Natural language processing analysis of the psychosocial stressors of mental health disorders during the pandemic.

Over the past few years, the COVID-19 pandemic has exerted various impacts on the world, notably concerning mental health. Nevertheless, the precise influence of psychosocial stressors on this mental health crisis remains largely unexplored. In this study, we employ natural language processing to examine chat text from a mental health helpline.

Regulating ethical experimentation: Impacts of the breakthrough therapy designation on drug R&D.

This article investigates patterns of pharmaceutical development activity around the 2012 creation of the FDA's Breakthrough Therapy Designation (BTD). The BTD introduced regulatory flexibility and support to avoid ethical challenges created by experimental therapies of exceptional performance in early stage clinical trials. We argue that the program's design indirectly created substantial incentives for the industry to pursue the designation.

Leveraging the E-commerce footprint for the surveillance of healthcare utilization.

The utilization of healthcare services serves as a barometer for current and future health outcomes. Even in countries with modern healthcare IT infrastructure, however, fragmentation and interoperability issues hinder the (short-term) monitoring of utilization, forcing policymakers to rely on secondary data sources, such as surveys. This deficiency may be particularly problematic during public health crises, when ensuring proper and timely access to healthcare acquires special importance.

Association between universal health coverage and the disease burden of acute illness and injury at the global level.

Background: This study examines the relationship between universal health coverage (UHC) and the burden of emergency diseases at a global level.

Methods: Data on Disability-Adjusted Life Years (DALYs) from emergency conditions were extracted from the Institute for Health Metrics and Evaluation (IHME) database for the years 2015 and 2019. Data on UHC, measured using two variables 1) coverage of essential health services and 2) proportion of the population spending more than 10% of household income on out-of-pocket health care expenditure, were extracted from the World Bank Database for years preceding our outcome of interest.

COVID-19 unemployment and access to statin medications in the United States.

Objective: To quantify the effect of the unemployment created by COVID-19 on access to (sales of) statin drugs in the United States population.

Methods: Approximately half a billion transactions for statin drugs in the United States between January 2018 and September 2020 are analyzed. We studied the potential causal relation between abnormal levels of unemployment during the first wave of COVID-19 in the U.

Prospective adverse event risk evaluation in clinical trials.

Proactive and objective regulatory risk management of ongoing clinical trials is limited, especially when it involves the safety of the trial. We seek to prospectively evaluate the risk of facing adverse outcomes from standardized and routinely collected protocol data. We conducted a retrospective cohort study of 2860 Phase 2 and Phase 3 trials that were started and completed between 1993 and 2017 and documented in ClinicalTrials.

The SRC Inhibitor Dasatinib Induces Stem Cell-Like Properties in Head and Neck Cancer Cells that are Effectively Counteracted by the Mithralog EC-8042.

The frequent dysregulation of SRC family kinases (SFK) in multiple cancers prompted various inhibitors to be actively tested in preclinical and clinical trials. Disappointingly, dasatinib and saracatinib failed to demonstrate monotherapeutic efficacy in patients with head and neck squamous cell carcinomas (HNSCC). Deeper functional and mechanistic knowledge of the actions of these drugs is therefore needed to improve clinical outcome and to develop more efficient combinational strategies.

The multikinase inhibitor EC-70124 synergistically increased the antitumor activity of doxorubicin in sarcomas.

Cytotoxic drugs like doxorubicin remain as the most utilized agents in sarcoma treatment. However, advanced sarcomas are often resistant, thus stressing the need for new therapies aimed to overcome this resistance. Multikinase inhibitors provide an efficient way to target several pro-tumorigenic pathways using a single agent and may constitute a valuable strategy in the treatment of sarcomas, which frequently show an aberrant activation of pro-tumoral kinases.

Use of online recruitment strategies in a randomized trial of cancer survivors.

Background/aims: Despite widespread Internet adoption, online advertising remains an underutilized tool to recruit participants into clinical trials. Whether online advertising is a cost-effective method to enroll participants compared to other traditional forms of recruitment is not known.

