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.

A study protocol for a cluster-randomised controlled trial of smartphone-activated first responders with ultraportable defibrillators in out-of-hospital cardiac arrest: The First Responder Shock Trial (FIRST).

Objective: To describe the First Responder Shock Trial (FIRST), which aims to determine whether equipping frequently responding, smartphone-activated (GoodSAM) first responders with an ultraportable AED can increase 30-day survival rates in OHCA. Methods: The FIRST trial is an investigator-initiated, bi-national (Victoria, Australia and New Zealand), registry-nested cluster-randomised controlled trial where the unit of randomisation is the smartphone-activated (GoodSAM) first responder. High-frequency GoodSAM responders are randomised 1:1 to receive an ultraportable, single-use AED or standard alert procedures using the GoodSAM app.The primary outcome is survival to 30 days. The secondary outcome measures (shockable rhythm, return of spontaneous circulation, event survival, and time to first shock delivery) are routinely collected by OHCA registries in both regions. The trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) (Registration: ACTRN12622000448741) on 22 March 2022. Results: The trial started in November 2022 and the last patient is expected to be enrolled in November 2024. We aim to detect a 7% increase in the proportion of 30-day survivors, from 9% in patients attended by control responders to 16% in patients attended by responders randomised to the ultraportable AED intervention arm. With 80% power, an alpha of 0.05, a cluster size of 1.5 and a coefficient of variation for cluster sizes of 1, the sample size required to detect this difference is 714 (357 per arm). Conclusion: The FIRST study will increase our understanding of the potential role of portable AED use by smartphone-activated community responders and their impact on survival outcomes.

Evaluation of baseline behavioral tests in ferrets.

As the smallest mammal with a gyrencephalic cerebral cortex, ferrets are becoming increasingly important animal models to study neurological disorders. In order for them to be optimally used, typical behavioral measurements are highly desirable. To ascertain a baseline level of behavior, we conducted a battery of tests assessing motor, social, memory, headache, and aspects of depressive-like behavior. Adult male ferrets participated in open field, beam walk, sucrose preference, eye contact, light/dark box, socialization, and novel object recognition tests. The animals were assessed in three cohorts, which differed in age, with the youngest group being approximately 1 year younger than the oldest. Small, but significant, differences occurred between the youngest cohort and the older groups in several areas, suggesting that age may be an important factor when evaluating ferret behavior. Ferrets showed a high level of sociability in the eye contact tests and with novel animal preference. These experiments represent an important baseline of expected normative results that can provide a reference for normal ferret behavior and expected variability. The data reported here may serve as a reference for future intervention studies using the ferret. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Merit-Based Incentive Payment System (MIPS) Participation in Radiation Oncology Practices - A Simple Survey.

PURPOSE: Our purpose was to survey nationwide radiation oncology practices on their participation in, burden of, and satisfaction with the Medicare Access and Children's Health Insurance Program Reauthorization Act of 2015 (MACRA) payment programs. METHODS AND MATERIALS: All radiation oncology practices accredited by a national specialty organization were invited to participate in a voluntary online survey from December 2018 to January 2019. Questions focused on participation in the Merit-based Incentive Payment System (MIPS) in 2017 and 2018, as by the time of this survey, radiation oncology did not yet have a specialty-specific advanced Alternative Payment Model. RESULTS: Of n = 705 solicited practices, n = 199 completed the survey for an overall response rate of 28.2%. Practices varied significantly in their duration of participation in MACRA programs, means of data submission, and reported improvement activities under MIPS. Forty-nine percent of respondents described being either somewhat or extremely dissatisfied with the ease of submitting measures and data in 2018. The estimated cost to the practices of compliance with MACRA was queried in bins; of users able to estimate the cost of compliance for 2018, the median reported bin was $10,001 to $20,000 (range, less than $1000-100,000 or more). CONCLUSIONS: The participation style in MACRA among radiation oncology practices varied substantially in the years 2017 and 2018. The Center for Medicare & Medicaid Services gave no precise estimates on the cost of compliance for MIPS, but estimated a $3019.47 cost of compliance with the mandated Radiation Oncology Alternative Payment Model in the 2020 Final Rule for selected practices. In this survey, respondents commonly reported the cost of compliance with MACRA significantly exceeded this estimate.

