A practical guide to adopting Bayesian analyses in clinical research.

Background: Bayesian statistical approaches are extensively used in new statistical methods but have not been adopted at the same rate in clinical and translational (C&T) research. The goal of this paper is to accelerate the transition of new methods into practice by improving the C&T researcher's ability to gain confidence in interpreting and implementing Bayesian analyses. Methods: We developed a Bayesian data analysis plan and implemented that plan for a two-arm clinical trial comparing the effectiveness of a new opioid in reducing time to discharge from the post-operative anesthesia unit and nerve block usage in surgery. Through this application, we offer a brief tutorial on Bayesian methods and exhibit how to apply four Bayesian statistical packages from STATA, SAS, and RStan to conduct linear and logistic regression analyses in clinical research. Results: The analysis results in our application were robust to statistical package and consistent across a wide range of prior distributions. STATA was the most approachable package for linear regression but was more limited in the models that could be fitted and easily summarized. SAS and R offered more straightforward documentation and data management for the posteriors. They also offered direct programming of the likelihood making them more easily extendable to complex problems. Conclusion: Bayesian analysis is now accessible to a broad range of data analysts and should be considered in more C&T research analyses. This will allow C&T research teams the ability to adopt and interpret Bayesian methodology in more complex problems where Bayesian approaches are often needed.

Exotic Grasses Reduce Infiltration and Moisture Availability in a Temperate Oak Savanna.

Biological invasions represent one of the most urgent conservation challenges. Oregon white oak (Quercus garryana) savannas, a complex of grassland and transitional forest, are especially sensitive to these invasions. These ecosystems have been severely degraded and fragmented over the past century and are being encroached by conifers, and oak seedlings are failing to emerge from the understory at many locations. Understanding competitive interactions between Oregon white oak and associated native and exotic vegetation would provide insight into forest-grassland dynamics and the role of exotic grasses in the decline of native species, the processes that maintain temperate savanna ecosystems, and the role of soil water uptake by individual savanna species in contributing to overall species assemblages. In this study, we quantified the soil moisture budget for invaded and uninvaded oak-associated ecosystems. From February to October 2007 we used a split paired plot experiment in Duncan, British Columbia, Canada to measure soil moisture on treatment sites where exotic grasses were removed with herbicide and control plots where they were not, using three depths (5, 20, and 35 or 50 cm) in the soil profile. Our results show that the plots that contained exotic vegetation had a faster rate of soil drying following precipitation events at the 5 cm depth than plots with the predominantly native species. We attribute this difference to the capacity of exotic vegetation to exploit soil moisture more rapidly than native vegetation at times of the year when native vegetation cannot. These results provide insight into one mechanism by which exotic grasses affect associated native plants and could help guide restoration efforts.

Sublingual Sufentanil vs. Intravenous Fentanyl for the Treatment of Acute Postoperative Pain in the Ambulatory Surgery Center: A Randomized Clinical Trial.

Objectives: Sublingual sufentanil is a novel opioid medication to treat moderate to severe pain postoperatively. This study's aim was to determine if a single dose of a sublingual sufentanil tablet (SST) is as efficacious as a single dose of intravenous (IV) fentanyl in readiness to discharge from ambulatory surgery. Methods: This was a two-arm, parallel group, randomized prospective outcomes study conducted at a single, free-standing ambulatory surgery center. Patients aged 18-80 undergoing general anesthesia who developed a postoperative pain score of ≥ 4 were enrolled and randomized to receive either 30 mcg SST or 50 mcg IV fentanyl. After their initial randomized dose, rescue IV fentanyl followed by oral oxycodone if needed. Recovery length of stay from arrival in the postanesthesia care unit until readiness to discharge criteria was met based on phase 2 discharge criteria. Results: 75 patients were analyzed. Readiness to discharge from the recovery room was not significantly different between either group (IV fentanyl median 65 minutes; IQR 56-89; SST 73 min, IQR 58-89; p=0.903). There was no significant difference in the amount of morphine equivalents (MME) of rescue opioids needed (IV fentanyl median rescue MME of 22.5, IQR 13.1-23.4; SST median rescue MME of 15.0, IQR 7.5-30.0; p=0.742). The change in pain from PACU initially, and on discharge was not significantly different (IV fentanyl initial pain minus pain on discharge median 3, IQR 2-4; SST initial pain minus pain on discharge median 4, IQR 2-5.5; p=0.079). There was no difference in the six-item screener and the Overall Benefit of Analgesic Survey Score. Discussion. In conclusion, patients who received a sublingual sufentanil 30 mcg tablet had no significant differences in PACU length of stay or rescue analgesic usage when compared to intravenous fentanyl 50 mcg.

