Identification of Selective Imidazopyridine CSF1R Inhibitors.

Colony stimulating factor-1 receptor (CSF1R or c-FMS), a class III receptor tyrosine kinase expressed on members of the mononuclear phagocyte system (MPS), plays a key role in the proper functioning of macrophages, microglia, and related cells. Aberrant signaling through CSF1R has been associated with a variety of disease states, including cancer, inflammation, and neurodegeneration. In this Letter, we detail our efforts to develop novel CSF1R inhibitors. Drawing on previously described compounds, including GW2580 (4), we have discovered a novel series of compounds based on the imidazo[4,5-b]pyridine scaffold. Initial structure-activity relationship studies culminated in the identification of 36, a lead compound with potent CSF1R biochemical and cellular activity, acceptable in vitro ADME properties, and oral exposure in rat.

Implementation of a hotline ("S-T-I-C-K") to expedite management of occupational bloodborne pathogen exposures at an academic medical center: A Process Improvement Initiative.

Previously, blood and body fluid exposures were managed by a visit to the University Employee Health Clinic during normal business hours and the Emergency Department after hours. We implemented the "S-T-I-C-K" program where health care personnel were evaluated immediately after exposure by a nurse-driven 24/7 hotline. Increasing accessibility to care and a simplified process for exposure management led to a significant decrease in Emergency Department utilization and time between the exposure and receipt of post-exposure prophylaxis.

Coronavirus disease 2019 (COVID-19) among nonphysician healthcare personnel by work location at a tertiary-care center, Iowa, 2020-2021.

We describe COVID-19 cases among nonphysician healthcare personnel (HCP) by work location. The proportion of HCP with coronavirus disease 2019 (COVID-19) was highest in the emergency department and lowest among those working remotely. COVID-19 and non-COVID-19 units had similar proportions of HCP with COVID-19 (13%). Cases decreased across all work locations following COVID-19 vaccination.

Blood culture practices in patients with a central line at an academic medical center-Iowa, 2020.

We analyzed blood-culture practices to characterize the utilization of the Infectious Diseases Society of America (IDSA) recommendations related to catheter-related bloodstream infection (CRBSI) blood cultures. Most patients with a central line had only peripheral blood cultures. Increasing the utilization of CRBSI guidelines may improve clinical care, but may also affect other quality metrics.

Association between job role and coronavirus disease 2019 (COVID-19) among healthcare personnel, Iowa, 2021.

We describe the association between job roles and coronavirus disease 2019 (COVID-19) among healthcare personnel. A wide range of hazard ratios were observed across job roles. Medical assistants had higher hazard ratios than nurses, while attending physicians, food service workers, laboratory technicians, pharmacists, residents and fellows, and temporary workers had lower hazard ratios.

Impact of COVID-19 on an infection prevention and control program, Iowa 2020-2021.

BACKGROUND: The COVID-19 pandemic has affected infection prevention and control (IPC) programs worldwide. We evaluated the impact of COVID-19 on the University of Iowa Hospitals & Clinics IPC program by measuring the volume of calls to the program, changes in healthcare-associated infection rates, and team member perceptions. METHODS: We retrieved the IPC call log and healthcare-associated infection trends for 2018-2020. We defined 2 periods: pre-COVID-19 (2018-2019) and COVID-19 (January-December 2020). We also conducted one-on-one interviews and focus group interviews with members of the IPC program and describe changes in their working conditions during the COVID-19 period. RESULTS: A total of 6,564 calls were recorded during 2018-2020. The pre-COVID-19 period had a median of 71 calls and/or month (range: 50-119). During the COVID-19 period, the median call volume increased to 368/month (range: 149-829), and most calls were related to isolation precautions (50%). During the COVID-19 period, the central line-associated bloodstream infection incidence increased significantly. Infection preventionists reported that the ambiguity and conflicting guidance during the pandemic were major challenges. CONCLUSIONS: Our IPC program experienced a 500% increase in consultation requests. Planning for future bio-emergencies should include creative strategies to increase response capacity within IPC programs.

