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Background: It is difficult to diagnose and grade bony stress injury (BSI) in the athletic adolescent population without advanced imaging. Radiographs are recommended as a first imaging modality, but have limited sensitivity and, even when findings are present, advanced imaging is often recommended. Hypothesis: It was hypothesized that the significance of radiographs is underestimated for BSI in the adolescent with positive clinical examination and history findings. Study design: Case series Level of evidence: Level 4 Methods: A total of 80 adolescent athletes with a history of shin pain underwent clinical examination by an orthopaedic surgeon. On the day of clinical examination, full-length bilateral tibial radiographs and magnetic resonance imaging (MRI) scans were obtained. MRI scans were reviewed using Fredericson grading for BSI. At the completion of the study, radiographic images were re-evaluated by 2 musculoskeletal (MSK) radiologists, blinded to MRI and clinical examination results, who reviewed the radiographs for evidence of BSI. Radiographic results were compared with clinical examination and MRI findings. Sensitivity, specificity, negative predictive value, and positive predictive value were calculated based on comparison with MRI. Results: All radiographs were originally read as normal. Of the tibia studied, 80% (127 of 160) showed evidence of BSI on MRI. None of the original radiographs demonstrated a fracture line on initial review by the orthopaedic surgeons. Retrospective review by 2 MSK radiologists identified 27% of radiographs (34 of 127) with evidence of abnormality, which correlated with clinical examination and significant findings on MRI. Review of radiographs found evidence of new bone on 0 of 28 Fredericson grade 0, 0 of 19 Fredericson grade I, 11 of 80 (13.7%) Fredericson grade II, 18 of 28 (64%) Fredericson grade III, and 5 of 5 (100%) Fredericson grade IV. Sensitivity of radiographs showed evidence of new bone on 27% (34 of 127) of initial radiographs, with presence more common with greater degree of BSI, as 23 of 33 (70%) were higher-grade injuries (III of IV) of BSI. Specificity and positive predictive value were 100%, while negative predictive value was 17%. Conclusion: These findings highlight the importance of initial radiographs in identifying high-grade BSI. As radiographs are readily available in most office settings of sports medicine physicians, this information can influence the management of adolescent athletic BSI without the need to delay treatment to obtain an MRI. Clinical Relevance: Adolescent athletes with radiographic evidence of BSI should be treated in a timely and more conservative manner, given the likelihood of higher-grade BSI. In addition, clinicians knowledgeable of the radiographic findings of high-grade BSI should feel more confident that a negative initial radiograph is not likely to be a high-grade BSI and can modify their treatment plans accordingly.

Purpose The risk of acute kidney injury (AKI) associated with concomitant vancomycin and piperacillin/tazobactam in the intensive care unit (ICU) remains controversial. The aim of this study was to compare the AKI incidence associated with concomitant vancomycin and piperacillin/tazobactam compared to either cefepime or meropenem with vancomycin in the ICU. Materials and methods A multicenter, retrospective, propensity score-matched cohort study was conducted in adult ICU patients administered vancomycin in combination with either piperacillin/tazobactam, cefepime, or meropenem were included. Patients developing AKI ≤48 h following combination therapy initiation were excluded. The primary endpoint was to compare the incidence of AKI associated with concomitant antimicrobial therapy. Multivariable Cox regression modeling in predicting AKI was also conducted. Results A total of 1044 patients were matched. The AKI incidence in vancomycin- piperacillin/tazobactam and vancomycin-cefepime/meropenem groups were 21.9% and 16.8%, respectively (p = 0.068). Multivariable prediction models showed concomitant vancomycin-piperacillin/tazobactam was an independent risk factor of AKI using serum creatinine only (HR 1.52, 1.10–2.10, p = 0.011) and serum creatinine with urine output-based KDIGO criteria (HR 1.77, 1.18–2.67, p = 0.006). No significant differences between groups were observed for AKI recovery patterns or mortality. Conclusion Concomitant vancomycin and piperacillin/tazobactam administration in adult ICU patients was independently associated with an increased risk of AKI.

The clinical utility of methicillin-resistantThe objective of this study was to compare the predictive value of culture-based MRSA nasal screening for pneumonia and bacteremia in ICU and general ward patients.This multicenter, retrospective study was conducted over a 23-month period. Adult patients with MRSA nasal screening ≤48 hours of collecting a respiratory and/or blood culture with concurrent initiation of anti-MRSA therapy were included. The primary endpoint was to compare the negative predictive value (NPV) associated with culture-based MRSA nasal screening between ICU and general ward patients with suspected pneumonia.A total of 5106 patients representing the ICU (n = 2515) and general ward (n = 2591) were evaluated. The NPV of the MRSA nares for suspected pneumonia was not significantly different between ICU and general ward patient populations (98.3% and 97.6%, respectively;Our findings support the routine use of MRSA nasal screening using the culture-based method in ICU patients with pneumonia. Further research on the clinical performance for MRSA bacteremia in the ICU is warranted.

