bluuebunny/crossref_metadata_2025 huggingface dataset:
Teenager with paranoia and hallucinations preceded by a decline in academic and social functioning
Authors: Pereira Joseph A.
Published: June 2021

Schizophrenia is a primary psychotic disorder characterized by two or more of hallucinations, delusions, disorganized speech, disorganized or catatonic behavior, and/or negative symptoms. At least one of the symptoms must be hallucinations, delusions, or disorganized speech. There must be continuous signs of the disturbance for at least six months, although the duration may be shortened with appropriate treatment. The symptoms of schizophrenia typically begin between the ages of 15 and 30 years. Active symptoms are typically preceded by a prodromal phase, marked by a decline in academic and social functioning. The assessment of an adolescent with suspected schizophrenia should include a psychiatric assessment and complete medical history to rule out medical conditions that mimic psychosis. The primary treatment is antipsychotic medications. Adjunctive psychological and social interventions can improve treatment adherence and clinical outcomes.
Several weeks of low mood, decreased appetite, and poor sleep after changing schools
Authors: Grossman Mila N.
Published: June 2021

Major depressive disorder (MDD) is one of the most common psychiatric disorders affecting children and adolescents. The diagnostic criteria require the history of one or more depressive episodes in the absence of a history of mania. In contrast to adults, youth may experience predominantly irritable rather than sad mood. The assessment of depression should include a psychiatric evaluation, medical history, and focused laboratory studies to rule out medical and/or substance-related causes. The evaluation should also consider potential precipitants such as recent losses, interpersonal problems, or trauma. The patient should be asked directly about suicidal ideation, plans, and past attempts. Psychotherapy alone or in combination with antidepressant therapy is effective for the treatment of pediatric depression. Cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT) are the most well-studied psychotherapies. Selective serotonin reuptake inhibitors (SSRIs) are the first-line medication class and should be considered in moderate to severe cases of depression.
A fear of dogs
Authors: Hill Kevin M.
Published: June 2021

Specific phobia is a marked fear or anxiety about a specific object or situation. The fear or anxiety is out of proportion to the actual danger posed by the situation and the symptoms cause clinically significant distress or impairment in functioning. Often patients have more than one specific phobia. Children may be less able to spontaneously articulate their fears and the presenting symptoms may include nonspecific behaviors such as crying, tantrums, freezing, or clinging. A specific phobia can be distinguished from a developmentally appropriate fear by the persistence, severity, and degree of associated functional impairment. The treatment of choice for specific phobia is cognitive behavioral therapy (CBT) including exposure therapy and systematic desensitization.
Decreased food intake after a choking incident
Authors: Czepiel Kathryn S.
Published: June 2021

Avoidant/restrictive food intake disorder (ARFID) is an eating disorder characterized by problematic eating habits that place the patient at risk for nutritional deficiencies, weight loss, dependence on enteral feeding or nutritional supplements, or marked interference with psychosocial functioning. Unlike most other eating disorders, the abnormal eating behaviors seen in ARFID are not motivated by a disturbance in body image or the desire to be thinner. Compared to other eating disorders, ARFID is more likely to present in younger males with a median age of onset of 11 to 12 years. Symptoms of ARFID may develop after a traumatic food event such as choking. The assessment of ARFID should include a history including eating habits and a medical workup that evaluates for coexisting medical conditions. Successful treatment plans employ a multidisciplinary approach that includes weight stabilization and exposure-based cognitive behavioral therapy.
Recurrent episodes of binging and purging
Authors: Macenski Christina L.
Published: June 2021

Bulimia nervosa (BN) is an eating disorder that consists of recurrent binging episodes and inappropriate compensatory behaviors. Binge eating is defined as eating a large amount of food within a discrete time period accompanied by a sense of lack of control over eating during the episode. Examples of inappropriate compensatory behaviors include self-induced vomiting, fasting, excessive exercise, and laxative or diuretic misuse. Additionally, patients with BN experience body image disturbance, where their self-evaluation is unduly affected by weight and body shape concerns. Bulimia nervosa typically begins in late adolescence or young adulthood. Patients either are typically of normal weight or are overweight. Physical examination and laboratory findings are typically normal; however, medical complications can include electrolyte disturbances, cardiac arrhythmia, and dental caries. Fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat BN. A nutritional consultation is another important component of care. Finally, cognitive behavioral therapy (CBT) and family therapy are the psychotherapies of choice.
A young boy with stool soiling
Authors: Czepiel Kathryn S.
Published: June 2021

Encopresis is an elimination disorder in which an individual has recurrent passage of feces into inappropriate places such as their clothing or the floor that is not due to the physiological effects of a substance or another medical condition aside from constipation. The child must be at least four years of age or the equivalent developmental level. The most common cause of functional encopresis is constipation with overflow incontinence. It typically occurs in children between the ages of five and 10 years. It often occurs during points of childhood transition, for example, when the child starts school. A medical history and physical examination by a pediatrician or pediatric gastroenterologist are required to rule out gastrointestinal or other causes of encopresis. The primary treatment of encopresis is treatment of constipation through the use of laxatives and dietary modifications. Behavioral therapy may also be necessary to help break the cycle of stool withholding.
An adolescent with new-onset inattention
Authors: Taylor Samantha M. , Beckmann David L.
Published: June 2021

