Publications by authors named "Michael Weiß"

493 Publications

Adult provider perspectives on transition and transfer to adult care: A multi-specialty, multi-institutional exploration.

J Pediatr Nurs 2021 Apr 28;59:173-180. Epub 2021 Apr 28.

Children's Health of Orange County, Orange, CA, United States of America.

Purpose: To identify barriers that transcend multiple adult care specialties and identify potential solutions.

Design And Methods: Twenty-one adult care providers practicing in the specialty areas of internal medicine, family medicine, gastroenterology, endocrinology, and neurology participated in one of six semi-structured focus group interviews. Data were coded and analyzed according to the Socio-ecological Model of Adolescent/Young Adult Readiness for Transition (SMART).

Results: Three themes and one subtheme emerged from the data. These fell within the beliefs/expectations, knowledge, access/insurance, and relationships (subtheme) domains of the SMART model. Family beliefs/expectations regarding the provider role, difficulty accessing reliable information, and limited access to mental health and behavioral providers reportedly affect providers' ability to provide optimal health care.

Conclusions: Adult providers identified several barriers affecting their ability to care for newly transferred patients. Increased education of families and improved methods of communication between providers were recommended. Barriers related to access and insurance are common and require larger systems-level collaborations between health care systems and payor sources.

Practical Implications: Some recommendations (e.g., educating families on the distinct roles of the PCP vs. specialist, highlighting new treatment opportunities in adult care, conveying trust and endorsing the new provider), represent concrete steps pediatric providers can immediately take to improve transfer. Other steps will require forging bridges across the pediatric and adult care world to expand patient access to medical, mental health, and behavioral services.
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http://dx.doi.org/10.1016/j.pedn.2021.04.017DOI Listing
April 2021

Sporadic inclusion body myositis and primary Sjogren's syndrome: an overlooked diagnosis.

Clin Rheumatol 2021 Apr 21. Epub 2021 Apr 21.

Department of Medicine, Division of Rheumatology, University of Washington, Seattle, WA, USA.

Sporadic inclusion body myositis (sIBM) has been reported to occur in association with autoimmune diseases and in particular, primary Sjogren's syndrome (pSS). This brief report describes patients identified with a positive SSA antibody and diagnosis of sIBM at a large academic medical center over a 13.5-year period. A cohort identification tool was used to identify patients with positive SSA antibody and a diagnosis of sIBM between January 1, 2006 and June 1, 2019. All cases of sIBM had diagnostic confirmation by a neuromuscular specialist. Demographics, clinical features, autoantibodies, MRI and EMG findings, and muscle biopsy features were reviewed for each identified case. Eight patients were found to carry the diagnosis of pSS and sIBM. Two additional sIBM patients were SSA antibody positive without other pSS features. The mean time from initial symptom onset of muscle weakness to diagnosis was 5.4 years (range 1-15 years). All patients had alternative diagnoses offered for their myopathic symptoms prior to sIBM identification. The NT5c1A antibody was positive in 7 of 8 patients tested. No patient had a durable response to immunosuppressive therapy. The diagnosis of sIBM went unrecognized for over 5 years in our cohort of SSA antibody-positive patients with myopathy. The patients in this cohort were treated with a variety of immunosuppressive agents prior to diagnosis without benefit. Recognizing the clinical features of sIBM in patients with pSS is crucial in instituting appropriate therapy and avoiding unnecessary immunosuppression. Key Points • Sporadic inclusion body myositis (sIBM) can be associated with Sjogren's syndrome. • In this case series, prevalence of the NT5c1A antibody was higher among patients with associated Sjogren's syndrome compared to the cited prevalence of the NT5c1A antibody in patients with isolated sIBM. • It is crucial to consider sIBM in patients with Sjogren's syndrome presenting with motor weakness in order to avoid unnecessary immunosuppression and institute appropriate therapy.
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http://dx.doi.org/10.1007/s10067-021-05740-5DOI Listing
April 2021

Diabetes mellitus due to toxic misfolding of proinsulin variants.

Mol Metab 2021 Apr 3:101229. Epub 2021 Apr 3.

Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address:

Background: Dominant mutations in the human insulin gene (INS) lead to pancreatic β-cell dysfunction and diabetes mellitus (DM) due to toxic misfolding of a mutant proinsulin. Analogous to a classical mouse model of monogenic DM ("Akita"), this syndrome highlights the susceptibility of β-cells to endoreticulum (ER) stress due to protein misfolding and aberrant aggregation.

Scope Of Review: Diverse clinical mutations directly or indirectly perturb native disulfide pairing. Whereas most introduce or remove a cysteine (Cys; leading in either case to an unpaired thiol group), non-Cys-related mutations identify key determinants of folding efficiency. Studies of such mutations suggest that the hormone's evolution has been constrained not only by structure-function relationships but also by the susceptibility of its single-chain precursor to impaired foldability. An intriguing hypothesis posits that INS overexpression in response to peripheral insulin resistance likewise leads to chronic ER stress and β-cell dysfunction in the natural history of nonsyndromic Type 2 DM.

Major Conclusions: Cryptic contributions of conserved residues to folding efficiency, as uncovered by rare genetic variants, define molecular links between biophysical principles and the emerging paradigm of Darwinian medicine: Biosynthesis of proinsulin at the edge of nonfoldability provides a key determinant of "diabesity" as a pandemic disease of civilization.
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http://dx.doi.org/10.1016/j.molmet.2021.101229DOI Listing
April 2021

Dual trocar laparoscopy improves reduced-port surgery of the distal pancreas.

Minim Invasive Ther Allied Technol 2021 Apr 2:1-7. Epub 2021 Apr 2.

Department of Surgery, Saint John of God Hospital, Teaching Hospital of the Paracelsus Medical University Salzburg, Salzburg, Austria.

Background: The technical feasibility of transumbilical single-incision surgery (SIL) for pancreatic resections has been demonstrated. However, this technique is hampered by the limited degrees of freedom for instrument handling. Dual-incision laparoscopy (DIL) with an additional trocar may simplify dissection and allow drainage.

Material And Methods: Between December 2009 and May 2017, 21 patients were treated with SIL (12/2009 to 01/2014) or DIL (02/2014 to 05/2017) pancreatic resection. All data were collected in a database and retrospectively analysed.

Results: Demographic parameters of the patients did not differ significantly in the DIL or the SIL group. No conversion to open surgery was required. No intraoperative complication occurred in either group. The surgical difficulty score was significantly higher in the SIL group (4.4 ± 1.56 vs 2.18 ± 1.95;  = .006). Postoperative serum amylase levels were higher (101.9 U/l ± 50.11 vs 48.91 U/l ± 35.20;  = .01) and return to normal levels (6.4 ± 9.66 days vs 2.09 ± 1.98 days;  = .045) was later in the SIL group. Three complications requiring radiological or surgical intervention were witnessed in the SIL group and one complication in the DIL group ( = .42).