Different forms of vaccines have been developed to prevent the SARS-CoV-2 virus and subsequent COVID-19 disease. Several are in widespread use globally. OBJECTIVES: To assess the efficacy and safety of COVID-19 vaccines (as a full primary vaccination series or a booster dose) against SARS-CoV-2.We searched the Cochrane COVID-19 Study Register and the COVID-19 L·OVE platform (last search date 5 November 2021). We also searched the WHO International Clinical Trials Registry Platform, regulatory agency websites, and Retraction Watch.We included randomized controlled trials (RCTs) comparing COVID-19 vaccines to placebo, no vaccine, other active vaccines, or other vaccine schedules.We used standard Cochrane methods. We used GRADE to assess the certainty of evidence for all except immunogenicity outcomes. We synthesized data for each vaccine separately and presented summary effect estimates with 95% confidence intervals (CIs). MAIN RESULTS: We included and analyzed 41 RCTs assessing 12 different vaccines, including homologous and heterologous vaccine schedules and the effect of booster doses. Thirty-two RCTs were multicentre and five were multinational. The sample sizes of RCTs were 60 to 44,325 participants. Participants were aged: 18 years or older in 36 RCTs; 12 years or older in one RCT; 12 to 17 years in two RCTs; and three to 17 years in two RCTs. Twenty-nine RCTs provided results for individuals aged over 60 years, and three RCTs included immunocompromized patients. No trials included pregnant women. Sixteen RCTs had two-month follow-up or less, 20 RCTs had two to six months, and five RCTs had greater than six to 12 months or less. Eighteen reports were based on preplanned interim analyses. Overall risk of bias was low for all outcomes in eight RCTs, while 33 had concerns for at least one outcome. We identified 343 registered RCTs with results not yet available. This abstract reports results for the critical outcomes of confirmed symptomatic COVID-19, severe and critical COVID-19, and serious adverse events only for the 10 WHO-approved vaccines. For remaining outcomes and vaccines, see main text. The evidence for mortality was generally sparse and of low or very low certainty for all WHO-approved vaccines, except AD26.COV2.S (Janssen), which probably reduces the risk of all-cause mortality (risk ratio (RR) 0.25, 95% CI 0.09 to 0.67; 1 RCT, 43,783 participants; high-certainty evidence). Confirmed symptomatic COVID-19 High-certainty evidence found that BNT162b2 (BioNtech/Fosun Pharma/Pfizer), mRNA-1273 (ModernaTx), ChAdOx1 (Oxford/AstraZeneca), Ad26.COV2.S, BBIBP-CorV (Sinopharm-Beijing), and BBV152 (Bharat Biotect) reduce the incidence of symptomatic COVID-19 compared to placebo (vaccine efficacy (VE): BNT162b2: 97.84%, 95% CI 44.25% to 99.92%; 2 RCTs, 44,077 participants; mRNA-1273: 93.20%, 95% CI 91.06% to 94.83%; 2 RCTs, 31,632 participants; ChAdOx1: 70.23%, 95% CI 62.10% to 76.62%; 2 RCTs, 43,390 participants; Ad26.COV2.S: 66.90%, 95% CI 59.10% to 73.40%; 1 RCT, 39,058 participants; BBIBP-CorV: 78.10%, 95% CI 64.80% to 86.30%; 1 RCT, 25,463 participants; BBV152: 77.80%, 95% CI 65.20% to 86.40%; 1 RCT, 16,973 participants). Moderate-certainty evidence found that NVX-CoV2373 (Novavax) probably reduces the incidence of symptomatic COVID-19 compared to placebo (VE 82.91%, 95% CI 50.49% to 94.10%; 3 RCTs, 42,175 participants). There is low-certainty evidence for CoronaVac (Sinovac) for this outcome (VE 69.81%, 95% CI 12.27% to 89.61%; 2 RCTs, 19,852 participants). Severe or critical COVID-19 High-certainty evidence found that BNT162b2, mRNA-1273, Ad26.COV2.S, and BBV152 result in a large reduction in incidence of severe or critical disease due to COVID-19 compared to placebo (VE: BNT162b2: 95.70%, 95% CI 73.90% to 99.90%; 1 RCT, 46,077 participants; mRNA-1273: 98.20%, 95% CI 92.80% to 99.60%; 1 RCT, 28,451 participants; AD26.COV2.S: 76.30%, 95% CI 57.90% to 87.50%; 1 RCT, 39,058 participants; BBV152: 93.40%, 95% CI 57.10% to 99.80%; 1 RCT, 16,976 participants). Moderate-certainty evidence found that NVX-CoV2373 probably reduces the incidence of severe or critical COVID-19 (VE 100.00%, 95% CI 86.99% to 100.00%; 1 RCT, 25,452 participants). Two trials reported high efficacy of CoronaVac for severe or critical disease with wide CIs, but these results could not be pooled. Serious adverse events (SAEs) mRNA-1273, ChAdOx1 (Oxford-AstraZeneca)/SII-ChAdOx1 (Serum Institute of India), Ad26.COV2.S, and BBV152 probably result in little or no difference in SAEs compared to placebo (RR: mRNA-1273: 0.92, 95% CI 0.78 to 1.08; 2 RCTs, 34,072 participants; ChAdOx1/SII-ChAdOx1: 0.88, 95% CI 0.72 to 1.07; 7 RCTs, 58,182 participants; Ad26.COV2.S: 0.92, 95% CI 0.69 to 1.22; 1 RCT, 43,783 participants); BBV152: 0.65, 95% CI 0.43 to 0.97; 1 RCT, 25,928 participants). In each of these, the likely absolute difference in effects was fewer than 5/1000 participants. Evidence for SAEs is uncertain for BNT162b2, CoronaVac, BBIBP-CorV, and NVX-CoV2373 compared to placebo (RR: BNT162b2: 1.30, 95% CI 0.55 to 3.07; 2 RCTs, 46,107 participants; CoronaVac: 0.97, 95% CI 0.62 to 1.51; 4 RCTs, 23,139 participants; BBIBP-CorV: 0.76, 95% CI 0.54 to 1.06; 1 RCT, 26,924 participants; NVX-CoV2373: 0.92, 95% CI 0.74 to 1.14; 4 RCTs, 38,802 participants). For the evaluation of heterologous schedules, booster doses, and efficacy against variants of concern, see main text of review.Compared to placebo, most vaccines reduce, or likely reduce, the proportion of participants with confirmed symptomatic COVID-19, and for some, there is high-certainty evidence that they reduce severe or critical disease. There is probably little or no difference between most vaccines and placebo for serious adverse events. Over 300 registered RCTs are evaluating the efficacy of COVID-19 vaccines, and this review is updated regularly on the COVID-NMA platform (covid-nma.com). Implications for practice Due to the trial exclusions, these results cannot be generalized to pregnant women, individuals with a history of SARS-CoV-2 infection, or immunocompromized people. Most trials had a short follow-up and were conducted before the emergence of variants of concern. Implications for research Future research should evaluate the long-term effect of vaccines, compare different vaccines and vaccine schedules, assess vaccine efficacy and safety in specific populations, and include outcomes such as preventing long COVID-19. Ongoing evaluation of vaccine efficacy and effectiveness against emerging variants of concern is also vital.

