Impact of High Deductible Health Plans on Diabetes Care Quality and Outcomes: Systematic Review

ObjectiveTo provide a review of the impact of high deductible health plans (HDHPs) on the utilizations of services required for optimal management of diabetes and subsequent health outcomes.MethodsSystematic literature review of studies published between January 1, 2000, and May 7, 2021, was conducted that examined the impact of HDHP on diabetes monitoring (eg, recommended laboratory and surveillance testing), routine care (eg, ambulatory appointments), medication management (eg, medication initiation, adherence), and acute health care utilization (eg, emergency department visits, hospitalizations, incident complications).ResultsOf the 303 reviewed articles, 8 were relevant. These studies demonstrated that HDHPs lower spending at the expense of reduced high-value diabetes monitoring, routine care, and medication adherence, potentially contributing to the observed increases in acute health care utilization. Additionally, patient out-of-pocket costs for recommended screenings doubled, and total health care expenditures increased by 49.4% for HDHP enrollees compared with enrollees in traditional health plans. Reductions in disease monitoring and routine care and increases in acute health care utilization were greatest in lower-income patients. None of the studies examined the impact of HDHPs on access to diabetes self-management education, technology use, or glycemic control.ConclusionAlthough HDHPs reduce some health care utilization and costs, they appear to do so at the expense of limiting high-value care and medication adherence. Policymakers, providers, and payers should be more cognizant of the potential for negative consequences of HDHPs on patients’ health.     

Transforming growth factor-beta 1 enhances the suppression of human hematopoiesis by tumor necrosis factor-alpha or recombinant interferon-alpha

The effects of transforming growth factor-beta 1 (TGF-beta 1) on human hematopoiesis were evaluated in combination with two other regulatory cytokines, namely, recombinant human tumor necrosis factor-alpha (TNF-alpha) and recombinant human interferon-alpha (rIFN-alpha). Combinations of TNF-alpha and TGF-beta 1 resulted in a synergistic suppression of colony formation by erythroid progenitor cells (BFU-E) and an additive suppression of granulocyte-macrophage (CFU-GM) and multipotential (CFU-GEMM) progenitor cells. In addition, TGF-beta 1 synergized with rIFN-alpha to suppress CFU-GM formation, while the combined suppressive effects of both cytokines on CFU-GEMM and BFU-E were additive. When TGF-beta 1 was tested with TNF-alpha or IFN-alpha on granulocyte/macrophage colony-stimulating factor (GM-CSF)-stimulated bone marrow cells in a 5-day proliferation assay, the antiproliferative effects of TGF-beta 1 and TNF-alpha were additive, while those with TGF-beta 1 and rIFN-alpha were synergistic. A similar pattern was seen in the suppression of the myeloblastic cell line KG-1 where TGF-beta 1 in combination with TNF-alpha resulted in an additive suppression while inhibition by TGF-beta 1 and IFN-alpha was synergistic. These results demonstrate for the first time the cooperative effects between TGF-beta and TNF-alpha and IFN-alpha in the suppression of hematopoietic cell growth, raising the possibility that TGF-beta might be used in concert with TNF-alpha or IFN-alpha in the treatment of various myeloproliferative disorders.     

A cellular model for drug interactions on hematopoiesis: The use of human umbilical cord blood progenitors as a model for the study of drug-related myelosuppression of normal hematopoiesis

A cellular model of hematopoiesis which would be more convenient than bone marrow (BM) progenitors and directly relevant to human pathology is needed in order to investigate xenobiotic toxicity. Human umbilical cord blood (HCB), previously shown to be able to repopulate BM, provides a powerful in vitro model of normal human hematopoiesis. In order to validate the use of normal HCB progenitors as targets for dose-related myelosuppression, we used clonogenic assays and expansion in a liquid culture of progenitor-enriched cell suspensions from HCB. A series of 8 reference molecules, doxorubicin, cytosine-arabinoside, 5-fluorouracil, 3-azido-3-deoxythymidine, acetylsalicyclic acid, sodium valproate and two cephalosporin antibiotics, were tested. In vitro 50% inhibition concentrations (IC₅₀) were compared to those observed or reported with BM progenitors, and to the values of plasma concentrations from treated patients. HCB progenitors as in vitro targets for cytotoxic molecules were easy to access and handle, and their use was sensitive, specific and reproducible. They gave results similar to BM progenitors and allowed a qualitative approach to cellular metabolism and toxicity using morphological, flow cytometric and chromatographic methods.Abbreviations ARA-CC cytosine arabinoside - AS acetylsalicylic acid - AZTT 3-azido-3-deoxythymidine - BFUU burst-forming units - BM bone marrow - CFU colony-forming units - DOXX doxorubicin - FU 5-fluorouracil - glyAA glyAcophorin A - HCB human umbilical cord blood - IU international units - PCMEM human placenta-conditioned medium - VA sodium valproate     

Recovery of the simian immunodeficiency virus (SIV) and depression of colony formation in in vitro infected progenitor cell-enriched rhesus bone marrow (BM)

Rhesus progenitor-enriched BM was exposed overnight to SIV and cultured in a limiting dilution assay where the potential for progenitor interaction with lymphocytes or macrophages was low. Virus was consistently isolated late in culture, detection being aided by coculture with CEM₁₇₄ lymphoblasts. Although infected cells had reduced clonogenic activity, colonies were indistinguishable from those derived from uninfected BM with respect to proliferative potential, morphology, and longevity in culture. Primate immunodeficiency viruses, therefore, may infect immature BM populations, directly affecting hematopoietic activity.     

