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We test the behavior of the United States (US) West Coast ShakeAlert earthquake early warning (EEW) system during temporally close earthquake pairs to understand current performance and limitations. We consider performance metrics based on source parameter and ground-motion forecast accuracy, as well as on alerting timeliness. We generate ground-motion times series for synthesized earthquake sequences from real data by combining the signals from pairs of well-recorded earthquakes (4.4≤M≤7.1) using time shifts ranging from −60 to +180 s. We examine fore- and aftershock sequences, near-simultaneous events in different source regions, and simulated out-of-network and offshore earthquakes. We find that the operational ShakeAlert algorithms Earthquake Point-source Integrated Code (EPIC) and Finite-Fault Rupture Detector (FinDer) and the Propagation of Local Undamped Motion (PLUM) method perform largely as expected: EPIC provides the best source location estimates and is often fastest but can underestimate magnitudes or, in extreme cases, miss large earthquakes; FinDer provides real-time line-source models and unsaturated magnitude estimates for large earthquakes but currently cannot process concurrent events and may mislocate offshore earthquakes; PLUM identifies pockets of strong ground motion, but can overestimate alert areas. Implications for system performance are: (1) spatially and temporally close events are difficult to identify separately; (2) challenging scenarios with foreshocks that are close in space and time can lead to missed alerts for large earthquakes; and (3) in these situations the algorithms can often estimate ground motion better than source parameters. To improve EEW, our work suggests revisiting the current algorithm weighting in ShakeAlert, to continue developments that focus on using ground-motion data to aggregate alerts from multiple algorithms, and to investigate methods to optimally leverage algorithm ground-motion estimates. For testing and certification of EEW performance in ShakeAlert and other EEW systems where applicable, we also suggest that 25 of our 73 scenarios become part of the baseline data set.

Mislabeling samples or data with the wrong participant information can affect study integrity and lead investigators to draw inaccurate conclusions. Quality control to prevent these types of errors is commonly embedded into the analysis of genomic datasets, but a similar identification strategy is not standard for cytometric data. Here, we present a method for detecting sample identification errors in cytometric data using expression of human leukocyte antigen (HLA) class I alleles. We measured HLA-A*02 and HLA-B*07 expression in three longitudinal samples from 41 participants using a 33-marker CyTOF panel designed to identify major immune cell types. 3/123 samples (2.4%) showed HLA allele expression that did not match their longitudinal pairs. Furthermore, these same three samples' cytometric signature did not match qPCR HLA class I allele data, suggesting that they were accurately identified as mismatches. We conclude that this technique is useful for detecting sample-labeling errors in cytometric analyses of longitudinal data. This technique could also be used in conjunction with another method, like GWAS or PCR, to detect errors in cross-sectional data. We suggest widespread adoption of this or similar techniques will improve the quality of clinical studies that utilize cytometry.

The use of a standardized outcome metric enhances clinical trial conduct, interpretation, and cross-trial comparison. If a disease course is predictable, comparing modeled predictions with outcome data affords the precision and confidence needed to accelerate precision medicine. We demonstrate the power of this approach in type 1 diabetes (T1D) trials aiming to preserve endogenous insulin secretion measured by C-peptide. C-peptide is a predictable outcome given an individual’s age and baseline value; quantitative response (QR) adjusts for these variables and represents the difference between the observed and predicted outcome. Validated across 13 trials, the QR metric reduces each trial’s variance and markedly increases statistical power. As smaller studies are especially subject to random sampling variability, using QR as the outcome metric introduces alternative interpretations of previous clinical trial results analyzed by traditional statistical methods. QR can provide model-based estimates that quantify whether individuals or groups did better or worse than expected. QR also provides a purer metric to associate with biomarker data, enabling improved mechanistic insights. Using data from more than 1,300 participants, we demonstrate the value of QR in advancement of disease-modifying therapy (DMT) in T1D. QR applies to any disease where outcome is predictable by baseline covariates, rendering it useful for defining responders to therapy, comparing the effectiveness of different therapies, and understanding causal pathways in disease.

BACKGROUND: Peanut allergy affects 1% to 2% of European children. Early introduction of peanut into the diet reduces allergy in high-risk infants.OBJECTIVE: We aimed to determine the optimal target populations and timing of introduction of peanut products to prevent peanut allergy in the general population.METHODS: Data from the Enquiring About Tolerance (EAT; n = 1303; normal risk; 3-year follow-up; ISRCTN14254740) and Learning Early About Peanut Allergy study (LEAP; n = 640; high risk; 5-year follow-up; NCT00329784) randomized controlled trials plus the Peanut Allergy Sensitization (PAS; n = 194; low and very high risk; 5-year follow-up) observational study were used to model the intervention in a general population. Peanut allergy was defined by blinded peanut challenge or diagnostic skin prick test result.RESULTS: Targeting only the highest-risk infants with severe eczema reduced the population disease burden by only 4.6%. Greatest reductions in peanut allergy were seen when the intervention was targeted only to the larger but lower-risk groups. A 77% reduction in peanut allergy was estimated when peanut was introduced to the diet of all infants, at 4 months with eczema, and at 6 months without eczema. The estimated reduction in peanut allergy diminished with every month of delayed introduction. If introduction was delayed to 12 months, peanut allergy was only reduced by 33%.CONCLUSIONS: The preventive benefit of early introduction of peanut products into the diet decreases as age at introduction increases. In countries where peanut allergy is a public health concern, health care professionals should help parents introduce peanut products into their infants' diet at 4 to 6 months of life.

Effective communication between radiologists and physicians involved in the management of patients with chronic liver disease is paramount to ensuring appropriate and advantageous incorporation of liver imaging findings into patient care. This review discusses the clinical benefits of innovations in radiology reporting, what information the various stakeholders wish to know from the radiologist, and how radiology can help to ensure the effective communication of findings.

Context The presence of islet autoimmunity identifies individuals likely to progress to clinical type 1 diabetes (T1D). In clinical research studies, autoantibody screening followed by regular metabolic monitoring every 6 months reduces incidence of diabetic ketoacidosis (DKA) at diagnosis. Objective We hypothesized that DKA reduction can be achieved on a population basis with a reduced frequency of metabolic monitoring visits. We reasoned that prolonged time between the development of T1D and the time of clinical diagnosis (“undiagnosed time”) would more commonly result in DKA and thus that limiting undiagnosed time would decrease DKA. Methods An analysis was conducted of data from TrialNet's Pathway to Prevention (PTP), a cross-sectional longitudinal study that identifies and follows at-risk relatives of people with T1D. PTP is a population-based study enrolling across multiple countries. A total of 6193 autoantibody (AAB)-positive individuals participated in PTP from March 2004 to April 2019. We developed models of progression to clinical diagnosis for pediatric and adult populations with single or multiple AAB, and summarized results using estimated hazard rate. An optimal monitoring visit schedule was determined for each model to achieve a minimum average level of undiagnosed time for each population. Results Halving the number of monitoring visits usually conducted in research studies is likely to substantially lower the population incidence of DKA at diagnosis of T1D. Conclusion Our study has clinical implications for the metabolic monitoring of at-risk individuals. Fewer monitoring visits would reduce the clinical burden, suggesting a path toward transitioning monitoring beyond the research setting.