Bilateral knee dislocations are exceedingly rare in orthopaedics. Managing these injuries presents a difficult task given their high complication rate and guarded prognosis. We report the case of a 21-year-old male who presented to our institution with bilateral knee dislocations sustained in a motor vehicle collision. The patient subsequently underwent multiligament knee reconstruction surgeries for each knee at one and three weeks following the initial injury. At one-year follow-up, the patient has achieved a successful outcome and has returned to regular activities which include hiking and exercising at the gym.

Objective. This study aimed to assess compliance with current best practice guidelines on the use of antibiotics in the Department of Surgery in the Philippine General Hospital and to determine the impact of the dissemination of an institution-based guideline on compliance and on patient outcomes. Methods. Two antibiotic use surveys were performed 4 weeks before and 4 weeks after the implementation and dissemination of the PGH Surgical Antibiotic Use Guidelines in the Department of Surgery. The medical records of eligible patients were reviewed regarding patient and case characteristics, details on the administration of antibiotics and the collection of specimen for culture studies. Data relating to the occurrence of surgical site infection within 30 days of the operation was extracted. Compliance with antibiotic use guidelines was assessed for each case. The compliance rates in the pre- and post-intervention periods were compared. Results. The study included a total of 477 patients, 213 in the pre-implementation and 264 in the post implementation period. Compared with the pre-intervention period, rates of compliance with guidelines improved for all parameters in the post-implementation period except for correct dosing. The greatest improvement was seen in the selection of the recommended drug, and proper duration. There was modest improvement in the timing of the preoperative drug administration. There was poor compliance with recommendations for appropriate specimen collection for culture studies, with marked improvement in collection in the pediatric group post intervention. Overall, the in-hospital SSI rate was reduced from 6.8% to 1.1%, while there was little change in the 30-day SSI rate, post-intervention. Conclusion. A simple intervention to raise awareness of institutional guidelines on antibiotic use in the surgical setting lead to a modest improvement on overall compliance, although rates of total compliance with all relevant guidance on antibiotic use, choice, dose, timing and duration remained low. The impact on surgical site infection rates based on such compliance was modest.

Bandwidth throttling is widely employed in practice by online-service-providers (OSPs) as a server/network congestion management tool. However, this topic has been largely neglected in the academic literature. To the best of our knowledge, this is the first analytical study that aims at achieving an optimal (non-discriminatory) throttling mechanism for bandwidth when user demand is stochastic. In our setting, the demand dynamics of the OSP is governed by a geometric Brownian process. There are costs associated with maintaining and throttling demand; in particular, throttling cost includes both fixed and proportional costs. As users experience inferior service speeds during throttling, the proposed model modifies the demand dynamics to adequately capture users’ reactions to throttling. OSP’s objective is to determine the optimal throttling strategy that minimizes the total expected discounted cost of maintaining and throttling demand. By assuming the existence of an optimal strategy, we use a dynamic programming (Quasi-Variational Inequality) approach to show that it is optimal for the OSP to throttle the demand whenever it reaches a threshold level and downgrade the service speed by a fixed factor while the throttling is employed. Our numerical computations strongly suggest that it is always optimal for OSPs to induce negative (demand) growth rates during throttling to reduce unfavorable future demand. Moreover, our comparative statics analysis explains how OSPs should handle user demand with higher growth rates and volatility, service networks that face higher demand fluctuations/volatility during throttling, and the trade-off between non-monetary fixed and proportional cost associated with throttling.

Background: Agitation and delirium are common in mechanically ventilated adult intensive care unit (ICU) patients and may contribute to delayed extubation times. Difficult-to-wean ICU patients have been associated with an increased risk of longer ICU length of stays and mortality. The purpose of this systematic review and meta-analysis is to evaluate the evidence of dexmedetomidine facilitating successful mechanical ventilation extubation in difficult-to-wean ICU patients and clinical outcomes. Methods: A literature search was conducted using MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Global Health, Cochrane Central Register of Controlled Trials, Clinical Trial Registries, and the Health Technology Assessment Database from inception to December 5, 2019. Randomized controlled trials evaluating dexmedetomidine with the intended purpose to facilitate mechanical ventilation liberation in adult ICU patients (≥18 years) experiencing extubation failure were included. The primary outcome of time to extubation was evaluated using the weighted mean difference (WMD), with a random effects model. Secondary analyses included hospital and ICU length of stay, in-hospital mortality, hypotension, and bradycardia. Results: A total of 6 trials (n = 306 patients) were included. Dexmedetomidine significantly reduced the time to extubation (WMD: −11.61 hours, 95% CI: −16.5 to −6.7, P = .005) and ICU length of stay (WMD: −3.04 days; 95% CI: −4.66 to −1.43). Hypotension risk was increased with dexmedetomidine (risk ratio [RR]: 1.62, 95% CI: 1.05-2.51), but there was no difference in bradycardia risk (RR: 3.98, 95% CI: 0.70-22.78). No differences were observed in mortality rates (RR: 1.30, 95% CI: 0.45-3.75) or hospital length of stay (WMD: −2.67 days; 95% CI: −7.73 to 2.39). Conclusions: Dexmedetomidine was associated with a significant reduction in the time to extubation and shorter ICU stay in difficult-to-wean ICU patients. Although hypotension risk was increased with dexmedetomidine, no differences in other clinical outcomes were observed.