Comparing liposomal bupivacaine plus bupivacaine to bupivacaine alone in interscalene blocks for rotator cuff repair surgery: a randomized clinical trial.

BACKGROUND: Single-injection interscalene brachial plexus blocks are used for analgesia for rotator cuff repair (RCR) but have limited duration. The value of adding liposomal bupivacaine (LB) to prolong single-injection interscalene blocks is unclear. The purpose of this trial is to evaluate the addition of LB to regular bupivacaine interscalene blocks for patients undergoing arthroscopic RCR. METHODS: In this prospective, randomized trial, 70 patients undergoing primary RCR with equal group allocation were randomized by random number generator to receive an interscalene block with 20 mL of 0.5% bupivacaine or 10 mL 0.5% bupivacaine plus 133 mg LB. The primary outcome was cumulative opioid consumption within 72 hours of the procedure. Secondary outcomes included maximum pain scores and quality of recovery 15 survey scores. RESULTS: 70 of the 80 randomized patients were included in final analysis following exclusion for protocol violations and loss to follow-up. Cumulative opioid consumption (oral morphine equivalents) within 72 hours in patients receiving LB was a median (IQR) of 31.9 mg (0, 73.1) compared with 45.0 mg (15.0, 108.8) among patients receiving bupivacaine alone (p=0.312). Patients receiving LB demonstrated mixed results regarding worst pain scores with improvements at 24 hours and 72 hours, but not 48 hours. CONCLUSIONS: LB added to bupivacaine interscalene blocks does not reduce opioid consumption within 72 hours following arthroscopic RCR. TRIAL REGISTRATION NUMBER: NCT03587584.

Evaluation of Diaphragmatic Function after Interscalene Block with Liposomal Bupivacaine: A Randomized Controlled Trial.

BACKGROUND: Interscalene blocks provide analgesia for shoulder surgery but also cause phrenic nerve paralysis. Liposomal bupivacaine is approved for use in interscalene blocks with the potential to provide longer pain control. However, the impact of liposomal bupivacaine on the phrenic nerve has not been evaluated. It was hypothesized that patients who received an interscalene block with both bupivacaine and liposomal bupivacaine would have a decreased diaphragmatic excursion when compared to bupivacaine alone at 24 h. METHODS: This was a double-blinded study of adult patients who were randomized to receive an interscalene block with either 20 ml 0.5% bupivacaine (bupivacaine group) or 10 ml 0.5% bupivacaine plus 10 ml liposomal bupivacaine (liposomal bupivacaine group). Twenty-six patients were randomized with 22 included in the analysis. Diaphragmatic excursion (via ultrasound) and spirometry were assessed before the block, in the postanesthesia care unit, and at 24 h postblock. The primary outcome was diaphragm excursion with sigh. No adverse events were observed. RESULTS: At 24 h, the liposomal bupivacaine group median [25th, 75th], had a greater percent change in diaphragmatic excursion during sigh breath compared to the bupivacaine group, -24% [-30, -9] versus 9% [-8, 26], difference in location, 32 (95% CI, 12 to 52), P = 0.007. Five patients in the liposomal bupivacaine group had a greater than 25% reduction in diaphragmatic excursion at 24 h versus zero in the bupivacaine group. They also had a significantly greater percent reduction in forced expiratory volume in 1 s and forced vital capacity compared with the bupivacaine group at 24 h (median decrease of 22% vs. 2%, P = 0.006, and median decrease of 19% vs. 1%, P = 0.049, respectively). CONCLUSIONS: The addition of liposomal bupivacaine to bupivacaine in an interscalene block results in statistically significant reductions in diaphragm excursion and pulmonary function testing 24 h after block placement when compared to bupivacaine alone. This reduction, however, falls within the range of normal diaphragmatic function.

