Search

Background Clostridioides difficile infection (CDI) incidence estimates vary between geographic regions; few studies have evaluated the impact of CDI test order frequency on estimated CDI incidence. We evaluated this impact in a sample of hospitals at two CDC Emerging Infections Program (EIP) sites. Methods Daily surveillance was conducted for diarrhea among inpatients at 5 acute care hospitals (2,379 beds) in EIP sites in NY (2 hospitals) and GA (3 hospitals) during two 10-workday periods in 2020 and 2021. Diarrhea onset, test orders, and specimen collection status were ascertained. Stools were tested by PCR/NAAT initially or after negative EIA toxin. Differences in diarrhea incidence, testing frequency, and CDI positivity across site, care locations and hospitals were compared using Wilcoxon rank sum test. Correlates of CDI testing and positivity were assessed using modified Poisson regression. Estimates of incidence using EIP methodology at 5 hospitals was compared between sites using Mantel-Hanzel summary rate ratio. Results Surveillance of 38,365 patient-days (PD) identified 860 diarrhea cases from 107 patient-care locations mapped to 26 unique NHSN defined location-types. Incidence of diarrhea was 22.4/1000 PD (medians 25.8 NY, 16.2 GA, P< 0.01); with similar proportions of diarrhea being hospital-onset (66%) and CDI positive (17%) by site. Overall, 35% were tested for CDI (21% NY, 49% GA, P< 0.01). Percent tested varied by NHSN location type (Figure). Regression models identified location-type (oncology, critical care), laxatives use, chemotherapy, and residing in EIP catchment area predictive of testing (Figure). Adjusting for these factors, NY was 49% less likely than GA to test (aRR 0.51, 95% CI 0.40-0.63). Simulation of EIP methods estimated NY had a 38% lower incidence of CDI than GA (summary rate ratio 0.62, 95% CI, 0.54-0.71). Figure Incidence of Diarrheal Episodes (A) and Proportions Tested (B) among Hospitalized Patients, 2021 (solid, ward; open, critical care; grey, oncology), and adjusted relative risk (solid circles) with 95% confidence intervals (whisker) of independent predictors of testing for CDI (C). Conclusion After adjusting for patient characteristics (e.g., location-type, laxative use), the likelihood of testing still differed between NY and GA sites; the magnitude of the differences in testing was similar to that observed in estimated CDI incidence. Testing practices likely influence surveillance data and is a consideration when comparing data across regions. Disclosures Scott Fridkin, MD, Pfizer: Grant/Research Support christopher J. Myers, MS, Infectious diseases, Pfizer: Grant/Research Support Udodirim N. Onwubiko, MBBS MPH, Pfizer: Grant/Research Support William C. Dube, MPH, Pfizer: Grant/Research Support Sahil Khanna, MBBS, MS, Pfizer: Grant/Research Support Joann M. Zamparo, MPH, Pfizer: Employee|Pfizer: Stocks/Bonds Frederick J. Angulo, DVM PhD, Pfizer Vaccines: Employee|Pfizer Vaccines: Stocks/Bonds Ghinwa Dumyati, MD, Pfizer: Grant/Research Support.

Background Risk of infection with SARS-CoV-2 has remained high among health care personnel (HCP) throughout the pandemic, due to both exposure in the community and occupational settings. While vaccine uptake among health care workers is high, real-world continual monitoring of vaccine effectiveness (VE) among this population is crucial for informing future vaccination and prevention efforts. Methods Data for this analysis came from a test-negative case-control study conducted among HCP working at two acute care hospitals in Monroe County, NY from December 2020 through March 2022, performed as part of the CDC Emerging Infections Program. Case participants were identified as HCP who had at least one COVID-19 like symptom, and a positive polymerase-chain-reaction (PCR) SARS-CoV-2 test during the study time period. Control participants had a negative SARS-CoV-2 PCR test, regardless of presence of COVID-19 like symptoms. Cases and controls were matched based on the study week of their test date. Conditional logistic regression was used to assess vaccine effectiveness against symptomatic infection. Effectiveness was assessed between December 2020-May 2021, May 2021-October 2021, and October 2021-March 2022. Results From December 28th, 2020 through March 12th, 2022, 881 cases and 1794 controls were enrolled. Vaccine effectiveness against symptomatic infection was greatest from December 2020 through May 2021, with mRNA complete series effectiveness at 93.1% (95% CI: 86.9%-96.3%) with complete series VE falling to 25.1% (95% CI: 0.0%-50.9%) during May 2021-October 2021. Waning immunity following receipt of second dose was observed across all time periods. Vaccine effectiveness following receipt of one booster vaccine was found to be 59.2% (95% CI: 43.5-70.6), with evidence of waning immunity two months from receipt of the booster (VE: 46.6%; 95% CI: 14.6%-66.7%). Conclusion Protection provided by the COVID-19 mRNA vaccines against symptomatic infection is highly variable among HCP, based on the circulating dominant variant and the time since receipt of each dose. Monitoring of vaccine effectiveness, as well as waning immunity, among this high-risk population is essential to guide future vaccine policies. Disclosures christopher J. Myers, MS, Infectious diseases, Pfizer: Grant/Research Support Ghinwa Dumyati, MD, Pfizer: Grant/Research Support.