Conclusion: DIL surgery is a safe and feasible alternative to SIL surgery, facilitating key steps of distal pancreatic tail resection.
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http://dx.doi.org/10.1080/13645706.2021.1904263DOI Listing
April 2021

SARS-CoV-2 Acquisition and Immune Pathogenesis Among School-Aged Learners in Four K-12 Schools.

medRxiv 2021 Mar 26. Epub 2021 Mar 26.

Objectives: To directly measure SARS-CoV-2 infection in diverse schools with either remote or onsite learning.

Methods: 4 schools participated. Schools A and B served low-income Hispanic learners, school C special needs, and all three provided predominantly remote instruction. School D served middle and upper-middle income, White learners, with predominantly onsite instruction. 320 learners [10.5±2.1(SD); 7-17 y.o.]; 86% had phlebotomy. Testing occurred early in the fall (2020), at lower levels of COVID-19, and 6-8 weeks later during the fall-winter surge (tenfold increase in COVID-19 cases).

Results: Nasal RT-qPCR for SARS-CoV-2 and 21 respiratory pathogens was performed. Phlebotomy was obtained for circulating immunity. Face covering and physical distancing fidelity was measured by direct observation. 17 learners were SARS-CoV-2 positive during the surge. School A (97% remote) had the highest infection rate (9/70, 12.9%, p<0.01) and IgG positivity rate (13/70, 18.6%). School D had the lowest infection and IgG positive rate (1/86, 1.2%). Mitigation compliance [physical distancing (mean 87.4%) and face covering (91.3%)] was high at all schools. Learners with documented SARS-CoV-2 infection had neutralizing antibodies (94.7%), broad and robust IFN-γ+ T cell responses, reduced frequencies of monocytes, and lower levels of circulating inflammatory mediators.

Conclusions: Infection in the schools reflected regional rates rather than remote or onsite learning modalities. Schools can implement successful mitigation strategies across a wide range of income, school-type, and student diversity. Reduced monocyte and immune mediator concentrations coupled with robust humoral and cellular immunity may explain the generally milder symptoms in school-aged children.

Table Of Contents Summary: SARS-CoV-2 infection and immunobiology was measured in children at 4 diverse schools with varying degrees of onsite and remote learning.

What’s Known On This Subject: At the start of the COVID-19 pandemic, schools were reflexively closed as there were fears that agreggation of school-aged children would lead to increased infection. Infectivity and immunobiology of SARS-CoV-2 in children attending schools not understood.

What This Study Adds: School-associated infections reflected regional rates rather than remote or onsite learning. Successful mitigation was implemented across a diverse range of schools. Reduced immune mediator concentrations coupled with robust humoral and cellular immunity may explain the milder symptoms in school-aged children.
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http://dx.doi.org/10.1101/2021.03.20.21254035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010744PMC
March 2021

Prevalence and Factors Associated With Statin Use Among Patients With Nonalcoholic Fatty Liver Disease in the TARGET-NASH Study.

Clin Gastroenterol Hepatol 2021 Mar 26. Epub 2021 Mar 26.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. Electronic address:

Patients with nonalcoholic fatty liver disease (NAFLD) are at an increased risk of cardiovascular disease. Hydoxy-3-methyglutaryl-coenzyme reductase inhibitors, statins, reduce the risk of cardiovascular events. Studies have shown that statins are safe among patients with liver disease, including those with compensated cirrhosis, and their use is associated with lower mortality, hepatic decompensation, and possibly hepatocellular carcinoma. Despite these data, statins are under prescribed among patients with liver disease due to concerns about hepatotoxicity. This study aimed to assess prevalence and patient factors associated with indicated statin use in patients with NAFLD in a real-world cohort.
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http://dx.doi.org/10.1016/j.cgh.2021.03.031DOI Listing
March 2021

Invasive Treatments for Low Back Disorders.

J Occup Environ Med 2021 Apr;63(4):e215-e241

American College of Occupational and Environmental Medicine, Elk Grove Village, Illinois.

Objective: This abbreviated version of the American College of Occupational and Environmental Medicine's Low Back Disorders guideline reviews the evidence and recommendations developed for invasive treatments used to manage low back disorders.

Methods: Comprehensive systematic literature reviews were accomplished with article abstraction, critiquing, grading, evidence table compilation, and guideline finalization by a multidisciplinary expert panel and extensive peer-review to develop evidence-based guidance. Consensus recommendations were formulated when evidence was lacking and often relied on analogy to other disorders for which evidence exists. A total of 47 high-quality and 321 moderate-quality trials were identified for invasive management of low back disorders.

Results: Guidance has been developed for the invasive management of acute, subacute, and chronic low back disorders and rehabilitation. This includes 49 specific recommendations.

Conclusion: Quality evidence should guide invasive treatment for all phases of managing low back disorders.
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http://dx.doi.org/10.1097/JOM.0000000000001983DOI Listing
April 2021

The modularity of a social group does not affect the transmission speed of a novel, socially learned behaviour, or the formation of local variants.

Proc Biol Sci 2021 Mar 24;288(1947):20202614. Epub 2021 Mar 24.

Department of Psychology, University of Exeter, Exeter EX4 4QG, UK.

The structure of a group is critical in determining how a socially learnt behaviour will spread. Predictions from theoretical models indicate that specific parameters of social structure differentially influence social transmission. Modularity describes how the structure of a group or network is divided into distinct subgroups or clusters. Theoretical modelling indicates that the modularity of a network will predict the rate of behavioural spread within a group, with higher modularity slowing the rate of spread and facilitating the establishment of local behavioural variants which can prelude local cultures. Despite prolific modelling approaches, empirical tests via manipulations of group structure remain scarce. We experimentally manipulated the modularity of populations of domestic fowl chicks, to affect the transmission of a novel foraging behaviour. We compared the spread of behaviour in populations with networks of high or low modularity against control populations where social transmission was prevented. We found the foraging behaviour to spread socially between individuals when the social transmission was permitted; however, modularity did not increase the speed of behavioural spread nor lead to the initial establishments of shared behavioural variants. This result suggests that factors in the social transmission process additional to the network structure may influence behavioural spread.
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http://dx.doi.org/10.1098/rspb.2020.2614DOI Listing
March 2021

'Smart' insulin-delivery technologies and intrinsic glucose-responsive insulin analogues.

