil degradation worldwide.
Characterization ofPhytophthora infestansPopulations in Cyprus, the Southernmost Potato-Producing European Country
Authors: Kanetis Loukas I. , Pittas Lambros , Nikoloudakis Nikolaos , Cooke David E. L. , Ioannou Nikolaos
Published: May 2021

Cyprus is the southernmost island country of Europe, located in the Mediterranean. Despite its limited area, potato production is considered an integral source of the national agricultural revenue. During 2010–2012, a late blight epidemic period for the country, the population structure of Phytophthora infestans was analyzed via a sample of 539 isolates collected from all of the main potato-cultivating regions of Cyprus. We determined mating type, mefenoxam sensitivity, and genetic polymorphism at 12 simple sequence repeat (SSRs) loci. Although both mating types were detected in the country, a gradual but dynamic shift toward A2 dominance was manifested over time. The pathogen population also demonstrated reduced sensitivity to the phenylamide fungicide, since 96.2% of the tested isolates had high (70.3%) and intermediate (25.9%) resistance to mefenoxam, which suggests that it should be replaced with other active ingredients in local disease management strategies. The genotypic analysis also revealed the predominance of the highly aggressive mefenoxam-insensitive EU_13_A2 lineage across the country, with a frequency of 79.2%. Other samples comprised an older lineage EU_2_A1 (19.5%), a very low proportion of EU_23_A1 (0.37%), and others that did not match any known lineage (0.92%). SSRs data supported triploid genomes among the dominant lineages, and patterns of their asexual population history were also apparent. A high subclonal variation of the 13_A2 population was detected, which suggested introduction events of this widespread genotype to Cyprus from major tuber-exporting countries. Present data indicate the severe impact of inoculum migration to the structure of the local population; thus, current phytosanitary procedures should be reconsidered and possibly attuned. This is the first comprehensive study to elucidate the diversity of P. infestans in Cyprus and could serve as a baseline for future monitoring of this highly adaptive plant pathogen, given that late blight management strategies should be constantly refined according to the traits of the dominant genotypes of P. infestans.
APRNs' controlled substance prescribing and readiness following Florida legislative changes
Authors: Reynolds Annie M. , Reynolds Caleb J. , Craig-Rodriguez Alicia
Published: May 2021

Two years after the Florida legislature expanded APRN prescribing to include schedule II-IV drugs in 2017, we studied APRN utilization of this prescriptive authority. Study results reveal that Florida APRNs are meeting the educational requirements to prescribe and apply the use of these drugs in practice, improving patient access to care.
Management strategies for STE-ACS
Authors: El Hussein Mohamed Toufic , Hakkola Jonah
Published: May 2021

Using guideline-driven interventions, NPs are well suited for management of ST-segment elevation (STE)-acute coronary syndrome (ACS). This second article in a two-part series on ACS management presents an updated overview to help NPs in applying evidence-based interventions while caring for patients with STE-ACS.
Challenges of Diagnosing and Managing Designer Benzodiazepine Dependence and Withdrawal: A Case Report
Authors: Peng Linda , Lawrence David , Levander Ximena A.
Published: May 2021

Background:

Over the last 10 years, an increasing number of unregulated novel psychoactive substances, including “designer benzodiazepines” (DBZDs), have emerged on the recreational drug market. Despite the rapidly increasing usage of DBZDs, there is a significant lack of information regarding clinical management. Here we present a case illustrating the difficulties of diagnosing and managing DBZD related sedative-hypnotic use disorder.

Case Presentation:

Our patient is a 30-year-old man with severe opioid and sedative-hypnotic use disorders. He had a 10-year history of using heroin, clonazolam, and alprazolam. He stopped using heroin when on methadone maintenance therapy but continued using clonazolam and nonprescribed alprazolam. His opioid treatment program discontinued methadone due to benzodiazepine intoxication, and he returned to heroin use. He then presented for residential withdrawal management where he underwent successful buprenorphine induction and benzodiazepine withdrawal management. During a 3-month period of benzodiazepine abstinence, he struggled with ongoing cravings and post-acute withdrawal syndrome, ultimately leading to return to DBZD use.

Discussion:

Despite the increasing prevalence of DBZD use, the usage of DBZDs is likely under-recognized because these compounds are generally not included on standard in-office urine drug immunoassay tests. Initial studies suggest that DBZDs have high potencies, shorter half-lives, are more addictive, and can result in more severe withdrawal symptoms compared to known benzodiazepines. However, there remains a lack of information about the pharmacokinetics and pharmacodynamics of DBZDs, making clinical management for DBZD related sedative-hypnotic use disorders challenging to treat.
Pressure Necrosis Requiring Fasciotomy After Kratom Overdose
Authors: Tobarran Natasha , Wolf Carl , Cumpston Kirk L. , Wills Brandon K.
Published: May 2021

Introduction:

Kratom (Mitragyna speciosa) is a popular plant-based extract that has dose-dependent stimulatory and sedative effects. It has been used for self-treatment of opioid withdrawal and can result in seizures, hepatotoxicity, and infectious complications from bacterial contamination. Reports of morbidity and mortality associated with Kratom may be confounded by coingestants. We report a case of severe rhabdomyolysis and pressure necrosis leading to fasciotomy in a patient who was using Kratom.