Patient Complications after Interscalene Block: A Retrospective Comparison of Liposomal Bupivacaine to Nonliposomal Bupivacaine.

BACKGROUND: The purpose of this study was to investigate if the addition of liposome bupivacaine (LB) to an interscalene block (ISB) had an effect on the number of patients with surgical- or block-related complications. METHODS: This was a single-center retrospective chart view performed by identifying patients who received an ISB from January 1, 2014, through April 26, 2018, at the University of Minnesota. 1,518 patients were identified who received an ISB (LB = 784, nonliposomal bupivacaine = 734). Patients were divided into two groups those who did receive liposome bupivacaine in their ISB and those who did not receive liposome bupivacaine in their ISB. Medical records were individually reviewed for surgical procedure, block medications, complications related to the block or surgical procedure, phone calls to the healthcare system for issues related to opioids or pain within 3 and within 30 days, readmissions within 30 days, and emergency room visits for complications within 3 and 30 days. RESULTS: There was no significant difference in the number of patients with surgical or anesthetic complications. Only phone calls for pain within 3 days were significantly different. The LB group had 3.2% of patients call compared to 5.6% in the nonliposomal bupivacaine group (aOR = 1.71 (95% CI: 1.04-2.87), p=0.036). We found no significant difference in any of the other secondary outcomes. CONCLUSIONS: The use of LB in an ISB demonstrated no significant difference compared to nonliposomal bupivacaine in numbers of complications, emergency room visits, and readmissions.

The environmental consequences of climate-driven agricultural frontiers.

Growing conditions for crops such as coffee and wine grapes are shifting to track climate change. Research on these crop responses has focused principally on impacts to food production impacts, but evidence is emerging that they may have serious environmental consequences as well. Recent research has documented potential environmental impacts of shifting cropping patterns, including impacts on water, wildlife, pollinator interaction, carbon storage and nature conservation, on national to global scales. Multiple crops will be moving in response to shifting climatic suitability, and the cumulative environmental effects of these multi-crop shifts at global scales is not known. Here we model for the first time multiple major global commodity crop suitability changes due to climate change, to estimate the impacts of new crop suitability on water, biodiversity and carbon storage. Areas that become newly suitable for one or more crops are Climate-driven Agricultural Frontiers. These frontiers cover an area equivalent to over 30% of the current agricultural land on the planet and have major potential impacts on biodiversity in tropical mountains, on water resources downstream and on carbon storage in high latitude lands. Frontier soils contain up to 177 Gt of C, which might be subject to release, which is the equivalent of over a century of current United States CO2 emissions. Watersheds serving over 1.8 billion people would be impacted by the cultivation of the climate-driven frontiers. Frontiers intersect 19 global biodiversity hotspots and the habitat of 20% of all global restricted range birds. Sound planning and management of climate-driven agricultural frontiers can therefore help reduce globally significant impacts on people, ecosystems and the climate system.

Ultrasound-guided subcostal transversus abdominis plane block with liposomal bupivacaine compared to bupivacaine infiltration for patients undergoing robotic-assisted and laparoscopic hysterectomy: a prospective randomized study.

PURPOSE: To determine if a transversus abdominis plane (TAP) block with liposomal bupivacaine reduces total postoperative opioid use in the first 72 hrs following laparoscopic or robotic hysterectomy compared to port-site infiltration with 0.25% bupivacaine. METHODS: Patients received either a true TAP block procedure with 266 mg liposomal bupivacaine and 50 mg of 0.25% bupivacaine and sham port infiltration or sham TAP block procedure with true port-site infiltration with 100-125 mg of 0.25% bupivacaine. All patients had a standardized, scheduled, non-opioid pain management plan. The primary outcome was total IV morphine equivalents used in the first 72 hrs following surgery. Secondary outcomes included assessment of postoperative pain over the study period and quality of recovery measures. RESULTS: Patients undergoing TAP blockade required fewer total opioid equivalents during the observation period than patients allocated to infiltration (median 21 versus 25 mg IV Morphine equivalents, P=0.03). Opioid use was highest in the first 24 hrs after surgery, with less difference between the groups during days 2 and 3 postoperatively. There were 5 in the TAP group and 0 in the infiltration group were opioid free at 72 hrs. Those in the TAP group had improved quality of recovery (QoR15) with no change in overall benefit of analgesia score. CONCLUSION: TAP blockade reduced the requirement for opioid pain medication in the first 72 hrs after surgery, had more patients opioid free at 72 hrs, and improved patients' quality of their recovery.