We develop novel mispricing of markets under asymmetric information and jumps for informed and uninformed investors, called m-Double Poisson markets, driven by independent Double Poisson processes....

Background: The clinical utility of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening appears promising for antimicrobial stewardship programs. However, a paucity of data remains on the diagnostic performance of culture-based MRSA screen in the intensive care unit (ICU) for pneumonia and bacteremia. Objective: The objective of this study was to compare the predictive value of culture-based MRSA nasal screening for pneumonia and bacteremia in ICU and general ward patients. Methods: This multicenter, retrospective study was conducted over a 23-month period. Adult patients with MRSA nasal screening ≤48 hours of collecting a respiratory and/or blood culture with concurrent initiation of anti-MRSA therapy were included. The primary endpoint was to compare the negative predictive value (NPV) associated with culture-based MRSA nasal screening between ICU and general ward patients with suspected pneumonia. Results: A total of 5106 patients representing the ICU (n = 2515) and general ward (n = 2591) were evaluated. The NPV of the MRSA nares for suspected pneumonia was not significantly different between ICU and general ward patient populations (98.3% and 97.6%, respectively; P = 0.41). The MRSA nares screening tool also had a high NPV for suspected bacteremia in ICU (99.8%) and general ward groups (99.7%) ( P = 0.56). The overall positive MRSA nares rates in the ICU and general ward patient populations were 9.1% and 8.2%, respectively ( P = 0.283). Moreover, MRSA-positive respiratory and blood cultures among ICU patients were 5.8% and 0.8%, respectively. Conclusion and Relevance: Our findings support the routine use of MRSA nasal screening using the culture-based method in ICU patients with pneumonia. Further research on the clinical performance for MRSA bacteremia in the ICU is warranted.

Aims In this novel study in the Irish setting, we quantified the number items managed per General Practitioner (GP) consult, how each item is managed, and impact on a GP's job satisfaction. Methods Participating GPs at two surgeries completed a questionnaire - integrated into the practice management software - after each consultation that satisfied the inclusion criteria during a four-week period. Results Due to feasibility constraints, 500 of 857 (58.3%) completed questionnaires were randomly selected for our sample. GPs manage an average of 1.76 items per consultation. Older patients presented with more items. Greater number of presenting items led to less being managed on the day 71% (n=5) for 5 items vs. 95.2% (n= 246) for 1 item, longer consultation duration (mean = 14.63 minutes (4-45) and decreased GP satisfaction, mean 8/10 (2-10). Conclusion Increasing the number of items in a GP consultation has a statistically significant effect on duration of consultation, how each item is managed, and even GP satisfaction.

Background: Concurrent administration of vancomycin and piperacillin/tazobactam (VAN+PTZ) may increase the risk of acute kidney injury (AKI) in hospitalized patients. Comprehensive characterization of VAN+PTZ associated AKI and recovery patterns remains lacking in previous reports. Objective: To compare the incidence of AKI associated with VAN+PTZ compared to either cefepime (CEF) or meropenem (MER) with VAN in adult general ward patients. Methods: A multicenter, retrospective, propensity score cohort study was conducted in non-critically ill adult patients. Included patients were concurrently administered VAN+PTZ or VAN+CEF/MER. Patients developing AKI ≤48 hours following combination therapy were excluded. The primary endpoint was to compare the incidence of AKI between study groups. Multivariable Cox regression modeling in predicting AKI was also conducted. Results: A total of 3199 patients met inclusion criteria and were evaluated. The incidence of AKI in VAN+PTZ and VAN+CEF/MER groups were 16.4% and 8.7%, respectively ( P < .001). The onset to AKI was 1.8 days earlier with VAN+PTZ compared to VAN+CEF/MER ( P < .001). Multivariable prediction model showed concomitant VAN+PTZ was identified as an independent risk factor of developing AKI (HR 2.34, 1.82-3.01, P < .001). The VAN+PTZ group experienced significantly higher rates of severe AKI (stage II or III) compared to the VAN+CEF/MER group ( P = .002). No differences in the AKI recovery patterns were found between study groups. Conclusions: Concomitant VAN+PTZ in adult general ward patients was independently associated with an increased risk of AKI overall. More severe AKI was also associated with VAN+PTZ.

Background Vaccines may reduce antibiotic use and the development of resistance. Objectives To provide a comprehensive, up-to-date assessment of the evidence base relating to the effect of vaccines on antibiotic use. Data sources Ovid MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and WHO Trials Registry. Study eligibility criteria Randomized controlled trials (RCTs) and observational studies published from January 1998 to March 2018. Participants Any population. Interventions Vaccines versus placebo, no vaccine or another vaccine. Methods Titles, abstracts and full-texts were screened independently by two reviewers. Certainty of RCT evidence was assessed using GRADE. Results In all, 4980 records identified; 895 full-text reports assessed; 96 studies included (24 RCTs, 72 observational). There was high-certainty evidence that influenza vaccine reduces days of antibiotic use among healthy adults (one RCT; n = 4253; rate reduction 28·1%; 95% CI 16·0–38·4); moderate-certainty evidence that influenza vaccines probably reduce antibiotic use in children aged 6 months to 14 years (three RCTs; n = 610; ratio of means 0·62; 95% CI 0·54–0·70) and probably reduce community antibiotic use in children aged 3–15 years (one RCT; n = 10 985 person-seasons; risk ratio 0·69, 95% CI 0·58–0·83); and moderate-certainty evidence that pneumococcal vaccination probably reduces antibiotic use in children aged 6 weeks to 6 years (two RCTs; n = 47 945; rate ratio 0·93, 95% CI 0·87–0·99) and reduces illness episodes requiring antibiotics in children aged 12–35 months (one RCT; n = 264; rate ratio 0·85, 95% CI 0·75–0·97). Other RCT evidence was of low or very low certainty, and observational evidence was affected by confounding. Conclusions The evidence base is poor. Although some vaccines may reduce antibiotic use, collection of high-quality data in future vaccine trials is needed to improve the evidence base. PROSPERO registration CRD42018103881.

