Leveraging telehealth supportive oncology services to combat COVID-19 isolation in breast cancer patients: A cancer center’s perspective

During the COVID-19 pandemic, breast cancer patient in-person visits were converted to telehealth visits. Given our concerns about increased isolation amongst breast cancer patients during the pandemic, and the deleterious effects of such isolation on patient outcomes, we investigated utilization rates of psycho-social services amongst newly diagnosed breast cancer patients at our institution. We explored visit platforms (telehealth versus in-person) and time points prior to and encompassing the early pandemic. Despite decreased new breast cancer visits, there was a greater than 2-fold increase in supportive oncology service encounters in breast cancer patients during COVID-19 suggesting increased need for psycho-oncology resources. While services had not been offered virtually prior to the pandemic, the majority of the supportive oncology visits were conducted via telehealth during the initial months (73%) and year (59%) of the pandemic. 89% of breast cancer patients accessing psycho-social services were in-state patients, and service utilization increased amongst rural and urban residents during the pandemic. Total numbers of rural patients receiving supportive oncology services remained low compared to numbers of urban patients, however, though virtual visits predominated. While the number of out-of-state patients accessing psycho-oncology services during the pandemic was low, there was a 5-fold increase in psycho-social service utilization in this group during the pandemic. The majority of these visits were in-person. Telehealth services can be used to extend psycho-social support to breast cancer patients and combat the experience of isolation exacerbated by the pandemic. Virtual visits can be further utilized to increase outreach to rural and out-of-state patients. Experience Framework This article is associated with the Innovation & Technology lens of The Beryl Institute Experience Framework (https://theberylinstitute.org/experience-framework/). Access other PXJ articles related to this lens. Access other resources related to this lens

A Year of Gastrointestinal Bleeding: An Epidemiologic Study

Background: For decades the diagnosis and management of gastrointestinal bleeding (GIB) has been based largely on endoscopy. Studying a large cohort of patients presenting to the ED we may find cost-effective alternatives in the management of GIB. We analyzed the epidemiology and initial disposition of all patients who presented to our ED from the perspective of hematemesis versus non-hematemesis, to identify patterns among each cohort’s presentations to aid in this. Methods: Retrospective analysis of medical records for 338 patients presenting to the UMass ED. Two cohorts were identified: those with hematemesis (G1) or non-hematemesis (G2). Results: 105 patients presented to the ED with hematemesis (G1), 233 patients presented with non-hematemesis GIB (G2). G1 was younger than G2 (54.4 years vs. 65.6 years, p\u3c0.001). There were more males in G1 vs. G2 (61% vs. 53%, p=0.154). Comorbities in G1 were liver disease (21%), alcohol abuse (20%), and diabetes (11%). Comorbities in G2 were coronary artery disease (22%), atrial fibrillation (13.7%), and diverticulosis (8%). More patients in G2 than G1 used Coumadin (23% vs. 7%, p\u3c0.001), anti-platelet agents (12% and 3%, p\u3c0.004), and NSAIDs (40% and 32%y, p=0.203). Admission hematocrit was greater in G1 compared to G2 (34.1 vs. 30.0, p\u3c0.001). INR was greater in G2 compared to G1 (1.7 vs. 1.3, p=0.03). BUN was greater in G2 compared to G1 (30.2 vs. 23.6, p=0.021). More patients in G2 were admitted compared to G1 (89.6% vs. 78.1%, p=0.019). More were admitted to the ICU in G1 compared to G2 (46% vs. 38%, p=0.237).Discussion: This study uses a novel approach that elicits different patterns than the traditional delineation of upper versus lower GIB. These results may lead to new decision-making in patients presenting with GIB, allowing for new diagnostic and management paradigms, resulting in cost-effective care

Mild orotic aciduria in UMPS heterozygotes: a metabolic finding without clinical consequences