A binational survey of smartphone activated volunteer responders for out-of-hospital cardiac arrest: Availability, interventions, and post-traumatic stress.

BACKGROUND: Responder smartphone apps use global positioning data to enable emergency medical services to alert volunteer responders of nearby potential out-of-hospital cardiac arrests (OHCA). AIM: To assess volunteer availability, interventions provided and frequency of probable post traumatic stress disorder (PTSD) experienced by responders receiving a smartphone alert. METHODS: A web-based survey was emailed to alerted responders at week-two post-alert and a PTSD screening survey at week-six, in Victoria, Australia (1/08/2019-8/11/2020), and in New Zealand (18/02/2020-28/10/2020). RESULTS: We received 1,985 responses to the week-two survey and 1,443 responses to the week-six survey. Of the 1,985 responders, 1,744 (87.9%) had completed cardiopulmonary resuscitation (CPR) training in the last twelve months, and 1,514 (76.3%) had performed CPR at least once. The alert was seen by 1,501 (75.6%) responders, 749 (37.7%) accepted the alert, 538 (27.1%) arrived on scene, and 283 (14.3%) provided care to the patient. In the multivariable analysis, CPR training within twelve months was associated with increased odds of responders accepting alerts (AOR 1.41, 95%CI: 1.02-1.96; p=0.040). Responders who had performed CPR before, were more than twice as likely to provide patient care compared to responders who had not (AOR 2.54, 95%CI: 1.56-4.12; p<0.001). One responder screened positive for probable PTSD. CONCLUSION: Acceptance rates in Australia and New Zealand were consistent with other smartphone apps. Responder recruitment should be targeted at those with medical backgrounds who have prior CPR experience, as they are more likely to provide care. The very low risk of PTSD is reassuring information when recruiting volunteers.

2021 AAFP Feline Senior Care Guidelines.

The '2021 AAFP Feline Senior Care Guidelines' are authored by a Task Force of experts in feline clinical medicine and serve as an update and extension of those published in 2009. They emphasize the individual patient evaluation and the process of aging, with references to other feline practice guidelines for a more complete discussion of specific diseases. Focusing on each cat encourages and empowers the owner to become a part of the cat's care every step of the way. A comprehensive discussion during the physical examination and history taking allows for tailoring the approach to both the cat and the family involved in the care. Videos and analysis of serial historical measurements are brought into the assessment of each patient. These Guidelines introduce the emerging concept of frailty, with a description and methods of its incorporation into the senior cat assessment. Minimum database diagnostics are discussed, along with recommendations for additional investigative considerations. For example, blood pressure assessment is included as a minimum diagnostic procedure in both apparently healthy and ill cats. Cats age at a much faster rate than humans, so practical timelines for testing frequency are included and suggest an increased frequency of diagnostics with advancing age. The importance of nutrition, as well as senior cat nutritional needs and deficiencies, is considered. Pain is highlighted as its own syndrome, with an emphasis on consideration in every senior cat. The Task Force discusses anesthesia, along with strategies to allow aging cats to be safely anesthetized well into their senior years. The medical concept of quality of life is addressed with the latest information available in veterinary medicine. This includes end of life considerations like palliative and hospice care, as well as recommendations on the establishment of 'budgets of care', which greatly influence what can be done for the individual cat. Acknowledgement is given that each cat owner will be different in this regard; and establishing what is reasonable and practical for the individual owner is important. A discussion on euthanasia offers some recommendations to help the owner make a decision that reflects the best interests of the individual cat.

Pre-operative platelet-bound CD40 ligand is probably associated with peri-operative cardiac events in hip and knee arthroplasty.

