Effect of tacrolimus dispositional genetics on acute rejection in the first 2 weeks and estimated glomerular filtration rate in the first 3 months following kidney transplantation

Background CYP3A4/5 and P-glycoprotein (P-gp, ABCB1) affect tacrolimus (TAC) exposure in T cells and kidney cells. Genetic variability of these genes has been widely studied for effects on acute rejection and kidney function after transplantation, but findings remain contradictory. In addition, cytochrome P450 reductase (POR) is important for CYP3A4/5 activity, and the pregnane X receptor (NR1I2) regulates CYP3A4/5 and P-gp expression. However, the relationship between POR and NR1I2 genetics and acute rejection and kidney function has not been extensively investigated. Objective The aim of this study was to investigate the effect of ABCB1 (61A>G, 1199G>A, 1236C>T, 2677G>T, 3435C>T), CYP3A4*22, CYP3A5*3, NR1I2 (8055C>T, 63396C>T) and POR*28 genotypes/haplotypes on acute rejection and kidney function in the first 3 months after transplant. Participants and methods The study included 165 kidney transplant recipients, who received TAC, mycophenolate and prednisolone, and 129 donors. TAC dose was adjusted to target trough blood concentrations of 8–15 ng/ml by therapeutic drug monitoring. Recipient and donor genotype/haplotype differences in acute rejection incidence within the first 2 weeks after transplant were assessed by logistic regression, adjusting for induction therapy, human leucocyte antigen mismatches, kidney transplant number, peak panel-reactive antibodies and donor type. Recipient and donor genotype/haplotype differences in estimated glomerular filtration rate in the first 3 months after transplant were assessed by linear mixed effects analysis, adjusting for acute rejection, delayed graft function and donor type. Results No genetic factors significantly affected acute rejection or estimated glomerular filtration rate after correction for multiple comparisons (P>0.004). Conclusion Recipient and donor dispositional genetics had no significant effect on short-term clinical outcomes in kidney transplant patients receiving TAC therapeutic drug monitoring.

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Utility of human leukocyte antigen-B*58: 01 genotyping and patient outcomes

Aim Human leukocyte antigen (HLA-B*58:01) allele screening before allopurinol administration is recommended to prevent gene-mediated severe cutaneous adverse reactions (SCARs). The objective of the analysis was to examine the clinical utility and effects of HLA-B*58:01 genotyping on patient's outcomes in a practice setting. Patients and methods The electronic medical records covering diagnosis, laboratory results, and prescription dispensing for patients who were newly treated with allopurinol or tested for HLA-B*58:01 were obtained from a large medical organization in Taiwan between 2010 and 2014. The uptake of HLA-B*58:01 testing, incidence of allopurinol-associated SCAR, and changes in urate-lowering agent utilization were assessed. Results A total of 17 532 allopurinol new users were identified from 2010 to 2014, and the HLA-B*58:01 test was ordered for 2844 (21.76%) of 13 069 new users when available between 2011 and 2014 in the study. The allopurinol-related SCAR events decreased from 0.21% (22/4460) to 0 (0/2167) after the introduction of HLA-B*58:01 testing, accompanied by a gradual increase from 8% (326/4207) to 31% (674/2167) in genotype testing rate. However, the HLA-B*58:01 testing performed before allopurinol prescription was 60.34%, and ~40% of patients were tested after already taking allopurinol. A shift from allopurinol to other urate-lowering agent regimens appeared among new allopurinol users. Conclusion HLA-B*58:01 test was associated with the prevention of allopurinol-induced SCAR. The clinical utility of genotype testing may not be consistent with recommendations for testing, and treatment alternatives are a competitive intervention associated with effective implications in a real-world setting.

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Analytical validity of a genotyping assay for use with personalized antihypertensive and chronic kidney disease therapy

Hypertension and chronic kidney disease are inextricably linked. Hypertension is a well-recognized contributor to chronic kidney disease progression and, in turn, renal disease potentiates hypertension. A generalized approach to drug selection and dosage has not proven effective in managing these conditions, in part, because patients with heterogeneous kidney disease and hypertension etiologies are frequently grouped according to functional or severity classifications. Genetic testing may serve as an important tool in the armamentarium of clinicians who embrace precision medicine. Increasing scientific evidence has supported the utilization of genomic information to select efficacious antihypertensive therapy and understand hereditary contributors to chronic kidney disease progression. Given the wide array of antihypertensive agents available and diversity of genetic renal disease predictors, a panel-based approach to genotyping may be an efficient and economic means of establishing an individualized blood pressure response profile for patients with various forms of chronic kidney disease and hypertension. In this manuscript, we discuss the validation process of a Clinical Laboratory Improvement Amendments-approved genetic test to relay information on 72 genetic variants associated with kidney disease progression and hypertension therapy. These genomic-based interventions, in addition to routine clinical data, may help inform physicians to provide personalized therapy.

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Choice of ANesthesia for EndoVAScular Treatment of Acute Ischemic Stroke (CANVAS): Results of the CANVAS Pilot Randomized Controlled Trial

Background: The effect of choice of anesthesia on clinical outcome for endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) remains unclear. Methods: We conducted a pilot trial of 43 patients with acute anterior circulation ischemic stroke having EVT. Patients were randomly allocated to receive general anesthesia or conscious sedation. We documented the rate of recruitment and rate of conversion from conscious sedation to general anesthesia. In addition, we recorded the change in National Institute of Health stroke scale (NIHSS) on day 7, the rate of successful reperfusion and measured neurological function by certified researchers using modified Rankin Score (mRS 0 to 2) at 90 days. Results: The recruitment rate was 31.4% and majority of patients were excluded because of delay in hospital presentation and posterior circulation stroke. The rate of conversion from conscious sedation to general anesthesia was 18.2%. This was primarily related to excessive sedation and uncontrolled movement. Change in NIHSS score, rate of successful reperfusion and functional recovery were similar between groups. Conclusions: It was feasible to randomize AIS patients receiving either general anesthesia or conscious sedation for EVT. J.S. and F.L. contributed equally. Supported by the Beijing Municipal Administration of Hospitals Youth Program (code number: QML20150508), Ascent Plan (number: DFL20180502) Clinical Medicine Development of Special Funding Support (number: ZYLX201708) and China National key scientific research project (number: 2016YFC1301500). J.S., F.L., Y.P., Z.M., AW.G., M.T.V.C., and R.H.: helped with the study design and manuscript preparation. Y.P., and R.H.: equally contributed to the manuscript. J.S., F.L., Y.W., Y.Z., and Y.P.: involved in the data collection from neurosurgical anesthesia. L.Z. and Y.P.: helped with the data analyses. M.T.V.C. and R.H. are the members from the Editorial Board of Journal of Neurosurgical Anesthesiology. The remaining authors declare that they have nothing to disclose. Address correspondence to: Ruquan Han, MD, PhD, Department of Anesthesiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, PR China (e-mail: ruquan.han@ccmu.edu.cn). Received July 24, 2018 Accepted October 22, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