Cannabis use disorder is defined as a pattern of use that includes at least two signs or symptoms of problematic use. Cannabis is the second most commonly used psychoactive substance by adolescents. Cannabis use is associated with significant impairments in multiple cognitive domains, although even one week of abstinence can result in improved cognitive functioning. Cannabis use, particularly of products containing high concentrations of tetrahydrocannabinol (THC), increases the likelihood of developing schizophrenia. N-acetylcysteine (NAC) may be helpful for decreasing cravings and the risk of relapse. The most effective therapy modalities for cannabis use disorder are motivational enhancement therapy, contingency management, cognitive behavioral therapy (CBT), and family-based therapy.
Confusion and mental status changes in a medically ill child
Authors: Thom Robyn P.
Published: June 2021

Delirium is an acute, transient syndrome of global brain dysfunction that is the pathophysiological consequence of an underlying medical condition or toxic exposure. It affects 13% to 44% of hospitalized children. Signs and symptoms of delirium include disturbances in attention, awareness, and cognition that develop over a short period of time and fluctuate in severity. Patients with suspected delirium should undergo a physical examination and laboratory investigation to determine potential underlying medical etiologies. The primary treatment of delirium is identification and management of the underlying medical condition. Antipsychotics may be used to manage symptoms that threaten safety or impede the provision of medical care. Children with delirium may also benefit from supportive psychotherapy, involvement with child-life specialists, and other stress reduction strategies.
Detection of the cyanomidyl radical (HNCN): a new interstellar species with the NCN backbone
Authors: Rivilla V M , Jiménez-Serra I , García de la Concepción J , Martín-Pintado J , Colzi L , Rodríguez-Almeida L F , Tercero B , Rico-Villas F , Zeng S , Martín S , Requena-Torres M A , de Vicente P
Published: June 2021

We report here the first detection in the interstellar medium of the cyanomidyl radical (HNCN). Using the Yebes 40m and the IRAM 30m telescopes, we have targeted the doublets of the N = 2–1, 4–3, 5–4, 6–5, and 7–6 transitions of HNCN towards the molecular cloud G+0.693-0.027. We have detected three unblended lines of HNCN, these are the N = 6–5 doublet and one line of the N = 4–3 transition. Additionally, we present one line of the N = 5–4 transition partially blended with emission from other species. The local thermodynamic equilibrium best fit to the data gives a molecular abundance of (0.91 ± 0.05) × 10−10 with respect to H2. The relatively low abundance of this species in G+0.693-0.027 and its high reactivity suggest that HNCN is possibly produced by gas-phase chemistry. Our work shows that this highly reactive molecule is present in interstellar space, and thus it represents a plausible precursor of larger prebiotic molecules with the nitrogen–carbon–nitrogen backbone such as cyanamide (NH2CN), carbodiimide (HNCNH), and formamidine (NH2CHNH).
Prehistoric Copper Mining in Europe
Authors: O'Brien William
Published: June 2021

This volume examines prehistoric copper mining in Europe, from the first use of the metal eight thousand years ago in the Balkans to its widespread adoption during the Bronze Age. The history of research is examined, as is the survival of this mining archaeology in different geological settings. There is information on the technological processes of mineral prospecting, ore extraction, and metal production, as well as the logistics and organization of this activity and its environmental impact. The analysis is broadened to consider the economic and societal context of prehistoric copper mining and the nature of the distinctive communities involved. The study is based on a review of field data and research produced over many decades by the collaboration of archaeologists and geologists in a number of different countries, and covers such famous mining centres as the Mitterberg in Austria, Kargaly in Russia, the Great Orme in Wales, and those in Cyprus, from where the name of this metal derives. These regional studies are brought together for the first time to present a remarkable story of human endeavour and innovation, which marks a new stage in the mastery of our natural resources.
Assessing the Performance of Australian Federalism in Responding to the Pandemic
Authors: Murphy Julian R , Arban Erika
Published: June 2021

This article provides a comprehensive evaluation of the federalism-implicated aspects of Australia’s response to the COVID-19 pandemic. The article’s research question is: to what extent was Australia’s federal structure responsible for the relative successes and failures of the national pandemic response? The method chosen to answer this question is largely theoretical, supplemented by aspects of institutional and policy analysis. That is to say, the inquiry identifies what were widely considered to be important policies, and considers the extent to which the formulation and implementation of those policies was furthered or hindered by the institutions and relations forming Australia’s federal structure. Five policy areas are considered, namely: the National Cabinet; social distancing and related policies; international travel and quarantine; interstate travel; and cities and local government. The conclusions reached are that a number of policy responses achieved federalism’s objectives of enhancing local decision-making power, increasing state and federal cooperation, and cabining policy failure. While Australia’s was not an unmitigated success story, on the whole the pandemic galvanized and reinvigorated Australia’s federal structure and institutions.
Orbitofrontal cortex connectivity is associated with food reward and body weight in humans
Authors: Rolls Edmund T , Feng Ruiqing , Cheng Wei , Feng Jianfeng
Published: June 2021