As insect pollinator populations continue to decline, it is essential to understand the impacts of anthropogenic activities, including forest management, on pollinator communities. Although multiple studies have shown that clearcutting is beneficial for bees, other less intense, selective silvicultural methods that result in disproportionate increases in edge habitat within stands are less well understood. We investigated bee community characteristics across microsites (center of cut, edge of cut, and closed-canopy forest) in three mixed-mesophytic forest stands subjected to group selection cuttings. Results revealed bee communities in the center of cuts and their edges to differ from those in forest microsites, and their diversity measures were higher than in forest microsites. Within-stand edge microsites did not differ from their cut centers in terms of their communities or their diversity. Finally, center of cut and edge microsites combined, and forest microsites, were characterized by different indicator species, thereby exemplifying differences between these two microsite groupings. These results suggest that group selection harvests support differing communities of bees across microsites and sustain a wide range of bee species, and that edges within these forest stands behaved more like extensions of canopy gap openings despite differences in forest physiognomy.

There is an increased risk of potential drug–drug interactions (pDDIs) in critically ill patients based on the number of drugs received. The occurrence of pDDIs and clinical significance is not well described. The aim was to provide insight into important clinical issues and offer guidance on drug–drug interaction (DDI) surveillance through the performance of a systematic review. Five targeted objectives were developed, a priori, which guided study selection and data abstraction. Two independent reviewers extracted the definition, frequency, type, and clinical significance of pDDIs. A meta-analysis was performed to evaluate the proportion of patients exposed to a pDDI. Three data sources (PubMed, Embase, and Scopus) were utilized for the search to include studies that evaluated pDDIs in adult critically ill patients. Included studies in the systematic review and meta-analysis were required to be full text. A total of 39 studies met inclusion criteria. Definitions of pDDIs were diverse. Frequency of pDDIs varied by study, but was most commonly between one and five pDDIs per patient. Fifty-eight percent of patients were exposed to at least one pDDI during their intensive care unit admission. Types of pDDIs identified were numerous, with aspirin being the most common drug involved. As expected, not all pDDIs were clinically significant. Clinical significance was determined by varied definitions and sources. Improving the understanding of clinically significant pDDIs and alerts that clinicians encounter may guide better development of surveillance through clinical decision support and decrease alert fatigue.

The posterolateral corner (PLC) of the knee was regarded as the "dark side" of the knee because of limited understanding of its anatomy and biomechanics and because of poor outcomes after injuries to PLC structures. These injuries rarely occur in isolation, with 28% reported as isolated PLC injuries. Nonoperative treatment of these injuries has led to persistent instability, development of early osteoarthritis, and poor outcomes. Several techniques for reconstruction of the PLC have been described, and all are reported to improve outcomes. Biomechanically validated anatomic reconstructions are preferred because they restore native knee kinematics and improve clinical outcomes without over-constraining the knee.

Acute respiratory distress syndrome (ARDS) remains a common complication associated with significant negative outcomes in critically ill patients. Lung-protective mechanical ventilation strategies remain the cornerstone in the management of ARDS. Several therapeutic options are currently available including fluid management, neuromuscular blocking agents, prone positioning, extracorporeal membrane oxygenation, corticosteroids, and inhaled pulmonary vasodilating agents (prostacyclins and nitric oxide). Unfortunately, an evidence-based, standard-of-care approach in managing ARDS beyond lung-protective ventilation remains elusive, contributing to significant variability in clinical practice. Although the optimal therapeutic strategy for managing moderate to severe ARDS remains extremely controversial, therapies supported with more robust clinical evidence should be considered first. The purpose of this narrative review is to discuss the published clinical evidence for both pharmacologic and nonpharmacologic management strategies in adult patients with moderate to severe ARDS as well as to discuss practical considerations for implementation.

Background:Historically, radial meniscal tears were treated with partial or near-total meniscectomy, which usually resulted in poor outcomes. Radial meniscal tears function similar to a total meniscectomy and are challenging to treat. Repair of radial meniscal tears should be performed to prevent joint deterioration and the need for salvage procedures in the future.Purpose/Hypothesis:The purpose was to compare 3 repair techniques for radial tears of the medial meniscus: the 2-tunnel, hybrid, and hybrid tunnel techniques. It was hypothesized that there would be no differences among the 3 groups in regard to gapping and ultimate failure strength.Study Design:Controlled laboratory study.Methods:Thirty human male cadaver knees (10 matched pairs, n = 20; 10 unpaired, n = 10) were used to compare the 2-tunnel, hybrid, and hybrid tunnel repairs. A complete radial tear was made at the midbody of the medial meniscus. Repairs were performed according to the described techniques. Specimens were potted and mounted on a universal material testing machine where each specimen was cyclically loaded for 1000 cycles before experiencing a pull to failure. Gap distances at the tear site, ultimate failure load, and failure location were measured and recorded.Results:After 1000 cycles of cyclic loading, there were no significant differences in displacement among the 2-tunnel repair (3.0 ± 1.7 mm), hybrid repair (3.0 ± 0.9 mm), and hybrid tunnel repair (2.3 ± 1.0 mm; P = .4042). On pull-to-failure testing, there were also no significant differences in ultimate failure strength among the 2-tunnel repair (259 ± 103 N), hybrid repair (349 ± 149 N), and hybrid tunnel repair (365 ± 146 N; P = .26). However, the addition of vertical mattress sutures to act as a “rip stop” significantly reduced the likelihood of the sutures pulling through the meniscus during pull-to-failure testing for the hybrid and hybrid tunnel repairs (4 of 16, 25%) as compared with the 2-tunnel repair (7 of 9, 78%; P = .017).Conclusion:The results showed equivalent biomechanical testing with regard to gap distance and pull-to-failure strength among the 3 repairs. The addition of the vertical mattress sutures to act as a rip stop was effective in preventing meniscal cutout through the meniscus.Clinical Relevance:Effective healing of radial meniscal tears after repair is paramount to prevent joint deterioration and symptom development. Each tested repair showed a biomechanically equivalent and stable construct to use to repair radial meniscal tears. The authors recommend that rip stop vertical mattress sutures be used, especially in poor-quality meniscal tissue, to prevent suture cutout.