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Retrospective Analysis of Perioperative Variables Associated With Postoperative Delirium and Other Adverse Outcomes in Older Patients After Spine Surgery

Background: The aim of this retrospective study was to identify perioperative variables predictive of the development of delirium in older surgical patients after spine surgery. Materials and Methods: We collected preoperative, intraoperative, and postoperative data on patients 65 years of age and above having spine surgery between July 1, 2015 and March 15, 2017. The primary outcome was the development of postoperative delirium. Data were analyzed using univariate and multivariable analysis. Results: Among the 716 patients included in this study 127 (18%) developed postoperative delirium. On multivariable analysis, independent predictors of postoperative delirium included older age (odds ratio [OR]=1.04; 95% confidence interval [CI], 1.00-1.09; P=0.048), American Society of Anesthesiologists physical status >2 (OR=1.89 [95% CI, 1.04-3.59]; P=0.042), metabolic equivalents of task

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The Effect of PTCH1 on Ovarian Cancer Cell Proliferation and Apoptosis

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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The Effect of PTCH1 on Ovarian Cancer Cell Proliferation and Apoptosis

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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Yeast Models Of Phosphomannomutase 2 Deficiency, A Congenital Disorder Of Glycosylation

Phosphomannomutase 2 Deficiency (PMM2-CDG) is the most common monogenic congenital disorder of glycosylation (CDG) affecting at least 800 patients globally. PMM2 orthologs are present in model organisms, including the budding yeast Saccharomyces cerevisiae gene SEC53. Here we describe conserved genotype-phenotype relationships across yeast and human patients between five PMM2 loss-of-function missense mutations and their orthologous SEC53 mutations. These alleles range in severity from folding defective (hypomorph) to dimerization defective (severe hypomorph) to catalytic dead (null). We included the first and second most common missense mutations - R141H, F119L respectively- and the most common compound heterozygote genotype - PMM2^R141H/F119L - observed in PMM2-CDG patients. Each mutation described is expressed in haploid as well as homozygous and heterozygous diploid yeast cells at varying protein expression levels as either SEC53 protein variants or PMM2 protein variants. We developed a 384-well-plate, growth-based assay for use in a screen of the 2,560-compound Microsource Spectrum library of approved drugs, experimental drugs, tool compounds and natural products. We identified three compounds that suppress growth defects of SEC53 variants, F126L and V238M, based on the biochemical defect of the allele, protein abundance or ploidy. The rare PMM2 E139K protein variant is fully functional in yeast cells, suggesting that its pathogenicity in humans is due to the underlying DNA mutation that results in skipping of exon 5 and a nonfunctional truncated protein. Together, these results demonstrate that yeast models can be used to characterize known and novel PMM2 patient alleles in quantitative growth and enzymatic activity assays, and used as patient avatars for PMM2-CDG drug screens yielding compounds that could be rapidly cross-validated in zebrafish, rodent and human organoid models.

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Significant Morbidity and Mortality Associated with Fecal Impaction in Patients Who Present to the Emergency Department

Abstract

Background

Fecal impaction (FI) is defined as a large mass of stool in the rectum and/or colon that is unable to be evacuated. No study to date details demographics and outcomes in a sizeable sample of FI patients in the USA.

Aims

The present study aims to develop knowledge of FI by reporting descriptive measures and outcomes of patients presenting to a US emergency department (ED) with FI.

Methods

Medical charts coded with FI at Beth Israel Deaconess Medical Center from 2016 or 2017 were identified retrospectively. Patients diagnosed with FI in the ED or subsequent to direct hospital admission from the ED were included. Patient-specific demographics, visit-specific details, medical and medication histories, and hospital treatment and outcome measures were included in a database and analyzed.

Results

Thirty-two patients (mean age of 72.9 years, 62.5% female) had a total of 42 ED visits with FI. Patients had an average of 8.7 diagnoses and 11.2 medications listed in their charts. 54.8% of patients were taking at least one commonly prescribed constipating medication. The median total length of stay for admitted patients was 3 days, with nearly 90% of the ED visits with FI requiring hospital admission. 40.6% of patients experienced serious FI-related morbidities, and 21.9% of patients with FI died in the hospital.

Conclusion

Patients presenting with FI had high risk of morbidity and mortality, complex medical histories, and large numbers of active treatment regimens. Patients with FI should receive immediate treatment and close monitoring for morbidities and complications.

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Factors affecting vitamin D deficiency in active inflammatory bowel diseases

Hypovitaminosis D is prevalent in inflammatory bowel disease (IBD) and may be associated with disease activity.

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Coronal Deformity Angular Ratio May Serve as A Valuable Parameter to Predict In-brace Correction in Patients with Adolescent Idiopathic Scoliosis

In-brace correction (IBC) plays an important role in curve progression of patients with adolescent idiopathic scoliosis (AIS) under brace treatment. We evaluated the coronal deformity angular ratio (C-DAR) as a potential predictor of IBC. Based on our experience, we postulated that a high C-DAR may result in low IBC. This relationship had not been previously studied.

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Paraspinal muscle cross-sectional area predicts low back disability but not pain intensity

The lumbar paraspinal muscles, including the erector spinae and multifidus, play an important role in movement and control of the spine. However, our understanding of their contribution to low back pain and disability is unclear. Systematic reviews have reported conflicting evidence for an association between paraspinal muscle size and low back pain, and a paucity of data examining muscle cross-sectional area and low back disability.

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The Impact of Type 2 Diabetes on Bone Metabolism and Growth after Spinal Fusion

Some clinical reports suggest diabetes may have a negative effect on spinal fusion outcomes, although no conclusive experimental research has been conducted to investigate the causality, impact, and inherent risks of this growing patient population.

