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Objective: To compare hospital surgical performance in older and younger patients., Background: In-hospital mortality after surgical procedures varies widely among hospitals. Prior studies suggest that failure-to-rescue rates drive this variation for older adults, but the generalizability of these findings to younger patients remains unknown., Methods: We performed a retrospective cohort study of patients ≥18 years undergoing one of 10 common and complex general surgery operations in 16 states using the Healthcare Cost and Utilization Projects State Inpatient Databases (2016-2018). Patients were split into 2 populations: patients with Medicare ≥65 (older adult) and non-Medicare <65 (younger adult). Hospitals were sorted into quintiles using risk-adjusted in-hospital mortality rates for each age population. Correlations between hospitals in each mortality quintile across age populations were calculated. Complication and failure-to-rescue rates were compared across the highest and lowest mortality quintiles in each age population., Results: We identified 579,582 patients treated in 732 hospitals. The mortality rate was 3.6% among older adults and 0.7% among younger adults. Among older adults, high- relative to low-mortality hospitals had similar complication rates (32.0% vs 29.8%; P = 0.059) and significantly higher failure-to-rescue rates (16.0% vs 4.0%; P < 0.001). Among younger adults, high-relative to low-mortality hospitals had higher complications (15.4% vs 12.1%; P < 0.001) and failure-to-rescue rates (8.3% vs 0.7%; P < 0.001). The correlation between observed-to-expected mortality ratios in each age group was 0.385 ( P < 0.001)., Conclusions: High surgical mortality rates in younger patients may be driven by both complication and failure-to-rescue rates. There is little overlap between low-mortality hospitals in the older and younger adult populations. Future work must delve into the root causes of this age-based difference in hospital-level surgical outcomes., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Improving the overall care of children with medical complexity (CMC) is often beset by challenges in proactively identifying the population most in need of clinical management and quality improvement. The objective of the current study was to create a system to better capture longitudinal risk for sustained and elevated utilization across time using real-time electronic health record (EHR) data. A new Pediatric Population Management Classification (PPMC), drawn from visit diagnoses and continuity problem lists within the EHR of a tristate health system, was compared with an existing complex chronic conditions (CCC) system for agreement (with weighted κ) on identifying CCMC, as well as persistence of elevated charges and utilization from 2016 to 2019. Agreement of assignment PPMC was lower among primary care provider (PCP) populations than among other children traversing the health system for specialty or hospital services only (weighted κ 62% for PCP vs. 82% for non-PCP). The PPMC classification scheme, displaying greater precision in identifying CMC with persistently high utilization and charges for those who receive primary care within a large integrated health network, may offer a more pragmatic approach to selecting children with CMC for longitudinal care management.