Lineage specification in the fly nervous system and evolutionary implications

Over the last decades, it has become clear that glia are multifunctional and plastic cells endowed with key regulatory roles. They control the response to developmental and/or pathological signals, thereby affecting neural proliferation, remodeling, survival, and regeneration. It is, therefore, important to understand the biology of these cells and the molecular mechanisms controlling their development/activity. The fly community has made major breakthroughs by characterizing the bases of gliogenesis and function. Here we describe the regulation and the role of the fly glial determinant. Then, we discuss the impact of the determinant in cell plasticity and differentiation. Finally, we address the conservation of this pathway across evolution.     

Parallels,differences and lessons: a comparison of the management of foot-and-mouth disease and COVID-19 using UK 2001/2020 as points of reference

Foot-and-mouth disease (FMD) is an extremely infectious viral infection of cloven-hoofed animals which is highly challenging to control and can give rise to national animal health crises, especially if there is a lack of pre-existing immunity due to the emergence of new strains or following incursions into disease-free regions. The 2001 FMD epidemic in the UK was on a scale that initially overwhelmed the national veterinary services and was eventually controlled by livestock lockdown and slaughter on an unprecedented scale. In 2020, the rapid emergence of COVID-19 has led to a human pandemic unparalleled in living memory. The enormous logistics of multi-agency control efforts for COVID-19 are reminiscent of the 2001 FMD epidemic in the UK, as are the use of movement restrictions, not normally a feature of human disease control. The UK experience is internationally relevant as few countries have experienced national epidemic crises for both diseases. In this review, we reflect on the experiences and lessons learnt from UK and international responses to FMD and COVID-19 with respect to their management, including the challenge of preclinical viral transmission, threat awareness, early detection, different interpretations of scientific information, lockdown, biosecurity behaviour change, shortage of testing capacity and the choices for eradication versus living with infection. A major lesson is that the similarity of issues and critical resources needed to manage large-scale outbreaks demonstrates that there is benefit to a ‘One Health’ approach to preparedness, with potential for greater cooperation in planning and the consideration of shared critical resources.     

Impaired adult myeloid progenitor CMP and GMP cell function in conditional c-myb-knockout mice

The differentiation of myeloid progenitors to mature, terminally differentiated cells is a highly regulated process. Here, we showed that conditional disruption of the c-myb proto-oncogene in adult mice resulted in dramatic reductions in CMP, GMP and MEP myeloid progenitors, leading to a reduction of neutrophils, basophils, monocytes and platelets in peripheral blood. In addition, c-myb plays a critical role at multiple stages of myeloid development, from multipotent CMP and bipotent GMP to unipotent CFU-G and CFU-M progenitor cells. c-myb controls the differentiation of these cells and is required for the proper commitment, maturation and normal differentiation of CMPs and GMPs. Specifically, c-myb regulates the precise commitment to the megakaryocytic and granulo-monocytic pathways and governs the granulocytic-monocytic lineage choice. c-myb is also required for the commitment along the granulocytic pathway for early myeloid progenitor cells and for the maturation of committed precursor cells along this pathway. On the other hand, disruption of the c-myb gene favors the commitment to the monocytic lineage, although monocytic development was abnormal with cells appearing more mature with atypical CD41 surface markers. These results demonstrate that c-myb plays a pivotal role in the regulation of multiple stages in adult myelogenesis.     

The BTB-ZF transcription factors

The BTB-ZF (broad-complex, tramtrack and bric-à-brac - zinc finger) proteins are encoded by at least 49 genes in mouse and man and commonly serve as sequence-specific silencers of gene expression. This review will focus on the known physiological functions of mammalian BTB-ZF proteins, which include essential roles in the development of the immune system. We discuss their function in terminally differentiated lymphocytes and the progenitors that give rise to them, their action in hematopoietic malignancy and roles beyond the immune system.     

Prehospital Thrombolysis: A Manual from Berlin

In acute ischemic stroke, time from symptom onset to intervention is a decisive prognostic factor. In order to reduce this time, prehospital thrombolysis at the emergency site would be preferable. However, apart from neurological expertise and laboratory investigations a computed tomography (CT) scan is necessary to exclude hemorrhagic stroke prior to thrombolysis. Therefore, a specialized ambulance equipped with a CT scanner and point-of-care laboratory was designed and constructed. Further, a new stroke identifying interview algorithm was developed and implemented in the Berlin emergency medical services. Since February 2011 the identification of suspected stroke in the dispatch center of the Berlin Fire Brigade prompts the deployment of this ambulance, a stroke emergency mobile (STEMO). On arrival, a neurologist, experienced in stroke care and with additional training in emergency medicine, takes a neurological examination. If stroke is suspected a CT scan excludes intracranial hemorrhage. The CT-scans are telemetrically transmitted to the neuroradiologist on-call. If coagulation status of the patient is normal and patient''s medical history reveals no contraindication, prehospital thrombolysis is applied according to current guidelines (intravenous recombinant tissue plasminogen activator, iv rtPA, alteplase, Actilyse).Thereafter patients are transported to the nearest hospital with a certified stroke unit for further treatment and assessment of strokeaetiology. After a pilot-phase, weeks were randomized into blocks either with or without STEMO care. Primary end-point of this study is time from alarm to the initiation of thrombolysis. We hypothesized that alarm-to-treatment time can be reduced by at least 20 min compared to regular care.