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A Reproducible and Reliable Localization Technique for Lumbar Spine Surgery that Minimizes Unintended-Level Exposure and Wrong-Level Surgery

Exposure of unintended levels (defined as a spinal segment outside the intended surgical levels) is unnecessary and potentially adds to operative time and patient morbidity. Wrong-level surgery (defined as decompression, instrumentation, or fusion of a spinal segment not part of the intended surgical procedure) clearly adds to morbidity as well as putting the surgeon at medicolegal risk.

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Factors affecting vitamin D deficiency in active inflammatory bowel diseases

Hypovitaminosis D is prevalent in inflammatory bowel disease (IBD) and may be associated with disease activity.

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Cognitive and motor event-related potentials in Tourette syndrome and tic disorders: a systematic review

Tourette syndrome (TS) is a neurodevelopmental psychiatric disorder involving motor and phonic tics. Tics are conceptualized as involuntary motor contractions or vocalizations (American Psychiatric Association, 2013). These tics can be either simple or complex. Simple motor tics are the most frequent ones, and may take the form or eyeblinks, nose twitches, or head jerks, among others. While simple motor tics only involve one group of muscles, complex motors tics involve multiple groups of muscles in a coordinated sequence.

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Diagnostic sensitivity of electrophysiology and ultrasonography in ulnar neuropathies of different severity

Ulnar neuropathy is the second most common mono-neuropathy after carpal tunnel syndrome. It usually results from focal nerve abnormality around the elbow, with an estimated incidence of 24.7/105/year (Mondelli et al., 2005). It presents with paraesthesia or sensory loss in the little and ring fingers and weakness of ulnar innervated muscles. Untreated ulnar neuropathy can progress to cause severe disability. However, despite its relatively high incidence, diagnosis and management of ulnar neuropathy at the elbow can be still challenging.

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Risk loci for ADHD

Risk loci for ADHD

Risk loci for ADHD, Published online: 07 December 2018; doi:10.1038/s41576-018-0084-0

A study in Nature Genetics reports the first genome-wide significant loci for attention deficit/hyperactivity disorder and implicates biologically informative genes, such as FOXP2, as contributors to its aetiology.

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Acceptability, Feasibility and Uptake of HPV Self-Sampling Among Immigrant Minority Women: a Focused Literature Review

Abstract

This review uncovers the extent to which immigrant and minority women find HPV self-sampling an acceptable and feasible alternative to PAP testing for screening for cervical cancer. A focused literature review was conducted using CINAHL, Medline, Proquest and Pubmed databases to search for content relating to acceptability or feasibility of HPV self-testing for immigrant populations or minorities. 575 prospective relevant papers were included in the final analysis and 28 selected using the inclusion and exclusion criteria. HPV self-sampling was found to be acceptable and feasible among immigrant and minority women. Participants studied indicated the importance of providing in-depth educational documents, diagrams, illustrations and supplementary resources in future HPV self-sampling studies. HPV self-sampling has the potential to significantly increase cervical cancer screening participation rates amongst immigrant and minority women. Future research studies should incorporate methods to increase the efficacy and acceptability of HPV self-testing amongst immigrant and minority women.

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Paramedic - FT - Fargo, ND - Sanford Health

Provides high quality out of hospital care and transport by receiving emergency and non-emergency ambulance calls and responding to them promptly, efficiently and professionally.

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Should 911 dispatchers be considered first responders?

Our co-hosts talk about the reclassification possibility and also consider the idea of a national certification for all dispatchers

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Comparative transcriptome analysis in the hepatopancreas of Helice tientsinensis exposed to the toxic metal cadmium

Abstract

Background

The mudflat crab Helice tientsinensis is one of the most commercially valuable species for crabmeat production due to its delicious taste. These crabs are mainly found in coastal wetland where they are seriously threatened by toxic heavy metal pollution. In crustaceans, the hepatopancreas is an important organ for detoxification, and metal toxic substances can be converted to non-toxic or less toxic compounds in this organ.

Objective

To develop a better understanding of the molecular response of H. tientsinensis to the toxic metal cadmium (Cd) and provide a molecular basis for the toxic metal tolerance of H. tientsinensis.

Methods

In this study, we performed comparative hepatopancreas transcriptome analysis between H. tientsinensis unexposed (as control) and exposed to the toxic metal Cd for 48 h.

Results

We identified 1089 Cd stress significantly-upregulated and 1560 Cd stress significantly-downregulated unigenes. Functional categorization and annotation of these differentially-expressed genes (DEGs) demonstrated that the response to Cd stress in the hepatopancreas of H. tientsinensis mainly involves "antioxidant activity", "detoxification", "toxin degradation activity" and "immune system process". In addition, five genes (ABCC1, NDUFAF5, ASTL, DES1, CYP27A) were identified as possible major targets for toxic metal tolerance.

Conclusion

This is the first time reporting that the response of H. tientsinensis to Cd exposure at the transcriptome level, and it lays the foundation for understanding the molecular mechanisms of the response of H. tientsinensis to environmental toxic metal stress.

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The impact of empiric endoscopic biliary sphincterotomy on future gallstone-related complications in patients with non-severe acute biliary pancreatitis whose cholecystectomy was deferred or not performed

Abstract

Background

Early cholecystectomy (EC) is recommended in patients with acute biliary pancreatitis (ABP). In real-life practice, cholecystectomy is frequently deferred due to various reasons and delayed cholecystectomy (DC) is performed instead. Endoscopic sphincterotomy (ES) is an alternative to prevent recurrent pancreatitis, however other gallstone-related complications (GCs) may still develop. We aimed to determine the impact of ES on future GCs in patients with non-severe acute biliary pancreatitis whose cholecystectomy was deferred or not performed.

Methods

During 2006–2016, we included patients with non-severe ABP while those with severe pancreatitis and concurrent cholangitis were excluded. GC events were compared between those who had DC with ES and those who had DC without ES. A similar comparison was made in patients with and without ES who did not receive cholecystectomy.

Results

Of 266 patients with ABP, non-severe ABP was identified in 146. Only 16 (11%) had EC. Of patients with non-severe ABP who underwent DC (n = 88), recurrent ABP in the ES group was lower than those from the non-ES group (2% vs. 17%; p = 0.01). Acute cholecystitis was found in 0%, 6% and 10% of patients with EC, DC and those without cholecystectomy (p = 0.39). Of those who did not undergo cholecystectomy (n = 42), recurrent ABP in the ES group was still lower than the non-ES group (4% vs. 36%; p = 0.006). ES related complications were mild pancreatitis (4%) and post sphincterotomy bleeding (5%).