Case report:

A 31-year-old male with substance use presented to the emergency department after loss of consciousness for 6 hours after smoking Kratom. He was found to have rhabdomyolysis, acute renal and hepatic injury, and electrolyte disturbances. No ethanol was detected, and urine drug screen was negative. Over the next 3 hours, the patient developed signs of compartment syndrome and he was transferred to the operating room for fasciotomy. He required continuous renal replacement therapy for 48 hours and his labs and clinical status improved. He was discharged 18 days later. A serum and urine sample from the first day of presentation were analyzed for mitragynine and 7-hydroxymitragynine using an Ultra Performance Liquid Chromatography-Tandem Mass Spectrometer (UPLC-MSMS) method. The serum mitragynine was 5 ng/mL and the urine mitragynine 6 ng/mL.

Conclusions:

Although there are numerous reports of opioids resulting in prolonged periods of immobilization and rhabdomyolysis, this is not commonly reported in Kratom overdoses.

This case report highlights the profound sedative effect of Kratom and the potential of pressure necrosis injury resulting in rhabdomyolysis and compartment syndrome requiring fasciotomy.
The Use of Kratom (Mitragyna speciosa Korth.) Among People Who Co-use Heroin and Methamphetamine in Malaysia
Authors: Singh Darshan , Narayanan Suresh , Vicknasingam Balasingam , Prozialeck Walter C. , Smith Kirsten Elin , Corazza Ornella , Henningfield Jack E. , Grundmann Oliver
Published: May 2021

Objectives:

Kratom (Mitragyna speciosa Korth.), an indigenous medicinal plant, has been widely used as a traditional remedy in Southeast Asia. However, its combined consumption with other substances has received scarce attention. This study investigates the use of kratom among adults with a history of using heroin and methamphetamine in Malaysia.

Methods:

A total of 332 patients who were mandated to undergo drug rehabilitation participated in this cross-sectional study. The study data were collected through face-to-face interviews using a semi-structured questionnaire.

Results:

The majority were males (95%, n = 314/332) and Malays (98%, n = 325/332) with a mean age of 32.3 years (SD = 9.16). Over two thirds of the respondents used kratom to alleviate heroin withdrawal symptoms and to reduce methamphetamine intake; 59% used it as a substitute for heroin and methamphetamine. A similar proportion used kratom to reduce heroin intake (58%), while only 15% used it for its euphoric effects. Multivariate analysis showed that previous attendees of government rehabilitation programs had lower odds of using kratom as a heroin substitute.

Conclusions:

The potential of kratom to alleviate heroin withdrawal symptoms, and to reduce methamphetamine and heroin intake, among people who co-use heroin and methamphetamine warrants further research.
Muscular Forces Responsible for Proximal Humeral Deformity After Fracture
Authors: Chalmers Christen E. , Wright David J. , Patel Nilay , Hitchens Hunter , McGarry Michelle , Lee Thay Q. , Scolaro John A.
Published: May 2021

Objectives:

To evaluate the contribution of each of the rotator cuff muscles and deltoid to fracture deformity in a 2-part proximal humerus fracture model. Our hypothesis was that superior cuff muscles would have the greatest contribution to coronal plane deformity, whereas muscles with anterior and posterior attachments would have the greatest contribution to axial and sagittal plane deformity.

Methods:

A medial wedge osteotomy was created in 8 cadaveric shoulder specimens. A custom shoulder testing system was used to load each rotator cuff muscle and deltoid under increasing loading conditions. Fracture displacement was measured using a Microscribe digitizing system. The primary outcome was the contribution of each muscle to varus collapse. Secondary outcomes included contributions of each muscle to apex anterior/posterior deformity and humeral head anteversion/retroversion.

Results:

Unbalanced loading of the supraspinatus resulted in the greatest varus deformity (34.5 ± 2.3 degrees), followed by the infraspinatus (22.3 ± 3.6 degrees) and subscapularis (21.7 ± 3.1 degree) (P < 0.05). Unbalanced loading of the subscapularis induced the greatest apex posterior (27.5 ± 4.8 degrees, P < 0.05) and retroversion (39.0 ± 5.6 degrees, P < 0.05) deformity, whereas the infraspinatus induced the greatest apex anterior (8.7 ± 3.4 degrees, P > 0.05) and anteversion (17.7 ± 5.7 degrees, P > 0.05) deformity.