BACKGROUND: Elevated urinary excretion of orotic acid is associated with treatable disorders of the urea cycle and pyrimidine metabolism. Establishing the correct and timely diagnosis in a patient with orotic aciduria is key to effective treatment. Uridine monophosphate synthase is involved in de novo pyrimidine synthesis. Uridine monophosphate synthase deficiency (or hereditary orotic aciduria), due to biallelic mutations in UMPS, is a rare condition presenting with megaloblastic anemia in the first months of life. If not treated with the pyrimidine precursor uridine, neutropenia, failure to thrive, growth retardation, developmental delay, and intellectual disability may ensue. METHODS AND RESULTS: We identified mild and isolated orotic aciduria in 11 unrelated individuals with diverse clinical signs and symptoms, the most common denominator being intellectual disability/developmental delay. Of note, none had blood count abnormalities, relevant hyperammonemia or altered plasma amino acid profile. All individuals were found to have heterozygous alterations in UMPS. Four of these variants were predicted to be null alleles with complete loss of function. The remaining variants were missense changes and predicted to be damaging to the normal encoded protein. Interestingly, family screening revealed heterozygous UMPS variants in combination with mild orotic aciduria in 19 clinically asymptomatic family members. CONCLUSIONS: We therefore conclude that heterozygous UMPS-mutations can lead to mild and isolated orotic aciduria without clinical consequence. Partial UMPS-deficiency should be included in the differential diagnosis of mild orotic aciduria. The discovery of heterozygotes manifesting clinical symptoms such as hypotonia and developmental delay are likely due to ascertainment bias

Diversity and dynamics of a widespread bloom of the toxic dinoflagellate Alexandrium fundyense

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 6 (2011): e22965, doi:10.1371/journal.pone.0022965.Historically, cosmopolitan phytoplankton species were presumed to represent largely unstructured populations. However, the recent development of molecular tools to examine genetic diversity have revealed differences in phytoplankton taxa across geographic scales and provided insight into the physiology and ecology of blooms. Here we describe the genetic analysis of an extensive bloom of the toxic dinoflagellate Alexandrium fundyense that occurred in the Gulf of Maine in 2005. This bloom was notable for its intensity and duration, covering hundreds of kilometers and persisting for almost two months. Genotypic analyses based on microsatellite marker data indicate that the open waters of the northeastern U.S. harbor a single regional population of A. fundyense comprising two genetically distinct sub-populations. These subpopulations were characteristic of early- and late-bloom samples and were derived from the northern and southern areas of the bloom, respectively. The temporal changes observed during this study provide clear evidence of succession during a continuous bloom and show that selection can act on the timescale of weeks to significantly alter the representation of genotypes within a population. The effects of selection on population composition and turnover would be magnified if sexual reproduction were likewise influenced by environmental conditions. We hypothesize that the combined effects of differential growth and reproduction rates serves to reduce gene flow between the sub-populations, reinforcing population structure while maintaining the diversity of the overall regional population.This work was supported by the National Institute of Environmental Health Sciences (1-P50-ES012742 to DMA and DLE), by the National Science Foundation through the Woods Hole Center for Oceans and Human Health (OCE-0430724), and by the ECOHAB program (NOAA Grant NA06NOS4780245)

Integrated safety analysis of umbralisib, a dual PI3Kd/CK1« inhibitor, in relapsed/refractory lymphoid malignancies