Shock syndromes are associated with unacceptably high rates of mortality in critically ill patients despite advances in therapeutic options. Vasodilatory shock is the most common type encountered in the intensive care unit. It is manifested by cardiovascular failure, peripheral vasodilatation, and arterial hypotension leading to tissue hypoperfusion and organ failure. Hemodynamic support is typically initiated with fluid resuscitation strategies and administration of adrenergic vasopressor agents in nonresponsive patients to restore arterial pressure with subsequent adequate organ reperfusion. Unfortunately, high catecholamine dosing requirements may be necessary to achieve targeted hemodynamic goals that may increase the risk of vasopressor-induced adverse events. The purpose of this article is to review the clinical efficacy and safety data and potential role in therapy for catecholamine-sparing agents in vasodilatory shock. Adjunctive therapeutic options to reduce vasoactive support requirements without compromising arterial pressure include arginine vasopressin and analogs, corticosteroids, midodrine, methylene blue, and angiotensin II. Although concomitant vasopressin and corticosteroids have a more defined role in evidence-based guidelines for managing shock, clinicians may consider other potential catecholamine-sparing agents.

Non-emergent visits to emergency departments by uninsured patients impose unnecessary costs on both patients and safety-net institutions. We evaluated the health and economic impacts of providing free, walk-in care to low-income, uninsured adults-most of them Hispanic-at a free clinic between January 2013 and December 2016. Providing access to health care services for uninsured patients at Clínica Esperanza/Hope Clinic reduced emergency department expenditures in Rhode Island by approximately $448,876 (range: $410,377-$487,375) annually and may have also reduced future healthcare costs for this population by more than $48 million ($12,034,469 annually) over the four-year evaluation period. For every $1 in funding for walk-in clinic operation, delivering free care provided a return on investment of $71.18 (range: $70.95-71.40) in healthcare value. Providing access to non-emergent walk-in care at the more than 12,000 free healthcare clinics nationwide may save billions in ED costs while improving the health of uninsured individuals.

Overstory and understory treatments were established in natural oak stands and red pine plantations in Michigan in 1991 to test the hypotheses that (1) oak seedling survival and growth would be greater in pine than oak stands and (2) removal of competitors would enhance oak seedling performance. Late spring prescribed fires were implemented in 2002 and 2008 to investigate their effectiveness in controlling understory red maple. Performance of planted northern red oaks has been monitored since 1991 and the abundance of naturally regenerating oak and red maple seedlings and sprouts in different size classes has been documented since 2001. A subset of oaks has been protected against deer browsing since planting. Results suggest partial competitor removal enhances oak seedling and sprout performance, whereas complete removal increases mortality from browsing and frost. Increases in red maple abundance and decreases in oak abundance were documented after the prescribed fires in 2015. Greater growth and survival of planted oaks was observed in the pine stands, provided they were protected from browsing. Based on these results, the most viable management scenario for maximizing survival and growth of oak seedlings and sprouts in the study region would include protecting oak seedlings from deer in 25% canopy cover shelterwoods in pine plantations. Opportunities exist for developing systems involving alternating rotations and mixtures of oak and pine.

OBJECTIVES Clinicians learn from prior adverse events through pharmacovigilance allowing for improved medication safety in the medication use process; therefore, adverse drug reaction (ADR) reporting needs to be maximized. This systematic review was conducted to determine whether engaging patients/caregivers in ADR reporting during a patient's hospitalization provides further information about ADRs not obtained from traditional sources of reporting (i.e., voluntary reporting, medical record review). METHODS This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A literature search was conducted from January 2018 to June 2019 in PubMed, CINAHL, and Embase. Studies were included if they were (i) conducted in the inpatient setting, (ii) surveyed patients/caregivers, (iii) compared patient/caregiver reporting with another source of reporting, and (iv) evaluated ADRs. Studies completed in an outpatient setting or nursing home were excluded. RESULTS A total of 11 studies were included. Sources of ADR information from patient/caregiver were obtained through interviews, surveys, questionnaires, or open-ended responses. Patient reporting was compared with medical record reports (7 articles) and health care professional reporting (4 articles). Approximately 11% to 35% of ADRs reported from patients were not identified through voluntary reporting by health care professionals, and 5.6% to 66% of ADRs obtained from patient reporting were not provided in the medical record. CONCLUSIONS Patients/caregivers are important sources of safety information to improve system and practice of medication use that may not be recorded by other surveillance methods. Administrators and clinicians need to determine the best approach to integrate patients/caregivers into routine reporting for optimal engagement.