Methods: Recruitment for the Survivorship Promotion In Reducing IGF-1 Trial, a community-based study of cancer survivors, was conducted from June 2015 through December 2016 via in-person community fairs, advertisements in periodicals, and direct postal mailings.

Inhibition of FLT3 and PIM Kinases by EC-70124 Exerts Potent Activity in Preclinical Models of Acute Myeloid Leukemia.

Internal tandem duplication (ITD) or tyrosine kinase domain mutations of FLT3 is the most frequent genetic alteration in acute myelogenous leukemia (AML) and are associated with poor disease outcome. Despite considerable efforts to develop single-target FLT3 drugs, so far, the most promising clinical response has been achieved using the multikinase inhibitor midostaurin. Here, we explore the activity of the indolocarbazole EC-70124, from the same chemical space as midostaurin, in preclinical models of AML, focusing on those bearing FLT3-ITD mutations.

Inhibition of SP1 by the mithramycin analog EC-8042 efficiently targets tumor initiating cells in sarcoma.

Tumor initiating cells (TICs), responsible for tumor initiation, and cancer stem cells (CSCs), responsible for tumor expansion and propagation, are often resistant to chemotherapeutic agents. To find therapeutic targets against sarcoma initiating and propagating cells we used models of myxoid liposarcoma (MLS) and undifferentiated pleomorphic sarcoma (UPS) developed from human mesenchymal stromal/stem cells (hMSCs), which constitute the most likely cell-of-origin for sarcoma. We found that SP1-mediated transcription was among the most significantly altered signaling.

[Effectiveness and safety of lenalidomide in myelofibrosis patients: a case series from the Spanish compassionate use program].

Objective: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm (CMPN) characterized by clonal proliferation of the pluripotent hematopoietic germinal cell, fibrosis, and bone marrow angiogenesis, and with extra medullary hematopoiesis. Lenalidomide is an immunomodulatory and antiangiogenic agent that has shown clinical benefit in MF patients in several phase II clinical trials. In this work, we present the results of the retrospective assessment of a series of 32 patients diagnosed with MF that received treatment with lenalidomide within the Spanish program of hospital compassionate use.

Evaluation of tolerability and efficacy of imatinib mesylate in elderly patients with chronic phase CML: ELDERGLI study.

Imatinib mesylate (IM) is the treatment of choice in patients with newly diagnosed chronic myeloid leukemia (CML), irrespectively of their age. Nevertheless, information regarding tolerability and responses in advanced-age patients, a subgroup in which co-morbidities and other factors may influence outcome, is scarce, since they were excluded from most clinical trials. In this observational study (ELDERGLI), information regarding demographics, concomitant medication, physical examination, performance status, hemogram, biochemistry, hematologic, cytogenetic and molecular responses, time to progression, adverse events (AE) and severe adverse events (SAE) were prospectively recorded in a series of 36 elderly patients with CML, with a median age of 76.

Prospective study on the practice of central nervous system prophylaxis and treatment in non-Hodgkin's lymphoma in Spain.

Background And Objective: Central nervous system (CNS) involvement in patients diagnosed with non-Hodgkin's lymphoma (NHL) or other lymphoproliferative disorders is an infrequent complication with a poor prognosis. The prophylaxis and treatment of CNS involvement in these patients are not homogenous. The aim of this prospective longitudinal study was to report the current practice of CNS prophylaxis and treatment in patients with lymphoproliferative disorders in Spain.

Outcome and toxicity of salvage treatment on patients relapsing after autologous hematopoietic stem cell transplantation--experience from a single center.

Patients with hematological malignancies who relapse after autologous stem cell transplantation (auto-SCT) generally have poor prognosis. Salvage treatment is often associated with severe toxicities. The aim of our study was to evaluate retrospectively the toxicity and outcome of rescue therapy in patients with acute leukemias, non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD) and multiple myeloma (MM) relapsing after auto-SCT.