The addition of intrathecal morphine to a transversus abdominis plane block with liposome bupivacaine provides more effective analgesia than transversus abdominis plane block with liposome bupivacaine alone: a retrospective study.

OBJECTIVE: The purpose of this study was to determine if the standardization of using liposomal bupivacaine in transversus abdominis plane (LB TAP) blocks eliminated the benefit of intrathecal morphine (ITM) in patients after undergoing a cesarean section. METHODS: This was a retrospective review of 358 patients who underwent cesarean section over an 11-month period. Patients were divided into two groups: those who received only an LB TAP (67 patients) vs those who received an LB TAP and ITM (291 patients). All blocks were placed bilaterally under ultrasound guidance after closure of the surgical incision, and morphine was added to the spinal used for the case. RESULTS: The group that received ITM in addition to the LB TAP received less opioids in the first 24 hours (median 5 range 0-150 mg morphine equivalents [ME] vs 15 range 0-76 mg ME; P<0.001) and less opioids overall (35 mg range 0-450 mg ME vs 47.5 mg range 0-189 mg ME; P=0.041) when compared to the LB TAP block only group. There was no difference between the two groups in opioid use from 24 to 48 hours or 48 to 72 hours. CONCLUSION: Patients who received ITM in addition to an LB TAP block received less opioids in the first 24 hours and overall when compared to those who received an LB TAP alone. This suggests that ITM still plays a role in providing analgesia to patients who have also received an LB TAP block as a part of their multimodal pain regimen for cesarean sections.

Necessity of Intracranial Imaging in Infants and Children With Macrocephaly.

BACKGROUND: Macrocephaly is frequently encountered in pediatrics and often leads to imaging. There are no recommendations from the American Academy of Pediatrics or the American College of Radiology providing imaging guidelines for macrocephaly. The goal of this study is to identify risk factors for pathologic macrocephaly and to aid the clinician in identifying patients that would benefit from imaging. METHODS: We conducted a medical record review throughout a multistate health care system, Sanford Health, from January 1, 2012 to December 31, 2016. Patients with macrocephaly were identified by problem list in children aged less than 36 months. Data collection included basic demographics, imaging modality, developmental delay, prematurity, seizures, focal neurological symptoms, family history of macrocephaly, sedation used, and sedation complications. RESULTS: A total of 169 patients were included in the analysis. Imaging modalities included 39 magnetic resonance imagings (23.1%), 47 cranial computed tomographies (27.8%), and 83 head ultrasounds (49.1%). Imaging results demonstrated 13 abnormal studies with five of those studies being abnormal with high clinical yield. Patients with abnormal studies were more likely to have developmental delay (P = 0.04) or neurological symptoms (P = 0.015). Positive family history of macrocephaly was predictive of normal imaging (P = 0.004). There were no sedation complications. CONCLUSIONS: Intracranial imaging does not appear to be necessary in children with no risk factors and or a positive family history of macrocephaly. Risk factors such as developmental delay or neurological symptoms could identify children at risk for imaging abnormalities that require further management.

Sporadic Meningioangiomatosis: Bystander or Curious Culprit.

In this report, we describe two cases of sporadic meningioangiomatosis (MA) - a rare condition of the central nervous system known to cause headaches, seizures and other focal neurologic deficits. Both patients presented with headache and vision change, somewhat suggestive of migraine. The combination of magnetic resonance imaging (MRI) and computerized tomography (CT) can establish the diagnosis of MA.

Using a Mobile Device "App" and Proximal Remote Sensing Technologies to Assess Soil Cover Fractions on Agricultural Fields.

