Tempol augments the blunted cutaneous microvascular thermal reactivity in healthy young African Americans

Abstract

African Americans (AA) have elevated risk for cardiovascular disease relative to other populations. We hypothesized that cutaneous hyperemic response to local heating is reduced in young AA relative to CA and this is due to elevated oxidative stress. As such, ascorbic acid (a global antioxidant) and tempol (a superoxide dismutase mimetic) would improve this response in AA. Microdialysis fibers received (1) lactated Ringer's (Control), (2) 10 mm Ascorbic Acid, or (3) 10 μm 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) at a rate of 2.0 μl min⁻¹. Cutaneous vascular conductance (CVC) was calculated as red blood cell flux/mean arterial pressure. Data were presented as a percentage of maximal CVC (%CVCmax) induced by 44°C heating plus sodium nitroprusside. Twenty-four (12 AA, 12 CA) young (23 ± 4 yrs) subjects participated. During 39°C heating %CVCmax was lower in AA at Control (CA: 65 ± 20 % vs. AA: 47 ± 15 %; P < 0.05) and Ascorbic Acid (CA: 73 ± 14 % vs. AA: 49 ± 17 %; P < 0.01). At Tempol site, there were no differences between groups. This was followed by infusion of 10 mm Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) at all sites to assess nitric oxide (NO) contribution to vasodilation during local heating. The NO contribution was lower in AA relative to CA at 39°C; however, this was restored with Tempol. These data suggest that: (1) cutaneous vasodilation to local heating is blunted in AA relative to CA. (2) elevated O₂⁻ generation attenuates NO-mediated cutaneous vasodilation in AA.

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High fat diet blunts the effects of leptin on ventilation and on carotid body activity

Abstract

Leptin plays a role in the control of breathing, acting mainly on central nervous structures. Leptin receptor is expressed in the carotid body (CB) and this finding has been associated with a putative physiological role of leptin in the regulation of CB function. Since, the CBs are implicated in energy metabolism herein we tested the effects of different concentrations of leptin administration on ventilatory parameters and on carotid sinus nerve (CSN) activity in control and high-fat (HF) diet fed rats, in order to clarify the role of leptin in ventilation control in metabolic disease states. We also investigated the expression of leptin receptors and the neurotransmitters involved in leptin signalling in the CBs. We found that in non-disease conditions, leptin increases minute ventilation both in basal and hypoxic conditions. However, in the HF model, the effect of leptin in ventilatory control is blunted. We also observed that HF rats display an increased frequency of CSN discharge in basal conditions that is not altered by leptin, in contrast to what is observed in control animals. Leptin did not modify intracellular Ca²⁺ in CB chemoreceptor cells, but it produced an increase in the release of adenosine from the whole CB. We conclude that CBs represent an important target for leptin signalling, not only to coordinate peripheral ventilatory chemoreflexive drive, but probably also to modulate metabolic variables. We also concluded that leptin signalling is mediated by adenosine release and that HF diets blunt leptin responses in the CB, compromising ventilatory adaptation.

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Candida tropicalis Isolates from Mexican Republic Exhibit High Susceptibility to Bleomycin and Variable Susceptibility to Hydrogen Peroxide

Microbial Drug Resistance , Vol. 0, No. 0.


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Characterization of Isolates Associated with Emergence of OXA-48-Producing Klebsiella pneumoniae in Croatia

Microbial Drug Resistance , Vol. 0, No. 0.


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Hospital Outbreak of a Colistin-Resistant, NDM-1- and OXA-48-Producing Klebsiella pneumoniae: High Mortality from Pandrug Resistance

Microbial Drug Resistance , Vol. 0, No. 0.


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Preoperative Evaluation is not Predictive of Transpyloric Feeding Conversion in Gastrostomy Dependent Pediatric Patients

ABSTRACTObjectives:Limited literature exists as to whether preoperative gastrostomy (GT)evaluation may predict which patients will go onto require gastrojejunostomy tube (GJ) feeding. The goal of this study was to compare the preoperative evaluations between patients maintained on GT feeds versus patients who required conversion to GJ feeds.Methods:We identified patients at Boston Children's Hospital who underwent GT placement and required GJ feeding between 2006–2012. GT patients were matched according to age, neurologic, and cardiac status with GJ converted patients. Preoperative characteristics, rates of total hospitalizations, and respiratory related admissions were reviewed.Results:79 GJ patients (median (IQR): age 15 (4.3, 55.7) months; weight 8.8 (4.6, 14.5) kg) were matched with 79 GT patients (median (IQR): age 14.6 (4.7, 55.7) months; weight 8.5 (5, 13.6) kg). Median time from GT to GJ conversion was 8 (IQR 3, 16) months. Both groups had similar rates of successful preoperative nasogastric feeding trials (GT (84.5%) vs GJ (83.1%), p = 1.0), upper GI series (GT (89.1%) vs GJ (93.2%), p = 0.73), abnormal videofluoroscopic swallow studies (GT (53.8%) vs GJ (62.2%), p = 0.4), and completion of gastric emptying studies (GT (10.1%) vs GJ (5.1%), p = 0.22). No differences were seen in preoperative hospitalization rates (p = 0.25), respiratory admissions (p = 0.36), although GJ patients had a mean reduction in the number of hospitalization of −1.5 ± 0.5 days, p 

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Endotracheal Tube Connector: Holding Breaths!