Diabetologia 2021 May 12;64(5):1016-1029. Epub 2021 Mar 12.

Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.

Insulin replacement therapy for diabetes mellitus seeks to minimise excursions in blood glucose concentration above or below the therapeutic range (hyper- or hypoglycaemia). To mitigate acute and chronic risks of such excursions, glucose-responsive insulin-delivery technologies have long been sought for clinical application in type 1 and long-standing type 2 diabetes mellitus. Such 'smart' systems or insulin analogues seek to provide hormonal activity proportional to blood glucose levels without external monitoring. This review highlights three broad strategies to co-optimise mean glycaemic control and time in range: (1) coupling of continuous glucose monitoring (CGM) to delivery devices (algorithm-based 'closed-loop' systems); (2) glucose-responsive polymer encapsulation of insulin; and (3) mechanism-based hormone modifications. Innovations span control algorithms for CGM-based insulin-delivery systems, glucose-responsive polymer matrices, bio-inspired design based on insulin's conformational switch mechanism upon insulin receptor engagement, and glucose-responsive modifications of new insulin analogues. In each case, innovations in insulin chemistry and formulation may enhance clinical outcomes. Prospects are discussed for intrinsic glucose-responsive insulin analogues containing a reversible switch (regulating bioavailability or conformation) that can be activated by glucose at high concentrations.
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http://dx.doi.org/10.1007/s00125-021-05422-6DOI Listing
May 2021

Hypertension in neonates treated with intravitreal bevacizumab for retinopathy of prematurity.

J Perinatol 2021 Mar 8. Epub 2021 Mar 8.

Department of Pediatrics, University of Florida, Gainesville, Fl, USA.

Objective: To investigate if preterm neonates developed systemic hypertension after intravitreal bevacizumab for retinopathy of prematurity.

Methods: Patients who received treatment between January 1, 2011 and January 31, 2019 were eligible for inclusion. Patients with pre-existing hypertension, congenital eye disease, or who were discharged within 72 h of treatment were excluded. Charts were reviewed for baseline data, co-morbidities, and the development of systemic hypertension within 4 weeks post treatment.

Results: After exclusions, 64 patients were analyzed. New-onset systemic hypertension was identified in 44 (69%) infants. There were no statistical differences in the demographic characteristics or presence of co-morbidities between the hypertensive and non-hypertensive groups. Of those who developed hypertension, the majority presented within the first week post treatment (55%).

Conclusions: The majority of infants who received intravitreal bevacizumab developed new-onset systemic hypertension after treatment. Further studies may explore hypertension as a potential side effect of bevacizumab in the neonatal population.
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http://dx.doi.org/10.1038/s41372-021-01021-wDOI Listing
March 2021

Umbralisib, a Dual PI3Kδ/CK1ε Inhibitor in Patients With Relapsed or Refractory Indolent Lymphoma.

J Clin Oncol 2021 Mar 8:JCO2003433. Epub 2021 Mar 8.

IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli," Bologna, Italy.

Purpose: Phosphatidylinositol-3-kinase (PI3K) inhibitors have shown activity in relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). PI3K inhibitors have been hampered by poor long-term tolerability and toxicity, which interfere with continuous use. Umbralisib, a dual inhibitor of PI3Kδ/casein kinase-1ε, exhibits improved selectivity for PI3Kδ compared with other PI3K inhibitors. This phase IIb trial was designed to evaluate the efficacy and safety of umbralisib in patients with R/R iNHL.

Patients And Methods: In this multicohort, open-label, phase IIb study, 208 patients with R/R marginal zone, follicular, or small lymphocytic lymphoma (MZL, FL, or SLL) unresponsive to prior treatments (≥ 1 MZL; ≥ 2 FL/SLL), including ≥ 1 anti-CD20-based therapy, were administered umbralisib 800 mg orally once daily until disease progression, unacceptable toxicity, or study withdrawal. Primary end point is overall response rate; secondary end points include time to response, duration of response, progression-free survival, and safety.

Results: The median follow-up is 27.7 months (efficacy) and 21.4 months (safety). The overall response rate was 47.1%, and tumor reduction occurred in 86.4% of patients. The median time to response was 2.7-4.6 months. The median duration of response was not reached for MZL, 11.1 months for FL, and 18.3 months for SLL. Median progression-free survival was not reached for MZL, 10.6 months for FL, and 20.9 months for SLL. At least one grade ≥ 3 treatment-emergent adverse event (TEAE) was reported in 53.4% of patients. TEAEs led to umbralisib discontinuation in 32 patients (15.4%). A total of 31 patients (14.9%) discontinued because of a treatment-related adverse event. Grade ≥ 3 TEAEs reported in ≥ 10% of patients: neutropenia (11.5%) and diarrhea (10.1%). Increased ALT/AST (grade ≥ 3) occurred in 6.7%/7.2% of patients.

Conclusion: Umbralisib achieved meaningful clinical activity in heavily pretreated patients with iNHL. The safety profile was manageable, with a relatively low incidence of immune-mediated toxicities and adverse event-related discontinuations.
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http://dx.doi.org/10.1200/JCO.20.03433DOI Listing
March 2021

Ublituximab plus ibrutinib versus ibrutinib alone for patients with relapsed or refractory high-risk chronic lymphocytic leukaemia (GENUINE): a phase 3, multicentre, open-label, randomised trial.

Lancet Haematol 2021 Apr 22;8(4):e254-e266. Epub 2021 Feb 22.

Sarah Cannon Research Institute, Nashville, TN, USA.

Background: Patients with chronic lymphocytic leukaemia and high-risk features have poorer outcomes on ibrutinib than those without high-risk features. The aim of this study was to assess the benefit of adding ublituximab, an anti-CD20 monoclonal antibody, to ibrutinib therapy in this population.

Methods: We did a randomised, phase 3, multicentre study (GENUINE) of patients aged 18 years or older with relapsed or refractory chronic lymphocytic leukaemia with at least one of 17p deletion, 11q deletion, or TP53 mutation, at 119 clinics in the USA and Israel. Eligible patients had received at least one previous chronic lymphocytic leukaemia therapy and had an Eastern Cooperative Oncology Group performance status of 2 or lower. We randomised patients (1:1) using permuted block randomisation with a block size of four and stratified by previous lines of therapy (one vs two or more) to receive ibrutinib alone or ibrutinib in combination with ublituximab. Treatment allocation was not masked to patients or investigators. Ibrutinib was given orally daily at 420 mg for all cycles. Ublituximab was given intravenously in 28-day cycles, with increasing doses during cycle 1 (≤150 mg on day 1, 750 mg on day 2, and 900 mg on days 8 and 15) and continuing at 900 mg on day 1 of cycles 2-6. After cycle 6, ublituximab was given at 900 mg every three cycles. The study was initially designed with co-primary endpoints of progression-free survival and overall response rate but due to protracted patient accrual, the protocol was amended to have a single primary endpoint of independent review committee-assessed overall response rate (defined as the proportion of patients who had a partial response, complete response, or complete response with incomplete marrow recovery according to the 2008 International Workshop on CLL criteria) in the intention-to-treat population. Safety was evaluated in the population of patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02301156, and the final analysis is presented.