The aim was to investigate with very large-scale analyses whether there are underlying functional connectivity differences between humans that relate to food reward and whether these in turn are associated with being overweight. In 37 286 humans from the UK Biobank, resting-state functional connectivities of the orbitofrontal cortex (OFC), especially with the anterior cingulate cortex, were positively correlated with the liking for sweet foods (False Discovery Rate (FDR) P < 0.05). They were also positively correlated with the body mass index (BMI) (FDR P < 0.05). Moreover, in a sample of 502 492 people, the ‘liking for sweet foods’ was correlated with their BMI (r = 0.06, P < 10−125). In a cross-validation with 545 participants from the Human Connectome Project, a higher functional connectivity involving the OFC relative to other brain areas was associated with a high BMI (≥30) compared to a mid-BMI group (22–25; P = 6 × 10−5), and low OFC functional connectivity was associated with a low BMI (≤20.5; P < 0.024). It is proposed that a high BMI relates to increased efficacy of OFC food reward systems and a low BMI to decreased efficacy. This was found with no stimulation by food, so may be an underlying individual difference in brain connectivity that is related to food reward and BMI.
Metric variation in the postcranial skeleton of ostriches,Struthio(Aves: Palaeognathae), with new data on extinct subspecies
Authors: Elzanowski Andrzej , Louchart Antoine
Published: June 2021

As a result of numerous fossil and subfossil finds of ostriches, there is great demand for a comprehensive osteometric dataset for the living species and subspecies of the genus Struthio. We meet this demand by providing a set of > 100 measurements for a sample of 18 sexed skeletons, including all living and recently extinct species and subspecies of ostriches. We provide the first mensural data for two extinct subspecies, the hitherto questioned Struthio camelus spatzi from north-western Africa and the Arabian ostrich, Struthio camelus syriacus. The unique skeletal proportions of S. c. spatzi, with a relatively short wing, broad pelvis, short tarsometatarsus and big third toe, confirm the validity of this taxon and suggest an increased stability at the expense of cursoriality, which might have contributed to its extermination by humans. Our biometric analysis of the entire sample suggests a subtle sexual dimorphism in the ostrich skeleton, with females having more robust limb bones (especially wider and/or deeper at the ends) despite being on average smaller than males. If confirmed by further research, this size-independent dimorphism might reflect the independent regulation of the longitudinal and transverse dimensions of bones as revealed by several independent studies of morphological integration (covariance among morphological traits) in the avian skeleton.
Evaluation of the Inhibitory Effects of Wuyiencin, a Secondary Metabolite of Streptomyces albulus CK-15, Against Sclerotinia sclerotiorum In Vitro
Authors: Yang Miaoling , Zhang Wei , Lv Zhaoyang , Shi Liming , Zhang Kecheng , Ge Beibei
Published: June 2021

Sclerotinia sclerotiorum (Lib.) de Bary, a destructive fungal pathogen with an extensive host range, causes various diseases with the potential to cause huge economic losses to crops worldwide. Streptomyces species produce secondary metabolites with variable structures and biological activities that offer possible control methods for crop diseases. Herein, we evaluated the inhibitory effects of wuyiencin, a secondary metabolite of Streptomyces albulus CK-15, against S. sclerotiorum. The results showed that wuyiencin markedly inhibited mycelial growth and germination and the formation of sclerotia. It also increased cell membrane permeability, resulting in leakage of intracellular substances in pathogen mycelia. Wuyiencin markedly decreased oxalic acid content and the activities of polygalacturonase and pectin methyl-galacturonic enzymes. Moreover, it downregulated Nox1, ITL, pph1, Caf1, and sca1, all genes related to growth and infection. Lesions were smaller and less pronounced on soybean (Glycine max [L.] Merr.) leaves pretreated with wuyiencin in vitro, and the inhibition rate reached 78.36%. The results suggest that wuyiencin holds promise for the management of diseases caused by S. sclerotiorum, and the findings provide clues on the mechanism of action.
The Role of EPAs in Creating a National System of Time-Variable Competency-Based Medical Education
Authors: Karpinski Jolanta , Frank Jason R.
Published: June 2021

Entrustable professional activities (EPAs) have emerged as a meaningful framework for achieving competency-based medical education (CBME). However, little is known about how to adapt EPAs to large-scale, multispecialty, system-wide implementations. The authors describe the design and experience of creating such a system based on EPAs and the Van Melle Core Components Framework for all accredited training programs under the auspices of the Royal College of Physicians and Surgeons of Canada. The resulting design is a unique configuration and use of EPAs, called Royal College EPAs. Others looking to implement EPAs for large-scale health professions education systems may want to consider this design approach.
Revisiting the Core Entrustable Professional Activities for Entering Residency
Authors: Amiel Jonathan M. , Andriole Dorothy A. , Biskobing Diane M. , Brown David R. , Cutrer William B. , Emery Matthew T. , Mejicano George C. , Ryan Michael S. , Swails Jennifer L. , Wagner Dianne P.
Published: June 2021

The Core EPAs for Entering Residency Pilot project aimed to test the feasibility of implementing 13 entrustable professional activities (EPAs) at 10 U.S. medical schools and to gauge whether the use of the Core EPAs could improve graduates’ performance early in residency. In this manuscript, the authors (members of the pilot institutions and Association of American Medical Colleges staff supporting the project evaluation) describe the schools’ capacity to collect multimodal evidence about their students’ performance in each of the Core EPAs and the ability of faculty committees to use those data to make decisions regarding learners’ readiness for entrustment. In reviewing data for each of the Core EPAs, the authors reflected on how each activity performed as an EPA informed by how well it could be assessed and entrusted. For EPAs that did not perform well, the authors examined whether there are underlying practical and/or theoretical issues limiting its utility as a measure of student performance in medical school.
Does Cervical Alignment Matter? The Effect of 2-level Anterior Cervical Discectomy and Fusion on Sagittal Alignment and Patient-reported Outcomes
Authors: Quek Clara X. , Goh Graham S. , Soh Reuben C.C.
Published: June 2021

Study Design:

Retrospective review of prospectively collected data.