Background: Complex surgical care is often centralized to one high volume (hub) hospital within a system. The benefit of this centralization in common operations is unknown., Methods: Using the Healthcare Cost and Utilization Project's State Inpatient Databases, adult general surgical patients within hospital systems in 13 states (2016-2018) were identified. Risk-adjusted logistic regression estimated the odds of death or serious morbidity (DSM) and prolonged length of stay (LOS) at hubs relative to other system hospitals (spokes)., Results: We identified 122,895 patients across 43 hub-and-spoke systems. Hubs completed 83.2 ​% of complex and 59.6 ​% of common operations. For complex operations, odds of DSM were significantly lower in hubs (OR: 0.80; 95 ​% CI [0.65, 0.98]). For common operations, odds of DSM were similar between hubs and spokes, while odds of prolonged LOS were greater at hubs (OR 1.19; 95 ​% CI [1.16,1.24])., Conclusions: While hub hospitals had lower odds of DSM for complex operation, they had higher odds of prolonged length of stay for common operations. This finding shows an opportunity for improved system efficiency., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: To evaluate the long-term efficacy of high-frequency (10 kHz) spinal cord stimulation (SCS) for treating refractory painful diabetic neuropathy (PDN)., Methods: The SENZA-PDN study was a prospective, multicenter, randomized controlled trial that compared conventional medical management (CMM) alone with 10 kHz SCS plus CMM (10 kHz SCS+CMM) in 216 patients with refractory PDN. After 6 months, participants with insufficient pain relief could cross over to the other treatment. In total, 142 patients with a 10 kHz SCS system were followed for 24 months, including 84 initial 10 kHz SCS+CMM recipients and 58 crossovers from CMM alone. Assessments included pain intensity, health-related quality of life (HRQoL), sleep, and neurological function. Investigators assessed neurological function via sensory, reflex, and motor tests. They identified a clinically meaningful improvement relative to the baseline assessment if there was a significant persistent improvement in neurological function that impacted the participant's well-being and was attributable to a neurological finding., Results: At 24 months, 10 kHz SCS reduced pain by a mean of 79.9% compared to baseline, with 90.1% of participants experiencing ≥50% pain relief. Participants had significantly improved HRQoL and sleep, and 65.7% demonstrated clinically meaningful neurological improvement. Five (3.2%) SCS systems were explanted due to infection., Conclusions: Over 24 months, 10 kHz SCS provided durable pain relief and significant improvements in HRQoL and sleep. Furthermore, the majority of participants demonstrated neurological improvement. These long-term data support 10 kHz SCS as a safe and highly effective therapy for PDN., Trial Registration: ClincalTrials.gov Identifier, NCT03228420., Competing Interests: Declaration of competing interest Author Erika A. Petersen has received consulting fees from Abbott Laboratories, Biotronik, Boston Scientific, Medtronic Neuromodulation, Nalu Medical, Neuros Medical, Nevro Corp, Presidio Medical, Saluda, and Vertos Medical, research support from Mainstay, Medtronic Neuromodulation, Nalu Medical, Neuros Medical, Nevro Corp, ReNeuron, Saluda, and SPR, and stock options from neuro42 and SynerFuse. Author Thomas G. Stauss has received research support from Nevro Corp. Author James A. Scowcroft has received research support from Boston Scientific, Nevro Corp, Saluda Medical, and Vertiflex. Author Michael J. Jaasma is an employee of Nevro Corp. Author Elizabeth S. Brooks was an employee of Nevro Corp during her contributions to the work associated with this manuscript. Author Deborah R. Edgar received consulting fees from Nevro in her capacity as an independent medical writer. Author Judith L. White has received consulting fees from California Institute for Biomedical Research and Eli Lilly and research support from Nevro Corp. Author Shawn M. Sills has received research support from Nevro Corp. Author Kasra Amirdelfan has received consulting fees from Biotronik, Medtronic, Nalu Medical, Nevro Corp, and Saluda Medical, as well as research support from Biotronik, IPM Medical Group, Nevro Corp, Saluda Medical, SPR Therapeutics, and Vivex Biologics. Author Maged N. Guirguis has received consulting fees from Abbott Laboratories, Avanos Medical, Avertis Pharmacy, Boston Scientific, Nevro Corp, and Saluda Medical, as well as research support from Abbott Laboratories, Avanos Medical, Boston Scientific, Nalu Medical, Neuros Medical, Nevro Corp, and Saluda Medical. Author Jijun Xu has received research support from the Cleveland Clinic Velosano Program, the National Institutes of Health, the Steve and Melody Golding Foundation, and Nevro Corp. Author Cong Yu has received research support from Nevro Corp. Author Ali Nairizi has received consulting fees from Aurora Spine, Flowonix, and Nevro Corp as well as research support from Nevro Corp. Author Denis G. Patterson has received consulting fees from Abbott Laboratories, AIS Healthcare, Allergan, Amgen, Aurora Spine, CornerLoc, Flowonix, Lundbeck, Pajunk Medical, Saluda Medical, Spark Biomedical, and Vertos Medical, research support from Abbott Laboratories, Aurora Spine, Flowonix, Nevro Corp, and Saluda Medical, speakers’ bureau or honoraria from Abbott Laboratories, Allergan, Amgen, CornerLoc, Lundbeck, Saluda Medical, and Vertos Medical, and stock options from CornerLoc. Author Michael J. Creamer has received research support from Nevro Corp. Author Vincent Galan has received research support from Biotronik, Medtronic, Nevro Corp, PainTEQ, SPR Therapeutics, and St. Jude. Author Richard H. Bundschu has received research support from Nevro Corp. Author Neel D. Mehta has received consulting fees from Averitas, Nevro Corp, and Salix Pharmaceuticals, as well as research support from Boston Scientific and Nevro Corp. Author Dawood Sayed has received consulting fees from Abbott Laboratories, Boston Scientific, Flowonix, Medtronic, Nevro Corp, Vertiflex, and Vertos Medical, as well as research support from Abbott Laboratories, Biotronic, Nevro Corp, Vertiflex, and Vertos Medical. Author Shivanand P. Lad has received consulting fees from Nevro Corp and research support from Nevro Corp. Author David J. DiBenedetto has received research support from Nevro Corp, as well as funding for serving as principal investigator of a study supported by SPR Therapeutics paid to his institution. Author Khalid A. Sethi has received research support from Nevro Corp. Author Johnathan H. Goree has received consulting fees from Abbott Laboratories and Stratus Medical. Author Paul W. Wu has received research support from Nevro Corp. Author Charles E. Argoff has received consulting fees from AbbVie, Amgen, Biohaven, Clexio Biosciences, Collegium, Eli Lilly, Elsevier, Flowonix, Gene Pharma, Lundbeck, Nevro Corp, Novartis, Pfizer, SK Life Science, Teva Pharmaceutical, and Vertex as well as research support from AbbVie, Allergan, Amgen, Daiichi Sankyo, Eli Lilly, Novartis, Teva Pharmaceutical, and Vertex Pharmaceuticals. Author Christian E. Nasr has received consulting fees from Exelixis, Neurogastrx, and Nevro Corp as well as research support from Nevro Corp. Author Rod S. Taylor has received consulting fees from Nevro Corp, Medtronic, and Saluda Medical. Author David L. Caraway is an employee of Nevro Corp. Author Nagy A. Mekhail has received consulting fees from Nevro Corp, Relievant Medsystems, Saluda Medical, Sollis Therapeutics, and Vertos Medical, as well as research support from Avanos Medical, Mesoblast, Neuros Medical, and Nevro Corp., (Copyright © 2023. Published by Elsevier B.V.)

Phosphorus (P) budgets can be useful tools for understanding nutrient cycling and quantifying the effectiveness of nutrient management planning and policies; however, uncertainties in agricultural nutrient budgets are not often quantitatively assessed. The objective of this study was to evaluate uncertainty in P fluxes (fertilizer/manure application, atmospheric deposition, irrigation, crop removal, surface runoff, and leachate) and the propagation of these uncertainties to annual P budgets. Data from 56 cropping systems in the P-FLUX database, which spans diverse rotations and landscapes across the United States and Canada, were evaluated. Results showed that across cropping systems, average annual P budget was 22.4 kg P ha -1 (range = -32.7 to 340.6 kg P ha -1 ), with an average uncertainty of 13.1 kg P ha -1 (range = 1.0-87.1 kg P ha -1 ). Fertilizer/manure application and crop removal were the largest P fluxes across cropping systems and, as a result, accounted for the largest fraction of uncertainty in annual budgets (61% and 37%, respectively). Remaining fluxes individually accounted for <2% of the budget uncertainty. Uncertainties were large enough that determining whether P was increasing, decreasing, or not changing was inconclusive in 39% of the budgets evaluated. Findings indicate that more careful and/or direct measurements of inputs, outputs, and stocks are needed. Recommendations for minimizing uncertainty in P budgets based on the results of the study were developed. Quantifying, communicating, and constraining uncertainty in budgets among production systems and multiple geographies is critical for engaging stakeholders, developing local and national strategies for P reduction, and informing policy., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA.)

