Influence of Antibiotic Exposure Intensity on the Risk of Clostridioides difficile Infection.

BACKGROUND: Antibiotics are a strong risk factor for Clostridioides difficile infection (CDI), and CDI incidence is often measured as an important outcome metric for antimicrobial stewardship interventions aiming to reduce antibiotic use. However, risk of CDI from antibiotics varies by agent and dependent on the intensity (i.e., spectrum and duration) of antibiotic therapy. Thus, the impact of stewardship interventions on CDI incidence is variable, and understanding this risk requires a more granular measure of intensity of therapy than traditionally used measures like days of therapy (DOT). METHODS: We performed a retrospective cohort study to measure the independent association between intensity of antibiotic therapy, as measured by the antibiotic spectrum index (ASI), and hospital-associated CDI (HA-CDI) at a large academic medical center between January 2018 and March 2020. We constructed a marginal Poisson regression model to generate adjusted relative risks for a unit increase in ASI per antibiotic day. RESULTS: We included 35,457 inpatient encounters in our cohort. Sixty-eight percent of patients received at least one antibiotic. We identified 128 HA-CDI cases, which corresponds to an incidence rate of 4.1 cases per 10,000 patient-days. After adjusting for known confounders, each additional unit increase in ASI per antibiotic day is associated with 1.09 times the risk of HA-CDI (Relative Risk = 1.09, 95% Confidence Interval: 1.06 to 1.13). CONCLUSIONS: ASI was strongly associated with HA-CDI and could be a useful tool in evaluating the impact of antibiotic stewardship on HA-CDI rates, providing more granular information than the more commonly used days of therapy.

Hypofractionated Radiation Therapy for Localized Prostate Cancer: Executive Summary of an ASTRO, ASCO and AUA Evidence-Based Guideline.

PURPOSE: The aim of this guideline is to present recommendations regarding moderately hypofractionated (240-340 cGy per fraction) and ultrahypofractionated (500 cGy or more per fraction) radiation therapy for localized prostate cancer. METHODS AND MATERIALS: The American Society for Radiation Oncology convened a task force to address 8 key questions on appropriate indications and dose-fractionation for moderately and ultrahypofractionated radiation therapy, as well as technical issues, including normal tissue dose constraints, treatment volumes, and use of image guided and intensity modulated radiation therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and Society-approved tools for grading evidence quality and recommendation strength. RESULTS: Based on high-quality evidence, strong consensus was reached for offering moderate hypofractionation across risk groups to patients choosing external beam radiation therapy. The task force conditionally recommends ultrahypofractionated radiation may be offered for low- and intermediate-risk prostate cancer but strongly encourages treatment of intermediate-risk patients on a clinical trial or multi-institutional registry. For high-risk patients, the task force conditionally recommends against routine use of ultrahypofractionated external beam radiation therapy. With any hypofractionated approach, the task force strongly recommends image guided radiation therapy and avoidance of nonmodulated 3-dimensional conformal techniques. CONCLUSIONS: Hypofractionated radiation therapy provides important potential advantages in cost and convenience for patients, and these recommendations are intended to provide guidance on moderate hypofractionation and ultrahypofractionation for localized prostate cancer. The limits in the current evidentiary base-especially for ultrahypofractionation-highlight the imperative to support large-scale randomized clinical trials and underscore the importance of shared decision making between clinicians and patients.

Prescribing Associated with High-Risk Opioid Exposures Among Non-cancer Chronic Users of Opioid Analgesics: a Social Network Analysis.