The impact of body mass index (BMI) on outcomes after open or laparoscopic surgery for rectal cancer remains unclear. The objective of this retrospective cohort study was to examine the interaction of body mass index and surgical modality (i.e., laparoscopy versus open) with respect to short-term clinical outcomes in patients with rectal cancer. The ACS-NSQIP database (2012–2016) was reviewed for patients undergoing open or laparoscopic surgery for rectal cancer. The primary outcome was 30-day all-cause morbidity. Logistic regression and Cox proportional hazard models were used for analysis. A total of 16,145 patients were grouped into open (N = 6759, 42%) and laparoscopic (N = 9386, 58%) cohorts. Patients with higher BMI (p

To assess for changes in trends of GP chest radiograph reporting over a 10-year period and to assess if there has been a change in recommendations for follow-up. Retrospective study of an Irish tertiary referral center. The total number of GP-referred chest x-rays performed per year from 2007 to 2017 are recorded. One-hundred male/100 female GP-referred chest x-rays are chosen at random from NIMIS data for each of 2007, 2010, 2013, and 2017. Reports are analyzed with regard to abnormal findings, recommendation for follow-up, and yield of follow-up imaging. There were 4917 GP CXRs performed in 2007, 4856 in 2010, 5561 in 2013, and 6492 in 2017. Follow-up was recommended in 17 studies(8.5%) in 2007, 19 studies(9.5%) in 2010, 22 studies(11%) in 2013, and 27 studies(13.5%) in 2017. Indications for follow-up recommendation were largely to ensure resolution of infection (52%) or for nodule surveillance (43%). There has been a notable increase in lung nodule follow-up, with suggested follow-ups increasing from 6 in 2007, to 7 in 2010, 9 in 2013, and 14 in 2017, an increase of 58%. Along with the increase in the quantity of GP-referred chest radiographs over the past 10 years, suggestions for follow-up have increased, particularly for nodule surveillance. Reasons for this increase may include lack of availability of CT to GPs for lung cancer screening, insensitivity of plain radiographs to early cancer detection, and possible fear of litigation for missing lesions, making radiologists more cautious.

© 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., Background: Understanding the discrepancy between IgE sensitization and allergic reactions to peanut could facilitate diagnosis and lead to novel means of treating peanut allergy. Objective: To identify differences in IgE and IgG4 binding to peanut peptides between peanut-allergic (PA) and peanut-sensitized but tolerant (PS) children. Methods: PA (n = 56), PS (n = 42) and nonsensitized nonallergic (NA, n = 10) patients were studied. Synthetic overlapping 15-mer peptides of peanut allergens (Ara h 1-11) were spotted onto microarray slides, and patients' samples were tested for IgE and IgG4 binding using immunofluorescence. IgE and IgG4 levels to selected peptides were quantified using ImmunoCAP. Diagnostic model comparisons were performed using likelihood-ratio tests between each specified nominal logistic regression models. Results: Seven peptides on Ara h 1, Ara h 2, and Ara h 3 were bound more by IgE of PA compared to PS patients on the microarray. IgE binding to one peptide on Ara h 5 and IgG4 binding to one Ara h 9 peptide were greater in PS than in PA patients. Using ImmunoCAP, IgE to the Ara h 2 peptides enhanced the diagnostic accuracy of Ara h 2-specific IgE. Ratios of IgG4/IgE to 4 out of the 7 peptides were higher in PS than in PA subjects. Conclusions: Ara h 2 peptide-specific IgE added diagnostic value to Ara h 2-specific IgE. Ability of peptide-specific IgG4 to surmount their IgE counterpart seems to be important in established peanut tolerance., This work was supported by the Medical Research Council (MRC Clinical Research Training Fellowship G090218, MRC Centenary Early Career Award and MRC Clinician Scientist Fellowship MR/M008517/1, all awarded to A. F. Santos), the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust; the US Department of Agriculture, Agricultural Research Service (USDA-ARS6054-43440-046-00D; USDA-NIFA) and the National Peanut Board (GRANT12229460).

The PALISADE study, an international, phase 3 trial of peanut oral immunotherapy (POIT) with AR101, resulted in desensitization in children and adolescents who were highly allergic to peanut. An improved understanding of the immune mechanism induced in response to food allergen immunotherapy would enable more informed and effective therapeutic strategies. Our main purpose was to examine the immunological changes in blood samples from a subset of peanut-allergic individuals undergoing oral desensitization immunotherapy with AR101.Blood samples obtained as part of enrollment screening and at multiple time points during PALISADE study were used to assess basophil and CD4+ T-cell reactivity to peanut.The absence of clinical reactivity to the entry double-blinded placebo-controlled peanut challenge (DBPCFC) was accompanied by a significantly lower basophil sensitivity and T-cell reactivity to peanut compared with DBPCFC reactors. At baseline, peanut-reactive TH2A cells were observed in many but not all peanut-allergic patients and their level in peripheral blood correlates with T-cell reactivity to peanut and with serum peanut-specific IgE and IgG4 levels. POIT reshaped circulating peanut-reactive T-cell responses in a subset-dependent manner. Changes in basophil and T-cell responses to peanut closely paralleled clinical benefits to AR101 therapy and resemble responses in those with lower clinical sensitivity to peanut. However, no difference in peanut-reactive Treg cell frequency was observed between groups.Oral desensitization therapy with AR101 leads to decreased basophil sensitivity to peanut and reshapes peanut-reactive T effector cell responses supporting its potential as an immunomodulatory therapy.

Human islet antigen reactive CD4+ memory T cells (IAR T cells) play a key role in the pathogenesis of autoimmune type 1 diabetes (T1D). Using single-cell RNA sequencing (scRNA-Seq) to identify T cell receptors (TCRs) in IAR T cells, we have identified a class of TCRs that share TCRα chains between individuals ("public" chains). We isolated IAR T cells from blood of healthy, new-onset T1D and established T1D donors using multiplexed CD154 enrichment and identified paired TCRαβ sequences from 2767 individual cells. More than a quarter of cells shared TCR junctions between 2 or more cells ("expanded"), and 29/47 (~62%) of expanded TCRs tested showed specificity for islet antigen epitopes. Public TCRs sharing TCRα junctions were most prominent in new-onset T1D. Public TCR sequences were more germline like than expanded unique, or "private," TCRs, and had shorter junction sequences, suggestive of fewer random nucleotide insertions. Public TCRα junctions were often paired with mismatched TCRβ junctions in TCRs; remarkably, a subset of these TCRs exhibited cross-reactivity toward distinct islet antigen peptides. Our findings demonstrate a prevalent population of IAR T cells with diverse specificities determined by TCRs with restricted TCRα junctions and germline-constrained antigen recognition properties. Since these "innate-like" TCRs differ from previously described immunodominant TCRβ chains in autoimmunity, they have implications for fundamental studies of disease mechanisms. Self-reactive restricted TCRα chains and their associated epitopes should be considered in fundamental and translational investigations of TCRs in T1D.