Quantifying the amount of crop residue left in the field after harvest is a key issue for sustainability. Conventional assessment approaches (e.g., line-transect) are labor intensive, time-consuming and costly. Many proximal remote sensing devices and systems have been developed for agricultural applications such as cover crop and residue mapping. For instance, current mobile devices (smartphones & tablets) are usually equipped with digital cameras and global positioning systems and use applications (apps) for in-field data collection and analysis. In this study, we assess the feasibility and strength of a mobile device app developed to estimate crop residue cover. The performance of this novel technique (from here on referred to as "app" method) was compared against two point counting approaches: an established digital photograph-grid method and a new automated residue counting script developed in MATLAB at the University of Guelph. Both photograph-grid and script methods were used to count residue under 100 grid points. Residue percent cover was estimated using the app, script and photograph-grid methods on 54 vertical digital photographs (images of the ground taken from above at a height of 1.5 m) collected from eighteen fields (9 corn and 9 soybean, 3 samples each) located in southern Ontario. Results showed that residue estimates from the app method were in good agreement with those obtained from both photograph-grid and script methods (R² = 0.86 and 0.84, respectively). This study has found that the app underestimates the residue coverage by -6.3% and -10.8% when compared to the photograph-grid and script methods, respectively. With regards to residue type, soybean has a slightly lower bias than corn (i.e., -5.3% vs. -7.4%). For photos with residue <30%, the app derived residue measurements are within ±5% difference (bias) of both photograph-grid- and script-derived residue measurements. These methods could therefore be used to track the recommended minimum soil residue cover of 30%, implemented to reduce farmland topsoil and nutrient losses that impact water quality. Overall, the app method was found to be a good alternative to the point counting methods, which are more time-consuming.

Development and Assessment of the SMAP Enhanced Passive Soil Moisture Product.

Launched in January 2015, the National Aeronautics and Space Administration (NASA) Soil Moisture Active Passive (SMAP) observatory was designed to provide frequent global mapping of high-resolution soil moisture and freeze-thaw state every two to three days using a radar and a radiometer operating at L-band frequencies. Despite a hardware mishap that rendered the radar inoperable shortly after launch, the radiometer continues to operate nominally, returning more than two years of science data that have helped to improve existing hydrological applications and foster new ones. Beginning in late 2016 the SMAP project launched a suite of new data products with the objective of recovering some high-resolution observation capability loss resulting from the radar malfunction. Among these new data products are the SMAP Enhanced Passive Soil Moisture Product that was released in December 2016, followed by the SMAP/Sentinel-1 Active-Passive Soil Moisture Product in April 2017. This article covers the development and assessment of the SMAP Level 2 Enhanced Passive Soil Moisture Product (L2_SM_P_E). The product distinguishes itself from the current SMAP Level 2 Passive Soil Moisture Product (L2_SM_P) in that the soil moisture retrieval is posted on a 9 km grid instead of a 36 km grid. This is made possible by first applying the Backus-Gilbert optimal interpolation technique to the antenna temperature (TA) data in the original SMAP Level 1B Brightness Temperature Product to take advantage of the overlapped radiometer footprints on orbit. The resulting interpolated TA data then go through various correction/calibration procedures to become the SMAP Level 1C Enhanced Brightness Temperature Product (LiC_TB_E). The LiC_TB_E product, posted on a 9 km grid, is then used as the primary input to the current operational SMAP baseline soil moisture retrieval algorithm to produce L2_SM_P_E as the final output. Images of the new product reveal enhanced visual features that are not apparent in the standard product. Based on in situ data from core validation sites and sparse networks representing different seasons and biomes all over the world, comparisons between L2_SM_P_E and in situ data were performed for the duration of April 1, 2015 - October 30, 2016. It was found that the performance of the enhanced 9 km L2_SM_P_E is equivalent to that of the standard 36 km L2_SM_P, attaining a retrieval uncertainty below 0.040 m3/m3 unbiased root-mean-square error (ubRMSE) and a correlation coefficient above 0.800. This assessment also affirmed that the Single Channel Algorithm using the V-polarized TB channel (SCA-V) delivered the best retrieval performance among the various algorithms implemented for L2_SM_P_E, a result similar to a previous assessment for L2_SM_P.