This commentary provides a background on gene therapy and identifies a critical gap in pharmacy practice education. The history and handling of gene therapy is contextualized with current pharmacy practice. With the increasing numbers of gene and cell-based therapies approaching the market, the need for appropriate training is greater than ever. There are few gene therapy training resources for pharmacists, and gene therapies require complex handing and administration. Pharmacists play a vital role in bringing new therapies to health care institutions and training other health care providers. Pharmacy organizations and health systems should work to develop gene therapy training resources for health-system pharmacists.

The binary switch is a basic component of digital information. From phase-change alloys to nanomechanical beams, molecules and atoms, new strategies for controlled bistability hold great interest for emerging technologies. We present a generic methodology for precise and parallel spatiotemporal control of nanometre-scale matter in a fluid, and demonstrate the ability to attain digital functionalities such as switching, gating and data storage in a single colloid, with further implications for signal amplification and logic operations. This fluid-phase bit can be arrayed at high densities, manipulated by either electrical or optical fields, supports low-energy, high-speed operation and marks a first step toward 'colloidal information'. The principle generalizes to any system where spatial perturbation of a particle elicits a differential response amenable to readout.

Summary Clostridium scindens biotransforms primary bile acids into secondary bile acids, and is correlated with inhibition of Clostridium difficile growth in vivo. The aim of the current study was to determine how C. scindens regulates C. difficile growth in vitro and if these interactions might relate to the regulation of gut microbiome structure in vivo. The bile acid 7α-dehydroxylating gut bacteria, C. scindens and C. sordellii, were found to secrete the tryptophan-derived antibiotics, 1-acetyl-β-carboline and turbomycin A, respectively. Both antibiotics inhibited growth of C. difficile and other gut bacteria. The secondary bile acids, deoxycholic acid and lithocholic acid, but not cholic acid, enhanced the inhibitory activity of these antibiotics. These antibiotics appear to inhibit cell division of C. difficile. The results help explain how endogenously synthesized antibiotics and secondary bile acids may regulate C. difficile growth and the structure of the gut microbiome in health and disease.

Tension, ischemia, and technical error are factors leading to anastomotic complications such as leak, stricture, and ulceration with bleeding. Currently, surgeons evaluate tissue ischemia without any simple routine measurement technique. A new tissue surface probe, T-Stat 303, provides continuous measurement of tissue hemoglobin oxygen saturation (StO(2)) and may have clinical utility for intraoperative assessment of blood flow in areas of surgical anastomosis. This pilot study aimed to determine local StO(2) during gut stapling using various staple sizes for the purpose of assessing the tool's ability to measure changes and the reproducibility of those changes with stapling.Measurements were made in nine anesthetized adult swine during laparotomy. Various staple heights were used to transect small bowel and colon. Serosal and mucosal surface measurements were obtained at baseline and on each side of the transection using the T-Stat device adjacent to the staple line and 2 cm away from it.Both small bowel and colon mucosal StO(2) adjacent to the staple line showed significant ischemia compared with baseline (p0.001) and 2 cm away from the staple line (p0.001) using all staple heights. The serosa of both small bowel and colon adjacent to the staple line was not significantly different from baseline serosa (p0.11) except when the grey stapler was used (baseline, 58 +/- 6.6 vs. staple line, 51 +/- 15.1; p = 0.022). The baseline mucosa of the small bowel and colon did not differ from mucosa 2 cm away from the staple line (p0.08). The small bowel serosa 2 cm away from the staple line did not differ from baseline mucosa, whereas the colon serosa 2 cm away significantly increased after stapling compared with baseline mucosa (p0.012). No statistically significant StO(2) difference was found between the various staple load sizes.Mucosal ischemia occurs after gastrointestinal stapling and is not affected by various staple heights. The T-Stat probe provides a real-time method for assessment of gut ischemia by surgeons during surgical procedures.