No abstract available

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Mu-Opioid Receptors in Ganglia, But Not in Muscle, Mediate Peripheral Analgesia in Rat Muscle Pain

BACKGROUND: Previous studies have demonstrated the participation of peripheral μ-opioid receptors (MOR) in the antinociceptive effect of systemically administered morphine and loperamide in an orofacial muscle pain model, induced by hypertonic saline, but not in a spinally innervated one, in rats. In this study, we determine whether this peripheral antinociceptive effect is due to the activation of MOR localized in the muscle, ganglia, or both. METHODS: To determine the local antinociceptive effect of morphine and loperamide, 2 models of acute muscle pain (trigeminal and spinal) were used. Also, to study the MOR expression, protein quantification was performed in the trigeminal and spinal ganglia, and in the muscles. RESULTS: The behavioral results show that the intramuscular injection of morphine and loperamide did not exert an antinociceptive effect in either muscle (morphine: P = .63, loperamide: P = .9). On the other hand, MOR expression was found in the ganglia but not in the muscles. This expression was on average 44% higher (95% CI, 33.3–53.9) in the trigeminal ganglia than in the spinal one. CONCLUSIONS: The peripheral antinociceptive effect of systemically administered opioids may be due to the activation of MOR in ganglia. The greater expression of MOR in trigeminal ganglia could explain the higher antinociceptive effect of opioids in orofacial muscle pain than in spinal muscle pain. Therefore, peripheral opioids could represent a promising approach for the treatment of orofacial pain. Accepted for publication October 23, 2017. Funding: This study was supported by the Ministry of Science and Innovation of Spain (SAF2012-40075-C02-01) and General Directorate for Scientific Research of Community of Madrid (S-2011/BMD-2308). The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Eva María Sánchez-Robles, PhD, Facultad Ciencias de la Salud, Área de Farmacología y Nutrición, Universidad Rey Juan Carlos, Avda Atenas, s/n. 28922 Alcorcón, Madrid, Spain. Address e-mail to eva.sanchez@urjc.es. © 2017 International Anesthesia Research Society

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The Effect of High-Frequency, Structured Expert Feedback on the Learning Curves of Basic Interventional Ultrasound Skills Applied to Regional Anesthesia

BACKGROUND: Proficiency in needle-to-ultrasound beam alignment and accurate approach to structures are pivotal for ultrasound-guided regional anesthesia. This study evaluated the effects of high-frequency, structured expert feedback on simulation training of such abilities. METHODS: Forty-two subjects randomly allocated as controls or intervention participated in two 25-trial experiments. Experiment 1 consisted of inserting a needle into a bovine muscular phantom parallel to the ultrasound beam while maintaining full imaging of the needle. In experiment 2, the needle aimed to contact a target inside the phantom. Intervention subjects received structured feedback between trials. Controls received a global critique after completing the trials. The slopes of the learning curves derived from the sequences of successes and failures were compared. Change-point analyses identified the start and the end of learning in trial sequences. The number of trials associated with learning, the number of technical errors, and the duration of training sessions were compared between intervention and controls. RESULTS: In experiment 1, learning curves departed from 73% (controls) and 76% (intervention) success rates; slopes (standard error) were 0.79% (0.02%) and 0.71% (0.04), respectively, with mean absolute difference of 0.18% (95% confidence interval [CI], 0.17%–0.19%; P = 0). Intervention subjects' learning curves were shorter and steeper than those of controls. In experiment 2, the learning curves departed from 43% (controls) and 80% (intervention) success rates; slopes (standard error) were 1.06% (0.02%) and 0.42% (0.03%), respectively, with a mean difference of 0.65% (95% CI, 0.64%–0.66%; P = 0). Feedback was associated with a greater number of trials associated with learning in both experiment 1 (mean difference, 1.55 trials; 95% CI, 0.15–3 trials; P = 0) and experiment 2 (mean difference, 4.25 trials; 95% CI, 1.47–7.03 trials; P = 0) and a lower number of technical errors per trial in experiments 1 (mean difference, 0.19; 95% CI, 0.07–0.30; P = .02) and 2 (mean difference, 0.58; 95% CI, 0.45–0.70; P = 0), but longer training sessions in both experiments 1 (mean difference, 9.2 minutes; 95% CI, 4.15–14.24 minutes; P = .01) and 2 (mean difference, 7.4 minutes; 95% CI, 1.17–13.59 minutes; P = .02). CONCLUSIONS: High-frequency, structured expert feedback compared favorably to self-directed learning, being associated with shorter learning curves, smaller number of technical errors, and longer duration of in-training improvement, but increased duration of the training sessions. Accepted for publication November 10, 2017. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Getúlio Rodrigues de Oliveira Filho, MD, PhD, Department of Surgery, Federal University of Santa Catarina, Rua Luiz Delfino 111/902, Florianópolis, Santa Catarina 88015, Brazil. Address e-mail to getulio.filho@ufsc.br. © 2017 International Anesthesia Research Society

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Why a Proactive Perioperative Medicine Policy Is Crucial for a Sustainable Population Health Strategy

No abstract available

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Intravenous Iron for Treatment of Anemia in the 3 Perisurgical Phases: A Review and Analysis of the Current Literature