AIMS/HYPOTHESIS: Age is known to be one of the most important stratifiers of disease progression in type 1 diabetes. However, what drives the difference in rate of progression between adults and children is poorly understood. Evidence suggests that many type 1 diabetes disease predictors do not have the same effect across the age spectrum. Without a comprehensive analysis describing the varying risk profiles of predictors over the age continuum, researchers and clinicians are susceptible to inappropriate assessment of risk when examining populations of differing ages. We aimed to systematically assess and characterise how the effect of key type 1 diabetes risk predictors changes with age. METHODS: Using longitudinal data from single- and multiple-autoantibody-positive at-risk individuals recruited between the ages of 1 and 45 years in TrialNet’s Pathway to Prevention Study, we assessed and visually characterised the age-varying effect of key demographic, immune and metabolic predictors of type 1 diabetes by employing a flexible spline model. Two progression outcomes were defined: participants with single autoantibodies (n=4893) were analysed for progression to multiple autoantibodies or type 1 diabetes, and participants with multiple autoantibodies were analysed (n=3856) for progression to type 1 diabetes. RESULTS: Several predictors exhibited significant age-varying effects on disease progression. Amongst single-autoantibody participants, HLA-DR3 (p=0.007), GAD65 autoantibody positivity (p=0.008), elevated BMI (p=0.007) and HOMA-IR (p=0.002) showed a significant increase in effect on disease progression with increasing age. Insulin autoantibody positivity had a diminishing effect with older age in single-autoantibody-positive participants (p

ImportanceThis study quantifies the trends in trimodality therapy use and its association with pathologic stage and overall survival of patients with rectal cancer at the population level.ObjectiveTo describe changes between 2006 and 2016 in the sequence and use of chemotherapy/radiation therapy (C/RT), multiagent (MA) chemotherapy, and total neoadjuvant therapy (TNT) for patients with stage 2/3 rectal cancer and identify associations with pathologic stage and survival over time.Design, Setting, and ParticipantsThis retrospective cohort analysis included patient records from the National Cancer Database between 2006 and 2016. Of 110 372 patient records, 77 905 were excluded owing to not receiving trimodality therapy and other predefined exclusion criteria. The final analytic cohort comprised 32 467 patients records treated with trimodality therapy, with 24 297 considered in the survival analysis. Data analysis was performed between June 2020 and December 2021.ExposuresTrimodality therapy was defined as including all of the following: definitive surgery; radiation therapy (RT), alone or in combination with chemotherapy; and neoadjuvant/adjuvant single-agent (SA) or multiagent (MA) chemotherapy independent of RT.Main Outcomes and MeasuresUsing Cox multivariable survival analyses across demographics, surgery type, stage, year of diagnosis, and facility type, treatment groups were allocated as the following: group A: TNT (n = 8883 [27%]); group B: preoperative C/RT plus postoperative SA chemotherapy (n = 5967 [18%]); group C: preoperative C/RT plus postoperative MA chemotherapy (n = 12 926 [40%]); and group D: postoperative C/RT plus MA chemotherapy (n = 4689 [14%]).ResultsThe final analytic cohort comprised 32 467 patients (mean [SD] age at diagnosis, 57.6 [11.6] years; 12 549 [38.7%] women and 19 918 [61.3%] men). Comparing 2016 with 2006, treatment shifted to fewer patients receiving postoperative C/RT (group D) (28% vs 8%; P P P Conclusions and RelevanceIn this cohort study, the shift toward preoperative C/RT and lower pathologic stage was associated with improved overall survival in stage 2/3 rectal cancers.

Effective communication between radiologists and physicians involved in the management of patients with chronic liver disease is paramount to ensuring appropriate and advantageous incorporation of liver imaging findings into patient care. This review discusses the clinical benefits of innovations in radiology reporting, what information the various stakeholders wish to know from the radiologist, and how radiology can help to ensure the effective communication of findings.

The impact of body mass index (BMI) on outcomes after open or laparoscopic surgery for rectal cancer remains unclear. The objective of this retrospective cohort study was to examine the interaction of body mass index and surgical modality (i.e., laparoscopy versus open) with respect to short-term clinical outcomes in patients with rectal cancer.The ACS-NSQIP database (2012-2016) was reviewed for patients undergoing open or laparoscopic surgery for rectal cancer. The primary outcome was 30-day all-cause morbidity. Logistic regression and Cox proportional hazard models were used for analysis.A total of 16,145 patients were grouped into open (N = 6759, 42%) and laparoscopic (N = 9386, 58%) cohorts. Patients with higher BMI (p 0.001) and those undergoing open surgery (p 0.001) were at increased risk of all-cause morbidity. There was no significant change in the odds ratio of experiencing all-cause morbidity between open and laparoscopic surgery with increasing BMI (p = 0.572). Median length of stay was significantly shorter in the laparoscopy group (4 days vs. 6 days; p 0.001), at the cost of increased operative time (239 min vs. 210 min, p 0.001). The difference in operative time between laparoscopy and open surgery did not increase with rising BMI (i.e., ∆37 min vs. ∆39 min at BMI 25 kg/mBMI may not be a strong modifier for surgical approach with respect to short-term clinical outcomes in patients with obesity and rectal cancer. Laparoscopic surgery was associated with improved short-term clinical outcomes, without much change in the absolute difference in operative time compared with open surgery, even at higher BMIs.

AIM To assess the performance of a prospective adverse event (AE) reporting system. MATERIALS AND METHODS Four hundred and seventy-one consecutive arterial procedures were performed in 465 patients (median age, 65 years; interquartile range, 54–77; 276 men) over 2 years by four interventional radiologists at a single centre where clinical follow-up was not performed routinely by interventional radiology (IR). AEs were reported prospectively using a radiology information system or in interventional radiologists' electronic records and combined in a departmental listing of adverse events (DLAE). A retrospective medical record review was performed to identify a reference standard list of AEs for this observational cohort study. AEs were graded according to the Society of Interventional Radiology AE classification system. Descriptive statistics were calculated for the performance of the DLAE. A model comparing the rate of reporting of AEs with and without integration of clinical follow-up was tested for significance. RESULTS Thirty-eight of the 471 (8%) IR procedures had an AE according to the reference standard. The DLAE identified 20/38 (53%) of AEs (K=0.67 [good agreement], 95% confidence interval [CI] agreement=0.53–0.81; p=0.0001; sensitivity 52.6% [95% CI, 36–69%], specificity 100% [95% CI, 99–100%], positive predictive value [PPV] 100%, negative predictive value [NPV] 96 [95% CI, 94.5–97%], accuracy 96% [95% CI, 94–97%]). The performance of the AE reporting system will improve with integration of clinical follow-up (p=0.0015). CONCLUSION A prospective AE reporting system without clinical integration will not detect all procedure complications.