BACKGROUND: The continued rise in fatalities from opioid analgesics despite a steady decline in the number of individual prescriptions directing ≥ 90 morphine milligram equivalents (MME)/day may be explained by patient exposures to redundant prescriptions from multiple prescribers. OBJECTIVES: We evaluated prescribers' specialty and social network characteristics associated with high-risk opioid exposures resulting from single-prescriber high-daily dose prescriptions or multi-prescriber discoordination. DESIGN: Retrospective cohort study. PARTICIPANTS: A cohort of prescribers with opioid analgesic prescription claims for non-cancer chronic opioid users in an Illinois Medicaid managed care program in 2015-2016. MAIN MEASURES: Per prescriber rates of single-prescriber high-daily-dose prescriptions or multi-prescriber discoordination. KEY RESULTS: For 2280 beneficiaries, 36,798 opioid prescription claims were submitted by 3532 prescribers. Compared to 3% of prescriptions (involving 6% of prescribers and 7% of beneficiaries) that directed ≥ 90 MME/day, discoordination accounted for a greater share of high-risk exposures-13% of prescriptions (involving 23% of prescribers and 24% of beneficiaries). The following specialties were at highest risk of discoordinated prescribing compared to internal medicine: dental (incident rate ratio (95% confidence interval) 5.9 (4.6, 7.5)), emergency medicine (4.7 (3.8, 5.8)), and surgical subspecialties (4.2 (3.0, 5.8)). Social network analysis identified 2 small interconnected prescriber communities of high-volume pain management specialists, and 3 sparsely connected groups of predominantly low-volume primary care or emergency medicine clinicians. Using multivariate models, we found that the sparsely connected sociometric positions were a risk factor for high-risk exposures. CONCLUSION: Low-volume prescribers in the social network's periphery were at greater risk of intended or discoordinated prescribing than interconnected high-volume prescribers. Interventions addressing discoordination among low-volume opioid prescribers in non-integrated practices should be a priority. Demands for enhanced functionality and integration of Prescription Drug Monitoring Programs or referrals to specialized multidisciplinary pain management centers are potential policy implications.

Regional Spread of an Outbreak of Carbapenem-Resistant Enterobacteriaceae Through an Ego Network of Healthcare Facilities.

Background: In 2013, New Delhi metallo-ß-lactamase (NDM)-producing Escherichia coli, a type of carbapenem-resistant Enterobacteriaceae uncommon in the United States, was identified in a tertiary care hospital (hospital A) in northeastern Illinois. The outbreak was traced to a contaminated duodenoscope. Patient-sharing patterns can be described through social network analysis and ego networks, which could be used to identify hospitals most likely to accept patients from a hospital with an outbreak. Methods: Using Illinois' hospital discharge data and the Illinois extensively drug-resistant organism (XDRO) registry, we constructed an ego network around hospital A. We identified which facilities NDM outbreak patients subsequently visited and whether the facilities reported NDM cases. Results: Of the 31 outbreak cases entered into the XDRO registry who visited hospital A, 19 (61%) were subsequently admitted to 13 other hospitals during the following 12 months. Of the 13 hospitals, the majority (n = 9; 69%) were in our defined ego network, and 5 of those 9 hospitals consequently reported at least 1 additional NDM case. Ego network facilities were more likely to identify cases compared to a geographically defined group of facilities (9/22 vs 10/66; P = .01); only 1 reported case fell outside of the ego network. Conclusions: The outbreak hospital's ego network accurately predicted which hospitals the outbreak patients would visit. Many of these hospitals reported additional NDM cases. Prior knowledge of this ego network could have efficiently focused public health resources on these high-risk facilities.

Spread of Carbapenem-Resistant Enterobacteriaceae Among Illinois Healthcare Facilities: The Role of Patient Sharing.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) spread regionally throughout healthcare facilities through patient transfer and cause difficult-to-treat infections. We developed a state-wide patient-sharing matrix and applied social network analyses to determine whether greater connectedness (centrality) to other healthcare facilities and greater patient sharing with long-term acute care hospitals (LTACHs) predicted higher facility CRE rates. METHODS: We combined CRE case information from the Illinois extensively drug-resistant organism registry with measures of centrality calculated from a state-wide hospital discharge dataset to predict facility-level CRE rates, adjusting for hospital size and geographic characteristics. RESULTS: Higher CRE rates were observed among facilities with greater patient sharing, as measured by degree centrality. Each additional hospital connection (unit of degree) conferred a 6% increase in CRE rate in rural facilities (relative risk [RR] = 1.056; 95% confidence interval [CI], 1.030-1.082) and a 3% increase among Chicagoland and non-Chicago urban facilities (RR = 1.027; 95% CI, 1.002-1.052 and RR = 1.025; 95% CI, 1.002-1.048, respectively). Sharing 4 or more patients with LTACHs was associated with higher CRE rates, but this association may have been due to chance (RR = 2.08; 95% CI, .85-5.08; P = .11). CONCLUSIONS: Hospitals with greater connectedness to other hospitals in a statewide patient-sharing network had higher CRE burden. Centrality had a greater effect on CRE rates in rural counties, which do not have LTACHs. Social network analysis likely identifies hospitals at higher risk of CRE exposure, enabling focused clinical and public health interventions.