Anemia is a common comorbidity throughout the entire hospital stay. Treatment options include intravenous (IV) iron, oral iron, erythropoietin, and red blood cell (RBC) transfusions. IV iron has gained in popularity with the implementation of patient blood management programs. A variety of studies have been performed to investigate the use of IV iron in preoperative, perioperative, and postoperative settings. An objective review on these studies has yet to be performed. The current narrative review provides an overview of trials investigating IV iron use in the preoperative, perioperative, and postoperative settings. We performed a literature research of English articles published between 1964 and March 2017 in Pubmed including Medline and The Cochrane Library. Only studies with a control group were included. The final review includes 20 randomized controlled trials (RCTs), 7 observational trials, and 5 retrospective studies. Measured outcomes included hemoglobin (Hb) levels, reticulocyte counts, and/or RBC concentrates. Meta-analyses of RCTs using IV iron administration before surgery led to an increase in Hb levels, a reduction of RBC use, and an improvement in patient outcome. Only a few studies investigated the use of IV iron in the perioperative setting. These studies recommended the use of perioperative IV iron in cases of severe anemia in orthopedic surgery but not in all types of surgery. Published RCTs in the postoperative setting have shown positive effects of IV iron on Hb levels, length of hospital stay, and transfusion requirements. Some studies demonstrated an increase of Hb of 0.5–1 g/dL over 4 weeks postoperatively, but the clinical relevance and effect of this increase on an improvement of patient's long-term outcomes are uncertain. To summarize, the evidence to use IV iron is strongest in the preoperative setting, while it remains an individual treatment decision to administer IV iron perioperatively or postoperatively. Accepted for publication September 15, 2017. Funding: A.U.S. is supported by a DFG grant (STE-1895-4/1). The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Andrea U. Steinbicker, MD, MPH, Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Albert-Schweitzer Campus 1, Bldg A1, 48149 Muenster, Germany. Address e-mail to andrea.steinbicker@ukmuenster.de. © 2017 International Anesthesia Research Society

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Prospective Observational Study of Intraoperative Anesthetic Events in District Hospitals in Namibia

BACKGROUND: Access to safe surgery and anesthesia care is grossly inadequate in low- and middle-income countries, with a shortage of anesthesia providers contributing to this crisis. In Namibia, medical officers typically receive no >3 months of informal training in anesthesia. This study sought to determine the prevalence, currently unknown, of intraoperative adverse anesthetic events in this setting. Further, we assessed surgical volume, complications, and mortality outcomes at the district hospital level. METHODS: This was a prospective observational study over 7 months involving 4 district hospitals from geographically separate and diverse areas of Namibia. A standardized protocol was used to record adverse anesthetic events during surgery, surgical volume, and complications including mortality. RESULTS: A total of 737 surgical procedures were performed during the study period. There was a 10% prevalence of adverse anesthetic events intraoperatively. Of these, 70% were related to hypotension and 17% due to hypoxia and/or difficult/failed intubation. Ninety-eight percent of patients were classed as low risk (American Society of Anesthesiologists I or II). Seventy-two percent of the surgical workload was in obstetrics and gynecology, with over half being for urgent obstetrics. Perioperative mortality rate was 1.4/1000, with an overall surgical complication rate of 1.6% and a surgical infection rate of 0.8%. CONCLUSIONS: We found a 10% prevalence of adverse anesthetic events intraoperatively when anesthesia was administered by medical officers with no >3 months of informal training in this low-resource environment. The patients were considered low risk by the medical officers responsible for the anesthesia, yet these events had the potential to lead to patient harm. Accepted for publication October 23, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Andrew J. Ottaway, BMBS, MPH, FANZCA, Hobart Anaesthetic Group, 303 Macquarie St, Hobart, Tasmania 7000, Australia. Address e-mail to aottaway@internode.on.net. © 2017 International Anesthesia Research Society

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Continuous Noninvasive Arterial Pressure Monitoring Using the Vascular Unloading Technique (CNAP System) in Obese Patients During Laparoscopic Bariatric Operations

BACKGROUND: Increasing rates of obesity create new challenges for hemodynamic monitoring in the perioperative phase. Continuous monitoring of arterial pressure (AP) is important in severely obese patients who are at particular risk for cardiovascular complications. Innovative technologies for continuous noninvasive AP monitoring are now available. In this study, we aimed to compare continuous noninvasive AP measurements using the vascular unloading technique (CNAP system; CNSystems, Graz, Austria) compared with invasive AP measurements (radial arterial catheter) in severely obese patients during laparoscopic bariatric surgery. METHODS: In 29 severely obese patients (mean body mass index 48.1 kg/m2), we simultaneously recorded noninvasive and invasive AP measurements over a period of 45 minutes and averaged the measurements using 10-second episodes. We compared noninvasive (test method) and invasive (reference method) AP measurements using Bland-Altman analysis and 4-quadrant plot/concordance analysis (2-minute interval). RESULTS: We observed a mean of the differences (±SD, 95% limits of agreement) between the AP values obtained by the CNAP system and the invasively assessed AP values of 7.9 mm Hg (±9.6 mm Hg, −11.2 to 27.0 mm Hg) for mean AP, 4.8 mm Hg (±15.8 mm Hg, −26.5 to 36.0 mm Hg) for systolic AP, and 9.5 mm Hg (±10.3 mm Hg, −10.9 to 29.9 mm Hg) for diastolic AP, respectively. The concordance rate was 97.5% for mean AP, 95.0% for systolic AP, and 96.7% for diastolic AP, respectively. CONCLUSIONS: In the setting of laparoscopic bariatric surgery, continuous noninvasive AP monitoring with the CNAP system showed good trending capabilities compared with continuous invasive AP measurements obtained with a radial arterial catheter. However, absolute CNAP- and arterial catheter–derived AP values were not interchangeable. Accepted for publication September 27, 2017. Funding: CNSystems Medizintechnik AG (Graz, Austria) provided the technical equipment for the study. CNSystems Medizintechnik AG was not involved in the collection of the data, drafting of the manuscript, or decision to submit the manuscript for publication. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Dorothea E. Rogge, MD, Department of Anesthesiology, Centre of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Address e-mail to d.rogge@uke.de. © 2017 International Anesthesia Research Society

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Misaligned Feeding May Aggravate Pain by Disruption of Sleep–Awake Rhythm

