Citations

Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long‐term outcomes in pediatric PSC patients. We evaluated GGT normalization (< 50 IU/L) at 1 year among a multicenter cohort of children with PSC who did or did not receive treatment with ursodeoxycholic acid (UDCA). We compared rates of event‐free survival (no portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or liver‐related death) at 5 years. Of the 287 children, mean age of 11.4 years old, UDCA was used in 81% at a mean dose of 17 mg/kg/day. Treated and untreated groups had similar GGT at diagnosis (314 versus 300, P= not significant [NS]). The mean GGT was reduced at 1 year in both groups, with lower values seen in treated (versus untreated) patients (99 versus 175, P= 0.002), but 5‐year event‐free survival was similar (74% versus 77%, P= NS). In patients with GGT normalization (versus no normalization) by 1 year, regardless of UDCA treatment status, 5‐year event‐free survival was better (91% versus 67%, P< 0.001). Similarly, larger reduction in GGT over 1 year (> 75% versus < 25% reduction) was also associated with improved outcome (5‐year event‐free survival 88% versus 61%, P= 0.005). Conclusion:A GGT < 50 and/or GGT reduction of > 75% by 1 year after PSC diagnosis predicts favorable 5‐year outcomes in children. GGT has promise as a potential surrogate endpoint in future clinical trials for pediatric PSC.

Coccidioidomycosis is an invasive fungal infection caused by the inhalation of aerosolized spores of Coccidioides spp., which reside in the arid soil of the southwestern United States and northern Mexico. The primary infection occurs in the lungs; however, less than 40% of patients are symptomatic. Dissemination of coccidioidomycosis is rare (1-5%), but can lead to extra pulmonic disease involving any organ. Skeletal coccidioidomycosis occurs in 10% to 50% of disseminated infections. Skeletal coccidioidomycosis is a chronic and progressive infection that eventually results in bone destruction and loss of function and often involves adjacent structures such as joints, muscles, tendons and other soft tissues. This infection is frequently multifocal with axial skeletal involvement. Although radiographs and other imaging methods identify relevant abnormalities, histopathologic examination with culture of the involved bone is the only means to confirm the diagnosis. Serologic testing is adjunctive, and complement fixation titers can be evaluated serially to assess response to treatment. Skeletal coccidioidomycosis is difficult to treat, and a combination of medical therapy and surgical debridement often is needed. Early diagnosis and treatment are critical to avoid long-term problems.

Purpose Women with atypical hyperplasia (AH) on breast biopsy have an aggregate increased risk of breast cancer (BC), but existing risk prediction models do not provide accurate individualized estimates of risk in this subset of high-risk women. Here, we used the Mayo benign breast disease cohort to develop and validate a model of BC risk prediction that is specifically for women with AH, which we have designated as AH-BC. Patients and Methods Retrospective cohorts of women age 18 to 85 years with pathologically confirmed benign AH from Rochester, MN, and Nashville, TN, were used for model development and external validation, respectively. Clinical risk factors and histologic features of the tissue biopsy were selected using L1-penalized Cox proportional hazards regression. Identified features were included in a Fine and Gray regression model to estimate BC risk, with death as a competing risk. Model discrimination and calibration were assessed in the model-building set and an external validation set. Results The model-building set consisted of 699 women with AH, 142 of whom developed BC (median follow-up, 8.1 years), and the external validation set consisted of 461 women with 114 later BC events (median follow-up, 11.4 years). The final AH-BC model included three covariates: age at biopsy, age at biopsy squared, and number of foci of AH. At 10 years, the AH-BC model demonstrated good discrimination (0.63 [95% CI, 0.57 to 0.70]) and calibration (0.87 [95% CI, 0.66 to 1.24]). In the external validation set, the model showed acceptable discrimination (0.59 [95% CI, 0.51 to 0.67]) and calibration (0.91 [95% CI, 0.65 to 1.42]). Conclusion We have created a new model with which to refine BC risk prediction for women with AH. The AH-BC model demonstrates good discrimination and calibration, and it validates in an external data set.