Conclusions:

In this proximal humerus fracture model, the supraspinatus was the primary driver of varus deformity, whereas the subscapularis and infraspinatus contributed to apex posterior/retroversion and apex anterior/anteversion, respectively. The subscapularis and infraspinatus are also important secondary drivers of varus deformity. This study establishes a physiologically relevant fracture model that mimics in vivo conditions for future biomechanical testing.
Volume Resuscitation and Progression to Organ Failure in Shiga Toxin-Producing Escherichia coli Infection in Adults
Authors: Volk Charles G. , Cusmano Paul M. , Bower Richard J. , Sanders Terrel , Maves Ryan C.
Published: May 2021

OBJECTIVES:

Shiga toxin-producing Escherichia coli infection is associated with dysentery and the hemolytic uremic syndrome, marked by the triad of microangiopathic hemolytic anemia, acute kidney failure, and thrombocytopenia. Descriptions of Shiga toxin-producing Escherichia coli outbreaks causing hemolytic uremic syndrome in adults are sparse, and management strategies are largely adapted from pediatric literature where aggressive fluid administration is recommended. However, these may not be ideal for adults.

DESIGN:

We present a case series of an Shiga toxin-producing Escherichia coli outbreak in U.S. Marine Corps recruits.

SETTING:

We review the clinical course, laboratory data, and fluid resuscitation used in hospitalized patients during the 2017 Shiga toxin-producing Escherichia coli outbreak at Marine Corps Recruit Depot, San Diego.

PATIENTS:

Patients admitted to the hospital for complications from Shiga toxin-producing Escherichia coli infection. All were previously healthy men between the ages of 17 and 20 years.

INTERVENTIONS:

Isotonic crystalloid fluid resuscitation during the first 72 hours.

MEASUREMENTS AND MAIN RESULTS:

Of 244 identified cases of Shiga toxin-producing Escherichia coli infection, 30 required hospitalization, 15 progressed to hemolytic uremic syndrome, and five required hemodialysis. Patients were admitted and given aggressive IV fluid hydration. Those who progressed to hemolytic uremic syndrome received on average 8.4 L of isotonic crystalloid over the initial 72 hours, with up to 18% of body weight delivered. The six critically ill patients received a mean 12.2 L in the first 72 hours. Those who did not progress to hemolytic uremic syndrome received a mean 3.0 L of crystalloid. If oligoanuria developed, a net-even fluid balance was maintained. The amount of volume infused was not associated with improved outcomes. The patients with the highest fluid balance totals more often required dialysis than those who received less fluid. One hemolytic uremic syndrome patient developed flash pulmonary edema.

CONCLUSIONS:

The aggressive IV hydration protocols (as a percentage of body weight) in the pediatric literature may not be applicable to adults diagnosed with hemolytic uremic syndrome. A more conservative fluid strategy in adults with hemolytic uremic syndrome merits further investigation.
Comparison of Attention-Deficit Hyperactivity Disorder in Typically Developing Children and Children with Down Syndrome
Authors: Esbensen Anna J. , Epstein Jeffery N. , Vincent Lori B. , Kamimura-Nishimura Kelly , Wiley Susan , Angkustsiri Kathleen , Abbeduto Leonard , Fidler Deborah , Froehlich Tanya E.
Published: May 2021

Objective:

This study aimed to evaluate attention-deficit hyperactivity disorder (ADHD) symptom patterns among children with Down syndrome (DS) with or without ADHD and typically developing (TD) children with ADHD.

Methods:

Parents and teachers rated symptoms of inattention, hyperactivity, and general behavioral concerns for 22 children with DS and comorbid diagnoses of ADHD (DS + ADHD), 66 gender-matched and age-matched children with DS with no diagnosis of ADHD (DS − ADHD), and 66 gender-matched and age-matched TD children with ADHD (TD + ADHD). Children with DS were recruited from the community. TD children with ADHD were recruited from a specialty clinic evaluating for ADHD.

Results:

Parents tended to report higher scores of inattention and hyperactivity for TD children with ADHD compared with children with DS and no ADHD. Although mean ADHD symptom summary scores were not significantly different in DS + ADHD and DS − ADHD, specific parent-report items (e.g., distractibility and being “on the go”) did tend to differentiate these groups. By contrast, teachers tended to report higher inattention and hyperactivity scores for DS + ADHD compared with both DS − ADHD and TD + ADHD. Specific teacher-reported items tending to differentiate DS + ADHD and DS − ADHD included difficulties following through on tasks, avoiding tasks, leaving one's seat, and excessive talking.

Conclusion:

Variability in response patterns between parent and teacher reports for children with and without DS highlights the need to evaluate ADHD symptoms across environments. Our findings also suggest specific items that may particularly be helpful in distinguishing children with DS who do and do not have ADHD, although replication is needed.
A Trial Emulation Approach for Policy Evaluations with Group-level Longitudinal Data
Authors: Ben-Michael Eli , Feller Avi , Stuart Elizabeth A.
Published: May 2021