BACKGROUND: Increasing evidence suggests that patients with eating disorders are more likely to develop chronic pain. A misaligned diet has been reported to disrupt the sleep–awake rhythms. Combined with our previous investigation on circadian pain, we aimed to investigate the role of misaligned diet in the pain sensitivity and the underlying mechanisms. METHODS: Two-month-old C57BL/6J male mice were administered chronic constriction injury (CCI) surgery to establish neuropathic pain models. CCI mice were randomized to scheduled food access throughout the whole day (CCI-free), during the daytime (CCI-misaligned), and at night (CCI-aligned), respectively. The paw withdrawal mechanical threshold, indicating pain behavior, was measured by Von Frey. The gross motor activity pattern indicating the sleep–awake rhythm was monitored by Mini-Mitter. Melatonin (Mel) was administered to ameliorate the sleep–awake rhythm (CCI-free + Mel and CCI-misaligned + Mel). The expressions of circadian pain–related proteins were detected by quantitative polymerase chain reaction and western blot. The primary outcome is the pain threshold and the secondary outcome is the sleep–awake rhythm. RESULTS: Misaligned diet during the peri-CCI surgery period significantly decreased the paw withdrawal mechanical threshold compared with the CCI-free mice (day 14: 0.40 ± 0.09 vs 0.64 ± 0.15; P = .03;) and altered the sleep–awake rhythm. Mel pretreatment alleviated the increased pain (day 14, CCI-misaligned + Mel versus CCI-misaligned: day 14: 0.60 ± 0.13 vs 0.35 ± 0.12; P = .022) and the disrupted sleep–awake rhythm caused by misaligned feeding. The mRNA levels of N-methyl-D-aspartate receptor subtype 2B (NR2B), Ca2+/calmodulin-dependent protein kinase II (CaMKII), and cyclic adenosine monophosphate-response element binding protein (CREB) in the spinal dorsal horn increased in CCI-misaligned mice compared with the CCI-free mice. The phosphor-NR2B, phosphor-CaMKII, and phosphor-CREB also increased in CCI-misaligned mice compared with the CCI-free mice. However, the expressions of NR2B, CaMKII, and CREB were decreased in CCI-misaligned + Mel mice compared to CCI-misaligned mice at both transcriptional and translational levels. CONCLUSIONS: Misaligned diet might aggravate pain sensitivity through the disruption of the sleep–awake cycle, which could be recovered by Mel. NR2B-CaMKII-CREB may participate in the disruption of sleep–awake rhythm–mediated pain aggravation. Accepted for publication November 2, 2017. Funding: This study was supported by National Natural Science Foundation of China (81371207, 81171047, 81070892, and 81171048), Natural Science Foundation of Jiangsu Province (BK2010105), and the Grant from the Department of Health of Jiangsu Province of China (XK201140, RC2011006). The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). The first authors Xu and Zhao contributed equally to this study. The authors Ma and Gu contributed equally to this study. Reprints will not be available from the authors. Address correspondence to Xiaoping Gu, PhD, MD, and Zhengliang Ma, PhD, MD, Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, 321 Zhong Shan Rd, Nanjing, Jiangsu 210008, People's Republic of China. Address e-mail to xiaopinggu@nju.edu.cn and mazhengliang1964@nju.edu.cn. © 2017 International Anesthesia Research Society

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Extracorporeal Membrane Oxygenation Appropriateness: An Interdisciplinary Consensus-Based Approach

We describe a quality improvement initiative aimed at achieving interdisciplinary consensus about the appropriate delivery of extracorporeal membrane oxygenation (ECMO). Interdisciplinary rounds were implemented for all patients on ECMO and addressed whether care was consistent with a patient's minimally acceptable outcome, maximally acceptable burden, and relative likelihood of achieving either. The rounding process was associated with decreased days on venoarterial ECMO, from a median of 6 days in 2014 (first quartile [Q1]–third quartile [Q3], 3–10) to 5 days in 2015 (Q1–Q3, 2.5–8) and in 2016 (Q1–Q3, 1–8). Our statistical methods do not allow us to conclude that this change was due to our intervention, and it is possible that the observed decreases would have occurred whether or not the rounding process was implemented. Accepted for publication October 26, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Michael Nurok, MBChB, PhD, Division of Cardiac Surgery, Department of Surgery and Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, 127 San Vicente Blvd, Suite 3100, Los Angeles, CA 90048. Address e-mail to michael.nurok@cshs.org. © 2017 International Anesthesia Research Society

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Benefits of Resistance Training with Blood Flow Restriction in Knee Osteoarthritis

ABSTRACTPurposeEvaluate the effects of a low-intensity resistance training program associated with partial blood flow restriction on selected clinical outcomes in patients with knee osteoarthritis (OA).MethodsForty-eight women with knee OA were randomized into one of the three groups: low-intensity resistance training (30% one repetition maximum 1-RM) associated (BFRT) or not (LI-RT) with partial blood flow restriction, and high-intensity resistance training (HI-RT: 80% 1-RM). Patients underwent a 12-week supervised training program and were assessed for lower-limb 1-RM, quadriceps cross-sectional area (CSA), functionality (timed-stands test - TST and timed-up-and-go test - TUG), and disease-specific inventory (Western Ontario and McMaster Universities Osteoarthritis Index - WOMAC) before (PRE) and after the protocol (POST).ResultsSimilar within-group increases were observed in leg-press (26% and 33%, all p

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Predictive Modeling of Hamstring Strain Injuries in Elite Australian Footballers