Findings: 224 patients were assessed for eligibility, of whom 126 patients were enrolled and randomly assigned to receive ublituximab plus ibrutinib (n=64) or ibrutinib alone (n=62) between Feb 6, 2015, and Dec 19, 2016. After a median follow-up of 41·6 months (IQR 36·7-47·3), the overall response rate was 53 (83%) of 64 patients in the ublituximab plus ibrutinib group and 40 (65%) of 62 patients in the ibrutinib group (p=0·020). 117 patients, including 59 in the ublituximab plus ibrutinib group and 58 in the ibrutinib group, received at least one dose of treatment and were included in safety analyses. Most adverse events were grade 1 or 2. The most common grade 3 and 4 adverse events were neutropenia (11 [19%] patients in the ublituximab plus ibrutinib group and seven [12%] in the ibrutinib group), anaemia (five [8%] and five [9%]), and diarrhoea (six [10%] and three [5%]). The most common serious adverse events were pneumonia (six [10%] in the ublituximab plus ibrutinib group and four [7%] in the ibrutinib group), atrial fibrillation (four [7%] and one [2%]), sepsis (four [7%] and one [2%]), and febrile neutropenia (three [5%] and one [2%]). Two patients in the ublituximab plus ibrutinib group died due to adverse events (one cardiac arrest and one failure to thrive), neither of which were treatment-related. Five patients in the ibrutinib group died due to adverse events, including one cardiac arrest, one cerebral infarction, one intracranial haemorrhage, one Pneumocystis jirovecii pneumonia infection, and one unexplained death; the death due to cardiac arrest was considered to be treatment-related.

Interpretation: The addition of ublituximab to ibrutinib resulted in a statistically higher overall response rate without affecting the safety profile of ibrutinib monotherapy in patients with relapsed or refractory high-risk chronic lymphocytic leukaemia. These findings provide support for the addition of ublituximab to Bruton tyrosine kinase inhibitors for the treatment of these patients.

Funding: TG Therapeutics.
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http://dx.doi.org/10.1016/S2352-3026(20)30433-6DOI Listing
April 2021

Long-standing Multifocal Motor Neuropathy Presenting With Delayed Clinical Features of Anti-Myelin-Associated Glycoprotein Neuropathy and Elevated Anti-Myelin-Associated Glycoprotein Antibody Titers.

J Clin Neuromuscul Dis 2021 Mar;22(3):169-172

Department of Neurology, University of Washington Medical Center, Seattle, WA.

Abstract: Multifocal motor neuropathy with conduction block (MMN) and anti-myelin-associated glycoprotein (MAG) neuropathy are rare chronic acquired demyelinating neuropathies with distinct clinical and electrophysiological characteristics. These neuropathies are generally not known to coexist. This report describes a patient with long-standing MMN who subsequently developed clinical features of anti-MAG neuropathy. This suggests that subtypes of chronic inflammatory neuropathies may not be sharply defined. In addition, a presentation of MMN with anti-MAG titers may be a prognostic indicator of poor response to standard MMN treatment.
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http://dx.doi.org/10.1097/CND.0000000000000334DOI Listing
March 2021

Multicenter study of risk factors of unplanned 30-day readmissions in pediatric oncology.

Cancer Rep (Hoboken) 2021 Feb 2:e1343. Epub 2021 Feb 2.

Children's Hospital of Orange County, Orange, California, USA.

Background: Pediatric oncology patients have high rates of hospital readmission but there is a dearth of research into risk factors for unplanned 30-day readmissions among this high-risk population.

Aim: In this study, we built a statistical model to provide insight into risk factors of unplanned readmissions in this pediatric oncology.

Methods: We retrieved 32 667 encounters from 10 418 pediatric patients with a neoplastic condition from 16 hospitals in the Cerner Health Facts Database and built a mixed-effects model with patients nested within hospitals for inference on 75% of the data and reserved the remaining as an independent test dataset.

Results: The mixed-effects model indicated that patients with acute lymphoid leukemia (in relapse), neuroblastoma, rhabdomyosarcoma, or bone/cartilage cancer have increased odds of readmission. The number of cancer medications taken by the patient and the administration of chemotherapy were associated with increased odds of readmission for all cancer types. Wilms Tumor had a significant interaction with administration of chemotherapy, indicating that the risk due to chemotherapy is exacerbated in patients with Wilms Tumor. A second two-way interaction between recent history of chemotherapy treatment and infections was associated with increased odds of readmission. The area under the receiver operator characteristic curve (and corresponding 95% confidence interval) of the mixed-effects model was 0.714 (0.702, 0.725) on the independent test dataset.

Conclusion: Readmission risk in oncology is modified by the specific type of cancer, current and past administration of chemotherapy, and increased health care utilization. Oncology-specific models can provide decision support where model built on other or mixed population has failed.
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http://dx.doi.org/10.1002/cnr2.1343DOI Listing
February 2021

The Shift from Multiport to Single Port Increases the Amount of Bleeding in Laparoscopic Major Hepatectomy.

J Clin Med 2021 Jan 20;10(3). Epub 2021 Jan 20.

Surgical Department, St John of God Hospital, Teaching Hospital of the Paracelsus Medical University Salzburg, Kajetanerplatz 1, 5010 Salzburg, Austria.

Background: Bleeding is a negative outcome predictor in liver surgery. Reduction in the abdominal wall trauma in major hepatectomy is challenging but might offer possible benefits for the patient. This study was conducted to assess hemostasis techniques in single-port major hepatectomies (SP-MajH) as compared to multiport major hepatectomies (MP-MajH).

Methods: The non-randomized study comprised 34 SP-MajH in selected patients; 14 MP-MajH served as the control group. Intraoperative blood loss and number of blood units transfused served as the primary endpoints. Secondary endpoints were complications and oncologic five-year outcome.