Conclusions

In patient with non-severe ABP, ES is an alternative to reduce recurrent ABP, however without EC, future cholecystitis may still develop.

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Robotic-assisted versus laparoscopic unilateral inguinal hernia repair: a comprehensive cost analysis

Abstract

Background

Cost-effectiveness of robotic-assisted surgery is still debatable. Robotic-assisted inguinal hernia repair has no clear clinical benefit over laparoscopic repair. We performed a comprehensive cost-analysis comparison between the two approaches for evaluation of their cost-effectiveness in a large healthcare system in the Western United States.

Methods

Health records in 32 hospitals were queried for procedural costs of inguinal hernia repairs between January 2015 and March 2017. Elective robotic-assisted or laparoscopic unilateral inguinal hernia repairs were included. Cost calculations were done using a utilization-based costing model. Total cost included: fixed cost, which comprises medical device and personnel costs, and variable cost, which comprises disposables and reusable instruments costs. Other outcome measures were length of stay (LOS), conversion to open, and operative times. Statistics were done using t test for continuous variables and χ² test for categorical variables. A p-value < 0.05 was considered significant.

Results

A total of 2405 cases, 734 robotic-assisted (633 Primary: 101 recurrent) and 1671 laparoscopic (1471 Primary: 200 recurrent), were included. The average total cost was significantly higher (p < 0.001) in the robotic-assisted group ($5517) compared to the laparoscopic group ($3269). However, the average laparoscopic variable cost ($1105) was significantly higher (p < 0.001) than the robotic-assisted cost ($933). Whereas there was no significant difference between the two groups for LOS and conversion to open, average operative times were significantly higher in the robotic-assisted group (p < 0.001). Subgroup analysis for primary and recurrent inguinal hernias matched the overall results.

Conclusions

Robotic-assisted inguinal hernia repair has a significantly higher cost and significantly longer operative times, compared to the laparoscopic approach. The study has shown that only fixed cost contributes to the cost difference between the two approaches. Medical device cost plus the longer operative times are the main factors driving the cost difference. Laparoscopic unilateral inguinal hernia repair is more cost-effective compared to a robotic-assisted approach.

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The treatment indication and optimal management of fluid collection after laparoscopic distal pancreatectomy

Abstract

Background

Recently, laparoscopic distal pancreatectomy (LDP) has become the standard procedure for resection of left-sided pancreatic tumors. Fluid collection (FC) at the resection margin of the pancreatic stump after LDP is a frequent radiological finding. However, there have been few treatment guidelines and the optimal management for this clinical finding is unclear. The aim of present study is to define the incidence of FC and suggest the optimal management for FC after LDP.

Methods

A total of 1227 patients who underwent LDP between March 2005 and December 2015 were collected. FC was considered present when the longest diameter of the lesion on CT scan was > 3 cm.

Results

A follow-up with at least two CT image was available for 1102 patients. Of these, 689 (62.5%) patients showed initial fluid collection (IFC) at the pancreas resection site in immediate postoperative CT. IFC (+) group had higher proportion of men, BMI, and higher rate of concomitant splenectomy than IFC (−) group. Among patients with FC after LDP, the treatment group had more frequent leukocytosis and accompanying symptoms than the observation group. Seventy-seven patients underwent therapeutic interventions for FC after LDP. Among them, 55 (71.4%) patients underwent endoscopic ultrasonography-guided gastrocystostomy (EUS-GC). EUS-GC group had a higher success rate (85.6 vs. 63.6%, p < 0.033) and shorter hospital stay after the intervention (5.2 vs. 13.3 days, p < 0.001) than those who underwent other procedures.

Conclusions

High BMI, male, and concomitant splenectomy contribute to the occurrence of FC after LDP. In most cases, FC after LDP resolved spontaneously over time with observation. The patients with symptomatic FC ultimately required treatment. EUS-GC is the optimal intervention therapy for FC after LDP.

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Risk loci for ADHD

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Neuropathic pain, dysautonomia, and nerve hyperexcitability: Expanding the spectrum of LGI1 autoimmunity

Publication date: Available online 7 December 2018

Source: Clinical Neurophysiology

Author(s): Giulia Berzero, Timothée Lenglet, Marine Giry, Jacques D'Anglejan, Bastien Joubert, Fleur Cohen, Dimitri Psimaras

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Exploration of cardiac sympathetic adrenergic nerve activity in narcolepsy

Publication date: Available online 6 December 2018

Source: Clinical Neurophysiology

Author(s): Lucie Barateau, Régis Lopez, Sofiene Chenini, Elisa Evangelista, Meriem Benkiran, Denis Mariano-Goulart, Isabelle Jaussent, Yves Dauvilliers

Abstract

Objective

To compare cardiac sympathetic adrenergic nerve activity in patients with narcolepsy type 1 (NT1) and controls using ¹²³I-MIBG myocardial scintigraphy, and to determine the clinical and neurophysiological variables associated with ¹²³I-MIBG scintigraphy results in NT1.

Methods

Fifty-six NT1 patients and 91 controls without neurological diseases underwent a cardiac scintigraphy. MIBG uptake was quantified by delayed heart/mediastinum (H/M) ratio. Clinical, neurophysiological and biological determinants of a low H/M were assessed in NT1.

Results

MIBG uptake did not differ between NT1 and controls in crude and adjusted associations. Five patients had low MIBG uptake (<1.42, first decile of controls), often with advanced age, cardiovascular (CV) diseases, stimulants intake, and REM sleep behavior disorder. Patients with H/M<1.62 (lowest tertile) were older, with higher BMI, microarousal index and CV comorbidities. A three-fold increase of phasic/tonic REM sleep motor activities was found in those patients, confirmed in a subanalysis of 40 drug-free patients. No association was found with CSF hypocretin levels.

Conclusion

A direct measure of the heart adrenergic nerve activity revealed no sympathetic denervation in NT1.

Significance

Our results indicate normal cardiac sympathetic innervation in NT1. However, few patients with low MIBG uptake also presented CV comorbidities and REM sleep motor deregulation, potentially at high CV risk, requiring a careful follow-up.