To limit the spread of the novel coronavirus, governments across the world implemented extraordinary physical distancing policies, such as stay-at-home orders. Numerous studies aim to estimate the effects of these policies. Many statistical and econometric methods, such as difference-in-differences, leverage repeated measurements, and variation in timing to estimate policy effects, including in the COVID-19 context. Although these methods are less common in epidemiology, epidemiologic researchers are well accustomed to handling similar complexities in studies of individual-level interventions. Target trial emulation emphasizes the need to carefully design a nonexperimental study in terms of inclusion and exclusion criteria, covariates, exposure definition, and outcome measurement—and the timing of those variables. We argue that policy evaluations using group-level longitudinal (“panel”) data need to take a similar careful approach to study design that we refer to as policy trial emulation. This approach is especially important when intervention timing varies across jurisdictions; the main idea is to construct target trials separately for each treatment cohort (states that implement the policy at the same time) and then aggregate. We present a stylized analysis of the impact of state-level stay-at-home orders on total coronavirus cases. We argue that estimates from panel methods—with the right data and careful modeling and diagnostics—can help add to our understanding of many policies, though doing so is often challenging.
Decreased Susceptibility of Marginal Odds Ratios to Finite-sample Bias
Authors: Ross Rachael K. , Cole Stephen R. , Richardson David B.
Published: May 2021

Parameters representing adjusted treatment effects may be defined marginally or conditionally on covariates. The choice between a marginal or covariate-conditional parameter should be driven by the study question. However, an unappreciated benefit of marginal estimators is a reduction in susceptibility to finite-sample bias relative to the unpenalized maximum likelihood estimator of the covariate-conditional odds ratio (OR). Using simulation, we compare the finite-sample bias of different marginal and conditional estimators of the OR. We simulated a logistic model to have 15 events per parameter and two events per parameter. We estimated the covariate-conditional OR by maximum likelihood with and without Firth’s penalization. We used three estimators of the marginal OR: g-computation, inverse probability of treatment weighting, and augmented inverse probability of treatment weighting. At 15 events per parameter, as expected, all estimators were effectively unbiased. At two events per parameter, the unpenalized covariate-conditional estimator was notably biased but penalized covariate-conditional and marginal estimators exhibited minimal bias.
Treatment of Hypertension Because of Immunosuppressive Therapy After Solid Organ Transplantation—Pharmacological Approach
Authors: Gilewski Wojciech , Banach Joanna , Rogowicz Daniel , Wołowiec Łukasz , Sielski Sławomir , Grześk Grzegorz
Published: May 2021

Solid organs transplantation procedures have been performed for more than half a century. Growing knowledge of immune response and development of new immunosuppressive regimens guarantee more and more successful outcomes. However, many of the applied drugs lead to cardiovascular complications, the most frequent of which is hypertension. This article describes epidemiology, pathogenetic mechanisms, and treatment of hypertension induced by immunosuppressive medication. The main impact is focused on drugs belonging to the following groups: calcineurin inhibitors, the inhibitors of the mammalian target of rapamycin, and glucocorticosteroids. We analyze the mechanism of action of the main hypertensive drugs and their influence on the reversing hypertonic action of the immunosuppressive agents. In the absence of current guidelines addressing this problem, this article is an attempt to fill the gap, helping clinicians to choose proper medication.
Effect of Levosimendan on Ventricular Systolic and Diastolic Functions in Heart Failure Patients: A Meta-Analysis of Randomized Controlled Trials
Authors: Long Yu-Xiang , Cui Di-Yu , Kuang Xue , Hu Shuang , Hu Yue , Liu Zeng-Zhang
Published: May 2021

Levosimendan, a calcium sensitizer, exerts inotropic action through improving left ventricular ejection fraction. We noticed that only few clinical studies are published in which the effects of levosimendan on cardiac function are studied by echocardiography. When screening the literature (PubMed, Embase, and CENTRAL, from inception to August 2020), we found 29 randomized controlled trials on levosimendan containing echocardiographic data. We included those studies, describing a total of 574 heart failure patients, in our meta-analysis and extracted 14 ultrasonic parameters, pooling the effect estimates using a random-effect model. Our analysis of the diastolic parameters of the left ventricle shows that levosimendan reduce the early/late transmitral diastolic peak flow velocity ratio [standardized mean difference (SMD) −0.45 to 95% confidence interval (CI) (−0.87 to −0.03), P = 0.037] and E/e' (e': mitral annulus peak early diastolic wave velocity using tissue-doppler imaging) [SMD −0.59, 95% CI (−0.8 to −0.39), P < 0.001]. As it regards the systolic parameters of the right ventricle, levosimendan increased tricuspid annular plane systolic excursion [SMD 0.62, 95% CI (0.28 to 0.95), P < 0.001] and tricuspid annular peak systolic velocity [SMD 0.75, 95% CI (0.35 to 1.16), P < 0.001], and reduced systolic pulmonary artery pressure [SMD −1.02, 95% CI (−1.32, −0.73), P < 0.001]. As it regards the diastolic parameters of the right ventricle, levosimendan was associated with the decrease of Aa (peak late diastolic tricuspid annular velocity using tissue-doppler imaging) [SMD −0.38, 95% CI (−0.76 to 0), P = 0.047] and increase of Ea (peak early diastolic tricuspid annular velocity using tissue-doppler imaging) [SMD 1.03, 95% CI (0.63 to 1.42), P < 0.001] and Ea/Aa [SMD 0.86, 95% CI (0.18 to 1.54), P = 0.013]. We show that levosimendan is associated with an amelioration in the diastolic and systolic functions of both ventricles in heart failure patients.
Could Dapagliflozin Attenuate COVID-19 Progression in High-Risk Patients With or Without Diabetes? Behind DARE-19 Concept
Authors: Anastasiou Georgia , Hatziagelaki Erifili , Liberopoulos Evangelos
Published: May 2021