Results: All resections were completed without converting to open surgery. Time for hepatectomy did not differ between SP-MajH and MP-MajH. Blood loss and number of patients with blood loss > 25 mL were significantly larger in MP-MajH ( = 0.001). In contrast, bleeding control was more difficult in SP-MajH, resulting in more transfusions ( = 0.008). One intestinal laceration (SP-MajH) accounted for the only intraoperative complication; 90-day mortality was zero. Postoperative complications were noted in total in 20.6% and 21.4% of patients for SP-MajH and MP-MajH, respectively. No incisional hernia occurred. During a median oncologic follow-up at 61 and 56 months (SP-MajH and MP-MajH), no local tumor recurrence was observed.

Conclusions: SP-MajH requires sophisticated techniques to ensure operative safety. Substantial blood loss requiring transfusion is more likely to occur in SP-MajH than in MP-MajH.
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http://dx.doi.org/10.3390/jcm10030374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863947PMC
January 2021

Weight Loss and Weight Regain in Usual Clinical Practice: Results From the TARGET-NASH Observational Cohort.

Clin Gastroenterol Hepatol 2021 Jan 21. Epub 2021 Jan 21.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. Electronic address:

First-line treatment for nonalcoholic fatty liver disease (NAFLD) focuses on weight loss through lifestyle modifications. Weight loss ≥5% results in reduction of steatosis and weight loss ≥10% has been associated with improvement in hepatic inflammation and fibrosis. The incidence and sustainability of weight loss among patients with NAFLD were estimated and associating factors identified.
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http://dx.doi.org/10.1016/j.cgh.2021.01.023DOI Listing
January 2021

The Impact of Telephonic Follow-Up Within 2 Business Days Postdischarge on 30-Day Readmissions for Patients With Heart Failure.

J Dr Nurs Pract 2021 Jan 19. Epub 2021 Jan 19.

Senior Health Economist-Populytics, Inc., Allentown, PA.

Background: Heart failure (HF) is a chronic condition associated with high rates of hospital readmissions. The prevalence and costs of HF are expected to rise dramatically by 2030 (Heidenreich,et al., 2013).

Objective: A 24-month, retrospective study was conducted using electronic medical record (EMR) chart review, seeking to identify if postdischarge follow-up phone calls decreased 30-day readmissions in individuals with HF.

Methods: The study included 705 adult participants who were admitted to the hospital for HF. Some received a postdischarge call within 2 business days of discharge, and some did not.

Results: Participants who received the postdischarge call were less likely to be readmitted (20.1%) than participants who did not receive a postdischarge call (28.8%; = .007). Participants who received the postdischarge call were more likely to have a follow-up visit within 14 days (70.1%) than participants who did not receive a postdischarge call (30.2%; < .001).

Conclusions: The findings from this study may help to drive future transitional care strategies for individuals diagnosed with HF.

Implications For Nursing: Nurse-led transitional care interventions offer potential solutions to ensure safe, effective hospital discharges.
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http://dx.doi.org/10.1891/JDNP-D-19-00079DOI Listing
January 2021

Enhanced Memory for Vocal Melodies in Autism Spectrum Disorder and Williams Syndrome.

Autism Res 2021 Jan 4. Epub 2021 Jan 4.

Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario, Canada.

Adults and children with typical development (TD) remember vocal melodies (without lyrics) better than instrumental melodies, which is attributed to the biological and social significance of human vocalizations. Here we asked whether children with autism spectrum disorder (ASD), who have persistent difficulties with communication and social interaction, and adolescents and adults with Williams syndrome (WS), who are highly sociable, even indiscriminately friendly, exhibit a memory advantage for vocal melodies like that observed in individuals with TD. We tested 26 children with ASD, 26 adolescents and adults with WS of similar mental age, and 26 children with TD on their memory for vocal and instrumental (piano, marimba) melodies. After exposing them to 12 unfamiliar folk melodies with different timbres, we required them to indicate whether each of 24 melodies (half heard previously) was old (heard before) or new (not heard before) during an unexpected recognition test. Although the groups successfully distinguished the old from the new melodies, they differed in overall memory. Nevertheless, they exhibited a comparable advantage for vocal melodies. In short, individuals with ASD and WS show enhanced processing of socially significant auditory signals in the context of music. LAY SUMMARY: Typically developing children and adults remember vocal melodies better than instrumental melodies. In this study, we found that children with Autistic Spectrum Disorder, who have severe social processing deficits, and children and adults with Williams syndrome, who are highly sociable, exhibit comparable memory advantages for vocal melodies. The results have implications for musical interventions with these populations.
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http://dx.doi.org/10.1002/aur.2462DOI Listing
January 2021

What Makes Musical Prodigies?

Front Psychol 2020 11;11:566373. Epub 2020 Dec 11.

Department of Psychology, International Laboratory for Brain, Music, and Sound Research, University of Montreal, Montreal, QC, Canada.

Musical prodigies reach exceptionally high levels of achievement before adolescence. Despite longstanding interest and fascination in musical prodigies, little is known about their psychological profile. Here we assess to what extent practice, intelligence, and personality make musical prodigies a distinct category of musician. Nineteen former or current musical prodigies (aged 12-34) were compared to 35 musicians (aged 14-37) with either an early (mean age 6) or late (mean age 10) start but similar amount of musical training, and 16 non-musicians (aged 14-34). All completed a Wechsler IQ test, the Big Five Inventory, the Autism Spectrum Quotient, the Barcelona Music Reward Questionnaire, the Dispositional Flow Scale, and a detailed history of their lifetime music practice. None of the psychological traits distinguished musical prodigies from control musicians or non-musicians except their propensity to report flow during practice. The other aspects that differentiated musical prodigies from their peers were the intensity of their practice before adolescence, and the source of their motivation when they began to play. Thus practice, by itself, does not make a prodigy. The results are compatible with multifactorial models of expertise, with prodigies lying at the high end of the continuum. In summary, prodigies are expected to present brain predispositions facilitating their success in learning an instrument, which could be amplified by their early and intense practice happening at a moment when brain plasticity is heightened.
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http://dx.doi.org/10.3389/fpsyg.2020.566373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759486PMC
December 2020

Effects of mexiletine on hyperexcitability in sporadic amyotrophic lateral sclerosis: Preliminary findings from a small phase II randomized controlled trial.

Muscle Nerve 2021 03 31;63(3):371-383. Epub 2020 Dec 31.

Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Background: To collect preliminary data on the effects of mexiletine on cortical and axonal hyperexcitability in sporadic amyotrophic lateral sclerosis (ALS) in a phase 2 double-blind randomized controlled trial.

Methods: Twenty ALS subjects were randomized to placebo and mexiletine 300 or 600 mg daily for 4 wk and assessed by transcranial magnetic stimulation and axonal excitability studies. The primary endpoint was change in resting motor threshold (RMT).