X-ray micro-computed tomography in willow reveals tissue patterning of reaction wood and delay in programmed cell death.

BACKGROUND: Variation in the reaction wood (RW) response has been shown to be a principle component driving differences in lignocellulosic sugar yield from the bioenergy crop willow. The phenotypic cause(s) behind these differences in sugar yield, beyond their common elicitor, however, remain unclear. Here we use X-ray micro-computed tomography (µCT) to investigate RW-associated alterations in secondary xylem tissue patterning in three dimensions (3D). RESULTS: Major architectural alterations were successfully quantified in 3D and attributed to RW induction. Whilst the frequency of vessels was reduced in tension wood tissue (TW), the total vessel volume was significantly increased. Interestingly, a delay in programmed-cell-death (PCD) associated with TW was also clearly observed and readily quantified by µCT. CONCLUSIONS: The surprising degree to which the volume of vessels was increased illustrates the substantial xylem tissue remodelling involved in reaction wood formation. The remodelling suggests an important physiological compromise between structural and hydraulic architecture necessary for extensive alteration of biomass and helps to demonstrate the power of improving our perspective of cell and tissue architecture. The precise observation of xylem tissue development and quantification of the extent of delay in PCD provides a valuable and exciting insight into this bioenergy crop trait.

Use of electronic health record data to identify hospital-associated Clostridioides difficile infections: a validation study.

Background: Clinical research focused on the burden and impact of Clostridioides difficile infection (CDI) often relies upon accurate identification of cases using existing health record data. Use of diagnosis codes alone can lead to misclassification of cases. Our goal was to develop and validate a multi-component algorithm to identify hospital-associated CDI (HA-CDI) cases using electronic health record (EHR) data. Methods: We performed a validation study using a random sample of adult inpatients at a large academic hospital setting in Portland, Oregon from January 2018 to March 2020. We excluded patients with CDI on admission and those with short lengths of stay (< 4 days). We tested a multi-component algorithm to identify HA-CDI; case patients were required to have received an inpatient course of metronidazole, oral vancomycin, or fidaxomicin and have at least one of the following: a positive C. difficile laboratory test or the International Classification of Diseases, Tenth Revision (ICD-10) code for non-recurrent CDI. For a random sample of 80 algorithm-identified HA-CDI cases and 80 non-cases, we performed manual EHR review to identify gold standard of HA-CDI diagnosis. We then calculated overall percent accuracy, sensitivity, specificity, and positive and negative predictive value for the algorithm overall and for the individual components. Results: Our case definition algorithm identified HA-CDI cases with 94% accuracy (95% Confidence Interval (CI): 88% to 97%). We achieved 100% sensitivity (94% to 100%), 89% specificity (81% to 95%), 88% positive predictive value (78% to 94%), and 100% negative predictive value (95% to 100%). Requiring a positive C. difficile test as our gold standard further improved diagnostic performance (97% accuracy [93% to 99%], 93% PPV [85% to 98%]). Conclusions: Our algorithm accurately detected true HA-CDI cases from EHR data in our patient population. A multi-component algorithm performs better than any isolated component. Requiring a positive laboratory test for C. difficile strengthens diagnostic performance even further. Accurate detection could have important implications for CDI tracking and research.

Effect of surfactant type and redox polymer type on single-walled carbon nanotube modified electrodes.