Epidemiological studies indicate that diabetes is the second most common comorbidity in COVID-19 (coronavirus disease 2019). Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, exerts direct cardioprotective and nephroprotective effects. DARE-19 (Dapagliflozin in Respiratory Failure in Patients With COVID-19), an ongoing clinical trial, is designed to investigate the impact of dapagliflozin on COVID-19 progression. This article discusses the potential favorable impact of dapagliflozin on COVID-19 and its complications.
Aprocitentan (a Dual Endothelin-Receptor Antagonist) for Treatment-Resistant Hypertension
Authors: McCoy Emily K. , Lisenby Katelin M.
Published: May 2021

Treatment-resistant hypertension (TRH) is associated with increased cardiovascular risks and progression of chronic kidney disease. The pathophysiology of TRH is multifactorial, including overactivity of the renin–angiotensin–aldosterone system and sympathetic nervous system, endothelial dysfunction, and volume overload. Endothelin-1 is a vasoconstrictive peptide that causes neurohormonal and sympathetic activation, increased aldosterone synthesis and secretion, endothelial dysfunction, vascular hypertrophy and remodeling, and fibrosis. Endothelin-1 acts through 2 receptors, ETA and ETB. Activation of ETA receptors in vascular smooth muscle cells results in vasoconstriction, whereas ETB receptor activation results in vasoconstriction in the vascular smooth muscle cells and vasodilation through nitric oxide release in endothelial cells. Aprocitentan is novel, oral, dual endothelin-receptor antagonist that has demonstrated a more favorable tolerability and safety profile in early clinical trials compared with other endothelin-receptor antagonists studied. Phase 2 trial data support a significant reduction in blood pressure compared to placebo and similar blood pressure reduction compared to a moderately dosed angiotensin-converting enzyme inhibitor in patients with essential hypertension. An ongoing phase 3 randomized clinical trial is evaluating aprocitentan's efficacy and safety in patients with TRH receiving multiple antihypertensives. Additional research is needed to determine aprocitentan's role in therapy, but this agent may be a suitable treatment option for TRH.
Takotsubo Cardiomyopathy as Epiphenomenon of Cardiotoxicity in Patients With Cancer: A Meta-summary of Case Reports
Authors: Carbone Andreina , Bottino Roberta , Russo Vincenzo , D'Andrea Antonello , Liccardo Biagio , Maurea Nicola , Quagliariello Vincenzo , Cimmino Giovanni , Golino Paolo
Published: May 2021

Many antitumoral drugs have been linked to takotsubo cardiomyopathy, with no clear pathogenetic mechanisms. Data about this condition are lacking in literature. The aim of this meta-summary is to summarize the characteristics of patients with antitumoral drug–induced takotsubo cardiomyopathy, described in case reports available in literature. We searched for published case reports in PubMed, Google Scholar, EMBASE, and Scopus from 2009 about stress cardiomyopathy and antiblastic drugs. We selected 41 case reports. All cases underwent chemotherapy/immunotherapy for different types of cancer. The median age was 58 years, and 61% of them were women. The most common comorbidities were hypertension (12.2%) and dyslipidemia (4.9%), but most of the population had no cardiological clinical history. Takotsubo cardiomyopathy is associated to the 5-fluorouracil (36.5%), capecitabine (9.7%), trastuzumab (9.7%), and immune check point inhibitor (9.7%) treatment. The median time of onset was 2 days (1–150). Cardiogenic shock was the first manifestation in 11 patients (26.8%). Left ventricle ejection fraction recovery was showed in 33 patients (89%) with mean ejection fraction 57.7 ± 7%, after a median of 30-day (4–300) follow-up. Patients with cancer experienced takotsubo cardiomyopathy within few days from the beginning of therapy, and the most of them normalized the heart function in few weeks. Cardiogenic shock showed high prevalence in this setting of patients. Larger studies are needed to better understand the pathological mechanisms of antiblastic drug–induced stress cardiomyopathy, to find risk factors associated and preventive strategies for limit this type of cardiotoxicities.
Facial Feminization Surgery under Insurance: The University of California Los Angeles Experience
Authors: Hu Allison C. , Dang Brian N. , Bertrand Anthony A. , Jain Nirbhay S. , Chan Candace H. , Lee Justine C.
Published: May 2021

Background:

Despite improved insurance coverage for gender confirmation surgeries in the United States, coverage for facial feminization surgery (FFS) continues to be difficult. Here, we describe our institutional experience on navigation, time, and costs of the FFS insurance authorization process.