Objective:

This study aimed to determine the change in cervical sagittal balance following 2-level anterior cervical discectomy and fusion (ACDF) and whether the degree of change was associated with improvement in patient-reported outcomes (PROs).

Summary of Background Data:

Sagittal balance in cervical spine surgery has been recognized as an important surgical goal. However, its influence on clinical outcomes following anterior decompressive procedures remains debatable.

Materials and Methods:

Patients who underwent primary 2-level ACDF for cervical spondylotic radiculopathy and/or myelopathy were identified from an institutional spine registry. Radiographic measurements were done preoperatively, postoperatively, and at minimum 24 months follow-up. Measurements comprised segmental lordosis (SL), C2−C7 cervical lordosis (CL), C2−C7 sagittal vertical axis, C7 slope (C7S), T1 slope (T1S) and C7 slope minus cervical lordosis (C7S−CL). Disk heights were measured preoperatively and postoperatively. PROs including the Neck Disability Index, Short Form-36, and Visual Analog Scale for neck pain and arm pain were collected preoperatively and at 24 months postoperatively.

Results:

In total, 90 patients were included. Mean follow-up was 58.6±22.9 months. Significant improvement in all PROs was achieved at 24 months (P<0.05). SL was −1.2±8.2 degrees preoperatively, increased to 5.2±5.9 degrees postoperatively (P<0.001), and decreased to 1.2±6.2 degrees at follow-up (P=0.005). CL was 8.5±12.5 degrees preoperatively, increased to 10.8±12.4 degrees postoperatively (P=0.018), and maintained at 10.9±11.2 degrees at follow-up (P=0.030). Sagittal vertical axis, C7S, T1S, and C7S−CL did not change significantly. Significant increases in disk heights were achieved postoperatively (P<0.001). Fusion rate was 98.9% at follow-up. PROs were not related to radiologic measurements. Maintaining or increasing CL or SL was not related to a greater degree of improvement in PROs.

Conclusions:

Two-level ACDF restored segmental and global CL, but changes in cervical sagittal alignment did not correlate with the magnitude of improvement in PROs. Adequate decompression with solid fusion remains fundamental to achieving good clinical outcomes in patients with degenerative cervical disease.
Identifiability and Estimation Under the Test-negative Design With Population Controls With the Goal of Identifying Risk and Preventive Factors for SARS-CoV-2 Infection
Authors: Schnitzer Mireille E. , Harel Daphna , Ho Vikki , Koushik Anita , Merckx Joanna
Published: June 2021

Owing to the rapidly evolving coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, quick public health investigations of the relationships between behaviors and infection risk are essential. Recently the test-negative design (TND) was proposed to recruit and survey participants who are symptomatic and being tested for SARS-CoV-2 infection with the goal of evaluating associations between the survey responses (including behaviors and environment) and testing positive on the test. It was also proposed to recruit additional controls who are part of the general population as a baseline comparison group to evaluate risk factors specific to SARS-CoV-2 infection. In this study, we consider an alternative design where we recruit among all individuals, symptomatic and asymptomatic, being tested for the virus in addition to population controls. We define a regression parameter related to a prospective risk factor analysis and investigate its identifiability under the two study designs. We review the difference between the prospective risk factor parameter and the parameter targeted in the typical TND where only symptomatic and tested people are recruited. Using missing data directed acyclic graphs, we provide conditions and required data collection under which identifiability of the prospective risk factor parameter is possible and compare the benefits and limitations of the alternative study designs and target parameters. We propose a novel inverse probability weighting estimator and demonstrate the performance of this estimator through simulation study.
A (Flexible) Synthetic Control Method for Count Data and Other Nonnegative Outcomes
Authors: Bonander Carl
Published: June 2021

The synthetic control method is a covariate balancing method that exploits data from untreated regions to construct a synthetic control that approximates a single, aggregate treatment unit on a time series of preintervention outcomes and covariates. The method is increasingly being used to evaluate population-level interventions in epidemiology. Although the original version can be used with bounded outcomes, it imposes strong constraints on the balancing weights to ensure that the counterfactuals are based solely on interpolation. This feature, while attractive from a causal inference perspective, is sometimes too conservative and can lead to unnecessary bias due to poor covariate balance. Alternatives exist that allow for extrapolation to improve balance but existing procedures may produce negative estimates of the counterfactual outcomes and are therefore inappropriate for count data. We propose an alternative way to allow for extrapolation, although ensuring that the estimated counterfactuals remain nonnegative. Following a related proposal, we add a penalty to the balancing procedure that favors interpolation over extrapolation whenever possible. As we demonstrate theoretically and using empirical examples, our proposal can serve as a useful alternative when existing approaches yield demonstrably poor or unrealistic counterfactuals. Finally, we provide functions to implement the method in R.
Effects of oral versus transdermal estradiol plus micronized progesterone on thyroid hormones, hepatic proteins, lipids, and quality of life in menopausal women with hypothyroidism: a clinical trial
Authors: Kaminski Juliana , Junior Cleo Mesa , Pavesi Helena , Drobrzenski Beatriz , Amaral Gisah M. do
Published: June 2021

Objective:

The aim of the study was to evaluate the effects of usual doses of oral estradiol with transdermal estradiol and the effects of these estrogens plus micronized progesterone (MP) in menopausal women with primary hypothyroidism.