Electrodes modified with single-walled carbon nanotubes (SWNTs) offer a number of attractive properties for developing novel electrochemical sensors. A common method to immobilize SWNTs onto the electrode surface is by placing a droplet of a SWNT suspension onto the electrode surface and allowing the solvent to evaporate. In order to maximize the properties of individual SWNTs, surfactants are normally present in these suspensions to provide stable and homogeneous SWNT dispersions. In this study we investigated the effect of different surfactants on the electrochemical and enzymatic performance of SWNT modified glassy carbon electrodes (GCEs). Amperometic biosensors for glucose were fabricated by a two-step procedure. In the first step, SWNT films were deposited onto GCEs by solution casting suspensions of SWNTs in water, Triton X-100, Tween 20, sodium cholate or sodium dodecylbenzenesulfonate (NaDDBS). In the second step, hydrogels containing a redox polymer and the enzyme, glucose oxidase (GOX), were deposited and cross-linked onto the SWNT-modified GCE. Three different redox polymers were tested: 3-ferrocenylpropyl-modified LPEI, (Fc-C3-LPEI), 6-ferrocenylhexyl-modified LPEI, (Fc-C6-LPEI), and poly[(vinylpyridine)Os(bipyridyl)2Cl](2+/3+)(PVP-Os). Biosensors constructed with SWNT films from suspensions of Triton X-100 or Tween 20 generally produced the highest electrochemical and enzymatic responses, with Triton X-100 films producing current densities of ~1.7-2.1 mA/cm(2) for the three different redox polymers. In contrast, biosensors constructed with SWNT films from sodium cholate suspensions resulted in significant decreases in the electrochemical and enzymatic response and in some cases showed no enzymatic activity. The results with SWNT films from NaDDBS suspensions were dependent upon the specific redox polymer used, but in general gave reduced enzymatic responses (~0.05-0.4 mA/cm(2)). These results demonstrate the importance of surfactant type in fabricating SWNT-modified electrode films.

The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors.

Pancreas development begins with the formation of buds at specific sites in the embryonic foregut endoderm. We used recombination-based lineage tracing in vivo to show that Ptf1a (also known as PTF1-p48) is expressed at these early stages in the progenitors of pancreatic ducts, exocrine and endocrine cells, rather than being an exocrine-specific gene as previously described. Moreover, inactivation of Ptf1a switches the character of pancreatic progenitors such that their progeny proliferate in and adopt the normal fates of duodenal epithelium, including its stem-cell compartment. Consistent with the proposal that Ptf1a supports the specification of precursors of all three pancreatic cell types, transgene-based expression of Pdx1, a gene essential to pancreas formation, from Ptf1a cis-regulatory sequences restores pancreas tissue to Pdx1-null mice that otherwise lack mature exocrine and endocrine cells because of an early arrest in organogenesis. These experiments provide evidence that Ptf1a expression is specifically connected to the acquisition of pancreatic fate by undifferentiated foregut endoderm.

No fear: Willingness of smartphone activated first responders to assist with cardiac arrest during the COVID-19 pandemic.

Aim: To understand the fear and willingness to respond of smartphone activated first responders during the COVID-19 pandemic. Methods: We invited smartphone activated first responders registered with the GoodSAM application in Victoria, Australia to take part in an online survey in November 2020. We assessed willingness to respond to an alert and provide CPR during the pandemic and administered the Fear of COVID-19 Scale questionnaire. Regression analysis was conducted to investigate associations between occupation, clinical training, and years of clinical experience with willingness to respond and fear of COVID-19. Results: The survey response rate was 5.1%. Responders (n = 348) had a median age (interquartile range) of 46 years (33-55). Most (67%) were aged 30-59 years and 43% were female. Responders spanned several occupations including paramedics (12.6%), registered nurses (14.7%), and non-clinical individuals (21.8%). Most (92%) reported they would feel comfortable responding to a GoodSAM alert during the pandemic. Almost all (>95%) reported they would provide CPR. About 20% reported being afraid of COVID-19 but only 3.2% reported they had a high-level of fear of COVID-19. The odds of paramedics being willing to respond to an alert was reduced by 73% during the pandemic (OR 0.27, 95% CI 0.11 to 0.69). No other associations were found with willingness or fear of COVID-19. Conclusion: Although willingness was high and fear of COVID-19 was low, some smartphone activated first responders were less willing to respond to an alert during the pandemic. These findings may inform future pandemic planning and decision-making around pausing first-responder programs.