Bat intrusions at a tertiary care center in Iowa, 2018-2020.

We described the epidemiology of bat intrusions into a hospital and subsequent management of exposures during 2018-2020. Most intrusions occurred in older buildings during the summer and fall months. Hospitals need bat intrusion surveillance systems and protocols for bat handling, exposure management, and intrusion mitigation.

Coronavirus disease 2019 (COVID-19) incidence after exposures in shared patient rooms in a tertiary-care center in Iowa, July 2020-May 2021.

The incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure in shared patient rooms was low at our institution: 1.8 per 1,000 shared-room patient days. However, the secondary attack rate (21.6%) was comparable to that reported in household exposures. Lengthier exposures were associated with SARS-CoV-2 conversion. Hospitals should implement measures to decrease shared-room exposures.

Coronavirus disease 2019 (COVID-19) admission screening and assessment of infectiousness at an academic medical center in Iowa, 2020.

OBJECTIVE: Patients admitted to the hospital may unknowingly carry severe acute respiratory coronavirus virus 2 (SARS-CoV-2), and hospitals have implemented SARS-CoV-2 admission screening. However, because SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) assays may remain positive for months after infection, positive results may represent active or past infection. We determined the prevalence and infectiousness of patients who were admitted for reasons unrelated to COVID-19 but tested positive for SARS-CoV-2 on admission screening. METHODS: We conducted an observational study at the University of Iowa Hospitals & Clinics from July 7 to October 25, 2020. All patients admitted without suspicion of COVID-19 were included, and medical records of those with a positive admission screening test were reviewed. Infectiousness was determined using patient history, PCR cycle threshold (Ct) value, and serology. RESULTS: In total, 5,913 patients were screened and admitted for reasons unrelated to COVID-19. Of these, 101 had positive admission RT-PCR results; 36 of these patients were excluded because they had respiratory signs/symptoms on admission on chart review. Also, 65 patients (1.1%) did not have respiratory symptoms. Finally, 55 patients had Ct values available and were included in this analysis. The median age of the final cohort was 56 years and 51% were male. Our assessment revealed that 23 patients (42%) were likely infectious. The median duration of in-hospital isolation was 5 days for those likely infectious and 2 days for those deemed noninfectious. CONCLUSIONS: SARS-CoV-2 was infrequent among patients admitted for reasons unrelated to COVID-19. An assessment of the likelihood of infectiousness using clinical history, RT-PCR Ct values, and serology may help in making the determination to discontinue isolation and conserve resources.

Stable Clostridioides difficile infection rates after the discontinuation of ultraviolet light for terminal disinfection at a tertiary care center, Iowa 2019-2020.

We compared the incidence of Clostridioides difficile infection before and after the discontinuation of Ultraviolet light used in addition to bleach in terminal disinfection of hospital rooms. We found no difference in C. difficile infection rates but found a decreased turn over time. The benefit of Ultraviolet light may be diminished in hospitals with a high thoroughness of manual cleaning.

Coronavirus Disease 2019 Serial Testing Among Hospitalized Patients in a Midwest Tertiary Medical Center, July-September 2020.

We implemented serial coronavirus disease 2019 testing for inpatients with a negative test on admission. The conversion rate (negative to positive) on repeat testing was 1%. We identified patients during their incubation period and hospital-onset cases, rapidly isolated them, and potentially reduced exposures. Serial testing and infectiousness determination were resource intensive.

Administrative coding methods impact surgical site infection rates.

We performed a retrospective analysis of the impact of using the International Classification of Diseases, Tenth Revision procedure coding system (ICD-10) or current procedural terminology (CPT) codes to calculate surgical site infection (SSI) rates. Denominators and SSI rates vary depending on the coding method used. The coding method used may influence interhospital performance comparisons.