AbstractPurposeThree of the most commonly identified hamstring strain injury (HSI) risk factors are age, previous HSI and low levels of eccentric hamstring strength. However, no study has investigated the ability of these risk factors to predict the incidence of HSI in elite Australian footballers. Accordingly, the purpose of this prospective cohort study was to investigate the predictive ability of HSI risk factors using machine learning techniques.MethodsEccentric hamstring strength, demographic and injury history data were collected at the start of pre-season for 186 and 176 elite Australian footballers in 2013 and 2015 respectively. Any prospectively occurring HSIs were reported to the research team. Using various machine learning techniques, predictive models were built for 2013 and 2015 within-year HSI prediction and between-year HSI prediction (2013 to 2015). The calculated probabilities of HSI were compared to the injury outcomes and area under the curve (AUC) was determined and used to assess the predictive performance of each model.ResultsThe minimum, maximum and median AUC values for the 2013 models were 0.26, 0.91 and 0.58 respectively. For the 2015 models, the minimum, maximum and median AUC values were, correspondingly, 0.24, 0.92 and 0.57. For the between-year predictive models the minimum, maximum and median AUC values were 0.37, 0.73 and 0.52 respectively.ConclusionWhile some iterations of the models achieved near perfect prediction, the large ranges in AUC highlight the fragility of the data. The 2013 models performed slightly better than the 2015 models. The predictive performance of between-year HSI models was poor however. In conclusion, risk factor data cannot be used to identify athletes at an increased risk of HSI with any consistency. Purpose Three of the most commonly identified hamstring strain injury (HSI) risk factors are age, previous HSI and low levels of eccentric hamstring strength. However, no study has investigated the ability of these risk factors to predict the incidence of HSI in elite Australian footballers. Accordingly, the purpose of this prospective cohort study was to investigate the predictive ability of HSI risk factors using machine learning techniques. Methods Eccentric hamstring strength, demographic and injury history data were collected at the start of pre-season for 186 and 176 elite Australian footballers in 2013 and 2015 respectively. Any prospectively occurring HSIs were reported to the research team. Using various machine learning techniques, predictive models were built for 2013 and 2015 within-year HSI prediction and between-year HSI prediction (2013 to 2015). The calculated probabilities of HSI were compared to the injury outcomes and area under the curve (AUC) was determined and used to assess the predictive performance of each model. Results The minimum, maximum and median AUC values for the 2013 models were 0.26, 0.91 and 0.58 respectively. For the 2015 models, the minimum, maximum and median AUC values were, correspondingly, 0.24, 0.92 and 0.57. For the between-year predictive models the minimum, maximum and median AUC values were 0.37, 0.73 and 0.52 respectively. Conclusion While some iterations of the models achieved near perfect prediction, the large ranges in AUC highlight the fragility of the data. The 2013 models performed slightly better than the 2015 models. The predictive performance of between-year HSI models was poor however. In conclusion, risk factor data cannot be used to identify athletes at an increased risk of HSI with any consistency. Corresponding author: Joshua D. Ruddy, joshua.ruddy@myacu.edu.au, 17 Young Street, Fitzroy, VIC, Australia, 3065 The authors declare that the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of this study do not constitute endorsement by ACSM. AS and DO are listed as co-inventors on a patent filed for a field testing device of eccentric hamstring strength (PCT/AU2012/001041.2012) as well as being minority shareholders in Vald Performance Pty Ltd, the company responsible for comercializng the device. The remaining authors declare no competing interests. No funding was received. Accepted for Publication: 14 December 2017 © 2017 American College of Sports Medicine

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Effect of Carbohydrate Mouth Rinse on Performance after Prolonged Submaximal Cycling

ABSTRACTPrevious studies have shown improved shorter-duration (~1 h) performance with carbohydrate (CHO) mouth-rinsing (WASH), especially in overnight fasted/non-fuelled subjects.Purposeto determine the effect of WASH on cycling time-trial (TT) performance and muscle activity (EMG) after 2 h of sub-maximal cycling while receiving CHO.MethodsIn a double-blind, placebo-controlled crossover design, 10 well-trained males cyclists (VO2max: 65 mL·kg-1·min-1) completed two experimental trials. Each trial consisted of a standardized pre-trial snack (2-h prior) followed by 120 min of steady-state (SS) cycling (~60% VO2max) followed by a ~30 min TT, randomized as follows: 1) FEDWASH: 30g CHO·h-1 during SS + WASH during TT (every 20% of TT); 2) FEDPLA: 30g CHO·h-1 during SS + placebo-wash during TT.ResultsWhile FEDWASH was not significantly different than FEDPLA (P = 0.51), there was a 1.7% (+6.4 to -3.2% 90% CI; ES = 0.21) decrease in TT time (35s) for FEDWASH compared to FEDPLA, with qualitative probabilities of a 60% positive and 23% trivial outcome. For EMG, Soleus showed significant increase while medial gastrocnemius showed significant decrease in muscle recruitment from the beginning 20% TT segment to the last 20% only in the FEDPLA condition, which coincided with a slower (P = 0.01) last 20% of the TT in FEDPLA vs. FEDWASH.ConclusionsContrary to previous studies, this investigation utilized conditions of high ecological validity including a pre-trial snack and CHO during SS. Significant changes in muscle recruitment and time over the last 20% of the TT, along with an average 1.7% improvement in TT time, suggest CHO mouth rinse helps maintain power output late in TT's compared to placebo. Although marginal gains were achieved with a CHO mouth rinse (35 s), small performance effects can have significant outcomes in real-world competitions. Previous studies have shown improved shorter-duration (~1 h) performance with carbohydrate (CHO) mouth-rinsing (WASH), especially in overnight fasted/non-fuelled subjects. Purpose to determine the effect of WASH on cycling time-trial (TT) performance and muscle activity (EMG) after 2 h of sub-maximal cycling while receiving CHO. Methods In a double-blind, placebo-controlled crossover design, 10 well-trained males cyclists (VO2max: 65 mL·kg-1·min-1) completed two experimental trials. Each trial consisted of a standardized pre-trial snack (2-h prior) followed by 120 min of steady-state (SS) cycling (~60% VO2max) followed by a ~30 min TT, randomized as follows: 1) FEDWASH: 30g CHO·h-1 during SS + WASH during TT (every 20% of TT); 2) FEDPLA: 30g CHO·h-1 during SS + placebo-wash during TT. Results While FEDWASH was not significantly different than FEDPLA (P = 0.51), there was a 1.7% (+6.4 to -3.2% 90% CI; ES = 0.21) decrease in TT time (35s) for FEDWASH compared to FEDPLA, with qualitative probabilities of a 60% positive and 23% trivial outcome. For EMG, Soleus showed significant increase while medial gastrocnemius showed significant decrease in muscle recruitment from the beginning 20% TT segment to the last 20% only in the FEDPLA condition, which coincided with a slower (P = 0.01) last 20% of the TT in FEDPLA vs. FEDWASH. Conclusions Contrary to previous studies, this investigation utilized conditions of high ecological validity including a pre-trial snack and CHO during SS. Significant changes in muscle recruitment and time over the last 20% of the TT, along with an average 1.7% improvement in TT time, suggest CHO mouth rinse helps maintain power output late in TT's compared to placebo. Although marginal gains were achieved with a CHO mouth rinse (35 s), small performance effects can have significant outcomes in real-world competitions. Correspondence: Matt Jensen, University of Victoria, Room 120, McKinnon Building, 3800 Finnerty Road, Victoria, BC V8P 5C2, Canada, Email: mpjensen@uvic.ca All authors approved the final version of the paper. This study was financially supported by MITACS accelerate fellowship and the Canadian Sport Institute - Pacific. The authors wish to thank all the participants for volunteering for the study. The authors have no conflict of interest and made every attempt to present the results of the study clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The authors also acknowledge that results of the present study do not constitute endorsement by ACSM. Accepted for Publication: 15 December 2017 © 2017 American College of Sports Medicine