Methods:

FFS consults (n = 40) at the University of California, Los Angeles (2018–2020) were reviewed for time and cost to definitive insurance authorization decision. Patients were stratified into 3 groups based on authorization process: Group A (standard approval, n = 26, 65.0%) including public and private insurances; Group B (extended approval, n = 10, 25.0%) consisting of private insurance plans that initially denied and required multi-level appeals for denial overturn; and Group C (denial, n = 4, 10.0%), including private insurance plans that denied even after multi-level appeals.

Results:

An estimated 90% of all patient consults were approved for FFS under insurance. Group A averaged 1.1 months for approval, requiring 1.4 hours of administrative time translating to $38.18 per patient. The addition of multi-level appeals in Groups B and C increased the total time for a definitive decision (7.0 and 5.1 months, respectively) and required both surgeon and administrative time to navigate the process (10.8 and 12.0 hours, respectively). The time spent on the presurgical authorization process for Groups B and C translated to an over 20-fold increase in cost ($855.00 and $988.38, respectively) compared with Group A.

Conclusion:

Navigation of the insurance process for FFS is challenging and time-consuming; however, coverage is a reality in California provided that multi-level appeals are exhausted.
Oral Beta-blocker in Problematic Infantile Hemangioma
Authors: AlHasan Rashed N. , Arabiyat Lamees , Ammar Hamad M. , Louri Nayef A.
Published: May 2021

One of the most common benign vascular endothelial tumors is infantile hemangioma. These lesions are commonly found in the head and neck, and sometimes it is a challenge to decide the method of treatment if the lesions are problematic hemangiomas, interfering with function or aesthetic appearance. This study reports a case of girl aged 3 years, 7 months, diagnosed with periorbital infantile hemangioma that was successfully treated with oral propranolol in specific doses and gradual tapering off dose. The patient had marked involution of the lesion with no significant side effects after starting her treatment at the age of 4 months, for a total of 13 months with no reported rebound growth after almost 2 years since the termination of treatment. Oral beta-blockers can be used safely in treatment of problematic infantile hemangioma as a single modality, without any surgical intervention.
Effectiveness of statin intensive therapy in type 2 diabetes mellitus with high visit-to-visit blood pressure variability
Authors: Ikeda Shota , Shinohara Keisuke , Enzan Nobuyuki , Matsushima Shouji , Tohyama Takeshi , Funakoshi Kouta , Kishimoto Junji , Itoh Hiroshi , Komuro Issei , Tsutsui Hiroyuki
Published: May 2021

Background:

Intensive lipid-lowering therapy is recommended in type 2 diabetes mellitus (T2DM) patients with target organ damage. However, the evidence is insufficient to stratify the patients who will benefit from the intensive therapy among them. High visit-to-visit variability in systolic blood pressure (SBP) is associated with increased risk of cardiovascular events. We investigated the effectiveness of intensive versus standard statin therapy in the primary prevention of cardiovascular events among T2DM patients with retinopathy stratified by visit-to-visit SBP variability.

Methods:

The standard versus intensive statin therapy for hypercholesterolemic patients with diabetic retinopathy study was the first trial comparing statin intensive therapy targeting low-density lipoprotein cholesterol (LDL-C) <70 mg/dl and standard therapy targeting LDL-C ≥100 to <120 mg/dl in T2DM patients with retinopathy without known cardiovascular disease. Using this dataset, we divided the patients into two subpopulations based on standard deviation (SD) and average real variability (ARV) of clinic SBP within the initial 6 months.

Results:

In a total of 4899 patients, 240 composite cardiovascular events were observed during a median follow-up of 37.3 months. In multivariable-adjusted model comparing intensive versus standard therapy, the hazard ratios for composite cardiovascular events were 0.64 (95% CI 0.45–0.90) and 1.21 (95% CI 0.82–1.80) in patients with high and low SBP variability as defined by SD, respectively. Interaction between SBP variability and statin therapy was significant (P = 0.018). The analysis using ARV of SBP showed similar results.

Conclusion:

Statin intensive therapy targeting LDL-C <70 mg/dl had benefits in primary prevention of cardiovascular events compared with standard therapy among T2DM patients with retinopathy having high, but not low, visit-to-visit SBP variability.
Adaptation of left ventricular diastolic function to pregnancy: a systematic review and meta-analysis
Authors: de Haas Sander , Spaanderman Marc E.A. , van Kuijk Sander M.J. , van Drongelen Joris , Mohseni Zenab , Jorissen Laura , Ghossein-Doha Chahinda
Published: May 2021

Objective:

To meta-analytically determine the adaptation of left ventricular diastolic function (LVDF)-indices to singleton normotensive pregnancies.

Methods:

Literature was retrieved from PubMed and Embase. We included studies that reported a nonpregnant reference measurement and LVDF indices (mitral inflow signals, left atrial volume and tissue Doppler measurements). Mean differences between pregnant and reference measurements and weighted means of absolute values were calculated using a random-effects model.