Although tissue ischemia at surgical anastomoses can cause leakage, stricture, and ulceration, surgeons rely on nonquantitative measures of detecting ischemia (e.g., color changes, pulsation), which are not likely to detect transient or small degrees of ischemia. A new microvascular tissue oximeter probe (T-Stat) provides noninvasive real-time measurement of tissue hemoglobin oxygen saturation (StO(2)). We measured local gastric StO(2) during stapling for transection/pouch creation to assess the reproducibility of measurements, the sensitivity of the mucosa versus serosa to ischemia, and the effect of the proximity to the staple line on the measurement.Anesthetized adult swine (n = 8) underwent laparotomy to transect gastric tissue in vivo with measurements made in 2 locations using 4.8-mm staple height cartridges.Both mucosal and serosal StO(2) decreased significantly when measured adjacent to the staple line compared with baseline (mucosa 3.0% +/- 5.6% versus 42.1% +/- 13.5%, serosa 48.2% +/- 15.1% versus 64.9% +/- 7.6%, P.05). No significant change was found in the mucosal or serosal StO(2) at baseline compared with 2 cm away (mucosa 42.1% +/- 13.5% versus 32.3% +/- 18.7%, serosa 64.9% +/- 7.6% versus 59.9 +/- 9.4; P.05). No color or pulsation changes were observed.Although significant reproducible mucosal and serosal decreases in StO(2) were seen in proximity to the gastric staple lines, the decrease in mucosal StO(2) was dramatic in the absence of any visible changes. The persistence of tissue ischemia with gastric stapling or in the creation of an anastomosis might contribute to the development of complications. The use of a real-time, noninvasive tissue probe could ultimately assist surgeons in identifying patients at risk of complications.

To facilitate endolumenal and natural orifice procedures, this study evaluated a novel technique using external and endoscopically placed magnets to create suture-free gastroenteral anastomoses.Seven anesthetized adult swine underwent endoscopic placement of magnets into the small bowel and stomach. Using external magnets, the endoscopically placed internal magnets were brought into opposition under endoscopic view. After 1-2 weeks, the pigs were killed and analyzed. At laparotomy and under sterile conditions, peritoneal cultures were obtained. The anastomoses were evaluated endoscopically and tested using an air insufflation test. Finally, the anastomoses were resected and evaluated microscopically.The average operative time for endoscopic placement of the magnets was 34.3 +/- 14.8 min. Successful placement and creation of anastomoses occurred in six of the pigs. One pig did not form an anastomosis because the magnets were too large to pass through the pylorus at the time of attempted magnet placement. Six swine experienced uncomplicated postoperative courses. One pig's postoperative course involved constipation for several days, requiring additional fluids and fiber supplementation. The findings at endoscopy showed that the magnets were adhered to the anastomosis, which were easily freed, or within the stomach. The air insufflation test results were negative for all the pigs. At laparotomy, there was no evidence of infection, abscess, or leak, but two peritoneal culture results were positive with scant growth of Staphylococcus aureus and coagulase-negative staphylococcus, presumably contaminants. Microscopically, the anastomoses illustrated granulation and fibrous connective tissue without evidence of infection or leak.Endoscopically placed magnets with external magnet guidance is a feasible and novel approach to creating patent gastroenteral anastomoses without abdominal incisions or sutures.

Background: Although tissue ischemia at surgical anastomoses may cause leak, stricture, and ulceration, surgeons rely on nonquantitative measures of detecting ischemia (e.g. color change, pulsation), not likely to detect transient or small degrees of ischemia. A microvascular tissue oximeter probe (T-STAT, Spectros, CA) provides non-invasive real-time measurement of tissue hemoglobin oxygen saturation (StO2). We measured local gastric StO2 during stapling for transection/pouch creation to assess the reproducibility of measurements, sensitivity of the mucosa versus serosa to ischemia, and the impact of proximity to the staple line. Methods: Anesthetized adult swine (n 8) underwent laparotomy to transect gastric tissue in vivo with measurements made in 2 locations using 4.8 mm staple height cartridges (Endo-GIA, Covidien, Connecticut). Results: Mucosal and serosal gastric StO2 measurements (Table, n 24 at each location) were compared. Mucosal baseline StO2 was lower than serosal baseline (t test, #p 0.05). Both mucosal and serosal StO2 decreased significantly in adjacent to the staple line, but not at 2 cm distance (ANOVA, *p 0.05). No color or pulsation changes were observed. Conclusion: Although significant reproducible mucosal and serosal decreases in StO2 were seen in proximity to gastric staple lines, the fall in mucosal StO2 was dramatic in the absence of any visible changes. Persistence of tissue ischemia with gastric stapling or in the creation of an anastomosis may contribute to complications. Utilization of a real-time, non-invasive tissue probe may ultimately assist surgeons in identifying patients at risk for complications.

Nonresponse bias in medical students' ratings of basic science instructors was studied by comparing the responses of initial respondents with those obtained through follow-up procedures. Three discriminant analyses were used to compare two groups of students' ratings using the six items on the instructor rating form as variables. It was concluded that these medical students' assessments of basic science instruction showed no significant bias from failure to obtain responses from all students. The results provide some evidence for allowing basic science instructors to have more confidence in the representativeness of student feedback on instruction provided by respondents. Studies to generalize these findings to other higher education populations are suggested.