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Physiatry Reviews for Evidence in Practice (PREP) Second-Order Peer Reviews of Clinically Relevant Articles for the Physiatrist: Effect of Inpatient Rehabilitation vs a Monitored Home-Based Program on Mobility in Patients With Total Knee Arthroplasty The HIHO Randomized Clinical Trial.

No abstract available

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Limbic and Basal Ganglia Neuroanatomical Correlates of Gait and Executive Function: Older Adults with Mild Cognitive Impairment and Intact Cognition

ABSTRACTOBJECTIVEThis study aimed to examine differences in spatiotemporal gait parameters between older adults with amnestic mild cognitive impairment (aMCI) and normal cognition (NC), and to examine limbic and basal ganglia neural correlates of gait and executive function in older adults without dementia.DESIGNThis was a cross sectional study of 46 community dwelling older adults, ages 70–95 with aMCI (n=23) and NC (n=23). Structural magnetic resonance imaging (MRI) was used to attain volumetric measures of limbic and basal ganglia structures. Quantitative motion analysis was used to measure spatiotemporal parameters of gait. The Trail Making Test was used to assess executive function.RESULTSDuring fast paced walking, older adults with aMCI demonstrated significantly slower gait speed and shorter stride length compare to older adults with NC. Stride length was positively correlated with hippocampal, anterior cingulate, and nucleus accumbens volumes (P

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Intraarticular Triamcinolone versus Hyaluronate Injections for Low Back Pain with Symptoms Suggestive of Lumbar Zygapophyseal Joint Arthropathy: A Pragmatic, Double Blind Randomized Controlled Trial

AbstractObjectiveTo compare hyaluronate to triamcinolone injections in treating chronic low back pain (CLBP) suggestive of lumbar zygopophyseal joint (ZJT) arthropathy.DesignProspective, double-blind, randomized controlled trial. 30 subjects were randomly assigned to receive bilateral L3-S1 ZJT injections with triamcinolone (KA) or Synvisc-One® (HA). Pain [Visual Analog Scale (VAS)] and Pain Disability Questionnaire (PDQ) scores at 1, 3, and 6-months were evaluated.ResultsNo significant inter-group differences (p>.05) in outcomes were noted in the 30 recruited subjects. (KA/HA, baseline; 1-month; 3-month; 6-month)-VAS scores: 70±15/74±10; 58±29/45±25; 58±29/56±25; 59±28/63±24. PDQ scores: 100±23/102±28; 77±30/74±34; 87±26/74±36; 96±25/79±25. Overall percent improvement@6months: KA(51±35) and HA(42±33) [p=.51]. HA group VAS scores improved significantly (70±20 to 45±25@1m, p=.008). PDQ scores improved at 1m (100±23 to 77±30, p=.009) in the KA group and at all time points in the HA group (102±28 to 74±34@1m, p=.002; 74±36@3m, p=.037; 79@6m [Median; 52-99.5, p<.001 medians and quartiles were used in statistical analysis when data did not pass normality.conclusionspatients with clbp suggestive of lumbar zjt arthropathy responded similarly to triamcinolone or hyaluronate injections. ha group showed significant short- long-term functional improvement short-term pain ka only benefit no improvement. objective compare injections treating chronic low back zygopophyseal joint arthropathy. design prospective double-blind randomized controlled trial. subjects randomly assigned receive bilateral l3-s1 synvisc-one analog scale disability questionnaire scores at evaluated. results inter-group differences>.05) in outcomes were noted in the 30 recruited subjects. (KA/HA, baseline; 1-month; 3-month; 6-month)-VAS scores: 70±15/74±10; 58±29/45±25; 58±29/56±25; 59±28/63±24. PDQ scores: 100±23/102±28; 77±30/74±34; 87±26/74±36; 96±25/79±25. Overall percent improvement@6months: KA(51±35) and HA(42±33) [p=.51]. HA group VAS scores improved significantly (70±20 to 45±25@1m, p=.008). PDQ scores improved at 1m (100±23 to 77±30, p=.009) in the KA group and at all time points in the HA group (102±28 to 74±34@1m, p=.002; 74±36@3m, p=.037; 79@6m [Median; 52-99.5, p<.001 medians and quartiles were used in statistical analysis when data did not pass normality. conclusions patients with clbp suggestive of lumbar zjt arthropathy responded similarly to triamcinolone or hyaluronate injections. ha group showed significant short- long-term functional improvement short-term pain ka only benefit no improvement. affiliation where the research was conducted correspondence: thiru m. annaswamy md ma s. lancaster road dallas tx-75216. email: thiru.annaswamy author disclosures: this funded by any grant foundation agency. paper is report a clinical trial. however trial time period at which point there requirements for all trials be registered. therefore rct does have registration registry. abstract previously presented at: tm armstead c avraham r carlson l bierner sm. scientific presentations: intraarticular vs. injections zygapophyseal joint arthropathy: pragmatic double blind randomized controlled presentation. annual assembly aapmr. boston ma. september pm page s91. doi: http: versus abstracts papers posters meeting association academic physiatrists san antonio tx. american journal physical medicine rehabilitation supplement a6-a7. march copyright wolters kluwer health inc. rights reserved.>