Results:

We included 34 eligible studies. Normotensive pregnancies were characterized by an initially larger increase in the passive left ventricular filling (E-wave peak velocity, 13%) compared to active left ventricular filling during diastole (A-wave peak velocity, 6%) resulting in a 16% increase of the E/A ratio in the first trimester. The E/A ratio progressively decreased during advancing gestation to −18% at term, resulting from stabilizing E-wave peak velocity and increased A-wave peak velocity. The E/e′ ratio was increased between 22 and 35 weeks (a maximal increase of 13%) in normotensive pregnancy. Left atrial volume (LAV) progressively increased from 15 weeks onwards with a maximal increase of 30% between 36 and 41 weeks.

Conclusion:

LVDF in normotensive pregnancy was improved in the first trimester after which LVDF progressively worsened. Large-scale studies in normotensive and hypertensive complicated pregnancies are needed for a more precise insight into LVDF changes during pregnancy.
An exploratory analysis of comparative plasma metabolomic and lipidomic profiling in salt-sensitive and salt-resistant individuals from The Dietary Approaches to Stop Hypertension Sodium Trial
Authors: Chaudhary Parul , Velkoska Elena , Wainford Richard D.
Published: May 2021

Objective:

This study conducted exploratory metabolomic and lipidomic profiling of plasma samples from the DASH (Dietary Approaches to Stop Hypertension) Sodium Trial to identify unique plasma biomarkers to identify salt-sensitive versus salt-resistant participants.

Methods:

Utilizing plasma samples from the DASH-Sodium Trial, we conducted untargeted metabolomic and lipidomic profiling on plasma from salt-sensitive and salt-resistant DASH-Sodium Trial participants. Study 1 analyzed plasma from 106 salt-sensitive and 85 salt-resistant participants obtained during screening when participants consumed their regular diet. Study 2 examined paired within-participant plasma samples in 20 salt-sensitive and 20 salt-resistant participants during a high-salt and low-salt dietary intervention. To investigate differences in metabolites or lipidomes that could discriminate between salt-sensitive and salt-resistant participants or the response to a dietary sodium intervention Principal Component Analysis and Orthogonal Partial Least Square Discriminant Analysis was conducted. Differential expression analysis was performed to validate observed variance and to determine the statistical significance.

Results:

Differential expression analysis between salt-sensitive and salt-resistant participants at screening revealed no difference in plasma metabolites or lipidomes. In contrast, three annotated plasma metabolites, tocopherol alpha, 2-ketoisocaproic acid, and citramalic acid, differed significantly between high-sodium and low-sodium dietary interventions in salt-sensitive participants.

Conclusion:

In DASH-Sodium Trial participants on a regular diet, plasma metabolomic or lipidomic signatures were not different between salt-sensitive and salt-resistant participants. High-sodium intake was associated with changes in specific circulating metabolites in salt-sensitive participants. Further studies are needed to validate the identified metabolites as potential biomarkers that are associated with the salt sensitivity of blood pressure.
Implications of Cloth COVID Masks for Size Distribution of Inhaled Plutonium, Respiratory Deposition, and Fecal Bioassay Monitoring
Authors: Klumpp John , Poudel Deepesh
Published: May 2021

This work considers the implications of cloth masks due to the COVID-19 pandemic on suspected plutonium inhalations and dose assessment. In a plutonium inhalation scenario, the greater filtration efficiency for large particles exhibited by cloth masks can reduce early fecal excretion without a corresponding reduction in dose. For plutonium incidents in which cloth masks are worn, urinary excretion should be the preferred method of inferring dose immediately after the inhalation, and fecal excretion should be considered unreliable for up to 10 days.
GEOGRAPHIC ACCESS DISPARITIES TO CLINICAL TRIALS IN RETINOPATHY OF PREMATURITY IN THE UNITED STATES
Authors: Soares Rebecca R. , Cai Louis Z. , Bowe Theodore , Samuelson Annika G. , Liu Catherine K. , Parikh Devayu , Patel Samir N. , Hinkle John W. , Yonekawa Yoshihiro
Published: May 2021

Background/Purpose:

To identify geographic and socioeconomic variables predictive of residential proximity to retinopathy of prematurity (ROP) clinical trial locations.

Methods:

This cross-sectional epidemiological study used census tract–level data from three national public data sets and trial-level data from ClinicalTrials.gov. Socioeconomic predictors of driving distance and time to the nearest ROP clinical trial location were identified. Primary outcomes were time >60 minutes and distance >60 miles traveled to the nearest ROP clinical trial site.

Results:

Multivariate analysis showed that residents were more likely to travel >60 minutes to the nearest ROP clinical trial site if they lived in census tracts that were rural (adjusted odds ratio 1.20, P = 0.0002), had higher percentages of the population living ≤ federal poverty level (fourth quartile vs. first quartile, adjusted odds ratio 1.19, P < 0.0001), or had less education (associate vs. bachelor's degree, adjusted odds ratio 1.01, P <0.007). By contrast, counties with higher percentages of births with birth weight <1500 g (adjusted odds ratio 0.88, P = 0.0062) were less likely to travel >60 minutes. Similar variables predicted travel distance.