We would like to thank Alhamar et al. (1) for their perspective on our article, which included questions regarding the utility of standard autoantibody measures in characterizing preclinical type 1 diabetes and recruitment of prevention trials. To summarize our findings, we reported that 96% of individuals with multiple autoantibodies sustain these autoantibodies over time (2). Further, we found that the 4% of individuals who did not sustain multiple-autoantibody status over time still retained a greater risk of progression to type 1 diabetes than those who never developed multiple autoantibodies. Indeed, decades of research in many population groups and different countries have repeatedly demonstrated that almost all individuals with multiple autoantibodies will eventually develop clinical disease. Additionally, among children at increased genetic risk for type 1 diabetes, those who reverted from a single autoantibody retained an increased risk for …

OBJECTIVE Most individuals with two or more islet autoantibodies progress to clinical type 1 diabetes. However, in some individuals, autoantibodies are subsequently lost. Here, our objectives were to determine the frequency of autoantibody loss (reversion) in multiple-autoantibody–positive individuals and to determine the association between reversion and progression to clinical disease. RESEARCH DESIGN AND METHODS We analyzed multiple-autoantibody–positive individuals participating in TrialNet’s Pathway to Prevention Study for reversion and determined the effect of reversion on progression to clinical disease using a Cox regression analysis. RESULTS Of 3,284 multiple-autoantibody–positive subjects, reversion occurred in 134 (4.1%) and was associated with reduced incidence of clinical disease. Reversion occurred more frequently with older age, lower autoantibody titers, and fewer positive autoantibodies. CONCLUSIONS Although reversion of multiple-autoantibody positivity is rare, when it occurs, the risk of progressing to clinical disease is reduced. This suggests unknown mechanisms promoting immune remission in some individuals.

Introduction Pulsatile tinnitus (PT) can harbor potentially life-threatening conditions (LTCs), whereby a delay in diagnosis could be disastrous. Objective The purpose of this study was to ascertain whether associated signs and symptoms at presentation could help identify a subgroup of high-risk patients. Materials and Methods A total of 66 patients with PT were retrospectively assessed. The diagnoses were classified as group I with an LTC or not in group II. Results There were 4 patients (6%) with a final diagnosis of LTC (group I) and 62 patients (94%) without a final diagnosis of LTC or no diagnosis (group II). The results were not quite statistically significant regarding the trauma and were strongly statistically significant regarding headache and the cranial nerve paralysis. Conclusion The combination of PT with any of the three features of occipital headache, cranial nerve palsy, and recent trauma should alert the clinician to potentially serious causes.

Adenoma detection rate (ADR) is a quality indicator for screening colonoscopy, but its calculation is time-consuming. Polyp detection rate (PDR) has been found to correlate with ADR; however, its use as a quality indicator has been criticized out of concern for endoscopists artificially inflating the PDR. We aim to evaluate whether active monitoring affects PDR. In March 2015, 14 endoscopists were made aware that their personal PDRs would be tracked monthly as a quality improvement project. Endoscopists received a report of their individual monthly and cumulative PDR, departmental averages, and a benchmark PDR. Following the intervention, data were collected for consecutive patients undergoing average risk screening colonoscopy for six months. PDR, ADR, and adenoma to polyp detection ratio quotient (APDRQ) were compared to a six-month pre-intervention period. 2203 patients were included in the study. There was no statistically significant difference in PDR when comparing pre- and post-intervention (44 vs. 45%, OR 1.04; 95% CI 0.77–1.36). No statistically significant difference in ADR was observed when comparing pre- and post-intervention (29 vs. 30%, OR 1.03; 95% CI 0.64–1.52). There was no statistically significant difference in APDRQ when comparing pre- and post-intervention (0.67 vs. 0.66, OR 0.99; 95% CI 0.69–1.33). Monthly report cards did not result in a change in PDR or APDRQ. In some environments, PDR can be used as a surrogate marker of ADR, despite endoscopist awareness that PDR is being measured.

The diagnostic evaluation of a PSA recurrence after RP in the Irish hospital setting involves multimodality imaging with MRI, CT, and bone scanning, despite the low diagnostic yield from imaging at low PSA levels. We aim to investigate the value of multimodality imaging in PC patients after RP with a PSA recurrence. Forty-eight patients with a PSA recurrence after RP who underwent multimodality imaging were evaluated. Demographic data, postoperative PSA levels, and imaging studies performed at those levels were evaluated. Eight (21%) MRIs, 6 (33%) CTs, and 4 (9%) bone scans had PCa-specific findings. Three (12%) patients had a positive MRI with a PSA

BACKGROUND Colorectal cancer (CRC) screening guidelines likely over-generalizes CRC risk, 35% of Americans are not up to date with screening, and there is growing incidence of CRC in younger patients. GOALS We developed a practical prediction model for high-risk colon adenomas in an average-risk population, including an expanded definition of high-risk polyps (≥3 nonadvanced adenomas), exposing higher than average-risk patients. We also compared results with previously created calculators. STUDY Patients aged 40 to 59 years, undergoing first-time average-risk screening or diagnostic colonoscopies were evaluated. Risk calculators for advanced adenomas and high-risk adenomas were created based on age, body mass index, sex, race, and smoking history. Previously established calculators with similar risk factors were selected for comparison of concordance statistic (c-statistic) and external validation. RESULTS A total of 5063 patients were included. Advanced adenomas, and high-risk adenomas were seen in 5.7% and 7.4% of the patient population, respectively. The c-statistic for our calculator was 0.639 for the prediction of advanced adenomas, and 0.650 for high-risk adenomas. When applied to our population, all previous models had lower c-statistic results although one performed similarly. CONCLUSIONS Our model compares favorably to previously established prediction models. Age and body mass index were used as continuous variables, likely improving the c-statistic. It also reports absolute predictive probabilities of advanced and high-risk polyps, allowing for more individualized risk assessment of CRC.

Background: Two versions of the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation form currently exist: the original version (1999) and a recently modified pediatric-specific version (2011). Comparison of the pediatric IKDC with the adult version in the adult population may reveal that either version could be used longitudinally. Hypothesis: We hypothesize that the scores for the adult IKDC and pediatric IKDC will not be clinically different among adult patients aged 18 to 50 years. Study Design: Randomized crossover study design. Level of Evidence: Level 2. Methods: The study consisted of 100 participants, aged 18 to 50 years, who presented to orthopaedic outpatient clinics with knee problems. All participants completed both adult and pediatric versions of the IKDC in random order with a 10-minute break in between. We used a paired t test to test for a difference between the scores and a Welch’s 2-sample t test to test for equivalence. A least-squares regression model was used to model adult scores as a function of pediatric scores, and vice versa. Results: A paired t test revealed a statistically significant 1.6-point difference between the mean adult and pediatric scores. However, the 95% confidence interval (0.54-2.66) for this difference did not exceed our a priori threshold of 5 points, indicating that this difference was not clinically important. Equivalence testing with an equivalence region of 5 points further supported this finding. The adult and pediatric scores had a linear relationship and were highly correlated with an R2 of 92.6%. Conclusion: There is no clinically relevant difference between the scores of the adult and pediatric IKDC forms in adults, aged 18 to 50 years, with knee conditions. Clinical Relevance: Either form, adult or pediatric, of the IKDC can be used in this population for longitudinal studies. If the pediatric version is administered in adolescence, it can be used for follow-up into adulthood.