BACKGROUND: Peri-operative cardiac events are common and associated with significant morbidity. A predictive biomarker would assist in pre-operative risk stratification of surgical patients. This study explored the utility of pre-operative measurements of platelet-bound CD40 ligand and other biomarkers for predicting peri-operative cardiac events in total hip or knee arthroplasty. METHODS: Blood samples were collected from 62 patients prior to surgery and tested for the biomarkers platelet CD40 ligand, platelet factor V/Va, platelet P-selectin, high-sensitivity C-reactive protein, B-type natriuretic peptide and soluble CD40 ligand. The Revised Cardiac Risk Index was also calculated. Patients were then followed up prospectively and screened for peri-operative cardiac events by means of ECG, serial troponin I, a cardiologist's review and an interview at 6 weeks post operation. RESULTS: Six of 62 (9.7%) patients had a cardiac event. Patients who experienced a cardiac event had higher pre-operative platelet CD40 ligand levels as measured by flow cytometry [median 0.55% vs. 0.29% (P = 0.02)]. In this sized sample, platelet CD40L was the only biomarker independently associated with cardiac events (P = 0.02), the area under the receiver-operator characteristic curve being 0.79. CONCLUSION: In a study of this number of patients, of the six biomarkers tested, only platelet CD40 ligand was found to have a probable association with peri-operative cardiac events in hip and knee arthroplasty.

Correlation between anatomical characteristics of ethanol organosolv pretreated Buddleja davidii and its enzymatic conversion to glucose.

Buddleja davidii is a unique biomass that has many attractive agroenergy features, especially its wide range of growth habitat. The anatomical characteristics of B. davidii were investigated before and after ethanol organosolv pretreatment (one of the leading pretreatment technologies) in order to further understand the alterations that occur to the cellular structure of the biomass which can then be correlated with its enzymatic digestibility. Results showed that the ethanol organosolv pretreatment of B. davidii selectively removes lignin from the middle lamella (ML), which does not significantly disrupt the crystalline structure of cellulose. The removal of ML lignin is a major factor in enhancing enzymatic cellulose-to-glucose hydrolysis. The pretreatment also causes cell deformation, resulting in cracks and breaks in the cell wall. These observations, together with characterization analysis of the cell wall polymer material, lend support to the hypothesis that the physical distribution of lignin in the biomass matrix is an important structural feature affecting biomass enzymatic digestibility.

Inhibition of mTOR radiosensitizes soft tissue sarcoma and tumor vasculature.

PURPOSE: The PI3K/Akt/mTOR prosurvival pathway is frequently up-regulated in soft tissue sarcoma. Mammalian target of rapamycin (mTOR) inhibitors, such as rapamycin, have recently shown clinical benefit in soft tissue sarcoma, and mTOR inhibition has also been associated with radiosensitization of carcinoma and endothelial cells. This study tested the hypothesis that rapamycin radiosensitizes soft tissue sarcoma and endothelial cells in vitro and in vivo through the inhibition of mTOR. EXPERIMENTAL DESIGN: Colony formation assays were done to determine the radiosensitizing properties of rapamycin on three human soft tissue sarcoma cell lines (SK-LMS-1, SW-872, and HT-1080) and human dermal microvascular endothelial cells (HDMEC). The functional effects of rapamycin and radiation on the endothelial compartment were evaluated with microvascular sprouting assays. The in vivo radiosensitizing activity of rapamycin was assessed with s.c. SK-LMS-1 nude mice xenografts treated with concurrent daily rapamycin, radiation, or both for three weeks. RESULTS: In vitro radiosensitization was shown in all three soft tissue sarcoma cell lines with minimally cytotoxic doses of rapamycin. SK-LMS-1 xenografts displayed significant tumor growth delay with rapamycin and radiation compared with either treatment alone. Radiation resulted in transient increased mTOR function, whereas rapamycin abolished this signaling in irradiated and unirradiated samples. In HDMEC, rapamycin and radiation reduced microvessel sprouting, but did not alter colony formation. CONCLUSIONS: Minimally cytotoxic concentrations of rapamycin inhibited the mTOR cascade in culture and in vivo while radiosensitizing soft tissue sarcoma, and produced synergistic effects with radiation on HDMEC microvessel formation. By targeting both tumor and endothelial compartments, rapamycin produced potent radiosensitization of soft tissue sarcoma xenografts. Clinical trials combining rapamycin and radiotherapy in soft tissue sarcoma are warranted.