Results: RMT was unchanged with 4 wk of mexiletine (combined active therapies) as compared to placebo, which showed a significant increase (P = .039). Reductions of motor evoked potential (MEP) amplitude (P = .013) and accommodation half-time (P = .002), secondary outcome measures of cortical and axonal excitability, respectively, were also evident at 4 wk on mexiletine.

Conclusions: The relative stabilization of RMT in the treated subjects was unexpected and could be attributed to unaccounted sources of error or chance. However, a possible alternative cause is neuromodulation preventing an increase. The change in MEP amplitude and accommodation half-time supports the reduction of cortical and axonal hyperexcitability with mexiletine.
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http://dx.doi.org/10.1002/mus.27146DOI Listing
March 2021

Comparing head ultrasounds and susceptibility-weighted imaging for the detection of low-grade hemorrhages in preterm infants.

J Perinatol 2021 Apr 14;41(4):736-742. Epub 2020 Dec 14.

Department of Pediatrics, University of Florida, Gainesville, FL, USA.

Objective: Intraventricular hemorrhage (IVH) is a complication of prematurity. Grades III and IV IVH lead to significant morbidity, but mounting evidence shows low-grade IVH (grades I-II) may be associated with adverse sequelae. Head ultrasounds (HUS) are used to screen infants for IVH but may miss low-grade IVH. Our study compared the results of HUS around 7 days of age to susceptibility-weighted imaging (SWI) obtained at term-corrected age in infants born at <30 wGA.

Study Design: Infants <30 weeks gestational age (GA) with an HUS and MRI at admission to UF Health were identified by a retrospective chart review. Images were re-read by a pediatric neuroradiologist.

Results: Ninety-four infants with a mean GA of 25.8 weeks were identified. Of those with normal HUS, 50% had low-grade IVH on the term-corrected MRI.

Conclusions: HUS are effective for screening for high-grade IVH. SWI is more sensitive in identifying low-grade IVH.
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http://dx.doi.org/10.1038/s41372-020-00890-xDOI Listing
April 2021

Phase 2 Study of the Safety and Efficacy of Umbralisib in Patients with CLL Who Are Intolerant to BTK or PI3Kδ Inhibitor Therapy.

Blood 2020 Dec 1. Epub 2020 Dec 1.

Duke University Health System, Durham, North Carolina, United States.

Purpose: Intolerance is the most common reason for kinase inhibitor (KI) discontinuation in CLL. Umbralisib a novel, highly selective PI3Kδ/CK1ε inhibitor, is active and well tolerated in CLL patients. This phase 2 trial evaluated umbralisib in CLL patients who are intolerant to prior BTK or PI3K inhibitor therapy.

Patients And Methods: In this phase 2 trial (NCT02742090), umbralisib was initiated at 800 mg oral daily in CLL patients requiring therapy per investigator discretion who were intolerant to prior BTK or PI3K inhibitor therapy, until progression or toxicity. Primary endpoint was progression-free survival (PFS). Secondary endpoints included time to treatment failure and umbralisib safety profile. DNA isolated from buccal swabs was genotyped for polymorphisms in CYP3A4, CYP3A5 and CYP2D6.

Results: Fifty-one patients were enrolled (44 BTKi and 7 PI3Kδi intolerant). Median age was 70 years (range 48-96), median of 2 prior lines of therapy (1-7), 24% had del17p and/or TP53 mutation, and 65% were IGHV unmutated. Most common AEs leading to prior KI discontinuation were rash (27%), arthralgia (18%), and atrial fibrillation (16%). Median progression free survival (PFS) was 23.5 months (95% CI 13.1-not estimable). 58% of patients were on umbralisib for a longer duration than prior KI. Most common (≥5%) grade ≥3 AEs on umbralisib (all causality) were neutropenia (18%), leukocytosis (14%), thrombocytopenia (12%), pneumonia (12%), and diarrhea (8%). Six patients (12%) discontinued umbralisib due to an AE. Eight patients (16%) had dose reductions and were successfully re-challenged.

Conclusions: Umbralisib is safe and effective in this BTK and alternate PI3K inhibitor intolerant CLL population. These are the first prospective data to confirm that switching from a BTK or alternate PI3K inhibitor to umbralisib can result in durable, well tolerated responses.
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http://dx.doi.org/10.1182/blood.2020007376DOI Listing
December 2020

The singing voice is special: Persistence of superior memory for vocal melodies despite vocal-motor distractions.

Cognition 2020 Nov 24:104514. Epub 2020 Nov 24.

International Laboratory for Brain, Music, and Sound Research (BRAMS), University of Montreal, Montreal, Quebec, Canada.

Vocal melodies sung without lyrics (la la) are remembered better than instrumental melodies. What causes the advantage? One possibility is that vocal music elicits subvocal imitation, which could promote enhanced motor representations of a melody. If this motor interpretation is correct, distracting the motor system during encoding should reduce the memory advantage for vocal over piano melodies. In Experiment 1, participants carried out movements of the mouth (i.e., chew gum) or hand (i.e., squeeze a beanbag) while listening to 24 unfamiliar folk melodies (half vocal, half piano). In a subsequent memory test, they rated the same melodies and 24 timbre-matched foils from '1-Definitely New' to '7-Definitely Old'. There was a memory advantage for vocal over piano melodies with no effect of group and no interaction. In Experiment 2, participants carried out motor activities during encoding more closely related to singing, either silently articulating (la la) or vocalizing without articulating (humming continuously). Once again, there was a significant advantage for vocal melodies with no effect or interaction of group. In Experiment 3, participants audibly whispered (la la) repeatedly during encoding. Again, the voice advantage was present and did not differ appreciably from prior research with no motor task during encoding. However, we observed that the spontaneous phase-locking of whisper rate and musical beat tended to predict enhanced memory for vocal melodies. Altogether the results challenge the notion that subvocal rehearsal of the melody drives enhanced memory for vocal melodies. Instead, the voice may enhance engagement.
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http://dx.doi.org/10.1016/j.cognition.2020.104514DOI Listing
November 2020

Effect of Ezogabine on Cortical and Spinal Motor Neuron Excitability in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.

JAMA Neurol 2021 Feb;78(2):186-196

Department of Neurology, University of California Irvine, Irvine.

Importance: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the motor nervous system. Clinical studies have demonstrated cortical and spinal motor neuron hyperexcitability using transcranial magnetic stimulation and threshold tracking nerve conduction studies, respectively, although metrics of excitability have not been used as pharmacodynamic biomarkers in multi-site clinical trials.

Objective: To ascertain whether ezogabine decreases cortical and spinal motor neuron excitability in ALS.