Methods:

Twenty women were randomized to 12 weeks of treatment with estradiol 1 mg tablets or estradiol 1 mg gel. Then, women with a uterus received a 100 mg capsule of oral MP. Thyroid function, thyroxine-binding globulin (TBG), sex hormone-binding globulin (SHBG), insulin-like growth factor 1 (IGF-1), lipid profiles, and quality of life were measured at baseline and after 12 and 24 weeks.

Results:

Oral estradiol led to an increase in total T4 levels (5.84 ± 1.11 vs 8.41 ± 1.61 μg/dL; P < 0.001); changes in thyroid-stimulating hormone (TSH) levels were clinically important in 3 of 10 participants who needed to increase their dose of levothyroxine. Significant changes were detected in hepatic proteins with oral estradiol: TBG and SHBG levels increased (15.29 ± 3.87 vs 20.84 ± 5.49 μg/mL, P < 0.001; 61.85 ± 33.6 vs 121.4 ± 49.36 nmol/L, P < 0.001; respectively), whereas IGF-1 levels decreased (152 ± 38.91 vs 96 ± 17.59 ng/mL; P < 0.001). Transdermal estradiol alone did not significantly affect the thyroid function. Transdermal estradiol plus MP led to a decrease in TSH levels (1.79 ± 1.05 vs 1.09 ± 0.52 mIU/L; P = 0.04), while total T4 levels increased (7.54 ± 1.34 vs 9.95 ± 2.24 μg/dL; P = 0.01). Hormonal therapy had a greater impact on depressed mood and vasomotor symptoms.

Conclusions:

Total T4 and TBG levels increase after oral estradiol in women with hypothyroidism and it may cause clinical changes in TSH levels. Conversely, transdermal estradiol alone or plus MP does not cause major changes in thyroid function in these women.

Video Summary:

http://links.lww.com/MENO/A783.
COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell Lymphoma
Authors: Gaitzsch Erik , Passerini Verena , Khatamzas Elham , Strobl Carolin D. , Muenchhoff Maximilian , Scherer Clemens , Osterman Andreas , Heide Michael , Reischer Anna , Subklewe Marion , Leutbecher Alexandra , Tast Benjamin , Ruhle Adrian , Weiglein Tobias , Stecher Stephanie-Susanne , Stemmler Hans J. , Dreyling Martin , Girl Philipp , Georgi Enrico , Wölfel Roman , Mateyka Laura , D’Ippolito Elvira , Schober Kilian , Busch Dirk H. , Kager Juliane , Spinner Christoph D. , Treiber Matthias , Rasch Sebastian , Lahmer Tobias , Iakoubov Roman , Schneider Jochen , Protzer Ulrike , Winter Christof , Ruland Jürgen , Quante Michael , Keppler Oliver T. , von Bergwelt-Baildon Michael , Hellmuth Johannes , Weigert Oliver
Published: June 2021

The clinical and immunological impact of B-cell depletion in the context of coronavirus disease 2019 (COVID-19) is unclear. We conducted a prospectively planned analysis of COVID-19 in patients who received B-cell depleting anti-CD20 antibodies and chemotherapy for B-cell lymphomas. The control cohort consisted of age- and sex-matched patients without lymphoma who were hospitalized because of COVID-19. We performed detailed clinical analyses, in-depth cellular and molecular immune profiling, and comprehensive virological studies in 12 patients with available biospecimens. B-cell depleted lymphoma patients had more severe and protracted clinical course (median hospitalization 88 versus 17 d). All patients actively receiving immunochemotherapy (n = 5) required ICU support including long-term mechanical ventilation. Neutrophil recovery following granulocyte colony stimulating factor stimulation coincided with hyperinflammation and clinical deterioration in 4 of the 5 patients. Immune cell profiling and gene expression analysis of peripheral blood mononuclear cells revealed early activation of monocytes/macrophages, neutrophils, and the complement system in B-cell depleted lymphoma patients, with subsequent exacerbation of the inflammatory response and dysfunctional interferon signaling at the time of clinical deterioration of COVID-19. Longitudinal immune cell profiling and functional in vitro assays showed SARS-CoV-2-specific CD8+ and CD4+ T-effector cell responses. Finally, we observed long-term detection of SARS-CoV-2 in respiratory specimens (median 84 versus 12 d) and an inability to mount lasting SARS-CoV-2 antibody responses in B-cell depleted lymphoma patients. In summary, we identified clinically relevant particularities of COVID-19 in lymphoma patients receiving B-cell depleting immunochemotherapies.
The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell Disease
Authors: Delgado Julio , Voltz Caroline , Stain Milena , Lapveteläinen Tuomo , Urach Susanne , Lähteenvuo Johanna , Penttilä Karri , Gisselbrecht Christian , Enzmann Harald , Pignatti Francesco
Published: June 2021