Objective: To examine the role of hub-and-spoke systems as a factor in structural racism and discrimination., Background: Health systems are often organized in a "hub-and-spoke" manner to centralize complex surgical care to 1 high-volume hospital. Although the surgical health care disparities are well described across health care systems, it is not known how they seem across a single system's hospitals., Methods: Adult patients who underwent 1 of 10 general surgery operations in 12 geographically diverse states (2016-2018) were identified using the Healthcare Cost and Utilization Project's State Inpatient Databases. System status was assigned using the American Hospital Association dataset. Hub designation was assigned in 2 ways: (1) the hospital performing the most complex operations (general hub) or (2) the hospital performing the most of each specific operation (procedure-specific hub). Independent multivariable logistic regression was used to evaluate the risk-adjusted odds of treatment at hubs by race and ethnicity., Results: We identified 122,236 patients across 133 hospitals in 43 systems. Most patients were White (73.4%), 14.2% were Black, and 12.4% Hispanic. A smaller proportion of Black and Hispanic patient underwent operations at general hubs compared with White patients (B: 59.6% H: 52.0% W: 62.0%, P <0.001). After adjustment, Black and Hispanic patients were less likely to receive care at hub hospitals relative to White patients for common and complex operations (general hub B: odds ratio: 0.88 CI, 0.85, 0.91 H: OR: 0.82 CI, 0.79, 0.85)., Conclusions: When White, Black, and Hispanic patients seek care at hospital systems, Black and Hispanic patients are less likely to receive treatment at hub hospitals. Given the published advantages of high-volume care, this new finding may highlight an opportunity in the pursuit of health equity., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate high-frequency (10-kHz) spinal cord stimulation (SCS) treatment in refractory painful diabetic neuropathy., Patients and Methods: A prospective, multicenter randomized controlled trial was conducted between Aug 28, 2017 and March 16, 2021, comparing conventional medical management (CMM) with 10-kHz SCS+CMM. The participants had hemoglobin A1c level of less than or equal to 10% and pain greater than or equal to 5 of 10 cm on visual analog scale, with painful diabetic neuropathy symptoms 12 months or more refractory to gabapentinoids and at least 1 other analgesic class. Assessments included measures of pain, neurologic function, and health-related quality of life (HRQoL) over 12 months with optional crossover at 6 months., Results: The participants were randomized 1:1 to CMM (n=103) or 10-kHz SCS+CMM (n=113). At 6 months, 77 of 95 (81%) CMM group participants opted for crossover, whereas none of the 10-kHz SCS group participants did so. At 12 months, the mean pain relief from baseline among participants implanted with 10-kHz SCS was 74.3% (95% CI, 70.1-78.5), and 121 of 142 (85%) participants were treatment responders (≥50% pain relief). Treatment with 10-kHz SCS improved HRQoL, including a mean improvement in the EuroQol 5-dimensional questionnaire index score of 0.136 (95% CI, 0.104-0.169). The participants also reported significantly less pain interference with sleep, mood, and daily activities. At 12 months, 131 of 142 (92%) participants were "satisfied" or "very satisfied" with the 10-kHz SCS treatment., Conclusion: The 10-kHz SCS treatment resulted in substantial pain relief and improvement in overall HRQoL 2.5- to 4.5-fold higher than the minimal clinically important difference. The outcomes were durable over 12 months and support 10-kHz SCS treatment in patients with refractory painful diabetic neuropathy., Trial Registration: clincaltrials.gov Identifier: NCT03228420., (© 2022 The Authors.)

The WEPPcloud interface is a new online decision-support tool for the Water Erosion Prediction Project (WEPP) model that facilitates data preparation and model runs, and summarizes model outputs into tables and maps that are easily interpretable by users. The interface can be used by land and water managers in United States, Europe, and Australia interested in simulating streamflow, sediment and pollutant loads from both undisturbed and disturbed (e.g. post-wildfire or post-treatment such as thinning or prescribed fires) forested watersheds. This article contains full hydrologic model runs for 28 forested watersheds in the U.S. Pacific Northwest with the WEPPcloud online interface. It also includes links to repositories with the individual model runs, a table containing default model parameters for disturbed conditions, and figures with model outputs as compared to observed data. The data in the repositories include all the raw data input and output from the model as well as the processed data, which can be accessed through tables and shapefiles to provide additional insights into the model outputs. Lastly, the article describes how the data are organized and the content of each folder containing the data. These model runs are useful for anyone interested in modeling forested watersheds with the WEPPcloud interface., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Diabetes is one of the most prevalent chronic health conditions and diabetic neuropathy one of its most prevalent and debilitating complications. While there are treatments available for painful diabetic peripheral neuropathy (pDPN), their effectiveness is limited., Method: This retrospective, multi-center, real-world review assessed pain relief and functional improvements for consecutive patients with diabetic neuropathy aged ≥18 years of age who were permanently implanted with a high-frequency (10 kHz) spinal cord stimulation (SCS) device. Available data were extracted from a commercial database., Results: In total 89 patients consented to being included in the analysis. Sixty-one percent (54/89) of participants were male and the average age was 64.4 years (SD = 9.1). Most patients (78.7%, 70/89) identified pain primarily in their feet or legs bilaterally. At the last assessment, 79.5% (58/73) of patients were treatment responders, defined as having at least 50% patient-reported pain relief from baseline. The average time of follow-up was 21.8 months (range: 4.3 to 46.3 months). A majority of patients reported improvements in sleep and overall function relative to their baseline., Conclusions: This real-world study in typical clinical practices found 10 kHz SCS provided meaningful pain relief for a substantial proportion of patients refractory to current pDPN management, similar to published literature. This patient population has tremendous unmet needs and this study helps demonstrate the potential for 10 kHz SCS to provide an alternative pain management approach.