Aim The study aimed to determine whether laparoscopic volume and type of training influence conversion during elective laparoscopic colorectal surgery. Method An Institutional Review Board-approved prospective database was reviewed for patients who underwent colorectal resection, performed by six colorectal surgeons, for all diagnoses from 2009 to 2014. Surgeons were designated as laparoscopic- or open-trained based on formal laparoscopic colorectal surgery training, and were classified as low laparoscopic volume (LLV) (i.e. had performed

Patients with prior foregut surgery requiring long-term enteral access typically undergo operative jejunostomy tube placement; however, direct percutaneous endoscopic jejunostomy (DPEJ) is a viable alternative. All de novo DPEJ procedures performed by surgical and advanced endoscopists from May 2003 to June 2015 were retrospectively reviewed following approval by the Institutional Review Board. There were 59 cases identified. Our cohort had a mean age of 50.3 ± 16.9 years and 35 (59.3%) were female. All but two patients previously had foregut surgery including 19 patients (34.5%) with prior bariatric surgery. The composite of malnutrition and dehydration was the indication for DPEJ in 29 patients (49.1%) and was the initial enteral access placed in 47 patients (79.7%). Moderate sedation was used in 32 cases (54.2%), and 29 procedures (49.2%) were performed in the operating room. Within 30 days, there were six complications in five patients, giving a peri-procedural complication rate of 12.5%. Beyond 30 days, the most common complications were peri-tube leakage and dislodgement (each 16.9%). The median time to complication was 197 days. In patients with surgically altered foregut anatomy, DPEJ offers a less invasive alternative to operative jejunostomy tube placement. DPEJ can be placed in the endoscopy suite or operating room with an acceptable risk of perioperative complications.

The detection of the high‐frequency fundamental‐mode Rayleigh‐wave Rg is important for explosion monitoring efforts because it indicates a shallow source, which is most often man‐made. We developed an automated Rg detector that successfully identifies Rg using the spectrogram of the seismic signal to find peaks in the characteristic Rg frequency band. We tested the detector using a network of over 200 seismometers in Wyoming, which recorded dozens of nearby coal‐mining blasts and active‐source tamped borehole shots. The detector finds peaks in the summed spectrogram amplitudes from 0.4 to 0.8 Hz for mining blasts and from 0.8 to 1.5 Hz for borehole shots. We achieved successful Rg detection of mining blasts across the entire array for the largest blasts, though smaller blasts had less success at distant stations, due to low signal amplitude. Similarly, Rg detection from borehole shots was successful at distances Finally, we compared our method with an existing Rg detection method based on finding retrograde particle motion, typical of Rg , in signal coming from the known source–receiver back azimuth. In our application, the detector worked well for more distant stations but failed at stations within the same basin as the source, where Rg has prograde particle motion. The two detectors are fundamentally different; the new detector is easier to automate but depends on Rg having larger amplitude than the pre‐ Rg time window, whereas the existing detector triggers based on the particle motion and the direction of arrival, independent of the amplitude. The new method, perhaps in conjunction with the existing method, can offer increased monitoring capability and higher confidence when detecting Rg . Electronic Supplement: Tables of source information and figures of example detection.

Background Oral food challenge (OFC) is the criterion standard to assess peanut allergy (PA), but it involves a risk of allergic reactions of unpredictable severity. Objective Our aim was to identify biomarkers for risk of severe reactions or low dose threshold during OFC to peanut. Methods We assessed Learning Early about Peanut Allergy study, Persistance of Oral Tolerance to Peanut study, and Peanut Allergy Sensitization study participants by administering the basophil activation test (BAT) and the skin prick test (SPT) and measuring the levels of peanut-specific IgE, Arachis hypogaea 2–specific IgE, and peanut-specific IgG4, and we analyzed the utility of the different biomarkers in relation to PA status, severity, and threshold dose of allergic reactions to peanut during OFC. Results When a previously defined optimal cutoff was used, the BAT diagnosed PA with 98% specificity and 75% sensitivity. The BAT identified severe reactions with 97% specificity and 100% sensitivity. The SPT, level of Arachis hypogaea 2–specific IgE, level of peanut-specific IgE, and IgG4/IgE ratio also had 100% sensitivity but slightly lower specificity (92%, 93%, 90%, and 88%, respectively) to predict severity. Participants with lower thresholds of reactivity had higher basophil activation to peanut in vitro. The SPT and the BAT were the best individual predictors of threshold. Multivariate models were superior to individual biomarkers and were used to generate nomograms to calculate the probability of serious adverse events during OFC for individual patients. Conclusions The BAT diagnosed PA with high specificity and identified severe reactors and low threshold with high specificity and high sensitivity. The BAT was the best biomarker for severity, surpassed only by the SPT in predicting threshold. Nomograms can help estimate the likelihood of severe reactions and reactions to a low dose of allergen in individual patients with PA., Graphical abstract

To determine the diagnostic accuracy and optimum cut-off value of SUVmax on PET to predict malignancy of supraclavicular lymph nodes (SCLNs) in patients with oesophageal carcinoma.All diagnosed cases of oesophageal cancer were retrospectively reviewed (2010-2016). Patients that had a confirmed diagnosis of oesophageal cancer with avid SCLNs on staging PET were included in the study. 33 SCLNs that subsequently underwent ultrasound guided biopsy for staging were analysed. The maximum uptake values (SUVmax) of the SCLNs and primary tumours were measured. A receiver operating characteristic (ROC) analysis was performed to determine the optimum cut off of SUVmax in predicting malignancy.24/33 PET-detected SCLNs were malignant. ROC analysis identified the best nodal SUVmax cut-off to be 3.0. The diagnostic accuracy of PET was 76.0 % (sensitivity = 78.9 %, specificity = 66.6 %). For SCLNs with SUVmax3.0, PET showed a positive predictor value of 88.2 %; for SCLNs3.0, PET showed a negative predictor value of 50 %. The median SUVmax of pathologically negative and positive nodes were 2.8 (range 1.8-6.0) and 5.3 (range 1.9-13.4). The median primary tumour SUVmax was 13.8 (range 3.7-30.0). The SUVmax of metastatic lymph nodes were significant higher than those of benign lesions (p0.05).Our study revealed an accuracy rate of 76 % for PET detected SCLNs in patients with oesophageal carcinoma. For SCLNs with SUVmax3.0, PET had a high PPV (88 %), which can minimize the need for further diagnostic tests.

While the majority of individuals with ≥2 autoantibodies (AAB) will progress to clinical T1D, there are reports that AAB disappear in some individuals. Clinical trials to delay or prevent disease progression often enroll those at stage 1 or 2, defined as individuals with ≥2 AAB confirmed on two separate occasions. Using data from TrialNet’s Pathway to Prevention study, we aimed to determine (a) how many individuals at stage 1 or 2 subsequently lost AAB, and (b) how this impacted the risk of T1D progression. Individuals confirmed to be at stage 1 or stage 2 diabetes with a mean follow-up of 2.2 years (0.1 to 13) were included (n=3267). 3141 (96%) maintained their status over time while 126 (4%) did not (non-maintainers). This affected their risk of progression (Figure). Conclusion: Reverting from stage 1 or stage 2 diabetes is rare; yet, if it occurs, the risk of progressing to stage 3 during the follow-up period is reduced. This suggests that there are unknown mechanisms that can lead to immune remission in some individuals. Disclosure C. O'Rourke: None. M. So: None. C. Greenbaum: Research Support; Self; Janssen Research & Development. H.T. Bahnson: None. C. Speake: None. Funding JDRF; National Institutes of Health

Cholecystectomy is the preferred treatment for acute cholecystitis with percutaneous cholecystostomy (PC) considered an alternative therapy in severely debilitated patients. The aim of this study was to evaluate the efficacy and outcomes of PC at a tertiary referral center.We retrospectively reviewed all patients that had undergone PC from 2000 to 2014. Data collected included baseline demographics, comorbidities, details of PC placement and management, and post-procedure outcomes. The Charlson comorbidity index (CCI) was calculated for all patients at the time of PC.Four hundred and twenty-four patients underwent PC placement from 2000 to 2014, and a total of 380 patients had long-term data available for review. Within this cohort, 223 (58.7 %) of the patients were male. The mean age at the time of PC placement was 65.3 ± 14.2 years of age, and the mean CCI was 3.2 ± 2.1 for all patients. One hundred and twenty-five (32.9 %) patients went on to have a cholecystectomy following PC placement. Comparison of patients who underwent PC followed by surgical intervention revealed that they were significantly younger (p = 0.0054) and had a lower CCI (p 0.0001) compared to those who underwent PC alone.PC placement appears to be a viable, long-term alternative to cholecystectomy for the management of biliary disease in high-risk patients. Old and frail patients benefit the most, and in this cohort PC may be the definitive treatment.