Crizanlizumab is a monoclonal antibody that binds to P-selectin. On October 28, 2020, a conditional marketing authorization valid through the European Union (EU) was issued for crizanlizumab for the prevention of recurrent vaso-occlusive crises (VOCs) in patients with sickle cell disease aged 16 years or older. Crizanlizumab was evaluated in a phase 2, double-blind, placebo-controlled randomized multicenter trial comparing high-dose (5 mg/kg) crizanlizumab, low-dose (2.5 mg/kg) crizanlizumab and placebo in patients with a history of 2–10 VOCs in the previous year. Patients who were receiving concomitant hydroxycarbamide (HC) as well as those not receiving HC were included in the study. The primary endpoint of the trial was the annual rate of sickle cell-related pain crises as adjudicated by a central review committee. High-dose crizanlizumab led to a 45.3% lower median annual rate of sickle cell-related pain crises compared to placebo (P = 0.010), with no statistically significant difference for the low dose. Treatment with high-dose crizanlizumab led to similar incidences of adverse events (AEs), grade 3 AEs, and serious AEs compared to placebo. Most frequently observed AEs that occurred more often in the crizanlizumab arm compared to placebo were infusion related reactions (34.8% versus 21%), arthralgia (18.2% versus 8.1%), diarrhea (10.6% versus 3.2%), and nausea (18.2% versus 11.3%). The aim of this article is to summarize the scientific review of the application leading to regulatory approval in the EU.
Trajectories of Function and Symptom Change in Desvenlafaxine Clinical Trials
Authors: Zilcha-Mano Sigal , Wang Xuemei , Wajsbrot Dalia B. , Boucher Matthieu , Fine Stuart A. , Rutherford Bret R.
Published: June 2021

Purpose/Background

Heterogeneity has been documented in trajectories of symptom change during antidepressant treatment for major depressive disorder (MDD). It is unclear whether distinct trajectories of change exist for functioning during antidepressant treatment.

Methods/Procedures

This analysis explored distinct trajectories of functioning in MDD and tested whether they corresponded to trajectories of symptom change. Data were from 4317 patients and were pooled from 9 randomized placebo-controlled trials. Growth mixture modeling was used to identify trajectories of Hamilton Rating Scale for Depression (HRSD) and Sheehan Disability Scale (SDS) for placebo- and desvenlafaxine-treated patients.

Findings/Results

Three trajectories were identified for symptoms (HRSD) in patients receiving placebo (mean reduction baseline to week 8, −18.4 [most favorable] to −2.6 points [least favorable]). Four HRSD trajectories were identified for patients receiving desvenlafaxine (mean reduction from baseline to week 8, −17.2 [most favorable] to −2.6 points [least favorable]). Four trajectories were identified for functioning (SDS) in patients receiving placebo (mean reduction baseline to week 8, −13.6 [most favorable] to −0.8 points [least favorable]), and 3 for desvenlafaxine (−12.8 to −1.4 points, respectively). Percentages of agreement between most favorable HRSD and SDS trajectories were 75% (placebo) and 85% (desvenlafaxine), and for least favorable trajectories were 88% (placebo) and 80% (desvenlafaxine).

Implications/Conclusions

Distinct trajectories of change based on symptoms and functioning were identified among patients with MDD receiving desvenlafaxine and among patients with MDD receiving placebo. Differentiating subpopulations of patients has the potential to provide a more personalized treatment of patients with MDD.

ClinicalTrials.gov
Identifiers: NCT00072774; NCT00277823; NCT00300378; NCT00384033; NCT00798707; NCT00863798; NCT01121484; NCT00824291; NCT01432457.
Predicting Unplanned Health Care Utilization and Cost
Authors: Kinsky Suzanne , Liang Qingfeng , Bellon Johanna , Helwig Amy , McCracken Polly , Minnier Tamra , Thirumala Parthasarathy D. , Hanmer Janel
Published: June 2021

Objectives:

There is little literature describing if and how payers are utilizing patient-reported outcomes to predict future costs. This study assessed if Patient-reported Outcomes Measurement Information System (PROMIS) domain scores, collected in routine practice at neurology clinics, improved payer predictive models for unplanned care utilization and cost.

Study Design:

Retrospective cohort analysis of private Health Plan-insured patients with visits at 18 Health Plan-affiliated neurology clinics.

Methods:

PROMIS domains (Anxiety v1.0, Cognitive Function Abilities v2.0, Depression v1.0, Fatigue v1.0, Pain Interference v1.0, Physical Function v2.0, Sleep Disturbance v1.0, and Ability to Participate in Social Roles and Activities v2.0) are collected as part of routine care. Data from patients’ first PROMIS measures between June 27, 2018 and April 16, 2019 were extracted and combined with claims data. Using (1) claims data alone and (2) PROMIS and claims data, we examined the association of covariates to utilization (using a logit model) and cost (using a generalized linear model). We evaluated model fit using area under the receiver operating characteristic curve (for unplanned care utilization), akaike information criterion (for unplanned care costs), and sensitivity and specificity in predicting top 15% of unplanned care costs.

Results:

Area under the receiver operating curve values were slightly higher, and akaike information criterion values were similar, for PROMIS plus claims covariates compared with claims alone. The PROMIS plus claims model had slightly higher sensitivity and equivalent specificity compared with claims-only models.