Introduction: The Affordable Care Act (ACA) expanded Medicaid (ME) and instituted Essential Health Benefits (EHB) that included bariatric surgery coverage on a state-by-state opt-in basis, increasing insurance coverage of bariatric surgery., Materials and Methods: Using a difference-in-differences framework, changes in bariatric surgery rates, defined as utilization in the population of people with obesity, before and after the ACA were evaluated in four states. Bariatric surgery procedure data were taken from the Healthcare Cost and Utilization Project's State In-patient Database 2012-2015. Adjusted multivariable regressions were run in the Medicaid and commercially insured populations., Results: We identified 36,456 bariatric surgeries across the 286 Health Service Areas and time periods, with 31,732 covered by commercial insurers and 4724 covered by Medicaid. An unadjusted increase in utilization rates was seen in the Medicaid and Commercial populations in both ME- and EHB-covered states as well as non-expansion and EHB opt-out states over time. In the Medicaid population, after adjusting for confounders, there was a significant increase of 24.77 cases per 100,000 people with obesity (95% confidence interval: 12.41, 37.13) in the expansion states relative to the control and pre-period. The commercial population experienced a nonsignificant change in the rates of bariatric surgery, decreasing by 2.89 cases per 100,000 people with obesity (95% confidence interval: - 21.59, 15.81)., Conclusions: There was a significant increase in bariatric surgery rates among Medicaid beneficiaries associated with Medicaid expansion, but there was no change among the commercially insured., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Insurance status has been strongly associated with both access to and outcomes of colon resection (CRS). Under the Affordable Care Act (ACA), individual states opted to participate in Medicaid expansion (ME) and adopt essential health benefits (EHB)., Methods: We performed a quasi-experimental difference-in-differences (DID) analysis of 2012-2017 state-level inpatient claims with risk adjustment. We examined frequency of emergent presentation and in-hospital death. Subset analyses were performed by insurance type., Results: Among the 73,961 CRS patients, 49.6% were in a state with both ME and EHB, 34.7% presented emergently, and 2.0% died. Adoption of ME and EHB was associated with a significant, 24%, reduction in the likelihood of in-hospital mortality, and no significant change in emergent presentation for CRS., Conclusions: The ACA's ME was strongly associated with a decrease in mortality following colon resection among Medicaid beneficiaries. These findings support the adoption of healthcare policies that improve access to insurance., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The growing concentration of fellowship-trained and integrated residency-trained subspecialty surgeons has encroached on the breadth and volume of a so-called "true" general surgery practice, leaving the role of new general surgeons in flux. We aimed to describe the surgical practice of new general surgeons with and without subspecialty fellowship training., Design: In this retrospective cohort study, state discharge data was linked to American Medical Association Masterfile and American Hospital Association annual survey data. New-to-practice general surgeons with and without subspecialty board-certification in colorectal surgery (CRS) or cardiothoracic surgery (CTS) were identified in 2008, and followed over 10 years. Surgeon overall inpatient case volume, colorectal resection case volume, and thoracic lobectomy case volume were compared between surgeons with and without related subspecialty training., Setting: NY and FL (2008-2017)., Participants: The study population included 276 new-to-practice surgeons with mean age of 36.9 years. New-to-practice surgeons were defined as those with zero to three years of experience in 2008., Results: Of all surgeons, 11.2% were subspecialty board-certified in CRS and 11.6% were subspecialty board-certified in CTS. Board-certified CRS surgeons performed more colorectal resections than the non-CRS general surgeons each year (p-value <0.001 for all). Overall, non-CRS general surgeons performed 60.7% of all colorectal resections. Board-certified CTS surgeons performed more thoracic lobectomies than non-CTS surgeons each year. Non-CTS surgeons performed 1.1% of all thoracic lobectomies., Conclusions: On average, new subspecialty surgeons perform significantly more specialty operations than non-subspecialty new general surgeons. However, as a group, new non-colorectal general surgeons perform the majority of colorectal resections. In contrast, new non-cardiothoracic general surgeons perform less than two percent of the thoracic lobectomies. This may have implications for a shift in the training paradigm going forward., (Copyright © 2021 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: It is unclear how the Affordable Care Act's state-based Medicaid Expansion (ME) has impacted surgeon selection for colorectal resections (CRS)., Methods: We performed a risk-adjusted DID analysis on state discharge data of CRS patients aged 26-64 from NY (Expansion) and FL (non-Expansion) before (2012-2013) and after (2016-2017) ME. Primary outcome was use of a high-volume or colorectal-boarded surgeon. Subset analysis performed on insurance status., Results: Among 78,866 CRS patients, ME was associated with a 5.9% increase in Medicaid enrollment. ME was associated with a 0.73 (95%CI: 0.67-0.69; p < 0.001) reduced odds of high-volume surgeon usage by commercially insured patients when compared to usage by commercially insured patients in the non-expansion state. No statistically significant difference was noted in the use of a colorectal-boarded surgeon following reform., Conclusions: ME was associated with an increase in Medicaid enrollment and a decrease in the use of high-volume surgeons by the commercially insured., Competing Interests: Declaration of competing interest The authors have no financial conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Despite the overall shift in care delivery to an ambulatory setting, the majority of general surgical education still relies on the experience of caring for inpatients. We aimed to investigate how the inpatient practice patterns of newly minted general surgeons (GS) have changed since 2008, in order to better inform education policies regarding both training approach and setting for modern surgical trainees., Methods: State discharge data from NY and FL (2008-2017) were linked to data on GS from the American Medical Association Masterfile, and to hospital data from the American Hospital Association annual survey. Mean annual inpatient case volume (CV) and case type breadth (CB) were compared between surgeons who were new-to-practice (0-3 years of experience) in 2008 and in 2013. Each new surgeon cohort was followed for 5 years. Case type was classified by organ system., Results: The 2008 cohort included 328 GS with a mean age of 37.1, 79.6% male and 94.2% board-certified. The 2013 cohort included 359 GS with a mean age of 36.2, 73.0% male and 93.9% board-certified. CV was higher among the 2008 cohort than the 2013 cohort for each year of practice in the study period. CB included at least 4 organ system types for all new GS with greater breadth among the 2008 cohort for each year in the study period., Conclusions: Declining rates of inpatient surgery affect general surgeons who were new-to-practice in 2013 significantly more than those entering practice only 5 years ahead of them. New surgeons continue to start their practices broadly, suggesting a need to continue broad training while expanding formal educational policies to include the full spectrum of ambulatory surgery., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Importance: Many patients with diabetic peripheral neuropathy experience chronic pain and inadequate relief despite best available medical treatments., Objective: To determine whether 10-kHz spinal cord stimulation (SCS) improves outcomes for patients with refractory painful diabetic neuropathy (PDN)., Design, Setting, and Participants: The prospective, multicenter, open-label SENZA-PDN randomized clinical trial compared conventional medical management (CMM) with 10-kHz SCS plus CMM. Participants with PDN for 1 year or more refractory to gabapentinoids and at least 1 other analgesic class, lower limb pain intensity of 5 cm or more on a 10-cm visual analogue scale (VAS), body mass index (calculated as weight in kilograms divided by height in meters squared) of 45 or less, hemoglobin A1c (HbA1c) of 10% or less, daily morphine equivalents of 120 mg or less, and medically appropriate for the procedure were recruited from clinic patient populations and digital advertising. Participants were enrolled from multiple sites across the US, including academic centers and community pain clinics, between August 2017 and August 2019 with 6-month follow-up and optional crossover at 6 months. Screening 430 patients resulted in 214 who were excluded or declined participation and 216 who were randomized. At 6-month follow-up, 187 patients were evaluated., Interventions: Implanted medical device delivering 10-kHz SCS., Main Outcomes and Measures: The prespecified primary end point was percentage of participants with 50% pain relief or more on VAS without worsening of baseline neurological deficits at 3 months. Secondary end points were tested hierarchically, as prespecified in the analysis plan. Measures included pain VAS, neurological examination, health-related quality of life (EuroQol Five-Dimension questionnaire), and HbA1c over 6 months., Results: Of 216 randomized patients, 136 (63.0%) were male, and the mean (SD) age was 60.8 (10.7) years. Additionally, the median (interquartile range) duration of diabetes and peripheral neuropathy were 10.9 (6.3-16.4) years and 5.6 (3.0-10.1) years, respectively. The primary end point assessed in the intention-to-treat population was met by 5 of 94 patients in the CMM group (5%) and 75 of 95 patients in the 10-kHz SCS plus CMM group (79%; difference, 73.6%; 95% CI, 64.2-83.0; P < .001). Infections requiring device explant occurred in 2 patients in the 10-kHz SCS plus CMM group (2%). For the CMM group, the mean pain VAS score was 7.0 cm (95% CI, 6.7-7.3) at baseline and 6.9 cm (95% CI, 6.5-7.3) at 6 months. For the 10-kHz SCS plus CMM group, the mean pain VAS score was 7.6 cm (95% CI, 7.3-7.9) at baseline and 1.7 cm (95% CI, 1.3-2.1) at 6 months. Investigators observed neurological examination improvements for 3 of 92 patients in the CMM group (3%) and 52 of 84 in the 10-kHz SCS plus CMM group (62%) at 6 months (difference, 58.6%; 95% CI, 47.6-69.6; P < .001)., Conclusions and Relevance: Substantial pain relief and improved health-related quality of life sustained over 6 months demonstrates 10-kHz SCS can safely and effectively treat patients with refractory PDN., Trial Registration: ClincalTrials.gov Identifier: NCT03228420.