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“I Just Want to Do Everything Right:” Primiparous Women's Accounts of Early Breastfeeding via an App-Based Diary

Our objective was to describe the early breastfeeding experience of primiparous women.

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90Sr specific activity of teeth of abandoned cattle after the Fukushima accident – teeth as an indicator of environmental pollution

Publication date: March 2018
Source:Journal of Environmental Radioactivity, Volume 183
Author(s): Kazuma Koarai, Yasushi Kino, Atsushi Takahashi, Toshihiko Suzuki, Yoshinaka Shimizu, Mirei Chiba, Ken Osaka, Keiichi Sasaki, Yusuke Urushihara, Tomokazu Fukuda, Emiko Isogai, Hideaki Yamashiro, Toshitaka Oka, Tsutomu Sekine, Manabu Fukumoto, Hisashi Shinoda
⁹⁰Sr specific activity in the teeth of young cattle that were abandoned in Kawauchi village and Okuma town located in the former evacuation areas of the Fukushima-Daiichi Nuclear Power Plant (FNPP) accident were measured. Additionally, specific activity in contaminated surface soils sampled from the same area was measured. (1) All cattle teeth examined were contaminated with ⁹⁰Sr. The specific activity, however, varied depending on the developmental stage of the teeth during the FNPP accident; teeth that had started development before the accident exhibited comparatively lower values, while teeth developed mainly after the accident showed higher values. (2) Values of ⁹⁰Sr-specific activity in teeth formed after the FNPP accident were higher than those of the bulk soil but similar to those in the exchangeable fraction (water and CH3COONH4 soluble fractions) of the soil. The findings suggest that ⁹⁰Sr was incorporated into the teeth during the process of development, and that ⁹⁰Sr in the soluble and/or leachable fractions of the soil might migrate into teeth and contribute to the amount of ⁹⁰Sr in the teeth. Thus, the concentration of ⁹⁰Sr in teeth formed after the FNPP accident might reflect the extent of ⁹⁰Sr pollution in the environment.



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The sweetness of successful goal pursuit: Approach-motivated pregoal states enhance the reward positivity during goal pursuit

Publication date: Available online 21 December 2017
Source:International Journal of Psychophysiology
Author(s): A. Hunter Threadgill, Philip A. Gable
Traditionally, the reward positivity (RewP) is thought to index a binary performance monitoring system sensitive to approach motivation. However, recent theoretical models have argued that feedback processing extends beyond simple "good" vs. "bad" associations, such that performance monitoring incorporates the complex, multi-step sequence of behaviors often necessary to attain rewards. The present study sought to go beyond simple stimulus-response paradigms to examine how approach-motivated states occurring in multi-step goal pursuit impacts the RewP. Additionally, outcome frequency was varied to examine how the P3, a neural marker of expectancy, influences the RewP. Using a modified monetary incentive delay paradigm, participants played a reaction time game where multiple correct responses were required to attain a reward. Additionally, each trial had the potential for a reward (approach-motivated state) or no reward (neutral state). Results revealed that RewP amplitudes were larger after reward trial win feedback than after reward trial no-win feedback across multiple stages of goal pursuit. Additionally, after for controlling outcome frequency via the P3, RewP amplitudes were larger in reward trials than in neutral trials across incremental stages of goal pursuit. The RewP appears to be sensitive to feedback indicating successfully completing sub-goals during pursuit of a goal, even when no immediate reward is given. Approach motivation enhances performance monitoring when multiple steps are needed to attain a desired outcome, which may increase the likelihood of goal acquisition and attainment.



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Variation in reward- and error-related neural measures attributable to age, gender, race, and ethnicity

Publication date: Available online 20 December 2017
Source:International Journal of Psychophysiology
Author(s): Kaylin E. Hill, Belel Ait Oumeziane, Keisha D. Novak, David Rollock, Dan Foti
Event-related potentials (ERPs) have been widely applied to the study of individual differences in reward and error processing, including recent proposals of several ERPs as possible biomarkers of mental illness. A criterion for all biomarkers, however, is that they be generalizable across the relevant populations, something which has yet to be demonstrated for many commonly studied reward- and error-related ERPs. The aim of this study was to examine variation in reward and error-related ERPs across core demographic variables: age, gender, race, and ethnicity. Data was drawn from three studies with relatively large samples (N range 207–527). Results demonstrated that ERPs varied across the demographic variables of interest. Several examples include attenuated reward-related ERPs with increasing age, larger error-related ERPs for men than women, and larger ERPs to feedback after losses for individuals who identified as Hispanic/Latino. Overall, these analyses suggest systematic variation in ERPs that is attributable to core demographic variables, which could give rise to seemingly inconsistent results across studies to the extent that these sample characteristics differ. Future psychophysiological studies should include these analyses as standard practice and assess how these differences might exacerbate, mask, or confound relationships of interest.



