Bringing Trial Activities to Participants-The Trials@Home RADIAL Proof-of-Concept Trial Investigating Decentralization of Trials.

The interest in trials in which activities are being moved to the participants' direct environment, that is, decentralized, has increased in recent years, but limited research has been conducted into the feasibility and acceptability of such approaches. The Trials@Home RADIAL proof-of-concept (PoC) trial aims to assess the scientific and operational feasibility and quality of a fully decentralized and hybrid trial approach compared to a conventional, site-based approach. RADIAL is a three-arm parallel-group, open-label, multi-center low-intervention phase IV trial conducted in people living with Type 2 diabetes mellitus in six European countries (DE, DK, ES, IT, PL, UK).

Goals of Care Assessment during Hospitalization for Sepsis.

Sepsis is a common cause of hospital mortality, as well as new morbidity among survivors. Clinical practice guidelines recommend assessing goals of care (GoCs) during sepsis hospitalization to ensure goal-concordant care is provided. To determine how often GoCs are assessed during sepsis hospitalization in routine practice.

Midline vs Peripherally Inserted Central Catheter for Outpatient Parenteral Antimicrobial Therapy.

Importance: Little is known about the safety of midline catheters vs peripherally inserted central catheters (PICCs) for outpatient parenteral antimicrobial therapy (OPAT).

Objective: To compare outcomes from midline catheters vs PICCs for OPAT.

Design, Setting, And Participants: This retrospective cohort study included patients who received antimicrobial therapy through a midline catheter or PICC between January 2017 and November 2023 across 69 Michigan hospitals.

Development and Validation of the Hospital Medicine Safety Sepsis Initiative Mortality Model.

Background: When comparing outcomes after sepsis, it is essential to account for patient case mix to make fair comparisons. We developed a model to assess risk-adjusted 30-day mortality in the Michigan Hospital Medicine Safety sepsis initiative (HMS-Sepsis).

Research Question: Can HMS-Sepsis registry data adequately predict risk of 30-day mortality? Do performance assessments using adjusted vs unadjusted data differ?

Study Design And Methods: Retrospective cohort of community-onset sepsis hospitalizations in the HMS-Sepsis registry (April 2022-September 2023), with split derivation (70%) and validation (30%) cohorts.

Awareness of peripheral IV catheters among nurses, physicians, and trainees: A prospective cohort study.

Background: Peripheral intravenous catheters (PIVs) are the most frequently used invasive device in hospitalized patients. These devices are not benign and are associated with complications. However, clinician awareness of them is variable and poorly understood.

Improving Appropriate Use of Peripherally Inserted Central Catheters Through a Statewide Collaborative Hospital Initiative: A Cost-Effectiveness Analysis.

Background: Quality improvement (QI) programs require significant financial investment. The authors evaluated the cost-effectiveness of a physician-led, performance-incentivized, QI intervention that increased appropriate peripherally inserted central catheter (PICC) use.

Methods: The authors used an economic evaluation from a health care sector perspective.

UV reflectance in crop remote sensing: Assessing the current state of knowledge and extending research with strawberry cultivars.

Remote sensing of spectral reflectance is a crucial parameter in precision agriculture. In particular, the visual color produced from reflected light can be used to determine plant health (VIS-IR) or attract pollinators (Near-UV). However, the UV spectral reflectance studies largely focus on non-crop plants, even though they provide essential information for plant-pollinator interactions.

Institutional Structures and Processes to Support Sepsis Care: A Multihospital Study.

Objectives: To identify opportunities for improving hospital-based sepsis care and to inform an ongoing statewide quality improvement initiative in Michigan.

Design: Surveys on hospital sepsis processes, including a self-assessment of practices using a 3-point Likert scale, were administered to 51 hospitals participating in the Michigan Hospital Medicine Safety Consortium, a Collaborative Quality Initiative sponsored by Blue Cross Blue Shield of Michigan, at two time points (2020, 2022). Forty-eight hospitals also submitted sepsis protocols for structured review.

Use and Outcomes of Peripheral Vasopressors in Early Sepsis-Induced Hypotension Across Michigan Hospitals: A Retrospective Cohort Study.

Background: Vasopressors traditionally are administered via central access, but newer data suggest that peripheral administration may be safe and may avoid delays and complications associated with central line placement.

Research Question: How commonly are vasopressors initiated through peripheral IV lines in routine practice? Is vasopressor initiation route associated with in-hospital mortality?

Study Design And Methods: This retrospective cohort study included adults hospitalized with sepsis (November 2020-September 2022) at 29 hospitals in the Michigan Hospital Medicine Safety Consortium, a Collaborative Quality Initiative sponsored by Blue Cross Blue Shield of Michigan. We assessed route of early vasopressor initiation, factors and outcomes associated with peripheral initiation, and timing of central line placement.

Midline catheters in patients with advanced chronic kidney disease.

Background: Midline catheters (midlines) are increasingly used in patients with advanced chronic kidney disease (CKD).

Objective: This study describes current practice and acute complications associated with midlines in CKD patients.