Oxygen consumption, heart rate, and blood lactate responses to an acute bout of plyometric depth jumps in college-aged men and women.

Although plyometrics are widely used in athletic conditioning, the acute physiologic responses to plyometrics have not been described. The purpose of this study was to investigate the oxygen consumption, heart rate, and blood lactate responses to a single session of plyometric depth jumps. Twenty recreationally trained college-aged subjects (10 men, 10 women) participated in a single session of 8 sets of 10 box depth jumps from a height of 0.8 m with 3 minutes of passive recovery between each set. Plyometric depth jumping elicited 82.5 +/- 3.1% and 77.8 +/- 3.1% of the measured maximal oxygen consumption (O2max) for women and men, respectively, with no difference in oxygen consumption in ml/kg/min or percent O2max between sexes or sets. Heart rate significantly increased (p < 0.05) from 68.1 +/- 2.9 beatsxmin-1 at rest to 169.6 +/- 1.2 beatsxmin-1 during depth jumping. Sets 5 to 8 elicited a higher (p < 0.05) heart rate (173.3 +/- 1.3 beatsxmin-1) than sets 1 to 4 (164.6 +/- 1.8 beatsxmin-1). Women exhibited a higher heart rate (p < 0.05) during sets 1 and 2 (169.9 +/- 2.8 beatsxmin-1) than men (150.7 +/- 4.4 beatsxmin-1). The blood lactate concentrations were significantly (p < 0.05) increased above resting throughout all sets (1.0 +/- 0.2 mmolxL-1 compared with 2.9 +/- 0.1 mmolxL-1), with no differences between sexes or sets. Plyometric depth jumping significantly increased oxygen consumption, heart rate, and blood lactate in both men and women, but no significant difference was found between the sexes. Plyometric depth jumping from a height of 0.8 m has similar energy system requirements to what Wilmore and Costill termed "Aerobic Power" training, which should enhance O2max, lactate tolerance, oxidative enzymes, and lactate threshold.

Antibiotic prescribing without documented indication in ambulatory care clinics: national cross sectional study.

OBJECTIVES: To identify the frequency with which antibiotics are prescribed in the absence of a documented indication in the ambulatory care setting, to quantify the potential effect on assessments of appropriateness of antibiotics, and to understand patient, provider, and visit level characteristics associated with antibiotic prescribing without a documented indication. DESIGN: Cross sectional study. SETTING: 2015 National Ambulatory Medical Care Survey. PARTICIPANTS: 28 332 sample visits representing 990.9 million ambulatory care visits nationwide. MAIN OUTCOME MEASURES: Overall antibiotic prescribing and whether each antibiotic prescription was accompanied by appropriate, inappropriate, or no documented indication as identified through ICD-9-CM (international classification of diseases, 9th revision, clinical modification) codes. Survey weighted multivariable logistic regression was used to evaluate potential risk factors for receipt of an antibiotic prescription without a documented indication. RESULTS: Antibiotics were prescribed during 13.2% (95% confidence interval 11.6% to 13.7%) of the estimated 990.8 million ambulatory care visits in 2015. According to the criteria, 57% (52% to 62%) of the 130.5 million prescriptions were for appropriate indications, 25% (21% to 29%) were inappropriate, and 18% (15% to 22%) had no documented indication. This corresponds to an estimated 24 million prescriptions without a documented indication. Being an adult male, spending more time with the provider, and seeing a non-primary care specialist were significantly positively associated with antibiotic prescribing without an indication. Sulfonamides and urinary anti-infective agents were the antibiotic classes most likely to be prescribed without documentation. CONCLUSIONS: This nationally representative study of ambulatory visits identified a large number of prescriptions for antibiotics without a documented indication. Antibiotic prescribing in the absence of a documented indication may severely bias national estimates of appropriate antibiotic use in this setting. This study identified a wide range of factors associated with antibiotic prescribing without a documented indication, which may be useful in directing initiatives aimed at supporting better documentation.