Background Early identification of serious adverse events following ventral hernia repair (VHR) could result in improved patient outcomes. Establishment of clinical markers that correlate with serious adverse events following VHR would help facilitate a more timely diagnosis of such events. We investigated the clinical utility of postoperative tachycardia to predict serious adverse events in patients undergoing VHR. Methods Consecutive patients undergoing VHR at the Cleveland Clinic Comprehensive Hernia Center from September 2013 through June 2015 were identified within the Americas Hernia Society Quality Collaborative database. Tachycardia was classified according to frequency and duration. Sustained tachycardia was defined as >8 consecutive hours of tachycardia on any postoperative day. Serious adverse events were defined as cardiac events, venous thromboembolism, infection, bleeding, and anastomotic leak or missed enterotomy. Association between tachycardia class and serious adverse events was investigated using the Pearson χ2 test. Results A total of 377 patients underwent VHR during the study period. A total of 119 (31.6%) patients experienced at least 1 episode of tachycardia. There were 26 (6.9%) patients with a serious adverse event. Tachycardia was present in 21 (80.7%) of these patients. Sustained tachycardia had a significant association with serious adverse events (P = .007). The presence of postoperative tachycardia was associated with the occurrence of a serious adverse event, having a positive likelihood ratio of 2.9 (95% confidence interval 2.2–3.7). Conclusion Postoperative tachycardia is common following VHR. Nevertheless, sustained tachycardia is associated with a significant risk for serious postoperative adverse events and mandates further investigation.

We used a dense seismic network to test the P / S amplitude ratio discriminant for earthquakes and explosions at distances from 20 to 200 km in a complex tectonic setting. We used data from several hundred seismic stations in northern Wyoming to observe 22 earthquakes, 37 mining blasts, and 24 borehole shots and compared their P / S amplitude ratios. Frequencies of 6–8 Hz and above achieved the best discrimination results for single‐shot borehole explosions, whereas 6–8 and 8–10 Hz passbands were best for mining blasts. The P / S method appears valid for 50–200 km but fails at distances

Study design Electronic survey. Objective To identify the surgical treatment patterns for low back pain (LBP), among U.S. spine surgeons. Specifically determine (1) differences in surgical treatment responses based on various demographic variables; (2) probability of disagreement based on surgeon subgroups. Summary of background data Multiple surgical and nonsurgical treatments exist for LBP. Without strong evidence or clear guidelines for the indications and optimal treatments, there is substantial variability in surgical treatments used. Methods A total of 445 U.S. spine surgeons completed a survey of clinical and radiographic case scenarios on patients with mechanical LBP, no leg pain, and concordant discograms. Surgical treatment options included no surgery, anterior lumbar interbody fusion (ALIF), posterolateral fusion with pedicle screws, transforaminal/posterior lumbar interbody fusion (TLIF/PLIF), etc. Statistical significance was set at 0.01 to account for multiple comparisons. Results There was substantial clinical equipoise (∼75% disagreement) among surgeons on the approach to treat patients with LBP. Disagreement was highest in the southwest and lowest in the Midwest (82% vs. 69%, respectively); there was significantly lower disagreement among those in academic practices versus those in private/hybrid practices (56% vs.79%, respectively). Those in academic practices had approximately four times greater odds of choosing no surgery as compared to those in hybrid and private practices, who were more likely to choose ALIF or PLIF/TLIF. Those with fellowship training had approximately two times greater odds of selecting no surgery and four times greater odds of selecting ALIF as compared to those without fellowship training who were more likely to select TLIF/PLIF. Conclusion Significant differences exist among U.S. spine surgeons in the treatment of LBP. These differences stem from geographical location of the practice, specialty, practice type, and fellowship training. Recognizing the substantial variability underlies the importance of additional studies aimed at identifying the proper indications and most cost-effective treatments for LBP. Level of evidence 3.

Background Up to 55% of total joint arthroplasty costs come from post–acute care, with large variability dependent on a patient’s discharge location. At our institution, we identified a group of surgeons using a preoperative discharge planning protocol emphasizing the merits of home discharge. We hypothesized that using the protocol would increase patients’ odds for discharge home. Methods Administrative data from 14,315 total hip and knee arthroplasties performed over a 3-year period were retrospectively analyzed to determine predictors of patient discharge location. Bayesian hierarchical logistic regression modeling was used to account for the complex multilevel structure within the data as we considered patient-, surgeon-, and hospital-level predictors. A simplified case-control data structure with logistic regression analysis was also used to better understand the impact of the preoperative discharge planning protocol. Results A variety of patient- and surgeon-level variables are predictive of patients being discharged home after total joint arthroplasty including a patient’s length of stay, age, illness severity, and insurance, as well as surgeon's affiliation. In the case-control data, patients exposed to the rapid recovery protocol had 45% increased odds of being discharged home compared to patients not exposed to the protocol. Conclusions Although patient factors are known to play a role in predicting postdischarge destination, this analysis describes additional surgeon- and hospital-level factors that predict discharge location. Exogenous factors based on how surgeons and hospital staff practice and interact with patients may impact the postdischarge decision-making process and provide a cost savings opportunity.

The utilization of normothermic machine perfusion (NMP) may be an effective strategy to resuscitate livers from donation after circulatory death (DCD). There is no consensus regarding the efficacy of different perfusates on graft and bile duct viability. The aim of this study was to compare, in an NMP porcine DCD model, the preservation potential of three different perfusates. Twenty porcine livers with 60 min of warm ischemia were separated into four preservation groups: cold storage (CS), NMP with Steen solution (Steen; XVIVO Perfusion Inc., Denver, CO), Steen plus red blood cells (RBCs), or whole blood (WB). All livers were preserved for 10 h and reperfused to simulate transplantation for 24 h. During preservation, the NMP with Steen group presented the highest hepatocellular injury. At reperfusion, the CS group had the lowest bile production and the worst hepatocellular injury compared with all other groups, followed by NMP with Steen; the Steen plus RBC and WB groups presented the best functional and hepatocellular injury outcomes, with WB livers showing lower aspartate aminotransferase release and a trend toward better results for most parameters. Based on our results, a perfusate that contains an oxygen carrier is most effective in a model of NMP porcine DCD livers compared with Steen solution. Specifically, WB-perfused livers showed a trend toward better outcomes compared with Steen plus RBCs.

