Effect of Medication Reconciliation at Hospital Admission on 30-Day Returns to Hospital: A Randomized Clinical Trial

Importance: According to international recommendations, hospitals should use medication reconciliation to prevent medication errors and improve patient safety. Objective: To assess the impact of medication reconciliation at hospital admission on patient-centered health care outcomes. Design, Setting, and Participants: This parallel group, open-label randomized controlled trial used centralized randomization to the intervention group (ie, individuals with medication reconciliation) or control group (ie, individuals with only standard, physician-acquired medication history). Outcome assessors and data analysts were blinded to group allocation. Participants included 1702 patients aged 85 years or older, with more than 10 medications at hospital admission, or meeting both conditions at 2 regional secondary teaching hospitals in southern Switzerland. Study duration was 14.5 months, from November 1, 2018, to January 15, 2020. Data were analyzed from December 2018 through March 2020. Interventions: Medication reconciliation was performed at hospital admission in 3 steps: (1) the pharmacy assistant obtained the list of the patient's current medications (ie, the best possible medication history [BPMH]); (2) the clinical pharmacist led reconciliation of the BPMH with the list of home medications recorded at hospital admission by the attending physician (according to the hospital standard procedure); and (3) medication discrepancies were communicated to the attending physician, and, when necessary, medications prescribed at admission were adapted. Main Outcomes and Measures: The primary outcome was a composite postdischarge health care use variable quantified as the proportion of patients with unplanned all-cause hospital visits (including visits to the emergency department and hospital readmissions) within 30 days after discharge from the hospital when medication reconciliation took place. A time-to-event analysis was performed. Results: Among 1702 patients (median [interquartile range] age, 86.0 [79.0-89.0] years; 720 [42.3%] men), 866 patients (50.9%) were allocated to the intervention group and 836 patients (49.1%) to the control group. The primary outcome occurred among 340 participants (39.3%) in the intervention group and 330 participants (39.5%) in the control group (P =.93). In time-to-event analyses at study closeout, unplanned all-cause hospital visits to the emergency department (log-rank P =.08) and unplanned all-cause hospital readmissions (log-rank P =.10) occurred similarly in the intervention and control groups. Conclusions and Relevance: These findings suggest that medication reconciliation at hospital admission has no impact on postdischarge health care outcomes among patients aged 85 years or older, with more than 10 medications at hospital admission, or meeting both conditions. Trial Registration: ClinicalTrials.gov Identifier: NCT03654963

Editorial: Physical Virology and the Nature of Virus Infections

Virus particles, ‘virions’, range in size from nano-scale to micro-scale. They have many different shapes and are composed of proteins, sugars, nucleic acids, lipids, water and solutes. Virions are autonomous entities and affect all forms of life in a parasitic relationship. They infect prokaryotic and eukaryotic cells. The physical properties of virions are tuned to the way they interact with cells. When virions interact with cells, they gain huge complexity and give rise to an infected cell, also known as ‘virus’. Virion–cell interactions entail the processes of entry, replication and assembly, as well as egress from the infected cell. Collectively, these steps can result in progeny virions, which is a productive infection, or in silencing of the virus, an abortive or latent infection. This book explores facets of the physical nature of virions and viruses and the impact of mechanical properties on infection processes at the cellular and subcellular levels

Characterization of Empty Adenovirus Particles Assembled in the Absence of a Functional Adenovirus IVa2 Protein▿

The molecular mechanism for packaging of the adenovirus (Ad) genome into the capsid is likely similar to that of DNA bacteriophages and herpesviruses—the insertion of viral DNA through a portal structure into a preformed prohead driven by an ATP-hydrolyzing molecular machine. It is speculated that the IVa2 protein of adenovirus is the ATPase providing the power stroke of the packaging machinery. Purified IVa2 binds ATP in vitro and, along with a second Ad protein, the L4 22-kilodalton protein (L4-22K), binds specifically to sequences in the Ad genome that are essential for packaging. The efficiency of binding of these proteins in vitro was correlated with the efficiency of packaging in vivo. By utilizing a virus unable to express IVa2, pm8002, it was reported that IVa2 plays a role in assembly of the empty virion. We wanted to address the question of whether the ATP binding, and hence the putative ATPase activity, of IVa2 was required for its role in virus assembly. Our results show that ATPase activity was not required for the assembly of empty virus particles. In addition, we present evidence that particles were assembled in the absence of IVa2 by using two viruses null for IVa2—a deletion mutant virus, ΔIVa2, and the previously described mutant virus, pm8002. Empty virus particles produced by these IVa2 mutant viruses did not contain detectable viral DNA. We conclude that the major role of IVa2 is in viral DNA packaging. A characterization of the empty particles obtained from the IVa2 mutant viruses compared to wild-type empty particles is presented

Subversion of CtBP1-controlled macropinocytosis by human adenovirus serotype 3

Endocytosis supports cell communication, growth, and pathogen infection. The species B human adenovirus serotype 3 (Ad3) is associated with epidemic conjunctivitis, and fatal respiratory and systemic disease. Here we show that Ad3 uses dynamin-independent endocytosis for rapid infectious entry into epithelial and haematopoietic cells. Unlike Ad5, which uses dynamin-dependent endocytosis, Ad3 endocytosis spatially and temporally coincided with enhanced fluid-phase uptake. It was sensitive to macropinocytosis inhibitors targeting F-actin, protein kinase C, the sodium–proton exchanger, and Rac1 but not Cdc42. Infectious Ad3 macropinocytosis required viral activation of p21-activated kinase 1 (PAK1) and the C-terminal binding protein 1 of E1A (CtBP1), recruited to macropinosomes. These macropinosomes also contained the Ad3 receptors CD46 and αv integrins. CtBP1 is a phosphorylation target of PAK1, and is bifunctionally involved in membrane traffic and transcriptional repression of cell cycle, cancer, and innate immunity pathways. Phosphorylation-defective S147A-CtBP1 blocked Ad3 but not Ad5 infection, providing a direct link between PAK1 and CtBP1. The data show that viruses induce macropinocytosis for infectious entry, a pathway used in antigen presentation and cell migration