The subsurface transport of dissolved reactive phosphorus (DRP) from artificially drained agricultural fields can impair water quality, especially in no-till fields. The distribution of soil P in the wheat (Triticum aestivum L.)-dominated Palouse region in the inland U.S. Pacific Northwest varies greatly due to its steep and complex topography, and a legacy (∼130 yr) of excessive soil erosion and deposition processes. The primary goal of this research was to better understand the magnitude and temporal dynamics of DRP export from an artificial drain line and the variability of subsurface DRP leaching within a long-term, no-till field. Dissolved reactive P in drain line effluent was monitored across three water years. Large intact soil cores were extracted at contrasting field locations (toe and top slope positions) to measure DRP leachate concentration and relative P sorption. Drain line DRP concentration was predominantly >0.05 mg L -1 and often exceeded 0.1 mg L -1 during winter and early spring. Mean leachate DRP levels were significantly higher in toe slope cores than in top slope cores (0.11 and 0.02 mg L -1 , respectively). Saturated hydraulic conductivity varied widely across cores and was not correlated with leachate DRP concentration. All soil cores exhibited high P sorption potential, even under conditions of preferential flow. These findings suggest that much of the DRP transport in these landscapes is derived from P hotspots located in toe slope positions. Application of soil P fertilizer amounts in variable rates that account for spatial variability in P transport may minimize P enrichment and subsequent leaching in these locations., (© 2020 The Authors. Journal of Environmental Quality published by Wiley Periodicals LLC on behalf of American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America.)

Objective: Primary care has been promoted as a setting to identify and manage adolescent depression. This study examined primary care-based adolescent depression identification and follow-up care when elevated symptoms were identified., Methods: Data came from a large pediatric care network with an organizational recommendation to screen for depression at age 16 well-visits using an electronic health record (EHR)-integrated standardized measure. Analyses examined rates of screening and elevated symptoms, pediatricians' initial responses to elevated scores, and types of follow-up care received over 1 year using retrospective EHR data extraction and manual chart reviews., Results: Across program sites, 76.3% (n = 6981) of patients attending their age 16 well-visits were screened. About one-quarter had an elevated score (19.2% mild and 6.7% moderate-to-severe), many of whom received active follow-up on their well-visit date. Over 1 year, three-fourths of patients with scores in the moderate-to-severe range and 40.0% of patients with scores in the mild range received follow-up care (e.g., antidepressant prescriptions) as per EHR extraction. Follow-up rates were higher as per manual chart reviews., Conclusion: Routine adolescent depression screening is feasible across diverse primary care sites. Most patients with elevated scores were not already receiving behavioral health services, suggesting screening identified previously undetected concerns. In turn, many adolescents with elevated scores initiated treatment after screening, which indicates providing screen results at the point of care may facilitate pediatrician actions. Still, gaps in follow-up care demonstrate the need for greater investment in primary care-based behavioral health services to support high-quality treatment and ultimately decrease the burden of adolescent depression.