Conclusion:

Although counties with higher incidences of very low-birth-weight infants were closer to ROP clinical trial sites, residents living in rural and low-income census tracts had significantly greater travel burdens.
MULTIMODAL IMAGING FINDINGS IN ACUTE WEST NILE VIRUS CHORIORETINITIS
Authors: Golshani Cyrus , Venkat Arthi , Srivastava Sunil K.
Published: May 2021

Purpose:

To describe multimodal imaging findings of acute West Nile virus chorioretinitis.

Methods:

Observational case report. Fundus photographs, fluorescein angiography, indocyanine green angiography, and swept-source optical coherence tomography angiography were used to characterize and describe the clinical findings.

Results:

A 58-year-old man presented with acute painless vision loss in the right eye. Multimodal imaging demonstrated multifocal pinpoint early-phase hyperfluorescence with late expanding leakage on fluorescein angiography and late hyperfluorescence on indocyanine green angiography. Swept-source optical coherence tomography angiography en face imaging of the ellipsoid zone layer revealed target-like lesions with central hyperreflectivity with surrounding hyporeflectivity. At 4-week follow-up, the chorioretinal lesions now demonstrated greater demarcation of borders with increased pigmentation. At 8-week follow-up, fundus examination revealed multiple target-like lesions with hyperpigmentation centrally surrounded by a hypopigmented rim. Repeat fluorescein angiography demonstrated central hypofluorescence with surrounding hyperfluorescent staining rim prompting workup for West Nile virus, which was later confirmed by laboratory testing. The patient's visual acuity and clinical examination remained stable on subsequent follow-up visits.

Conclusion:

Our case highlights multimodal imaging findings in the acute phase of West Nile virus chorioretinitis, which may be crucial to early diagnosis and identification.
ADULT-ONSET BEST1-VITELLIFORM DYSTROPHY ASSOCIATED WITH ANGIOID STREAK-LIKE CHANGES IN TWO SIBLINGS
Authors: Li Yafeng , Bracha Peter , Aleman Tomas S. , Brucker Alexander J.
Published: May 2021

Background/Purpose:

To describe the association between autosomal dominant Best disease and peripapillary angioid streak-like changes.

Methods:

Case report of two siblings.

Results:

A 76-year-old White man was referred for evaluation of bilateral macular changes and worsening visual distortion over the preceding 2 years. Best-corrected visual acuity measured 20/30 in the right eye and 20/80 in the left eye. Funduscopic examination revealed multifocal yellow lesions in the posterior pole that were hyperautofluorescent on short-wavelength excitation and corresponded with subretinal hyperreflective material on optical coherence tomography. The posterior pole examination was interesting because of the juxtapapillary involvement of the vitelliform lesions and the presence of bilateral peripapillary angioid streak-like changes despite no history of conditions associated with angioid streaks. On further workup, an electrooculogram revealed reduced Arden ratios and a known heterozygous missense mutation in BEST1 (c.903T>G; p.D301E) was found. The patient's 69-year-old younger brother was brought in and found to have a remarkably similar phenotype, including the presence of angioid streak-like changes associated with the same BEST1 mutation.

Conclusion:

These two cases demonstrate the possibility of late-onset multifocal vitelliform disease due to dominantly inherited BEST1. A consistent phenotype in this family with macular lesions extending into the peripapillary region, associated with angioid streak-like changes, suggests susceptibility of this region to changes in dominant BEST1-vitelliform macular dystrophy.
Miniscleral Contact Lens in Pediatric Age Group: Indications, Safety, and Efficacy
Authors: Alipour Fateme , Jamshidi Gohari Sadra , Azad Nikoo , Mehrdad Ramin
Published: May 2021

Objective:

To report indications, fitting feasibility, and safety of miniscleral design (MSD) lenses in children.

Methods:

Medical records of patients aged <18 years at the time of referral to Contact Lens Clinic of Farabi Eye Hospital, because of inadequate spectacle-corrected visual acuity, rigid gas-permeable or soft contact lens intolerance, and ocular surface disease were reviewed. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), best-corrected vision with the lens (CCVA), lens parameters, and comfortable daily wearing time (CDWT) were documented.

Results:

Seventy-two eyes of 52 pediatric patients were fitted with MSD lens over a 9-year period. The indications for MSD lens fitting were keratoconus (29 eyes), corneal scarring from ocular trauma (16 eyes), ocular surface diseases (25 eyes), and postkeratitis corneal scar (2 eyes). The average UCVA and the mean difference between CCVA and BSCVA were 1.20 and 0.55 logarithm of the minimal angle of resolution, respectively, which shows statistically significant improvement. This significant increase in vision was even seen in those who were referred for the management of ocular surface diseases. The mean CDWT for most patients was 10 hr/day.

Conclusion:

Miniscleral design lens can be used as a safe and helpful modality to provide good vision and comfort in children experiencing ectatic disorders, traumatic corneal scars, and ocular surface diseases.