Design, Setting, And Participants: This double-blind, placebo-controlled phase 2 randomized clinical trial sought consent from eligible participants from November 3, 2015, to November 9, 2017, and was conducted at 12 US sites within the Northeast ALS Consortium. Participants were randomized in equal numbers to a higher or lower dose of ezogabine or to an identical matched placebo, and they completed in-person visits at screening, baseline, week 6, and week 8 for clinical assessment and neurophysiological measurements.

Interventions: Participants were randomized to receive 600 mg/d or 900 mg/d of ezogabine or a matched placebo for 10 weeks.

Main Outcomes And Measures: The primary outcome was change in short-interval intracortical inhibition (SICI; SICI-1 was used in analysis to reflect stronger inhibition from an increase in amplitude) from pretreatment mean at screening and baseline to the full-dose treatment mean at weeks 6 and 8. The secondary outcomes included levels of cortical motor neuron excitability (including resting motor threshold) measured by transcranial magnetic stimulation and spinal motor neuron excitability (including strength-duration time constant) measured by threshold tracking nerve conduction studies.

Results: A total of 65 participants were randomized to placebo (23), 600 mg/d of ezogabine (23), and 900 mg/d of ezogabine (19 participants); 45 were men (69.2%) and the mean (SD) age was 58.3 (8.8) years. The SICI-1 increased by 53% (mean ratio, 1.53; 95% CI, 1.12-2.09; P = .009) in the 900-mg/d ezogabine group vs placebo group. The SICI-1 did not change in the 600-mg/d ezogabine group vs placebo group (mean ratio, 1.15; 95% CI, 0.87-1.52; P = .31). The resting motor threshold increased in the 600-mg/d ezogabine group vs placebo group (mean ratio, 4.61; 95% CI, 0.21-9.01; P = .04) but not in the 900-mg/d ezogabine group vs placebo group (mean ratio, 1.95; 95% CI, -2.64 to 6.54; P = .40). Ezogabine caused a dose-dependent decrease in excitability by several other metrics, including strength-duration time constant in the 900-mg/d ezogabine group vs placebo group (mean ratio, 0.73; 95% CI, 0.60 to 0.87; P < .001).

Conclusions And Relevance: Ezogabine decreased cortical and spinal motor neuron excitability in participants with ALS, suggesting that such neurophysiological metrics may be used as pharmacodynamic biomarkers in multisite clinical trials.

Trial Registration: ClinicalTrials.gov Identifier: NCT02450552.
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http://dx.doi.org/10.1001/jamaneurol.2020.4300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684515PMC
February 2021

Evolution of insulin at the edge of foldability and its medical implications.

Proc Natl Acad Sci U S A 2020 11 5;117(47):29618-29628. Epub 2020 Nov 5.

Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106;

Proteins have evolved to be foldable, and yet determinants of foldability may be inapparent once the native state is reached. Insight has emerged from studies of diseases of protein misfolding, exemplified by monogenic diabetes mellitus due to mutations in proinsulin leading to endoplasmic reticulum stress and β-cell death. Cellular foldability of human proinsulin requires an invariant Phe within a conserved crevice at the receptor-binding surface (position B24). Any substitution, even related aromatic residue Tyr, impairs insulin biosynthesis and secretion. As a seeming paradox, a monomeric Tyr insulin analog exhibits a native-like structure in solution with only a modest decrement in stability. Packing of Tyr is similar to that of Phe, adjoining core cystine B19-A20 to seal the core; the analog also exhibits native self-assembly. Although affinity for the insulin receptor is decreased ∼20-fold, biological activities in cells and rats were within the range of natural variation. Together, our findings suggest that the invariance of Phe among vertebrate insulins and insulin-like growth factors reflects an essential role in enabling efficient protein folding, trafficking, and secretion, a function that is inapparent in native structures. In particular, we envision that the -hydroxyl group of Tyr hinders pairing of cystine B19-A20 in an obligatory on-pathway folding intermediate. The absence of genetic variation at B24 and other conserved sites near this disulfide bridge-excluded due to β-cell dysfunction-suggests that insulin has evolved to the edge of foldability. Nonrobustness of a protein's fitness landscape underlies both a rare monogenic syndrome and "diabesity" as a pandemic disease of civilization.
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http://dx.doi.org/10.1073/pnas.2010908117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703552PMC
November 2020

["Crazy bitch!"-Experienced aggression and violence in the daily clinical routine of pediatricians].

Monatsschr Kinderheilkd 2020 Oct 16:1-9. Epub 2020 Oct 16.

Klinik für Kinder- und Jugendmedizin, Kinderkrankenhaus Amsterdamer Straße, Amsterdamer Str. 59, 50735 Köln, Deutschland.

Background: The indications for experienced aggression and violence towards doctors in children's hospitals are increasing and are the focus of this study. They are reported in contact with parents or relatives in emotionally highly charged situations caused by their child's illness. This empirical study investigated the extent to which experienced aggressive and violent behavior has been received by pediatricians in their everyday work in hospitals.

Methods: Data from two previously unpublished nationwide surveys in 2009 ( = 160) and 2017 ( = 190) were analyzed. Using the same questionnaire, the forms of aggressive action, such as exerting pressure, insulting, threatening physical violence, attempting to use violence and actually using violence as well as the descriptions of the associated situations were questioned. The wording of the insults and the type of threat could be specified via open questions.

Results: Approximately four out of five respondents said they have been the target of an aggressive action by parents or relatives. In 2017 approximately 3 out of 4 respondents (71.0%) considered the problem of aggressive behavior to be relevant to their everyday work compared to only every second respondent (51.9%) in 2009. Individual respondents reported up to 60 situations, in both survey waves at a median of 4.0 times per year.

Conclusion: Experienced aggression and violence are often and increasingly part of everyday clinical life in the pediatric wards, ranging from insults to physical violence. Prevention strategies, such as preventive training for communication and de-escalation are explicitly desired.
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http://dx.doi.org/10.1007/s00112-020-01034-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566583PMC
October 2020

Endocannabinoids and related lipids in serum from patients with amyotrophic lateral sclerosis.

Muscle Nerve 2021 01 3;63(1):120-126. Epub 2020 Nov 3.

Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA.

Background: The goals of this study were to determine whether serum concentrations of endocannabinoids (eCB) and related lipids predict disease status in patients with amyotrophic lateral sclerosis (ALS) relative to healthy controls, and whether concentrations correlate with disease duration and severity.

Methods: Serum concentrations of the eCBs 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA), and related lipids palmitoylethanolamine (PEA), oleoylethanolamine (OEA), and 2-oleoylglycerol (2-OG), were measured in samples from 47 patients with ALS and 19 healthy adults. Hierarchical binary logistic and linear regression analyses assessed whether lipid concentrations predicted disease status (ALS or healthy control), duration, or severity.