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Resting state connectivity in neocortical epilepsy: The epilepsy network as a patient-specific biomarker

Publication date: Available online 6 December 2018

Source: Clinical Neurophysiology

Author(s): Alexandria C. Marino, Genevieve J. Yang, Evgeniya Tyrtova, Kun Wu, Hitten P. Zaveri, Pue Farooque, Dennis D. Spencer, S. Kathleen Bandt

Abstract

Objective

Localization related epilepsy (LRE) is increasingly accepted as a network disorder. To better understand the network specific characteristics of LRE, we define individual epilepsy networks and compare them across patients.

Methods

The epilepsy network was defined in the slow cortical potential frequency band in 10 patients using intracranial EEG data obtained during interictal periods. Cortical regions were included in the epilepsy network if their connectivity pattern was similar to the connectivity pattern of the seizure onset electrode contact. Patients were subdivided into frontal, temporal, and posterior quadrant cohorts according to the anatomic location of seizure onset. Jaccard similarity was calculated within each cohort to assess for similarity of the epilepsy network between patients within each cohort.

Results

All patients exhibited an epilepsy network in the slow cortical potential frequency band. The topographic distribution of this correlated network activity was found to be unique at the single subject level.

Conclusions

The epilepsy network is unique at the single patient level, even between patients with similar seizure onset locations.

Significance

We demonstrate that the epilepsy network is patient-specific. This is in keeping with our current understanding of brain networks and identifies the patient-specific epilepsy network as a possible biomarker in LRE.

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Clinical and electrophysiological investigation of spastic muscle overactivity in patients with disorders of consciousness following severe brain injury

Publication date: Available online 6 December 2018

Source: Clinical Neurophysiology

Author(s): G. Martens, T. Deltombe, M. Foidart-Dessalle, S. Laureys, A. Thibaut

Abstract

Objective

The clinical and electrophysiological profile of spastic muscle overactivity (SMO) is poorly documented in patients with disorders of consciousness (DOC) following severe cortical and subcortical injury. We aim at investigating the link between the clinical observations of SMO and the electrophysiological spastic over-reactivity in patients with prolonged DOC.

Methods

We prospectively enrolled adult patients with DOC at least 3 months post traumatic or non-traumatic brain injury. The spastic profile was investigated using the Modified Ashworth Scale and the Hmax/Mmax ratio. T1 MRI data and impact of medication were analyzed as well.

Results

21 patients were included (mean age: 41±11 years; time since injury: 4±5 years; 9 women; 10 traumatic etiologies). Eighteen patients presented signs of SMO and 11 had an increased ratio. Eight patients presented signs of SMO but no increased ratio. We did not find any significant correlation between the ratio and the MAS score for each limb (all ps > 0.05). The presence of medication was not significantly associated with a reduction in MAS scores or Hmax/Mmax ratios.

Conclusions

In this preliminary study, the Hmax/Mmax ratio does not seem to reflect the clinical MAS scores in patients with DOC. This supports the fact they do not only present spasticity but other forms of SMO and contracture.

Significance

Patients with DOC are still in need of optimized tools to evaluate their spastic profile and therapeutic approaches should be adapted accordingly.

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The impact of acute mental stress on brachial artery flow-mediated dilation in women diagnosed with depression

Publication date: Available online 6 December 2018

Source: International Journal of Psychophysiology

Author(s): Katrina A. D'Urzo, Cherie L. La Rocque, Jennifer S. Williams, Troy J.R. Stuckless, Trevor J. King, Meghan D. Plotnick, Brendon J. Gurd, Kate L. Harkness, Kyra E. Pyke

Abstract

Endothelial function, assessed by flow-mediated dilation (FMD), may be transiently attenuated in healthy adults following acute mental stress. However, the impact of acute mental stress on endothelial function in the context of clinical depression is unknown. This study examined the impact of acute mental stress on FMD in women with a diagnosis of a depressive disorder. Forty-three otherwise healthy women (33 ± 14 years) participated. Brachial artery diameter and blood velocity were assessed with ultrasound. FMD was assessed immediately prior to and 15 min following the Trier Social Stress Test (TSST). The FMD protocol included 5 min of forearm cuff occlusion (pressure = 250 mm Hg), followed by release. Shear stress was estimated by calculating shear rate (SR = brachial artery blood velocity/diameter). Stress reactivity was assessed via changes in mean arterial pressure (MAP), heart rate (HR) and salivary cortisol. Results are mean ± SD. A significant stress response was elicited by the TSST [MAP, HR and salivary cortisol increased (p < 0.05)]. Neither the SR stimulus nor FMD response differed pre-versus post-stress (p = 0.124 and p = 0.641, respectively). There was a modest negative correlation between cortisol reactivity and change in FMD from pre- to post-stress (R = −0.392, p = 0.011). To conclude, acute mental stress did not consistently impair endothelial function in women diagnosed with a depressive disorder; however, higher cortisol reactivity may increase the likelihood of post-stress endothelial dysfunction. Further research is required to better understand the factors influencing the relationship between acute mental stress, cortisol and endothelial function in women with depression.

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Training Day: Mastering the 12-lead

Tips for training EMS providers on interpreting a 12-lead, from studying EKG renderings and understanding their clinical significance

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Training Day: Mastering the 12-lead

Tips for training EMS providers on interpreting a 12-lead, from studying EKG renderings and understanding their clinical significance

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3 Questions to ask when buying ambulance equipment mounts

Wall, surface and stretcher mounts help secure equipment within the ambulance, reducing the potential for injury to patients and providers

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Generalizing remotely supervised transcranial direct current stimulation (tDCS): feasibility and benefit in Parkinson’s disease

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has been shown to improve common symptoms of neurological disorders like depressed mood, fatigue, motor deficit...

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Spatial deconvolution of aerial radiometric survey and its application to the fallout from a radiological dispersal device

Publication date: February 2019

Source: Journal of Environmental Radioactivity, Volume 197

Author(s): Laurel E. Sinclair, Richard Fortin

Abstract

Mapping radioactive contamination using aerial survey measurements is an area under active investigation today. The radiometric aerial survey technique has been extensively applied following reactor accidents and also would provide a key tool for response to a malicious radiological or nuclear incident. Methods exist to calibrate the aerial survey system for quantification of the concentration of natural radionuclides, which can provide guidance. However, these methods have anticipated a spatial distribution of the source which is large in comparison to the survey altitude. In rapid emergency-response aerial surveys of areas of safety concern, deposits of relatively small spatial extent may be expected. The activity of such spatially restricted hot spots is underestimated using the traditional methods. We present here a spatial deconvolution method which can recover some of the variation smoothed out by the averaging due to survey at altitude. We show that the method can recover the true spatial distribution of concentration of a synthetic source. We then apply the method to real aerial survey data collected following detonation of a radiological dispersal device. The findings and implications of the deconvolution are then discussed by reference to a groundbased truckborne survey over the same contamination.