Background Among nurses, skill retention after an electrocardiography blended-learning course is unknown. Objectives To compare 3- and 8-week electrocardiography test scores, compare scores by nurse and work characteristics and self-assessed electrocardiographic competence, and compare 1-year work retention with 3- and 8-week scores and change in scores from week 3 to week 8. Methods Data were collected on demographics, comfort with electrocardiography expectations, electrocardiography competence levels, and 1-year work retention. Correlational and comparative statistics were used in analyses. Results Of 69 nurses, 58% were somewhat comfortable with interventions for abnormal rhythms. Test scores were higher at 3 weeks than at 8 weeks: mean difference, 26%; P < .001. Scores at 8 weeks reflected intermediate skill retention and were not associated with nurse characteristics, electrocardiography background, comfort with rhythms and measurements, or 1-year work retention. Nurses with greater comfort for intervening when rhythm abnormalities occurred had higher median 8-week scores (P = .01) than did nurses with less comfort, and perceptions of electrocardiographic competence were associated with 8-week scores (r = 0.28; P = .02). Reduction in scores at 8 weeks was less severe in nurses with greater comfort at 3 weeks in measuring electrocardiographic intervals (P = .008) and applying therapeutic interventions (P = .009). Conclusions Skill retention and competence in electrocardiographic interpretation were intermediate and correlated with baseline self-assessment. Electrocardiographic interpretation, measurement, and interventions should be reinforced at the bedside.

We took advantage of a high‐density seismic array deployed coincident with USArray to study small‐magnitude seismicity patterns in northern Wyoming. We detected and located a total of 89 earthquakes ranging in magnitude from −0.5 to 2.4 during the six‐month period of April to September 2010. Most events were located shallower than 25 km in the crust, with a few events as deep as 39 km and one very deep earthquake below the Moho, at 63 km. We also detected and recorded 1563 mining explosions in the area. We computed focal mechanism solutions for 14 earthquakes and observed dominantly normal faulting. Stress inversions obtained from these focal mechanisms show extension oriented ∼N20° E that matches borehole breakout data collected in the area. Though wastewater injection wells were active in the region, we see no evidence of induced seismicity in this catalog. The seismicity pattern shows earthquakes occurring beneath areas of high topography in the Bighorn and Owl Creek Mountain ranges. This may indicate a preference to slip on pre‐existing weaknesses created during mountain building. The absence of earthquakes between 39 and 63 km depths represents an aseismic zone in the lower crust that may indicate a rheological change between brittle and ductile behavior in the crust, and a strong mantle capable of brittle failure. Online Material: Maps of earthquake catalogs, figures of depth versus misfit, time of day histograms for earthquakes and mine explosions, earthquake density, and location of class II disposal wells relative to earthquakes.

Both the American Cancer Society and National Comprehensive Cancer Network recommend annual clinical breast examination (CBE) along with screening mammogram (SM) for patients starting at 40 years of age. However, patients with a palpable breast mass should have a diagnostic mammogram (DM) during workup. Review at our institution demonstrated that 11% of patients with newly diagnosed breast cancer and self-identified breast mass had SM instead of DM. This led us to question whether primary care physicians (PCP) perform CBE prior to ordering mammography. As part of the routine preimaging screening, patients were asked if they had undergone breast examination by a medical provider prior to mammogram order. Data on mammogram type, ordering physician specialty, and presence of symptoms on day of mammogram were recorded. Of 6,109 mammograms, 4,823 were ordered by PCPs. CBE was performed prior to 67.2% SM and 64.8% DM (p = 0.12). OB/GYN performed statistically significantly higher CBE (81.6%) compared to internal (45.4%) and family (50.5%) medicine physicians (p < 0.001). Of patients with self-reported breast symptoms, 8.7% had SM ordered rather than DM. Despite recommendations, approximately 1/3 of women report not having CBE prior to mammogram. The chances of having a CBE varied significantly by PCP specialty. Lack of CBE can lead to incorrect type of mammogram, with possibly increased cost and delay in diagnosis. Further evaluation is needed to understand why CBE was not performed in some patients.

Background A vaginal ring containing dapivirine, a non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. We examined the impact of dapivirine ring use at the time of HIV-1 acquisition on subsequent HIV-1 disease progression and responses to NNRTI-containing antiretroviral therapy (ART). Methods HIV-1 disease progression and virologic failure following initiation of ART were assessed among women who acquired HIV-1 while participating in Microbicide Trials Network–020, a randomized, placebo-controlled trial of a monthly, dapivirine vaginal ring. Results Among the 158 participants who acquired HIV-1 (65 dapivirine, 93 placebo), no differences between dapivirine and placebo participants were observed in CD4+ cell counts or plasma HIV-1 RNA over the first year after infection (prior to ART). During follow-up, 100/158 (63%) participants initiated NNRTI-containing ART (dapivirine: 39/65; placebo: 61/93); the median time to HIV-1 RNA Conclusions The acquisition of HIV-1 infection during dapivirine or placebo treatment in ASPIRE did not lead to differences in HIV-1 disease progression. After the initiation of NNRTI-containing ART, dapivirine and placebo participants had similar times to virologic suppression and risks of virologic failure. These results provide reassurance that NNRTI-based ART regimens are effective among women who acquired HIV-1 while receiving the dapivirine vaginal ring. Clinical Trials Registration NCT016170096 and NCT00514098.

Introduction: Pubo-vaginal sling placed at the bladder neck is the gold standard treatment for stress urinary incontinence (SUI). The synthetic mid-urethral sling (MUS) is now widely used, as morbidity rates with this technique are substantially reduced. This is an initial report on long-term outcomes of a polypropylene sling (PPS) placed in the traditional bladder neck location.Methods: A retrospective analysis of all patients who underwent PPS insertion at our institution between 2006 and 2014 was conducted. Patient and urodynamic demographics were recorded. Subjective and objective measures of success were determined by postoperative pad usage and validated incontinence questionnaires. Results: A total of 170 patients were followed for a median of four years (range 1–8). The mean age was 51 years (±10). Subjective response was assessed in 57% of patients; the overall subjective cure rate was 85.3% (n=145), subjective improvement rate was 4.1% (n=7), and the subjective failure rate was 10.6% (n=18). The mean Urogenital Distress Inventory (UDI)-6 score was 6.5 (±5.6) out of a maximum score of 24 and the Incontinence Impact Questionnaire (IIQ)-7 score was 5.5 (±6.3) out of a maximum score of 28. There was no significant difference in objective outcome measures in those with an abdominal leak-point pressure (ALPP) < or >60 cmH2O.Conclusions: Bladder neck placement of a PPS resulted in cure rates of 85% in this series. SUI secondary to intrinsic sphincter deficiency (ISD) and urethral hypermobility were treated with equal success. Bladder neck PPS placement has a role in the treatment of SUI. Our data may well reassure rectus fascia sling (RFS) surgeons who wish to take advantage of faster postoperative recovery using the less invasive PPS placed at the bladder neck.