Results: Binary logistic regression revealed that, after controlling for age and gender, 2-AG, 2-OG and AEA concentrations were unique predictors of the presence of ALS, demonstrating odds ratios of 0.86 (P = .039), 1.03 (P = .023), and 42.17 (P = .026), respectively. When all five lipids and covariates (age, sex, race, ethnicity, body mass index, presence of a feeding tube) were included, the resulting model had an overall classification accuracy of 92.9%. Hierarchical linear regression analyses indicated that in patients with ALS, AEA and OEA inversely correlated with disease duration (P = .030 and .031 respectively), while PEA demonstrated a positive relationship with disease duration (P = .013). None of the lipids examined predicted disease severity.

Conclusions: These findings support previous studies indicating significant alterations in concentrations of circulating lipids in patients with ALS. They suggest that arachidonic and oleic acid containing small lipids may serve as biomarkers for identifying the presence and duration of this disease.
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http://dx.doi.org/10.1002/mus.27096DOI Listing
January 2021

Unusual Distribution Kinetics of Gadoxetate in Healthy Human Subjects Genotyped for OATP1B1: Application of Population Analysis and a Minimal Physiological-Based Pharmacokinetic Model.

J Clin Pharmacol 2021 Apr 20;61(4):506-514. Epub 2020 Oct 20.

Department of Clinical Pharmacology, Center of Drug Absorption and Transport (C_DAT), University Medicine, Greifswald, Germany.

Gadoxetate (Gd-EOB-DTPA) is a hepatobiliary-specific contrast agent for magnetic resonance imaging. Using a minimal physiological-based pharmacokinetic (PBPK) model, it has been shown for the first time, that the rapid initial decline of plasma concentration after intravenous injection is the result of an uptake into hepatocytes rather than of a distribution into the extravascular extracellular space. About 50% of the steady-state distribution volume is related to hepatic uptake. The hepatic extraction ratio and hepatic clearance estimated based on the liver model as a part of the PBPK model were in accordance with literature data. The same holds for the predicted time course of the amount of gadoxetate in liver parenchyma. In elucidating the impact of OATP1B1 genotype (*1a/*1a and *15/*15) on the pharmacokinetics of gadoxetate, we found that tissue uptake and back-transfer rates were significantly reduced, whereas the hepatic sinusoidal efflux rate was significantly increased in carriers of the *15/*15 haplotype compared with those of the *1a/*1a (wild type). The model is potentially useful for determining hepatic kinetic parameters and distribution properties of drugs.
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http://dx.doi.org/10.1002/jcph.1762DOI Listing
April 2021

Race, Ethnicity, and Insurance: the Association with Opioid Use in a Pediatric Hospital Setting.

J Racial Ethn Health Disparities 2020 Sep 30. Epub 2020 Sep 30.

Department of Psychology, Chapman University, Orange, CA, 92866, USA.

Background: This study examined the association between race/ethnicity and health insurance payer type with pediatric opioid and non-opioid ordering in an inpatient hospital setting.

Methods: Cross-sectional inpatient encounter data from June 2013 to June 2018 was retrieved from a pediatric children's hospital in Southern California (N = 55,944), and statistical analyses were performed to determine associations with opioid ordering.

Results: There was a significant main effect of race/ethnicity on opioid and non-opioid orders. Physicians ordered significantly fewer opioid medications, but a greater number of non-opioid medications, for non-Hispanic African American children than non-Hispanic Asian, Hispanic/Latinx, and non-Hispanic White pediatric patients. There was also a main effect of health insurance payer type on non-opioid orders. Patients with government-sponsored plans (e.g., Medi-Cal, Medicare) received fewer non-opioid prescriptions compared with patients with both HMO and PPO coverage. Additionally, there was a significant race/ethnicity by insurance interaction on opioid orders. Non-Hispanic White patients with "other" insurance coverage received the greatest number of opioid orders. In non-Hispanic African American patients, children with PPO coverage received fewer opioids than those with government-sponsored and HMO insurance. For non-Hispanic Asian patients, children with PPO were prescribed more opioids than those with government-sponsored and HMO coverage.

Conclusion: Findings suggest that the relationship between race/ethnicity, insurance type, and physician decisions opioid prescribing is complex and multifaceted. Given that consistency in opioid prescribing should be seen regardless of patient background characteristics, future studies should continue to assess and monitor unequitable differences in care.
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http://dx.doi.org/10.1007/s40615-020-00882-9DOI Listing
September 2020

A Phase 2, Double-Blind, Randomized, Dose-Ranging Trial Of In Patients With ALS.

Amyotroph Lateral Scler Frontotemporal Degener 2021 05 24;22(3-4):287-299. Epub 2020 Sep 24.

Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.

Objective: To evaluate safety, dose response, and preliminary efficacy of over 12 weeks in patients with amyotrophic lateral sclerosis (ALS). Patients (≤2 years since diagnosis) with slow upright vital capacity (SVC) of ≥60% were randomized 1:1:1:1 to 150, 300, or 450 mg twice daily (bid) or placebo; active treatment was 12 weeks with 4-week follow-up. Primary endpoint was change in percent predicted SVC at 12 weeks; secondary measures included ALS Functional Rating Scale-Revised (ALSFRS-R) and muscle strength mega-score. Patients ( = 458) were enrolled; 85% completed 12-week treatment. The primary analysis failed to reach statistical significance ( = 0.11); secondary endpoints showed no statistically significant effects (ALSFRS-R,  = 0.09; muscle strength mega-score,  = 0.31). Post hoc analyses pooling all active -treated patients compared against placebo showed trends toward benefit in all endpoints (progression rate for SVC, ALSFRS-R, and muscle strength mega-score (nominal p values of 0.10, 0.01 and 0.20 respectively)). was well tolerated, with nausea and fatigue being the most common side effects. A dose-dependent decrease in estimated glomerular filtration rate was noted, and transaminase elevations were seen in approximately 5% of patients. Both hepatic and renal abnormalities trended toward resolution after study drug discontinuation. Although the primary efficacy analysis did not demonstrate statistical significance, there were trends favoring for all three endpoints, with effect sizes generally regarded as clinically important. Tolerability was good; modest hepatic and renal abnormalities were reversible. The impact of on patients with ALS should be assessed in a pivotal Phase 3 trial. (ClinicalTrials.gov Identifier: NCT03160898).
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http://dx.doi.org/10.1080/21678421.2020.1822410DOI Listing
May 2021