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Effectiveness of technology-based distance physical rehabilitation interventions for improving physical functioning in stroke: a systematic review and meta-analysis of randomized controlled trials

Publication date: Available online 6 December 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Aki Rintala, Ville Päivärinne, Sanna Hakala, Jaana Paltamaa, Ari Heinonen, Juha Karvanen, Tuulikki Sjögren

ABSTRACT

Objective

To study the effectiveness of technology-based distance physical rehabilitation interventions on physical functioning in stroke.

Data sources

A systematic literature search was conducted in six databases from January 2000 to May 2018.

Study selection

Inclusion criteria applied PICOS (Patient, Intervention, Comparison, Outcome, Study design) framework as follows: (P) stroke; (I) technology-based distance physical rehabilitation interventions; (C) any comparison without the use of technology; (O) physical functioning; (S) randomized controlled trials (RCTs). The search identified in total 693 studies, and the screening of 162 full-text studies revealed 13 eligible studies.

Data extraction

The studies were screened using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, and assessed for methodological quality and quality of evidence. Meta-analysis was performed if applicable.

Data synthesis

Thirteen studies were included, and online video monitoring was the most used technology. Seven outcomes of physical functioning were identified – activities of daily living (ADL), upper and lower extremity functioning, balance, walking, physical activity, and participation. A meta-analysis of six RCTs indicated that technology-based distance physical rehabilitation had a similar effect on ADL (standard mean difference (SMD) 0.06; 95%CI: -0.22 to 0.35, p = .67) compared to the combination of traditional treatments (usual care, similar and other treatment). Similar results were obtained for other outcomes, except inconsistent findings were noted for walking. Methodological quality of the studies and quality of evidence were considered low.

Conclusions

The findings suggest that the effectiveness of technology-based distance physical rehabilitation interventions on physical functioning might be similar compared to traditional treatments in stroke. Further research should be performed to confirm the effectiveness of technology-based distance physical rehabilitation interventions for improving physical functioning of persons with stroke.

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Employment and Gainful Earnings among those with Multiple Sclerosis

Publication date: Available online 6 December 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): James S. Krause, Clara E. Dismuke-Greer, Melinda Jarnecke, Chao Li, Karla S. Reed, Phillip Rumrill

ABSTRACT

Objective

To identify demographic, educational, and disease-related characteristics associated with the odds of employment and earnings among participants with multiple sclerosis (MS).

Design

Cross-sectional using self-report assessment obtained by mail or online

Setting

Medical University in the southeastern United States.

Participant

Participants with MS (n = 1059) were enrolled from a specialty hospital in the southeastern United States. All were adults under the age of 65 at the time of assessment.

Interventions

NA

Main Outcome Measures

Current employment status and earnings

Results

MS factors were highly related to employment, yet not as strongly to conditional earnings. Those with no symptoms reported 6.25 greater odds of employment than those with severe current symptoms. Compared with those with progressive MS, those with relapsing/remitting had a greater odds of employment (OR = 2.24). Participants with no perceived cognitive impairment had 1.83 greater odds of employment than those with moderate to severe perceived cognitive impairment. Those with less than 10 years since MS diagnosis had 2.74 greater odds of employment compared with those with more than 20 years since diagnosis. An absence of problematic fatigue was highly related to the probability of employment (OR = 5.01) and higher conditional earnings ($14,454), whereas the remaining MS variables were unrelated to conditional earnings. For non-MS variables, education was highly related to employment status and conditional earnings, as those with a postgraduate degree had 2.87 greater odds of employment and $44,346 greater earnings than those with no more than a high school certificate. Non-Hispanic Whites had 2.22 greater odds of employment and $16,118 greater conditional earnings than non-Hispanic Blacks, and men reported $30,730 more in conditional earnings than women.

Conclusions

MS indicators were significantly associated with employment status including time since diagnosis, fatigue, symptom severity, and presence of cognitive impairment. However, among those who were employed, conditional earnings were less highly related to these factors and more highly related to educational attainment.

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What lies beneath: Why some pressure injuries may be unpreventable for individuals with spinal cord injury

Publication date: Available online 6 December 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): D.P. Lemmer, N. Alvarado, M.K. Henzel, M.A. Richmond, J. McDaniel, J. Graebert, K. Schwartz, J. Sun, K.M. Bogie

Abstract

Objective

To investigate intersections between pressure injury (PrI) history, muscle composition and tissue health responses under physiologically relevant loading conditions for individuals with spinal cord injury (SCI).

Design

Repeated measures study design with annual follow-up for up to 3 years.

Setting

Tertiary Care Center.

Participants

38 persons with SCI. Exclusion criteria included having an open pelvic region PrI at the time of recruitment, presence of systemic disease and/or known sensitivity to contrast.

Interventions

Not applicable.

Main Outcome Measure(s)

Gluteal muscle composition, ischial interface pressures, tissue oxygenation.

Results

Ischial region mean interface pressures are the same for individuals with or without a PrI history. Tissue oxygenation is lower during sitting for persons with a PrI history. Individuals with greater than 15% gluteal intramuscular fat were statistically highly significantly (p<0.001) more likely to have a history of severe or recurrent PrI. IMAT levels within the gluteal muscle may remain low over time or muscle tissue in the gluteal muscle region may be almost entirely replaced by IMAT. In the current study cohort, it was found that muscle composition also continues to change over time even for individuals with long-standing SCI

Conclusions

Soft tissue compositional changes, specifically increased gluteal intramuscular fat (IMAT), provides a reliable indicator of PrI history and may provide a key to personalized PrI risk status for persons with SCI. The current findings confirm that interface pressure mapping alone is a limited indicator for PrI development.