Conclusion:

One-time PROMIS measure data combined with claims data slightly improved predictive model performance compared with claims alone, but likely not to an extent that indicates improved practical utility for payers.
Distinctions Between Self-Report and Performance-Based Measures of Physical Function in Older Patients Prior to Chemotherapy
Authors: Torstveit Ann Helen , Løyland Borghild , Grov Ellen Karine , Guren Marianne , Paul Steven M. , Ritchie Christine , Vistad Ingvild , Miaskowski Christine , Utne Inger
Published: June 2021

Background

The maintenance of physical function (PF) is an extremely important outcome for elderly people.

Objective

The aims of this study were to identify differences in the subjective and objective measures of PF between younger older adults (YOAs, 60-69 years of age) and older adults (OA, ≥70 years of age), to compare the PF scores with age-matched samples from the general population, and to evaluate for associations between the subjective and objective measures of PF.

Methods

Patients (n = 139) were assessed using subjective (ie, European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire) and objective (ie, Short Physical Performance Battery [SPPB]) measures prior to chemotherapy (CTX). Data were analyzed using parametric and nonparametric tests.

Results

No differences were found between the 2 age groups in any of the subjective or objective measures of PF. Compared with the age-matched general population, both YOAs and OAs had significantly lower scores in both measures of PF. Large effect sizes were found for differences in European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire role function, SPPB balance, and SPPB total scores between the YOA group and the age-matched general population samples. Correlations between the subjective and objective measures were low.

Conclusions

Older patients with cancer have lower PF than their age-matched general population prior to CTX. Longitudinal studies are warranted to evaluate for changes in PF during and following CTX.

Implications for Practice

Nurses need to perform routine assessments of PF in older oncology patients prior to CTX. Our findings suggest that SPPB gait speed may be a useful screening measure for PF in older patients.
MIBG Uptake in Pancreas as a Normal Variant
Authors: Wang Yu , Yang Xu , Wang Wei , Yang Jigang
Published: June 2021

A 5-year-old girl with high-risk neuroblastoma underwent 123I-MIBG scintigraphy for disease restaging. The whole-body images showed a faint MIBG uptake in the midabdomen. Abdominal SPECT/CT demonstrated the focus locating in the pancreatic head. However, this activity disappeared on delayed acquisition at 6-hour later. Follow-up MIBG scan after 6 months did not show the abnormal MIBG uptake in the pancreatic head. Delayed scan could be helpful for differential diagnosis.
Transoral Endoscopic Plating for Orbital Blowout Fractures
Authors: Abba Michael , Abramson Alex , Nahlieli Oded
Published: June 2021

Orbital fractures account for up to 40% of craniofacial injuries. In this article, the authors present the transoral endoscopy-assisted plating technique for treating orbital blowout fractures (OBF). A retrospective analysis of 56 cases treated with transoral endoscopy-assisted approach was performed. Immediate versus delayed surgery decision-making was performed by using our 2-week algorithm. The surgical technique included only transoral incisions, forced duction and “pulse” tests, osteotomy, endoscopic inspections, the reduction with a curved elevator and an indwelling balloon, the retrieval of prolapsed fatty tissue back into the orbit, removal of sharp bony fragments, adaptation of the titanium mesh to the orbital floor and its fixation with screws to stable bony structures, reattachment of the osteotomized lateral wall, and postoperative computed tomography (CT) scan with 3D CT reconstruction. The overall success rate of surgeries was 96%. The resolution of comorbidities resulted in a normal globe position, normal eye movement, and the resolution of diplopia. Postoperative complications were insignificant with one case of surgical edema and one case of infection and sequestration that appeared six months after surgery. These results remained unchanged after 20 to 24 months of follow-up. The suggested minimally invasive transoral technique can be effectively implemented in cases of OBF as well as in cases when the medial wall of the orbit is involved. Our results presented a high success rate with minimal rate of complications, thus our technique is a safe way with minimal morbidity for treating OBF.
Paradoxical Temporal Enlargement: An Expansion of Superficial Temporal Fat Pad Following Interfacial Technique for Pterional Craniotomy
Authors: Krug Randall G. , Kuruoglu Doga , Yan Maria , Van Gompel Jamie J. , Morris Jonathan M. , Kamath Marielle J. , Graffeo Christopher S. , Sharaf Basel
Published: June 2021

Objective:

Contour irregularities in the temporal region have been reported previously after procedures involving temporal dissection. In this study, we report paradoxical temporal enlargement (PTE) following interfascial pterional craniotomy.

Methods:

A retrospective review of patients who underwent a unilateral transcranial procedure with frontotemporal approach at our institution between September 2013 and December 2017 was performed. Patients with a previous craniotomy or bilateral craniotomy were excluded. Radiological imaging series including computed tomography and magnetic resonance imaging were utilized to calculate temporal soft tissue volumes both preoperatively and postoperatively by using advanced software technology. Relative soft tissue volume differences between the operative side and the contralateral side were calculated at different time-points including preoperative, 3-months follow-up (3M), 12-months (12M) follow-up, and the last follow-up (LFU, over 1-year).

