ABSTRACT
"Hospital at Home(HaH)" programs provide an alternative to traditional hospitalization. However, the incidence of adverse drug events in these programs is unknown. This study describes adverse drug events and potential adverse drug events in a new HaH program. We examined the charts of the first 50 patients admitted. We found 45 potential adverse drug events and 14 adverse drug events from admission to 30 days after HaH discharge. None of the adverse drug events were severe. Some events, like problems with medication administration, may be unique to the hospital at home setting. Monitoring for adverse drug events is feasible and important for hospital at home programs.
Subject(s)
Drug-Related Side Effects and Adverse Reactions/epidemiology , Hospitalization/trends , Aged , Aged, 80 and over , Drug-Related Side Effects and Adverse Reactions/etiology , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , New York , Patient Readmission/trends , Program Evaluation/methods , Retrospective StudiesABSTRACT
The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death in which cytoplasmic contents and pro-inflammatory cytokines, including IL-1ß, are released. This death pathway thus links the two signature events in HIV infection-CD4 T-cell depletion and chronic inflammation-and creates a pathogenic vicious cycle in which dying CD4 T cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase 1 inhibitors shown to be safe in humans, raising the possibility of a new class of 'anti-AIDS' therapeutics targeting the host rather than the virus.
Subject(s)
CD4-Positive T-Lymphocytes/pathology , Caspase 1/metabolism , HIV Infections/immunology , HIV Infections/pathology , HIV-1/pathogenicity , Administration, Oral , Adult , Anti-HIV Agents/pharmacology , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/metabolism , Caspase 3/metabolism , Caspase Inhibitors/administration & dosage , Caspase Inhibitors/pharmacology , Cell Death/drug effects , HIV Infections/drug therapy , HIV Infections/enzymology , HIV-1/drug effects , HIV-1/growth & development , Humans , In Vitro Techniques , Inflammasomes/immunology , Inflammasomes/metabolism , Inflammation/complications , Inflammation/immunology , Inflammation/pathology , Inflammation/virology , Interleukin-1beta/biosynthesis , Interleukin-1beta/metabolism , Lymph Nodes/enzymology , Male , Palatine Tonsil/drug effects , Palatine Tonsil/virology , Protein Precursors/biosynthesis , Spleen/drug effects , Spleen/virology , Virus ReplicationABSTRACT
The mechanism by which CD4 T cells are depleted in HIV-infected hosts remains poorly understood. In ex vivo cultures of human tonsil tissue, CD4 T cells undergo a pronounced cytopathic response following HIV infection. Strikingly, >95% of these dying cells are not productively infected but instead correspond to bystander cells. We now show that the death of these "bystander" cells involves abortive HIV infection. Inhibitors blocking HIV entry or early steps of reverse transcription prevent CD4 T cell death while inhibition of later events in the viral life cycle does not. We demonstrate that the nonpermissive state exhibited by the majority of resting CD4 tonsil T cells leads to accumulation of incomplete reverse transcripts. These cytoplasmic nucleic acids activate a host defense program that elicits a coordinated proapoptotic and proinflammatory response involving caspase-3 and caspase-1 activation. While this response likely evolved to protect the host, it centrally contributes to the immunopathogenic effects of HIV.