Safety data on pregnancy and fetal outcomes among women in HIV prevention trials are urgently needed to inform use of effective antiretroviral agents for HIV prevention. We describe an effective, efficient, and novel method to prospectively collect perinatal safety data concurrent with on-going parent clinical trials.The Microbicide Trials Network (MTN)-016 study is a multinational prospective pregnancy exposure registry designed to capture pregnancy and neonatal outcomes. Studies currently contributing data to this registry included phase I and II safety trials with planned exposures to candidate HIV prevention agents, as well as phase IIB and III efficacy trials capturing data on pregnancy and infant outcomes following inadvertent fetal exposure during study participation.To date, participants from two phase I studies and two effectiveness trials have participated in MTN-016, resulting in 420 pregnant women and 381 infants enrolled. Infant retention has been high, with 329 of 381 (86%) infants completing the 12-month follow-up visit.In a research setting context, it is feasible to establish and implement a prospective, multinational HIV chemoprophylaxis pregnancy registry that will generate pregnancy exposure data in a robust fashion.

Background Prompt identification of elevated intracranial pressure (eICP) is life-saving. Physical exam alone often fails to identify this problem and invasive monitoring is not always utilized appropriately. A non-invasive, rapid, reliable technique to detect eICP is needed and optic nerve sheath diameter (ONSD) is known to be a valid surrogate. Historically, ONSD in patients with eICP above 20 mmHg varied from 0.5 to 0.7 cm. Receiver operator curves predict that diameters below 0.5 to 0.58 cm correspond to normal pressures. Interobserver variability is low (0.01--0.03 cm). The learning curve was 25 and 10 procedures for novice and experienced sonographers, respectively. We report our initial experience using ultrasound to measure ONSD during initial trauma evaluation. Study design Transocular ultrasound was used to determine ONSD after traumatic brain injury. Data were correlated with CT and exam findings or measured ICP. Measurements were performed by a single trauma surgeon. Time to perform the measurement was recorded. Relevant literature from the past 15 years was reviewed. Results Physical exam was not a reliable indicator of eICP. In patients with eICP requiring surgery, ONSD averaged 0.62 cm. Normal pressures were ensured if the ONDS was Conclusions Determining ONSD with ultrasound is easy to learn, precise, and inexpensive. An ONSD of less than 5 mm ensures no eICP. This procedure can be added to the evaluation of trauma patients with no delay in care. Future prospective studies may validate and incorporate this technique into the trauma surgeon's armamentarium.

Background: The clinical benefit of chronic suppression with oral antibiotics as a salvage treatment for periprosthetic joint infection is unclear. The purpose of this study was to compare infection-free prosthetic survival rates between patients who received chronic oral antibiotics and those who did not following irrigation and debridement with polyethylene exchange or two-stage revision for periprosthetic joint infection. Methods: We reviewed the records on all irrigation and debridement procedures with polyethylene exchange and two-stage revisions performed at our institution from 1996 to 2010 for hip or knee periprosthetic joint infection. Of 625 patients treated with a total of 655 eligible revisions, ninety-two received chronic oral antibiotics for a minimum of six months and were eligible for inclusion in our study. These patients were compared with a matched cohort (ratio of 1:3) who did not receive chronic oral antibiotics. Results: The five-year infection-free prosthetic survival rate was 68.5% (95% confidence interval [CI] = 59.2% to 79.3%) for the antibiotic-suppression group and 41.1% (95% CI = 34.9% to 48.5%) for the non-suppression group (hazard ratio [HR] = 0.63, p = 0.008). Stratification by the type of surgery and the infecting organism showed a higher five-year survival rate for the patients in the suppression group who underwent irrigation and debridement with polyethylene exchange (64.7%) compared with those in the non-suppression group who underwent irrigation and debridement with polyethylene exchange (30.4%, p < 0.0001) and a higher five-year survival rate for the patients in the suppression group who had a Staphylococcus aureus infection (57.4%) compared with those in the non-suppression group who had a Staphylococcus aureus infection (40.1%, p = 0.047). Conclusions: Chronic suppression with oral antibiotics increased the infection-free prosthetic survival rate following surgical treatment for periprosthetic joint infection. Patients who underwent irrigation and debridement with polyethylene exchange and those who had a Staphylococcus aureus infection had the greatest benefit. Level of Evidence: Therapeutic Level III. See the Instructions for Authors for a complete description of levels of evidence.

Background. Evidence suggests that the average prediction across groups is more accurate than for individuals. Our goals were therefore to investigate accuracy of the average predictions for groups of clinicians and to compare this accuracy with a published statistical prediction model. Methods. Twenty-four expert clinicians attending an advisory board meeting were asked to make predictions for 25 patients from a research registry regarding the probability of having a positive bone scan 1 year from today if left untreated. Comparisons were made between the accuracy of average responses and that of an appropriate previously published statistical prediction model. Results. This study suggests that the mean of the clinicians’ predictions can quickly approach the accuracy of the best clinician using as few as 5 clinicians. When all 24 clinicians’ predictions were averaged, the concordance index reached 0.750, still far below that of the published statistical model with 0.812. Conclusions. Averaging clinician predictions may have merit over individual clinician predictions but still not reasonably replace a carefully built statistical model. However, averaging clinician predictions could prove helpful in situations where statistical models do not yet exist or where existing models are inadequate.

PURPOSE The aim of this study was to quantify clinical nurse specialist (CNS) work and determine if competencies are associated with personal characteristics, priorities, and quality outcomes. BACKGROUND The work of a CNS is difficult to quantify. Nurse leaders need quantifiable data to understand the impact of CNS work. DESIGN A prospective, single-center, correlational study with a convenience sample was conducted. SETTING AND SAMPLE The study was conducted in a 1200-bed quaternary care medical center in Northeast Ohio, using CNSs. METHODS The investigator-developed Role Tracker Tool (software) and a CNS questionnaire were used to collect baseline and monthly data for 5 months. Characteristics of the CNSs were summarized using descriptive statistics. Correlational statistics were used to measure associations. After mutually exclusive groups were created, tests for differences were completed using a Welch 2-sample t test and analysis of variance. Regression models were used to determine if relationships existed over time between competencies, priority ranking of competencies, and nursing characteristics. FINDINGS Among 14 CNSs, mean (SD) age was 45 (10.11) years; mean (SD) CNS experience was 5.57 (7.87) years. Of 6 competencies, CNSs ranked quality as most important, followed by clinical work. Research ranked low. Mean (SD) time spent in hours/8.5-hour workday over 5 months was highest for clinical work, at 1.9 (1) hours, and lowest for professional self-development, at 0.4 (0.4) hours. Time spent on specific competencies varied by specialty, years as a CNS and at current employer, and comfort in competencies and spheres after controlling for nurse characteristics and monthly trends. Of 9 quality initiative focuses, mean (SD) time in hours/8.5-hour workday was highest for heart failure, with 0.7(0.8) hours. Time spent on quality initiatives was not associated with changes in quality improvement outcomes. Clinical nurse specialist competency priorities, quality initiative focuses, and quality outcomes varied over time. IMPLICATIONS The work of CNSs can be captured and analyzed to enhance understanding of unique and varied CNS contributions in the healthcare matrix.

Mouth Cancer Awareness Day in Ireland was launched in September 2010 by survivors of the disease to promote public awareness of suspicious signs of oral cancer and to provide free dental examinations. To find out whether its introduction had increased public interest in the disease, we used Google Trends to find out how often users in Ireland had searched for "oral cancer" and "mouth cancer" across all Google domains between January 2005 and December 2013. The number of internet searches for these cancers has increased significantly (p