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A systematic review and a dose-response meta-analysis of coffee dose and nonalcoholic fatty liver disease

Clinical Nutrition

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Dietary patterns and risk of hepatocellular carcinoma among US men and women

Hepatology

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Risk factor for steatorrhea in pediatric chronic pancreatitis patients

BMC Gastroenterology

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Usefulness of transabdominal ultrasonography for assessing ulcerative colitis: A prospective, multicenter study

Journal of Gastroenterology

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Gallstone disease and type 2 diabetes risk: A Mendelian randomization study

Hepatology

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Ultrasonic assessment of liver stiffness and carotid artery elasticity in patients with chronic viral hepatitis

BMC Gastroenterology

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Restoration of Lumbar Lordosis After Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Systematic Review

Transforaminal lumbar interbody fusion (TLIF) is a well-accepted surgical technique for the treatment of degenerative spinal conditions and spinal deformity. The TLIF procedure can be performed open or using minimally invasive techniques. While several studies have found that minimally invasive TLIF (MI-TLIF) has advantages over open TLIF procedures with less blood loss, post-operative pain and hospital length of stay, opponents of the minimally invasive technique cite the lack of restoration of lumbar lordosis as a major drawback.

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Exploration of cardiac sympathetic adrenergic nerve activity in narcolepsy

Narcolepsy type 1 (NT1) is an orphan sleep disorder caused by the selective and irreversible loss of hypocretin/orexin neurons that widely project to brain, brainstem and intermediolateral nucleus neurons of the spinal cord, and have key roles in autonomic and cardiovascular (CV) regulation (Dun et al. 2000; Dauvilliers et al. 2007; Grimaldi et al. 2014). Hypocretin-deficient mice show lower arterial blood pressure (BP) during wakefulness and blunted non-rapid eye movement (REM) sleep and REM sleep-related BP decreases compared with wild type animals (Bastianini et al.

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Neuropathic pain, dysautonomia, and nerve hyperexcitability: Expanding the spectrum of LGI1 autoimmunity

Antibodies to Leucine-rich Glioma Inactivated 1 (LGI1) protein have primarily been associated with limbic encephalitis (van Sonderen et al., 2016). However, a more widespread autoantibody testing has recently allowed to expand the spectrum of LGI-1 autoimmunity, and peripheral impairment is increasingly reported, whether or not in association with central nervous system involvement (van Sonderen et al., 2016; Klein et al., 2012; Gadoth et al., 2017). The clinical and electrophysiological phenotype associated with LGI1-positive peripheral neuropathy has not been fully elucidated yet, and neurologists are not necessarily familiar with this entity.

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Clinical and electrophysiological investigation of spastic muscle overactivity in patients with disorders of consciousness following severe brain injury

About a third of patients who underwent a stroke or a traumatic brain injury will develop upper motor neuron (UMN) syndrome with spastic muscle overactivity (SMO) (Wissel et al. 2010, 2013; Martens et al. 2018). This syndrome can occur following any central nervous system lesion involving the corticospinal tract and parapyramidal tracts along the cortex, brainstem and spinal cord. UMN syndrome is classically described with positive (e.g., SMO) and negative signs (e.g., muscle weakness, fatigability) (Thibaut et al.

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Resting state connectivity in neocortical epilepsy: The epilepsy network as a patient-specific biomarker

Contrary to its historical roots, localization related epilepsy (LRE) is now increasingly recognized as a network disorder (Bartolomei et al., 2001, Spencer, 2002, van Diessen et al., 2013). With this paradigm shift in our understanding comes the need to reconsider all aspects of how we evaluate and manage patients afflicted with this burdensome disease. Clinicians have historically been trained to identify the seizure "focus", sometimes at the expense of considering the more diffuse pathology implicated in many epileptogenic substrates.

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The Effect of Cadence on the Mechanics and Energetics of Constant Power Cycling

At a constant power output, cyclists prefer to use a higher cadence than those that minimise metabolic cost. The neuromuscular mechanism underpinning the preferred higher cadence remains unclear. Purpose The aim of this study was to investigate the effect of cadence on joint level work and vastus lateralis (VL) fascicle mechanics while cycling at a constant, submaximal, power output. We hypothesised that preferred cycling cadence would enhance the power capacity of the VL muscle when compared to a more economical cadence. Furthermore, we predicted that the most economical cadence would coincide with minimal total electromyographic activity from the leg muscles. Methods Metabolic cost, lower limb kinematics, joint level work, VL fascicle mechanics, and muscle activation of the VL, rectus femoris, biceps femoris, gastrocnemius medialis and soleus muscles were measured during cycling at a constant power output of 2.5 W/kg and cadences of 40, 60, 80 and 100 revolutions per minute (RPM). A preferred condition was also performed where cadence feedback was hidden from the participant. Results Metabolic cost was lowest at 60 RPM, but the mean preferred cadence was 81 RPM. The distribution of joint work remained constant across cadences, with the majority of positive work being performed at the knee. The preferred cadence coincided with the highest VL power capacity, without a significant penalty to efficiency, based on fascicle shortening velocity. Conclusions Cycling at a higher cadence is preferred to ensure that the muscle's ability to produce positive power remains high. Further investigations are required to examine what feedback mechanism could be responsible for the optimisation of this motor pattern. Corresponding author: Scott F. Brennan, Liverpool John Moores University, Sport and Exercise Sciences, Tom Reilly Building, Byrom Street, Liverpool, L3 3AF, United Kingdom, email: S.Brennan@ljmu.ac.uk. phone: (+44) 151 904 8094 SF Brennan was supported by an Australian Postgraduate Award scholarship during the completion of this project. This project did not receive any external funding but did receive internal funding for the purchase of equipment. Conflict of Interest: The authors have no conflicts of interest to declare with professionals, companies or manufacturers who may benefit from the results of the present study. The results of the present study do not constitute endorsement by ACSM. The results of the study are presented clearly, honestly, and without inappropriate data manipulation. Accepted for Publication: 28 November 2018. © 2018 American College of Sports Medicine

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Sex-Specific Longitudinal Modeling of Short-Term Power in 11-18 Year-Olds

Purpose To investigate, longitudinally, short-term power output in relation to sex and concurrent changes in age, body mass, fat free mass (FFM), and maturity status. Methods Multiplicative multilevel modeling which enables the effects of variables to be partitioned concurrently within an allometric framework was used to analyze the peak power (PP) and mean power (MP) of 388 11-18 year-olds. Multilevel models were founded on 763 (405 from boys; 358 from girls) determinations of PP and MP from Wingate anaerobic tests, supported by anthropometric measures and maturity status. Results In both sexes, PP and MP were significantly (p

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Cardiorespiratory and Muscle Oxygenation Responses to Isokinetic Test in COPD