Phosphoinositide 3-kinase-d (PI3Kd) inhibitors are active in lymphoid malignancies, although associated toxicities can limit their use. Umbralisib is a dual inhibitor of PI3Kd and casein kinase-1« (CK1«). This study analyzed integrated comprehensive toxicity data from 4 open-label, phase 1 and 2 studies that included 371 adult patients (median age, 67 years) with relapsed/refractory non-Hodgkin lymphoma (follicular lymphoma [n 5 147]; marginal zone lymphoma [n 5 82]; diffuse large B-cell lymphoma/mantle cell lymphoma [n 5 74]; chronic lymphocytic leukemia [n 5 43]; and other tumor types [n 5 25]) who were treated with the recommended phase 2 dose of umbralisib 800 mg or higher once daily. At data cutoff, median duration of umbralisib treatment was 5.9 months (range, 0.1-75.1 months), and 107 patients (28.8%) received umbralisib for $12 months. Any-grade treatment-emergent adverse events (AEs) occurred in 366 (98.7%) of 371 patients, with the most frequent being diarrhea (52.3%), nausea (41.5%), and fatigue (31.8%). Grade 3 or higher treatment-emergent AEs occurred in 189 (50.9%) of 371 patients and included neutropenia (11.3%), diarrhea (7.3%), and increased aminotransferase levels (5.7%). Treatment-emergent serious AEs occurred in 95 (25.6%) of 371 patients. AEs of special interest were limited and included pneumonia (29 of 371 [7.8%]), noninfectious colitis (9 of 371 [2.4%]), and pneumonitis (4 of 371 [1.1%]). AEs led to discontinuation of umbralisib in 51 patients (13.7%). Four patients (1.1%) died of AEs, none of which was deemed related to umbralisib. No cumulative toxicities were reported. The favorable long-term tolerability profile and low rates of immune-mediated toxicities support the potential use of umbralisib for the benefit of a broad population of patients with lymphoid malignancies

Contextualizing privilege and disadvantage: lessons from women expatriates in the Middle East

This article explores how the simultaneity of privilege and disadvantage shapes the experiences of women expatriates in the Middle East. The article problematizes the simultaneity of being an elite group (e.g. expatriates) and a disadvantaged group (e.g. women) within the context of Gulf Cooperation Council countries. Drawing on the literature about women and work expatriation, the article analyses the narratives of women expatriates to highlight the complexity and multidimensionality of their experiences, positioning the discussion within the framework of gendered institutions. The article concludes that privilege and disadvantage are inseparable to the way the experiences of women expatriates unfold in the Middle East, and that institutional settings articulate this inseparability in order to regulate and help to maintain the gender social order. The article contributes a nuanced understanding of the experiences of women expatriates, challenging dominant views that present this group as generally privileged by virtue of their skilled and mobile status

Osteopetrosis

Osteopetrosis ("marble bone disease") is a descriptive term that refers to a group of rare, heritable disorders of the skeleton characterized by increased bone density on radiographs. The overall incidence of these conditions is difficult to estimate but autosomal recessive osteopetrosis (ARO) has an incidence of 1 in 250,000 births, and autosomal dominant osteopetrosis (ADO) has an incidence of 1 in 20,000 births. Osteopetrotic conditions vary greatly in their presentation and severity, ranging from neonatal onset with life-threatening complications such as bone marrow failure (e.g. classic or "malignant" ARO), to the incidental finding of osteopetrosis on radiographs (e.g. osteopoikilosis). Classic ARO is characterised by fractures, short stature, compressive neuropathies, hypocalcaemia with attendant tetanic seizures, and life-threatening pancytopaenia. The presence of primary neurodegeneration, mental retardation, skin and immune system involvement, or renal tubular acidosis may point to rarer osteopetrosis variants, whereas onset of primarily skeletal manifestations such as fractures and osteomyelitis in late childhood or adolescence is typical of ADO. Osteopetrosis is caused by failure of osteoclast development or function and mutations in at least 10 genes have been identified as causative in humans, accounting for 70% of all cases. These conditions can be inherited as autosomal recessive, dominant or X-linked traits with the most severe forms being autosomal recessive. Diagnosis is largely based on clinical and radiographic evaluation, confirmed by gene testing where applicable, and paves the way to understanding natural history, specific treatment where available, counselling regarding recurrence risks, and prenatal diagnosis in severe forms. Treatment of osteopetrotic conditions is largely symptomatic, although haematopoietic stem cell transplantation is employed for the most severe forms associated with bone marrow failure and currently offers the best chance of longer-term survival in this group. The severe infantile forms of osteopetrosis are associated with diminished life expectancy, with most untreated children dying in the first decade as a complication of bone marrow suppression. Life expectancy in the adult onset forms is normal. It is anticipated that further understanding of the molecular pathogenesis of these conditions will reveal new targets for pharmacotherapy