Factor XIII Subunit A Immunohistochemical Expression is Associated With Inferior Outcomes in Acute Promyelocytic Leukemia.

Coagulation factor XIII subunit A (FXIIIa) intracellular expression has been described in platelets, megakaryocytes, monocytic cells, and leukemic blasts. Flow cytometric-based studies have suggested prognostic implications of FXIIIa expression, especially within the acute promyelocytic leukemia (APL) subgroup of acute myeloid leukemia (AML); however, its prognostic correlate by immunohistochemistry (IHC) is unknown. The aims of this study were to (1) define the clinicopathologic features of FXIIIa IHC-positive AML and (2) compare APL with other AML subtypes. Eighty-seven bone marrow biopsies or clot/particle preparations from our institution were evaluated with FXIIIa IHC. The study cohort consisted of bone marrow evaluations of 36 consecutive pretherapy APL, 42 selected pretherapy non-APL AML, and 9 negative staging cases. FXIIIa IHC expression was correlated with clinical and pathologic features and overall survival (OS). Leukemic blast FXIIIa cytoplasmic positivity was noted in 56% (20/36) APL and 74% (31/42) non-APL AML (P=0.10). FXIIIa IHC expression was associated with inferior OS within the APL cohort (P=0.04). No OS differences were noted in comparing FXIIIa IHC expression in all AML (P=0.17), or FXIIIa IHC expression within favorable, intermediate or adverse cytogenetic groups (P=0.14, 0.22 and 0.87, respectively). FXIIIa IHC expression is observed among a broad spectrum of AML subtypes and is not characterized by specific pathologic features. However, within the APL subgroup, FXIIIa IHC expression is associated with an inferior outcome and may be useful for additional prognostic risk stratification.

Disseminated Blastomycosis Mimicking Malignancy.

Blastomycosis is an endemic fungal infection commonly found within the Mississippi and Ohio River basins and Great Lakes region. While patients typically present with acute pneumonia, Blastomyces dermatitidis has the potential to spread hematogenously, resulting in disseminated infection of multiple organs. In this report, we describe a 57-year-old male with disseminated blastomycosis acquired in South Dakota. The diagnostic evaluation was confounded by concern for malignancy given the involvement of multiple locations, including brain, lungs, adrenal glands, and testes. Despite aggressive therapy with amphotericin B, the patient succumbed to this infection.

Pre-Guideline Trends Associated with Chest Radiograph Usage for Pediatric Community-Acquired Pneumonia in Emergency Department Settings.

BACKGROUND: Health care spending in the U.S. totaled $3 trillion in 2014 and continues to increase rapidly. Minimizing waste through clinical guidelines is a promising strategy to reduce spending without compromising patient care. In 2011, clinical guidelines recommended against the use of chest X-ray (CXR) for diagnosis of community-acquired pneumonia (CAP) in pediatric ambulatory settings. However, use of CXR has not changed post-guideline. Thus, understanding the drivers of CXR utilization prior to guideline implementation could improve guideline adherence. METHODS: Retrospective study using 2009 Nationwide Emergency Department Sample data set consisting of a representative sample of all emergency room admissions. Inclusion criteria consisted of: 18 years of age or younger and the diagnosis of outpatient CAP. Population was segmented by the presence of a CXR obtained during the visit. Socioeconomic status was determined by quartile classification of the estimated median household income based on patient ZIP code. RESULTS: In 2009, children living in wealthier ZIP codes presenting to the emergency department (ED) who were diagnosed with CAP were more likely to receive diagnostic CXR. The use of chest radiograph was not statistically correlated to gender, weekday versus weekend admission, number of diagnoses at discharge, or total ED charges. CONCLUSION: The research demonstrates a strong correlation between socioeconomic status of the pediatric patient and use of chest radiograph for CAP in the ED setting prior to 2011 guideline publication. Further research to determine the reason for this correlation could give rise to focused efforts to successfully encourage adherence to clinical practice guidelines.