Purpose: Several reports have demonstrated similar effects on oxygenation between inhaled epoprostenol (iEPO) compared to inhaled nitric oxide (iNO) for acute respiratory distress syndrome (ARDS). Previous studies directly comparing oxygenation and clinical outcomes between iEPO and iNO exclusively in an adult ARDS patient population utilized a weight-based dosing strategy. The purpose of this study was to compare the clinical and economic impact between iNO and fixed-dosed iEPO for ARDS in adult intensive care unit (ICU) patients. Methods: This retrospective cohort study was conducted at a major academic medical center between January 1, 2014, and October 31, 2018. Patients ≥18 years of age with moderate-to-severe ARDS were included. The primary end point was to compare the mean change in partial arterial oxygen pressure to fraction of inspired oxygen (Pao 2: Fio 2) at 4 hours from baseline between iEPO and iNO. Other secondary aims were total acquisition drug costs, in-hospital mortality, ICU and hospital length of stay, and duration of mechanical ventilation. Results: A total of 239 patients were included with 139 (58.2%) and 100 (41.8%) in the iEPO and iNO groups, respectively. The mean change in Pao 2: Fio 2 at 4 hours from baseline in the iEPO and iNO groups were 31.4 ± 54.6 and 32.4 ± 42.7 mm Hg, respectively ( P = .88). The responder rate at 4 hours was similar between iEPO and iNO groups (64.7% and 66.0%, respectively, P = .84). Clinical outcomes including mortality, overall hospital and ICU length of stay, and mechanical ventilation duration were similar between iEPO and iNO groups. Estimated annual cost-savings realized with iEPO was USD1 074 433. Conclusion: Fixed-dose iEPO was comparable to iNO in patients with moderate-to-severe ARDS for oxygenation and ventilation parameters as well as clinical outcomes. Significant cost-savings were realized with iEPO use.

Vancomycin therapeutic drug monitoring is routinely performed but the specific measure used in practice is variable.To evaluate the relationship between the first measured vancomycin trough, area-under-the-curve (AUC), and failure in patients with MRSA bacteremia.This retrospective, cohort study included adult non-neutropenic patients with MRSA bacteremia who received vancomycin. The primary outcome was treatment failure. Initial trough and AUC values were compared between the failure and success groups. Classification and regression tree analysis was used to identify thresholds associated with failure. Multivariate analysis was performed to control for identified confounders.There were 89 patients. Failure occurred in 23 (26%). Trough and AUC values associated with failure were10.6 mg/L (39% vs. 13%; P = 0.006) and AUC410mg*h/L (40% vs. 17%; P = 0.014). Both remained significant after controlling covariates (trough10.6 mg/L, OR [95% CI] = 4.91 [1.6-15]; AUC410mg*h/L, OR [95% CI] = 3.13 [1.14-8.62]). Only AUC was predictive of nephrotoxicity.Failure was more common with troughs10.6 mg/L or AUC410 mg*h/L. Supratherapeutic AUCs, but not trough, were associated with nephrotoxicity.

We employ a simple numerical scheme to compute optimal portfolios and utilities of informed and uninformed investors in a mispriced Carr–Geman–Madan–Yor (CGMY) Levy market under information asymmetry using instantaneous centralized moments of returns (ICMR). We also investigate the impact on investors’ demand for stocks and indices at different levels of asymmetric information, mispricing, investment horizon, jump intensity, and volatility. Our simulations not only confirm that uninformed expected demand falls as information asymmetry increases but also offer strong evidence that informed expected demand behaves in a similar manner. In particular, expected demand of informed investors falls whenever information asymmetry exceeds 50%. The investor that demands more of the risky asset maintains that position over the entire investment horizon at each level of mispricing and information asymmetry. The absolute difference in expected demand between the uninformed and informed investors increases with the investment horizon, but decreases with the level of information asymmetry.

Exposure of organisms to high temperatures and various chemical and physical stressors can cause protein misfolding and aggregation. In turn, this can disrupt the functions of proteins, threatening both development and homeostasis. To overcome this, cells can initiate the highly conserved heat shock (HS) stress response pathway. In eukaryotes, this is a coordinated cellular response, in which the master HS activator, heat shock factor (HSF), is rapidly recruited to the HS protein genes, and triggers the recruitment of additional coactivator proteins that facilitate gene expression. This results in the production of HS proteins that function as nuclear and cytosolic molecular chaperones, to promote refolding of proteins and prevent aggregation and increase protein degradation pathways. Here, we describe a laboratory exercise in which students visualize and quantify Green Fluorescent Protein (GFP)-tagged HSF binding to the HS protein genes in living Drosophila salivary gland nuclei as an output of chemically induced protein misfolding. Students are assigned an array of chemicals, and using the scientific literature, predict impacts of these chemicals on protein folding. Students then test the effects of their chemicals by measuring GFP-tagged HSF binding to the HS genes in salivary glands using confocal microscopy. Designed for junior and senior level students in a cell/molecular biology course, this is a two-part lab, in which student work closely with an instructor to help familiarize them with developing hypotheses supported by scientific literature and testing these hypotheses by quantitating the levels of GFP-HSF binding, using confocal microscopy of living Drosophila cells. © 2018 International Union of Biochemistry and Molecular Biology, 46(5):445-452, 2018.

Proximal hamstring tendon ruptures are rare in children and adolescents. The typical pediatric hamstring injury pattern involves an apophyseal avulsion fracture. We present the case of a 14-year-old male with a widely displaced ischial avulsion fracture and a bony fragment that was too small to allow for bony fixation. The patient presented with left-buttock pain and ecchymosis, as well as tenderness at the ischial tuberosity, following an injury sustained while running 2 weeks prior. Imaging demonstrated an avulsion of the proximal hamstrings with a 4-mm bony fragment, too small to allow for repair. The patient underwent primary repair using two 3-mm suture anchors. The bony fragment was not excised but incorporated into the repair. Although most proximal hamstring injuries in children and adolescents are treated non-operatively, operative treatment may confer a small but clinically important difference in rates of healing and return to play in adolescent athletes. This case demonstrates successful treatment of a proximal hamstring rupture with suture anchor fixation, which may be considered for pediatric and adolescent displaced avulsion fractures when the bony fragment is too small to allow for bony fixation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11420-018-9620-x) contains supplementary material, which is available to authorized users.