Holoprosencephaly

Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the face. It is estimated to occur in 1/16,000 live births and 1/250 conceptuses. Three ranges of increasing severity are described: lobar, semi-lobar and alobar HPE. Another milder subtype of HPE called middle interhemispheric variant (MIHF) or syntelencephaly is also reported. In most of the cases, facial anomalies are observed in HPE, like cyclopia, proboscis, median or bilateral cleft lip/palate in severe forms, ocular hypotelorism or solitary median maxillary central incisor in minor forms. These latter midline defects can occur without the cerebral malformations and then are called microforms. Children with HPE have many medical problems: developmental delay and feeding difficulties, epilepsy, instability of temperature, heart rate and respiration. Endocrine disorders like diabetes insipidus, adrenal hypoplasia, hypogonadism, thyroid hypoplasia and growth hormone deficiency are frequent. To date, seven genes have been positively implicated in HPE: Sonic hedgehog (SHH), ZIC2, SIX3, TGIF, PTCH, GLI2 and TDGF1. A molecular diagnosis can be performed by gene sequencing and allele quantification for the four main genes SHH, ZIC2, SIX3 and TGIF. Major rearrangements of the subtelomeres can also be identified by multiplex ligation-dependent probe amplification (MLPA). Nevertheless, in about 70% of cases, the molecular basis of the disease remains unknown, suggesting the existence of several other candidate genes or environmental factors. Consequently, a "multiple-hit hypothesis" of genetic and/or environmental factors (like maternal diabetes) has been proposed to account for the extreme clinical variability. In a practical approach, prenatal diagnosis is based on ultrasound and magnetic resonance imaging (MRI) rather than on molecular diagnosis. Treatment is symptomatic and supportive, and requires a multidisciplinary management. Child outcome depends on the HPE severity and the medical and neurological complications associated. Severely affected children have a very poor prognosis. Mildly affected children may exhibit few symptoms and may live a normal life

Targeting histone deacetyalses in the treatment of B- and T-cell malignancies

HDAC inhibitors (HDACI) are now emerging as one of the most promising new classes of drugs for the treatment of select forms of non-Hodgkin’s lymphoma (NHL). They are particularly active in T-cell lymphomas, possibly hodgkin’s lymphoma and indolent B cell lymphomas. Presently, two of these agents, vorinostat and romidepsin, have been approved in the US for the treatment of relapsed and refractory cutaneous T cell lymphomas (CTCL). Initially, these agents were developed with the idea that they affected transcriptional activation and thus gene expression, by modulating chromatin condensation and decondensation. It is now clear that their effects go beyond chromatin and by affecting the acetylation status of histones and other intra-cellular proteins, they modify gene expression and cellular function via multiple pathways. Gene expression profiles and functional genetic analysis has led to further understanding of the various molecular pathways that are affected by these agents including cell cycle regulation, pathways of cellular proliferation, apoptosis and angiogenesis all important in lymphomagenesis. There is also increasing data to support the effects of these agents on T cell receptor and immune function which may explain the high level of activity of these agents in T cell lymphomas and hodgkin’s lymphoma. There is ample evidence of epigenetic dysregulation in lymphomas which may underlie the mechanisms of action of these agents but how these agents work is still not clear. Current HDAC inhibitors can be divided into at least four classes based on their chemical structure. At present several of these HDAC inhibitors are in clinical trials both as single agents and in combination with chemotherapy or other biological agents. They are easy to administer and are generally well tolerated with minimal side effects. Different dosing levels and schedules and the use of isospecific HDAC inhibitors are some of the strategies that are being employed to increase the therapeutic effect of these agents in the treatment of lymphomas. There may also be class differences that translate into specific activity against different lymphoma. HDAC inhibitors will likely be incorporated into combinations of targeted therapies both in the upfront and relapsed setting for lymphomas