Results:

Forty-three patients were included. Mean age was 52.7 ± 4.5 years. Mean follow-up was 27.9 ± 15.8 months. Significant changes of temporal fat pad relative-volume difference were observed between the preoperative and the corresponding 3M (t [82] = −2.8865, P = 0.0050); 12M (t [77] = −4.4321, P < 0.0001), and LFU (t [74] = −4.9862, P < 0.0001) postoperative time points. No significant change of the temporalis muscle was observed between the preoperative and the corresponding 3M (P = 0.3629), 12M (P = 0.1553), or LFU (P = 0.0715). Soft tissue volume showed a significant increase on the operative side between the preoperative and the corresponding LFU (t [74] = −2.5866, P =  0.0117).

Conclusions:

Paradoxical temporal enlargement with more than 10% volumetric change was observed in 24% of the patients at their LFU (>1-year). This change was not due to temporalis muscle changes. Paradoxical temporal enlargement was due to hypertrophy of the superficial temporal fat pad. Before surgical correction of postoperative temporal contour changes, it is important to obtain imaging and characterize the etiology of the deformity.
Outcomes of the First Virtual General Surgery Certifying Exam of the American Board of Surgery
Authors: Chen Herbert , Tseng Jennifer F. , Chaer Rabih , Spain David A. , Stewart John H. , Dent Daniel , Ibáñez Beatriz , Barry Carol L. , Jones Andrew T. , Buyske Jo
Published: June 2021

Objective:

To Study the Outcomes of the First Virtual General Surgery Certifying Exam of the American Board of Surgery.

Summary of Background Data:

The ABS General Surgery CE is normally an in-person oral examination. Due to the COVID-19 outbreak, the ABS was required to reschedule these. After 2 small pilots, the CE's October administration represented the first large-scale remote virtual exam. The purpose of this report is to compare the outcomes of this virtual and the previous in-person CEs.

Methods:

CE candidates were asked to provide feedback on their experience via a survey. The passing rate was compared to the 1025 candidates who took the 2019–2020 in-person CEs.

Results:

Of the 308 candidates who registered for the virtual CE, 306 completed the exam (99.4%) and 188 completed the survey (61.4%). The majority had a very positive experience. They rated the virtual CE as very good/excellent in security (90%), ease of exam platform (77%), audio quality (71%), video quality (69%), and overall satisfaction (86%). Notably, when asked their preference, 78% preferred the virtual exam. There were no differences in the passing rates between the virtual or in-person exams.

Conclusions:

The first virtual CE by the ABS was completed using available internet technology. There was high satisfaction, with the majority preferring the virtual platform. Compared to past in-person CEs, there was no difference in outcomes as measured by passing rates. These data suggest that expansion of the virtual CE may be desirable.
Liver Transplantation in the Time of a Pandemic
Authors: MacConmara Malcolm , Wang Benjamin , Patel Madhukar S. , Hwang Christine S. , DeGregorio Lucia , Shah Jigesh , Hanish Steven I. , Desai Dev , Lynch Raymond , Tanriover Bekir , Zeh Herbert , Vagefi Parsia A.
Published: June 2021

Objective:

During the initial wave of the COVID-19 pandemic, organ transplantation was classified a CMS Tier 3b procedure which should not be postponed. The differential impact of the pandemic on access to liver transplantation was assessed.

Summary Background Data:

Disparities in organ access and transplant outcomes among vulnerable populations have served as obstacles in liver transplantation.

Methods:

Using UNOS STARfile data, adult waitlisted candidates were identified from March 1, 2020 to November 30, 2020 (n = 21,702 pandemic) and March 1, 2019 to November 30, 2019 (n = 22,797 pre-pandemic), and further categorized and analyzed by time periods: March to May (Period 1), June to August (Period 2), and September to November (Period 3). Comparisons between pandemic and pre-pandemic groups included: Minority status, demographics, diagnosis, MELD, insurance type, and transplant center characteristics. Liver transplant centers (n = 113) were divided into tertiles by volume (small, medium, large) for further analyses. Multivariable logistic regression was fitted to assess odds of transplant. Competing risk regression was used to predict probability of removal from the waitlist due to transplantation or death and sickness. Additional temporal analyses were performed to assess changes in outcomes over the course of the pandemic.

Results:

During Period 1 of the pandemic, Minorities showed greater reduction in both listing (−14% vs −12% Whites), and transplant (−15% vs −7% Whites), despite a higher median MELD at transplant (23 vs 20 Whites, P < 0.001). Of candidates with public insurance, Minorities demonstrated an 18.5% decrease in transplants during Period 1 (vs −8% Whites). Although large programs increased transplants during Period 1, accounting for 61.5% of liver transplants versus 53.4% pre-pandemic (P < 0.001), Minorities constituted significantly fewer transplants at these programs during this time period (27.7% pandemic vs 31.7% pre-pandemic, P = 0.04). Although improvements in disparities in candidate listings, removals, and transplants were observed during Periods 2 and 3, the adjusted odds ratio of transplant for Minorities was 0.89 (95% CI 0.83–0.96, P = 0.001) over the entire pandemic period.

Conclusions:

COVID-19's effect on access to liver transplantation has been ubiquitous. However, Minorities, especially those with public insurance, have been disproportionately affected. Importantly, despite the uncertainty and challenges, our systems have remarkable resiliency, as demonstrated by the temporal improvements observed during Periods 2 and 3. As the pandemic persists, and the aftermath ensues, health care systems must consciously strive to identify and equitably serve vulnerable populations.