Mountain stewartia (Stewartia ovata) is the only member of the family Theaceae endemic to Tennessee. Apart from its physical description and rarity, little is known about this woody understory species. Accounts of stewartia populations and range descriptions are longstanding, but microsite descriptions are limited in detail. We quantified microsites supporting populations of stewartia across East Tennessee as a first step in determining whether stewartia is rare because of rare or altered habitat, limited sexual reproduction, poor dispersal, or a combination of these factors. Five populations of stewartia averaging 7.40 ± 1.08 stems per population were inventoried across four East Tennessee counties. Soils on all sites were strongly acidic, highly permeable, well-drained, cobbly loams associated with steep slopes and higher elevations and were low in phosphorus, potassium, calcium, and magnesium. A dense overstory comprised of sourwood (Oxydendrum arboreum), eastern hemlock (Tsuga canadensis), w...

One cannot overstate the importance of a thorough history and physical examination, supplemented with directed imaging, to help pinpoint the exact cause of the athlete's elbow pain. Although plain radiographs should not be overlooked, advanced imaging plays a critical role in diagnosis and management of pathology in the thrower's elbow, including computed tomography, magnetic resonance imaging, and stress ultrasound. By judiciously combining these elements, the clinician can appropriately manage these injuries in order to successfully return the athlete to their preinjury level of play.

Purpose The objective of this study was to evaluate the short-term hemodynamic effects as well as vasopressor requirements with concomitant vasopressin (AVP) and hydrocortisone (HCT) compared to either agent alone in refractory septic shock. Materials and methods This was a retrospective, cohort study conducted in adult septic shock patients. Patients received continuous infusion AVP at 0.04 units/min and/or HCT 200–300 mg intravenous daily in divided doses for refractory septic shock. Refractory septic shock was defined as systolic or mean blood pressure (MAP) of Results A total of 300 patients were evaluated. The rate of achieving a “response” (norepinephrine dose reduction by ≥ 50% without any decrease in MAP) at 4 h from baseline was significantly higher in patients receiving concomitant AVP/HCT (88.5%) compared to HCT alone (62.3%) or AVP alone (72.9%) (p = 0.0005). The AVP/HCT group had higher “response” rates over the HCT and AVP monotherapy groups at 12 (p = 0.052) and 24 h (p = 0.036). Multivariate regression showed combination therapy to be independently associated with response at 4 h. Conclusions Concomitant AVP and HCT was associated with an immediate, additive catecholamine-sparing effect over either agent alone in patients with refractory septic shock.

Establishing herbaceous groundcover is essential for oak woodland and savanna restoration. In the Appalachian region, woody vegetation in the understory can persist through many fires and interfere with achieving this goal. Herbicide applications could reduce such vegetation and interact with canopy-disturbance and fire to accelerate restoration. In stands thinned to woodland (16 m2 ha−1, 75% canopy closure) or savanna (5 m2 ha−1, 24% canopy closure) conditions and burned biennially in the fall (October) or spring (March), we economically applied triclopyr (Garlon® 3A) to understory woody plants using foliar and cut-surface techniques in the fall between fires. From 2011 to 2013, only minor differences in vegetation were observed between areas managed with canopy-disturbance and fire (CF) and areas where herbicides were also used (CFH). Small-sapling (≥1.4 m tall

Loblolly pine (Pinus taeda L.), shortleaf pine (Pinus echinata Mill.), and eastern white pine (Pinus strobus L.) seedlings were multi-cropped with standard and large-diameter white oak (Quercus alba L.) seedlings to test for neutral or positive effects of multi-cropping. The study was established in 2014 in three complete blocks within recent clearcuts in eastern Tennessee, USA. Each block consisted of six multi-cropped treatments and four monocultures randomly assigned to ten 14.63 × 21.95 m plots. Within each block, monocultures of white oak and each pine species were planted in four control plots. Multi-cropped treatments included loblolly pine planted with white oak at a 0.31 m spacing, loblolly pine planted with white oak in alternating rows at a 1.74 m spacing, shortleaf pine planted with white oak at a 0.31 m spacing, shortleaf pine planted with white oak at a 1.74 m spacing, eastern white pine planted with white oak at a 0.31 m spacing, and eastern white pine planted with white oak at a 1.74 m spacing. Each plot with white oak received 20 standard (~0.127 cm in basal diameter) and 20 large-diameter (~0.632 cm in basal diameter) white oak seedlings that were randomly assigned to planting locations. Initial height, basal diameter, and early survival were recorded for each seedling just after planting. Height growth, basal diameter growth, survival, herbivory, and insect damage were recorded in early December 2014, 2015, 2016, 2017, 2018, and 2019. In 2019, percent survival among treatments did not differ significantly for white oak (p = 0.152), loblolly pine (p = 0.396), shortleaf pine (p = 0.246), or eastern white pine (p = 0.065). In addition, mean height growth and mean basal diameter growth did not differ significantly among treatments for white oak (p = 0.698 and 0.437, respectively), loblolly pine (p = 0.630 and 0.762, respectively), shortleaf pine (p = 0.324 and 0.251, respectively), or eastern white pine (p = 0.623 and 0.823, respectively). Survival was greater for large-diameter white oak seedlings than standard seedlings (p