Designs, Setting, And Participants: Trained abstractors at 66 hospitals from the Michigan Hospital Medicine Safety (HMS) Consortium collected data on a sample of patients who received a midline during hospitalization.

Decentralised, patient-centric, site-less, virtual, and digital clinical trials? From confusion to consensus.

There is increasing interest in clinical trials that use technologies and other innovative operational approaches to organise trial activities around trial participants instead of investigator sites. A range of terms has been introduced to refer to this operational clinical trial model, including virtual, digital, remote, and decentralised clinical trials (DCTs). However, this lack of standardised terminology can cause confusion over what a particular trial model entails and for what purposes it can be used, hampering discussions by stakeholders on its acceptability and suitability.

A cross-sectional survey on the early impact of COVID-19 on the uptake of decentralised trial methods in the conduct of clinical trials.

Background: The COVID-19 pandemic significantly impacted the conduct of clinical trials through delay, interruption or cancellation. Decentralised methods in clinical trials could help to continue trials during a pandemic. This paper presents the results of an exploratory study conducted early in the pandemic to gain insight into and describe the experiences of organisations involved in clinical trials, with regard to the impact of COVID-19 on the conduct of trials, and the adoption of decentralised methods prior to, and as mitigation for the impact, of COVID-19.

Sodium zirconium cyclosilicate to increase lithium elimination.

Lithium is considered a mood stabilizer for bipolar affective disorders, but it has a narrow therapeutic index of 0.6-1.2 mEq/L.

Comparative hemostatic efficacy of 4F-PCC in patients with intracranial hemorrhage on factor Xa inhibitors versus warfarin.

Objective: Patients experiencing an intracranial hemorrhage (ICH) on oral anticoagulants often require rapid reversal. This study evaluated patients taking factor Xa inhibitors or warfarin that received reversal with 4-factor prothrombin complex concentrate (4F-PCC) for an ICH. The objective of the study was to determine if the efficacy of 4F-PCC for the reversal of factor Xa inhibitors is noninferior to its use in warfarin reversal in patients with ICH.

Activation of neural stem cells from quiescence drives reactive hippocampal neurogenesis after alcohol dependence.

Neural stem cell-driven adult neurogenesis contributes to the integrity of the hippocampus. Excessive alcohol consumption in alcoholism results in hippocampal degeneration that may recover with abstinence. Reactive, increased adult neurogenesis during abstinence following alcohol dependence may contribute to recovery, but the mechanism driving reactive neurogenesis is not known.

Comparative study of Tat vaccine regimens in Mauritian cynomolgus and Indian rhesus macaques: influence of Mauritian MHC haplotypes on susceptibility/resistance to SHIV(89.6P) infection.

Protection afforded by HIV Tat-based vaccines has differed in Indian rhesus and Mauritian cynomolgus macaques. We evaluated native Tat and Ad-HIVtat priming/Tat-boosting regimens in both species. Both vaccines were immunogenic.

A replication-competent adenovirus-human immunodeficiency virus (Ad-HIV) tat and Ad-HIV env priming/Tat and envelope protein boosting regimen elicits enhanced protective efficacy against simian/human immunodeficiency virus SHIV89.6P challenge in rhesus macaques.

We previously demonstrated that replication-competent adenovirus (Ad)-simian immunodeficiency virus (SIV) recombinant prime/protein boost regimens elicit potent immunogenicity and strong, durable protection of rhesus macaques against SIV(mac251). Additionally, native Tat vaccines have conferred strong protection against simian/human immunodeficiency virus SHIV(89.6P) challenge of cynomolgus monkeys, while native, inactivated, or vectored Tat vaccines have failed to elicit similar protective efficacy in rhesus macaques.

A complementary single-stranded docking site is required for enhancement of strand exchange by human immunodeficiency virus nucleocapsid protein on substrates that model viral recombination.

Enhancement of strand exchange by nucleocapsid protein (NC) is proposed to occur during retroviral recombination. The mechanism was examined using an RNA (donor)-DNA hybrid that mimicked a retrovirus replication intermediate. This consisted of a 25 base pair hybrid region flanked on each side by single-stranded RNA or DNA.

Differing roles of the N- and C-terminal zinc fingers in human immunodeficiency virus nucleocapsid protein-enhanced nucleic acid annealing.

The replication process of human immunodeficiency virus requires a number of nucleic acid annealing steps facilitated by the hybridization and helix-destabilizing activities of human immunodeficiency virus nucleocapsid (NC) protein. NC contains two CCHC zinc finger motifs numbered 1 and 2 from the N terminus. The amino acids surrounding the CCHC residues differ between the two zinc fingers.

Evidence for the differential effects of nucleocapsid protein on strand transfer in various regions of the HIV genome.

An in vitro strand transfer assay that mimicked recombinational events occurring during reverse transcription in HIV-1 was used to assess the role of nucleocapsid protein (NC) in strand transfer. Strand transfer in highly structured nucleic acid species from the U3 3' long terminal repeats, gag-pol frameshift region, and Rev response element were strongly enhanced by NC. In contrast, weakly structured templates from the env and pol-vif regions transferred well without NC and showed lower enhancement.