The Water Erosion Prediction Project (WEPP) model was applied to seven paired, nested watersheds within the Mica Creek Experimental Watershed located in northern Idaho, USA. The goal was to evaluate the ability of WEPP to simulate the direct and cumulative effects of clear-cutting and partial-cutting (50% canopy removal) on water and sediment yield. WEPP was modified to better represent changes in the Leaf Area Index during post-harvest forest vegetative recovery. Good agreement between simulated and observed streamflow was achieved with minimal to no calibration over a 16-year (1992-2007) period. For the seven watersheds and the entire study period, the overall Nash-Sutcliffe Efficiency (NSE), Kling-Gupta efficiency (KGE), and deviation of runoff volume (D V ) between observed and simulated daily streamflow ranged 0.58-0.71, 0.67-0.81, and -4% to 9%, respectively. Good agreement between predicted and observed suspended sediment yield was achieved through the calibration of a single channel critical shear stress parameter. For sediment yield, NSE, KGE, and D V ranged 0.62-0.97, 0.43-0.97, and -2% to 2%, respectively, for the calibration period, and 0.61-0.93, 0.42-0.95, and -24% to 13%, respectively, for the period of model performance assessment. Regression analysis of observed- and WEPP-simulated increase in water and sediment yield following clear-cut treatment was similar; however, the WEPP-simulated increase was lower compared to observations particularly from the partial-cut watershed. The variability in the critical shear parameter for different stream channels in the study watersheds was directly related to the observed mean particle size on the stream bed and suggests that applications of the WEPP model in ungauged basins could potentially set the critical shear parameter based on particle size. Overall, the simulated results demonstrate the potential of WEPP as a modeling tool for forestland watershed management, particularly for estimating the effects of forest harvest on hydrograph fluctuations and consequently, stream sediment transport., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Painful diabetic neuropathy (PDN), a debilitating and progressive chronic pain condition that significantly impacts quality of life, is one of the common complications seen with long-standing diabetes mellitus. Neither pharmacological treatments nor low-frequency spinal cord stimulation (SCS) has provided significant and long-term pain relief for patients with PDN. This study aims to document the value of 10-kHz SCS in addition to conventional medical management (CMM) compared with CMM alone in patients with refractory PDN., Methods: In a prospective, multicenter, randomized controlled trial (SENZA-PDN), 216 subjects with PDN will be assigned 1:1 to receive 10-kHz SCS combined with CMM or CMM alone after appropriate institutional review board approvals and followed for 24 months. Key inclusion criteria include (1) symptoms of PDN for at least 12 months, (2) average pain intensity of at least 5 cm-on a 0- to 10-cm visual analog scale (VAS)-in the lower limbs, and (3) an appropriate candidate for SCS. Key exclusion criteria include (1) large or gangrenous ulcers or (2) average pain intensity of at least 3 cm on VAS in the upper limbs or both. Along with pain VAS, neurological assessments, health-related quality of life, sleep quality, and patient satisfaction will be captured. The primary endpoint comparing responder rates (≥50% pain relief) and safety rates between the treatment groups will be assessed at 3 months. Several secondary endpoints will also be reported on., Discussion: Enrollment commenced in 2017 and was completed in 2019. This study will help to determine whether 10-kHz SCS improves clinical outcomes and health-related quality of life and is a cost-effective treatment for PDN that is refractory to CMM., Trial Registration: ClincalTrials.gov identifier: NCT03228420 (registered 24 July 2017).

Purpose: Chronic axial low-back pain is a debilitating disorder that impacts all aspects of an afflicted individual's life. Effective, durable treatments have historically been elusive. Interventional therapies, such as spinal cord stimulation (SCS), have shown limited efficacy at best. Recently, a novel treatment, 10 kHz SCS, has demonstrated superior pain relief compared with traditional SCS in a randomized controlled trial (RCT). In this manuscript, we report on the long-term improvements in quality of life (QoL) outcomes for subjects enrolled in this study., Methods: A prospective, multicenter, randomized controlled trial (SENZA-RCT) was conducted. Patients with both chronic back and leg pain were enrolled and randomized (1:1) into 10 kHz SCS or traditional SCS treatment groups. A total of 171 subjects received a permanent SCS device implant. QoL and functionality measures were collected up to 12 months. The device remote control utilization, which is an indication of patient interaction with the device for adjustments, was collected at 24-month post-implantation., Results: At 12 months, a higher proportion of 10 kHz SCS subjects had marked improvement of their disability (Oswestry Disability Index) to a "moderate" or "minimal" impact on their daily function versus the control group. The subjects also reported better improvement in the Global Assessment of Functioning, Clinician Global Impression of Change, Pittsburgh Sleep Quality Index, and short-form McGill Pain Questionnaire, compared to traditional SCS subjects. The 10 kHz SCS subjects also reported far higher rates of both driving and sleeping with their device turned on, as well as reduced reliance on their programmers to adjust therapy settings., Conclusions: In addition to superior pain relief, 10 kHz SCS provides long-term improvements in quality of life and functionality for subjects with chronic low-back and leg pain., Trial Registration: ClinicalTrials.gov (NCT01609972).

This study presents a stable isotope hydrology and geochemical analysis in the inland Pacific Northwest (PNW) of the USA. Isotope ratios were used to estimate mean transit times (MTTs) in natural and human-altered watersheds using the FLOWPC program. Isotope ratios in precipitation resulted in a regional meteoric water line of δ(2)H = 7.42·δ(18)O + 0.88 (n = 316; r(2) = 0.97). Isotope compositions exhibited a strong temperature-dependent seasonality. Despite this seasonal variation, the stream δ(18)O variation was small. A significant regression (τ = 0.11D(-1.09); r(2) = 0.83) between baseflow MTTs and the damping ratio was found. Baseflow MTTs ranged from 0.4 to 0.6 years (human-altered), 0.7 to 1.7 years (mining-altered), and 0.7 to 3.2 years (forested). Greater MTTs were represented by more homogenous aqueous chemistry whereas smaller MTTs resulted in more dynamic compositions. The isotope and geochemical data presented provide a baseline for future hydrological modelling in the inland PNW.

Introduction: The International Neuromodulation Society (INS) has determined that there is a need for guidance regarding safety and risk reduction for implantable neurostimulation devices. The INS convened an international committee of experts in the field to explore the evidence and clinical experience regarding safety, risks, and steps to risk reduction to improve outcomes., Methods: The Neuromodulation Appropriateness Consensus Committee (NACC) reviewed the world literature in English by searching MEDLINE, PubMed, and Google Scholar to evaluate the evidence for ways to reduce risks of neurostimulation therapies. This evidence, obtained from the relevant literature, and clinical experience obtained from the convened consensus panel were used to make final recommendations on improving safety and reducing risks., Results: The NACC determined that the ability to reduce risk associated with the use of neurostimulation devices is a valuable goal and possible with best practice. The NACC has recommended several practice modifications that will lead to improved care. The NACC also sets out the minimum training standards necessary to become an implanting physician., Conclusions: The NACC has identified the possibility of improving patient care and safety through practice modification. We recommend that all implanting physicians review this guidance and consider adapting their practice accordingly., (© 2014 International Neuromodulation Society.)