Purpose To describe cardiorespiratory, quadriceps oxygenation, and muscle fatigue responses during a one-legged quadriceps isokinetic endurance exercise in COPD and control subjects. Methods Fourteen patients with COPD and 14 control subjects performed a cardiopulmonary cycling exercise test (CPET) to exhaustion to assess peak oxygen consumption (V˙O2peak), minute ventilation (V˙E2peak) and heart rate (HRpeak). They also performed a quadriceps isokinetic endurance exercise consisting in 30 maximal knee-extensions at 90°/s with continuous monitoring of expired gases, cardiac output (CO) and oxygenation of the quadriceps by near-infrared spectroscopy. Total muscle work and fatigue index were also quantified. Results The total muscle work developed during the quadriceps isokinetic endurance exercise was 2.25±0.57 kJ in COPD and 3.12±0.60 kJ in controls, p

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Impact of Acute Dietary Nitrate Supplementation during Exercise in Hypertensive Women

Introduction the aim of the current investigation was to examine if dietary nitrate supplementation would improve vascular control in hypertensive post-menopausal women (PMW). We tested the hypotheses that acute dietary nitrate supplementation would 1) significantly decrease arterial blood pressure (BP) at rest and during exercise; 2) increase limb blood flow during steady-state exercise; and 3) improve functional sympatholysis during steady-state (SS) exercise. Methods ten hypertensive PMW underwent a randomized, double-blind placebo-controlled trial with a nitrate-rich (NR) or nitrate poor (NP) supplement. Beat-by-beat BP and heart rate were recorded throughout the trial on the non-exercising limb. Forearm blood flow (FBF) was measured via ultrasonography on the brachial artery of the exercising limb. All patients performed a resting cold pressor test (CPT) (2 min) and then 7 min of submaximal hand-grip exercise with a CPT applied during min 5-7. Results SS systolic (NR: 170±7; NP: 171±37 mmHg), diastolic (NR: 89±2; NP: 92±2 mmHg) and mean arterial (NR: 121±4; NP: 123±2 mmHg) pressures were not different between NP and NR treatment conditions (p>0.05). During SS exercise, FBF (NR:189±8; NP: 218±8 ml min-1; P=0.03) in the NR treatment was significantly lower compared to NP. When the CPT was applied during min 6-7 of exercise forearm vascular conductance was reduced by 15% in the NR condition, but only 7% in the NR condition. Conclusion in summary, an acute NR supplement improved functional sympatholysis by ~50% versus a NP placebo condition. Improvements in functional sympatholysis may have important implications regarding exercise tolerance in hypertensive PMW. Address for correspondence: Carl J. Ade, Ph.D., Department of Kinesiology, Kansas State University, 1A Natatorium, Manhattan, KS, 66506, Tel: 785.532.6765. E-mail: cade@ksu.edu The authors disclose funding for the current study was provided by Kansas State University start-up funds for Dr. Carl Ade. The authors declare that the results of the investigation are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation and the results of the present investigation do not constitute endorsement by ACSM. Accepted for Publication: 21 November 2018. © 2018 American College of Sports Medicine

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Effective Weight Loss and Maintenance by Intensive Start with Diet and Exercise

Introduction This 24-month study aimed to determine if exercise intervention added to weight loss treatment at 6 months is effective for weight loss and maintenance. Methods A total of 120 obese subjects (BMI > 30) were randomly assigned to behavioural modification (iBM) (n = 30), behavioural modification + exercise from 0 to 3 months (CWT1) (n = 30), behavioural modification + exercise from 6 to 9 months (CWT2) (n = 30), and a control group (CON) (n = 30). Health behavior, weight, waist circumference, and 2-hour glucose tolerance test with insulin measurements were measured at 0, 3, 9, and 24 months. Results Eighty-five subjects (mean age 46 years, BMI 36.3, 75.3% women) completed the trial. A significant weight loss occurred in CWT1 (−8.5 kg, p > 0.001), iBM (−5.5 kg, p > 0.001), and CWT2 (−4.4 kg, p = 0.007). CWT1 showed the highest reduction in waist circumference at 9 months (mean difference −11.5 cm, p

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Acute Exercise Effects among Young Adults with Analog Generalized Anxiety Disorder

Recent findings support positive effects of acute aerobic exercise on worry, state anxiety, and feelings of energy and fatigue among young adult women with subclinical, or analogue, Generalized Anxiety Disorder (GAD). However, exercise effects among young adult men with analogue GAD are unstudied. Purpose This study replicated initial findings of positive effects of acute vigorous-intensity aerobic exercise on worry, state anxiety, and feelings of energy and fatigue among young adult women with analogue GAD, examined responses among young adult men with analogue GAD, and explored sex-related differences and moderation by physical activity level, trait anxiety, depression, and poor sleep status. Methods Thirty-five young adults (21.4±2.3y; 19M; 16F) with Penn State Worry Questionnaire scores ≥45 (60±8) completed two counterbalanced 30-min conditions: treadmill running at ~71.2%±0.04% heart rate reserve and seated quiet rest. Outcomes included worry, worry engagement, absence of worry, state anxiety, and feelings of energy and fatigue. Results No outcome or moderator differed at baseline between sexes. Exercise significantly improved state anxiety (p

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Validation of a Mobile Application Water Planning Tool for Road Race Event Organizers

Water planning is an important risk management concern for road race event organizers. PURPOSE To compare water and cup prediction outputs from a mobile application (app) planning tool against: 1) measured group sweat losses, 2) documented event water and cup usage, and 3) traditional mathematical planning solutions. METHODS Group mean sweating rates (L/h) from 12 published outdoor running studies were each compared to 12 composite averages using the Road Race Water Planner© app (RRWP). Estimated water (gallons) and cup (#) needs were also compared to documented usage at a large marathon event and to traditional mathematical solutions. RESULTS Thirteen group mean sweating rates from 286 runners were compared to composite RRWP estimates. Predicted sweating rate accuracy was 92% for RRWP and ranged from 0 to 69% for traditional mathematical solutions. The 2017 Boston marathon included 27,222 runners on a day averaging 21.5°C. Water and cup usage was 31,740 gallons and 1,036,003 cups, respectively. RRWP estimates were 33,505 gallons and 1,072,160 cups, respectively. The difference in gallons expressed as liters was 0.236 L per person. For a ~4 h marathon, the difference per person as a rate was

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