AbstractObjectivesParamedics and emergency medical technicians (EMTs) perform triage at disaster sites. There is a need for disaster triage training. Live simulation training is costly and difficult to deliver. Screen‐based simulations may overcome these training barriers. We hypothesized that a screen‐based simulation, 60 Seconds to Survival (60S), would be associated with in‐game improvements in triage accuracy.MethodsThis was a prospective cohort study of a screen‐based simulation intervention, 60S. Participants included emergency medical services (EMS) personnel from 21 EMS agencies across 12 states. Participants performed assessments (e.g., check for pulse) and actions (e.g., reposition the airway) for 12 patients in each scenario and assigned color‐coded triage levels (red, yellow, green, or black) to each patient. Participants received on‐screen feedback about triage performance immediately after each scenario. A scoring system was designed to encourage accurate and timely triage decisions. Participants who played 60S included practicing EMTs, paramedics, and nurses as well as students studying to assume these roles. Participants played the game at least three times over 13 weeks.ResultsIn total, 2,234 participants began game play and 739 completed the study and were included in the analysis. Overall, the median number of plays of the game was just above the threshold inclusion criteria (three or more plays) with a median of four plays during the study period (interquartile range [IQR] = 3–7). There was a significant difference in triage accuracy from the first play of the game to the last play of the game. Median baseline triage accuracy in the game was 89.7% (IQR = 82.1%–94.9%), which then increased to a median of 100% at the last game play (IQR = 87.5%–100.0%; p < 0.001). There was some variability in median triage accuracy on fourth through 11th game plays, ranging from 95% to 100%, and on the 12th to 16th plays, the median accuracy was sustained at 100%. There was a significant decrease in the rate of undertriage: from 10.3% (IQR = 5.1%–18.0%) to 0 (IQR = 0%–12.5%; p < 0.001).Conclusion60 Seconds to Survival is associated with improved in‐game triage accuracy. Further study of the correlation between in‐game triage accuracy and improvements in live simulation or real‐world triage decisions is warranted.

Background: The 2017 American College of Cardiology/American Heart Association (ACC/AHA) Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults provides recommendations for the definition of hypertension, systolic and diastolic blood pressure (BP) thresholds for initiation of antihypertensive medication, and BP target goals. Objectives: This study sought to determine the prevalence of hypertension, implications of recommendations for antihypertensive medication, and prevalence of BP above the treatment goal among US adults using criteria from the 2017 ACC/AHA guideline and the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7). Methods: The authors analyzed data from the 2011 to 2014 National Health and Nutrition Examination Survey (N = 9 623). BP was measured 3 times following a standardized protocol and averaged. Results were weighted to produce US population estimates. Results: According to the 2017 ACC/AHA and JNC7 guidelines, the crude prevalence of hypertension among US adults was 45.6% (95% confidence interval [CI]: 43.6% to 47.6%) and 31.9% (95% CI: 30.1% to 33.7%), respectively, and antihypertensive medication was recommended for 36.2% (95% CI: 34.2% to 38.2%) and 34.3% (95% CI: 32.5% to 36.2%) of US adults, respectively. Nonpharmacological intervention is advised for the 9.4% of US adults with hypertension who are not recommended for antihypertensive medication according to the 2017 ACC/AHA guideline. Among US adults taking antihypertensive medication, 53.4% (95% CI: 49.9% to 56.8%) and 39.0% (95% CI: 36.4% to 41.6%) had BP above the treatment goal according to the 2017 ACC/AHA and JNC7 guidelines, respectively. Conclusions: Compared with the JNC7 guideline, the 2017 ACC/AHA guideline results in a substantial increase in the prevalence of hypertension, a small increase in the percentage of US adults recommended for antihypertensive medication, and more intensive BP lowering for many adults taking antihypertensive medication.

AbstractInvited for the cover of this issue is the group of Edwin Lewis, Mississippi State University, in collaboration with Frederick MacDonnell, University of Texas at Arlington, USA. The cover image shows Ru(phen)2(tatpp)]2+ binding to DNA.