Objective: We report 2 cases of spinal epidural hematoma formation after the removal of percutaneous spinal cord stimulator trial leads and discuss the possible etiologies of these complications., Case Report: Two patients developed spinal epidural hematomas shortly after removal of their percutaneous trial leads and required multilevel laminectomies for evacuation of the hematoma. Patient 1 reported taking aspirin the morning that his leads were pulled, whereas patient 2 had not taken aspirin in the 7 days before commencing his trial. There were 2 days between identification and evacuation of patient 1's hematoma, and he did not fully recover from the injury to his spinal cord. Patient 2 underwent surgery immediately with complete resolution of his symptoms., Conclusions: Currently, the neuromodulation community ascribes to the American Society of Regional Anesthesia and Pain Medicine guidelines, which state that nonsteroidal anti-inflammatory drugs do not significantly increase the risk for epidural hematoma with neuraxial anesthesia and, therefore, there is no need to discontinue these drugs before epidural or spinal anesthesia. We suggest that these guidelines may not be appropriate for neuromodulatory techniques that likely subject the surrounding vasculature to more trauma than neuraxial anesthesia. We recommend discontinuing nonsteroidal anti-inflammatory drugs, particularly aspirin, before neuromodulation procedures. Further investigation will establish a timeframe for holding these drugs to optimize patient safety.

Vesicular transporters are required for the storage of all classical and amino acid neurotransmitters in synaptic vesicles. Some neurons lack known vesicular transporters, suggesting additional neurotransmitter systems remain unidentified. Insect mushroom bodies (MBs) are critical for several behaviors, including learning, but the neurotransmitters released by the intrinsic Kenyon cells (KCs) remain unknown. Likewise, KCs do not express a known vesicular transporter. We report the identification of a novel Drosophila gene portabella (prt) that is structurally similar to known vesicular transporters. Both larval and adult brains express PRT in the KCs of the MBs. Additional PRT cells project to the central complex and optic ganglia. prt mutation causes an olfactory learning deficit and an unusual defect in the male's position during copulation that is rescued by expression in KCs. Because prt is expressed in neurons that lack other known vesicular transporters or neurotransmitters, it may define a previously unknown neurotransmitter system responsible for sexual behavior and a component of olfactory learning., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Dopamine is cytotoxic and may play a role in the development of Parkinson's disease. However, its interaction with environmental risk factors such as pesticides remains poorly understood. The vesicular monoamine transporter (VMAT) regulates intracellular dopamine content, and we have tested the neuroprotective effects of VMAT in vivo using the model organism Drosophila melanogaster. We find that Drosophila VMAT (dVMAT) mutants contain fewer dopaminergic neurons than wild type, consistent with a developmental effect, and that dopaminergic cell loss in the mutant is exacerbated by the pesticides rotenone and paraquat. Overexpression of DVMAT protein does not increase the survival of animals exposed to rotenone, but blocks the loss of dopaminergic neurons caused by this pesticide. These results are the first to demonstrate an interaction between a VMAT and pesticides in vivo, and provide an important model to investigate the mechanisms by which pesticides and cellular DA may interact to kill dopaminergic cells., ((c) 2010 Elsevier Inc. All rights reserved.)

Vesicular neurotransmitter transporters are required for the storage of all classical and amino acid neurotransmitters in secretory vesicles. Transporter expression can influence neurotransmitter storage and release, and trafficking targets the transporters to different types of secretory vesicles. Vesicular transporters traffic to synaptic vesicles (SVs) as well as large dense core vesicles and are recycled to SVs at the nerve terminal. Some of the intrinsic signals for these trafficking events have been defined and include a dileucine motif present in multiple transporter subtypes, an acidic cluster in the neural isoform of the vesicular monoamine transporter (VMAT) 2 and a polyproline motif in the vesicular glutamate transporter (VGLUT) 1. The sorting of VMAT2 and the vesicular acetylcholine transporter to secretory vesicles is regulated by phosphorylation. In addition, VGLUT1 uses alternative endocytic pathways for recycling back to SVs following exocytosis. Regulation of these sorting events has the potential to influence synaptic transmission and behavior.

Lysosome-related organelles comprise a group of specialized intracellular compartments that include melanosomes and platelet dense granules (in mammals) and eye pigment granules (in insects). In humans, the biogenesis of these organelles is defective in genetic disorders collectively known as Hermansky-Pudlak syndrome (HPS). Patients with HPS-2, and two murine HPS models, carry mutations in genes encoding subunits of adaptor protein (AP)-3. Other genes mutated in rodent models include those encoding VPS33A and Rab38. Orthologs of all of these genes in Drosophila melanogaster belong to the 'granule group' of eye pigmentation genes. Other genes associated with HPS encode subunits of three complexes of unknown function, named biogenesis of lysosome-related organelles complex (BLOC)-1, -2 and -3, for which the Drosophila counterparts had not been characterized. Here, we report that the gene encoding the Drosophila ortholog of the HPS5 subunit of BLOC-2 is identical to the granule group gene pink (p), which was first studied in 1910 but had not been identified at the molecular level. The phenotype of pink mutants was exacerbated by mutations in AP-3 subunits or in the orthologs of VPS33A and Rab38. These results validate D. melanogaster as a genetic model to study the function of the BLOCs.

Aminergic signaling pathways have been implicated in a variety of neuropsychiatric illnesses, but the mechanisms by which these pathways influence complex behavior remain obscure. Vesicular monoamine transporters (VMATs) have been shown to regulate the amount of monoamine neurotransmitter that is stored and released from synaptic vesicles in mammalian systems, and an increase in their expression has been observed in bipolar patients. The model organism Drosophila melanogaster provides a powerful, but underutilized genetic system for studying how dopamine (DA) and serotonin (5HT) may influence behavior. We show that a Drosophila isoform of VMAT (DVMAT-A) is expressed in both dopaminergic and serotonergic neurons in the adult Drosophila brain. Overexpression of DVMAT-A in these cells potentiates stereotypic grooming behaviors and locomotion and can be reversed by reserpine, which blocks DVMAT activity, and haloperidol, a DA receptor antagonist. We also observe a prolongation of courtship behavior, a decrease in successful mating and a decrease in fertility, suggesting a role for aminergic circuits in the modulation of sexual behaviors. Finally, we find that DMVAT-A overexpression decreases the fly's sensitivity to cocaine, suggesting that the synaptic machinery responsible for this behavior may be downregulated. DVMAT transgenes may be targeted to additional neuronal pathways using standard Drosophila techniques, and our results provide a novel paradigm to study the mechanisms by which monoamines regulate complex behaviors relevant to neuropsychiatric illness.

Quantal size is a fundamental parameter controlling the strength of synaptic transmission. The transmitter content of synaptic vesicles is one mechanism that can affect the physiological response to the release of a single vesicle. At glutamatergic synapses, vesicular glutamate transporters (VGLUTs) are responsible for filling synaptic vesicles with glutamate. To investigate how VGLUT expression can regulate synaptic strength in vivo, we have identified the Drosophila vesicular glutamate transporter, which we name DVGLUT. DVGLUT mRNA is expressed in glutamatergic motoneurons and a large number of interneurons in the Drosophila CNS. DVGLUT protein resides on synaptic vesicles and localizes to the presynaptic terminals of all known glutamatergic neuromuscular junctions as well as to synapses throughout the CNS neuropil. Increasing the expression of DVGLUT in motoneurons leads to an increase in quantal size that is accompanied by an increase in synaptic vesicle volume. At synapses confronted with increased glutamate release from each vesicle, there is a compensatory decrease in the number of synaptic vesicles released that maintains normal levels of synaptic excitation. These results demonstrate that (1) expression of DVGLUT determines the size and glutamate content of synaptic vesicles and (2) homeostatic mechanisms exist to attenuate the excitatory effects of excess glutamate release.

Presently, 25.7% of the U.S. population is comprised of Blacks/African Americans, Hispanics, and Native Americans. The dental school enrollment of underrepresented minorities (URM) does not reflect this demographic distribution. In 1994, URM students comprised 12.68% of enrolled dental students, but in 1999, enrollment decreased to 10.53%. This trend is evident at Baylor College of Dentistry (BCD). Bridge to Dentistry involves formal linkages with local school districts, Texas colleges and universities, community organizations, dental clinics, community dentists, and BCD. The program is unique in that it targets students from kindergarten through dental school. The key components are awareness, attraction, preliminary education, facilitated-entry, admissions, financial aid, and retention. Some important features of the program are visits to area schools, visits to colleges and universities, summer enrichment programs, and academic advising. Preliminary results indicate the effectiveness of the program. BCD has increased its enrollment of URM students 325% over that of 1998. In 1998, 4.7% of the college's first-year student enrollment was URMs. In 2001, 14.6% of Baylor's first-year student enrollment was URMs. Since 1995, BCD has retained 90.6% of its URM students.

Purpose: The purpose of this investigation was to assess the level of consensus regarding the definition of centric relation and its clinical use in 7 US dental schools., Materials and Methods: The preclinical and clinical faculty in the departments of prosthodontics, operative, and general dentistry (n = 137) at 7 dental schools and a convenience sample of fourth year students (n = 150) at the same schools were invited to complete 2-page surveys regarding the definitions and use of centric relation at their institutions. The faculty and student survey included 6 commonly used centric relation definitions from the 1994 Glossary of Prosthodontic Terms, and provided space for writing in definitions not listed on the form. The participants were asked to identify which definition was used at their school., Results: Return rate was 85% for faculty and 75% for students. Both faculty and students identified a low level of consensus regarding the definition and clinical use of centric relation at their dental school. Numerous definitions are in use at each institution. Extramural practice participation and the number of years since dental school graduation were variables associated with the faculty's choice of definition. The faculty who did not participate in an extramural practice chose older definitions. Dental educators graduating before 1975 selected either the oldest or the most recent centric relation definition, whereas the more recent graduates frequently selected the newer definitions. There were no statistical differences between prosthodontic specialists and nonspecialists in choice of definitions. Three courses identified by the students as having the most influence on their understanding of centric relation were preclinical removable prosthodontics, preclinical occlusion, and clinical removable prosthodontics., Conclusion: The results of this survey suggest that the controversy will continue, because to date there is no consensus regarding the definition of centric relation within the 7 dental schools surveyed.

Purpose: To examine the effect of mixing techniques (hand-mixing vs. trituration) on fluoride release from chemically-cured (Fuji II) and resin-modified (Fuji II LC) glass ionomer products., Materials and Methods: Fluoride measurements were determined and comparisons made between hand-mixed-type materials that were both hand-mixed (60 seconds) and triturated (10 seconds). Hand-mixed specimens were made using the manufacturer's recommended powder/liquid ratio. Triturated specimens of the same material were made using the same powder/liquid ratio. Disk specimens (8.5 mm diameter, 2 mm thickness; n = 6) were stored in deionized water for 23 hours to obtain Day 1 solutions. Solutions were also obtained at 2, 3, 4, 5, 6, 7, 14, 21, and 28 days after fabrication and were changed 24 hours before fluoride concentration was determined using a fluoride ion selective electrode. Daily rates of fluoride release and 28-day cumulative fluoride totals were calculated. Cumulative data were analyzed by two-way ANOVA and Scheffé's test (alpha = 0.05). Daily results were analyzed by the Mann-Whitney U-test., Results: A significant difference was observed between materials (P < 0.001). Depending on the kind of material used, the method of manipulation affected the fluoride release. Data analysis revealed that: (1) Fuji II LC released significantly more fluoride than Fuji II for both triturated (P = 0.005) and hand-mixed (P < 0.005); (2) the triturated Fuji II released significantly more fluoride than the hand-mixed (P = 0.02); and (3) the hand-mixed Fuji II LC released more fluoride than the triturated, but was not statistically significant (P = 0.16).