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Novel ultrasound-guided inter-semispinal plane block: a comparative pilot study in healthy volunteers

Abstract

We previously reported that a novel multifidus cervicis plane (MCP) block could anesthetize the dorsal rami of the cervical spinal nerves. While MCP sonoanatomy is easily detectable in most patients, it is sometimes difficult to recognize the MCP injection plane, especially in elderly patients. Thus, we proposed the inter-semispinal plane (ISP) block as an alternative for the MCP block. The aim of this study was to evaluate the utility of the ISP block by evaluating the area and duration of anesthesia, compared with that of the MCP block in eight healthy volunteers. Each participant underwent unilateral ultrasound-guided MCP block and ISP block. For each block, 20 ml of ropivacaine 0.2% was injected, and the area of anesthesia was determined using the pinprick test. The anesthetic area ranged from C4 to T2 (3/8; 37.5%), T3 (2/8; 25%), or T4 (3/8; 37.5%) in the MCP block, and from C4 to T1 (1/8; 12.5%), T2 (3/8; 37.5%), T3 (2/8; 25%), or T4 (1/8; 12.5%) in the ISP block. The mean (standard deviation) duration of sensory loss following MCP and ISP blocks was 329 (77) min and 349 (70) min, respectively. Thus, the ISP block may be a reliable alternative to the MCP block.

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Clinical tests have limited predictive value for Chronic Ankle Instability when conducted in the acute phase of a first-time lateral ankle sprain injury

Publication date: Available online 21 December 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Cailbhe Doherty, Chris Bleakley, Jay Hertel, Brian Caulfield, John Ryan, Eamonn Delahunt
ObjectiveTo evaluate whether a battery of clinical assessments for acute lateral ankle sprain (LAS) can be used to predict long-term recovery.DesignCohort studySettingUniversity biomechanics laboratoryParticipantsEighty-two individuals were assessed using a clinical test battery within two-weeks of incurring a first-time LAS.Main Outcome MeasuresThe clinical test battery included scores on the 'talar-glide' (deg), anterior-drawer, talar-tilt, figure-of-eight [figure8] for swelling (mm), knee-to-wall (mm) and hand-held goniometric range-of-motion [inversion; eversion; plantar-flexion (in degrees)]. Scores on the the Cumberland Ankle Instability Tool (CAIT) taken 12-months after the clinical test battery were used to classify participants as having Chronic Ankle Instability (CAI) or as being LAS 'copers'ResultsForty percent of participants were designated as having CAI with 60% being designated as LAS copers. A logistic regression analysis revealed that a combined model using scores from the talar-glide, talar-tilt and anterior-drawer tests in addition to plantar-flexion ROM was statistically significant (p <0.01) and correctly classified cases with moderate accuracy (68.8%). The final model had moderate sensitivity (64%) and good specificity (72%).ConclusionsThe clinical tests utilised in this investigation have limited predictive value for CAI when conducted in the acute phase of a first-time lateral ankle sprain injury.



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Where do Peer Providers Fit into Newly Integrated Mental Health and Primary Care Teams? A Mixed Method Study

Abstract

Little is known about the involvement of peer providers in integrated behavioral health teams. This study asks where peer providers fit within integrated care teams in Los Angeles County. Social network analysis combined with qualitative fieldwork was used to understand the network positions of peer providers in 14 integrated pilot programs. Four programs' peer providers were highly central, while 3 programs' were on the network's periphery. Positional variation appeared to be related to the peers' mental health status. Targeted efforts are needed to support the implementation of peer providers on integrated teams at the program and system levels.

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Acute exhaustive rowing exercise reduces skin microvascular dilator function in young adult rowing athletes

Abstract

Purpose

The effect of acute exhaustive exercise session on skin microvascular reactivity was assessed in professional rowers and sedentary subjects. A potential involvement of altered hemodynamic parameters and/or oxidative stress level in the regulation of skin microvascular blood flow by acute exercise were determined.

Methods

Anthropometric, biochemical, and hemodynamic parameters were measured in 18 young healthy sedentary men and 20 professional rowers who underwent a single acute exercise session. Post-occlusive reactive hyperemia (PORH), endothelium-dependent acetylcholine (ACh), and endothelium-independent sodium nitroprusside (SNP) microvascular responses were assessed by laser Doppler flowmetry in skin microcirculation before and after acute exercise. Serum lipid peroxidation products and plasma antioxidant capacity were measured using spectrophotometry.

Results

At baseline, rowers had significantly lower diastolic blood pressure (DBP) and heart rate (HR), and higher stroke volume (SV), PORH, and endothelium-dependent vasodilation than sedentary. Acute exercise caused a significant increase in systolic blood pressure, DBP, HR, and SV and a decrease in total peripheral resistance in both groups. Acute exercise induced a significant impairment in PORH and ACh-induced response in rowers, but not in sedentary, whereas the SNP-induced vasodilation was not affected by acute exercise in any group. Antioxidant capacity significantly increased only in sedentary after acute exercise.

Conclusion

Single acute exercise session impaired microvascular reactivity and endothelial function in rowers but not in sedentary, possibly due to (1) more rowing grades and higher exercise intensity achieved by rowers; (2) a higher increase in arterial pressure in rowers than in sedentary men; and (3) a lower antioxidant capacity in rowers.

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A novel SAMD9 mutation causing MIRAGE syndrome: An expansion and review of phenotype, dysmorphology, and natural history

Germline gain-of-function variants in SAMD9 have been associated with a high risk of mortality and a newly recognized constellation of symptoms described by the acronym MIRAGE: Myelodysplasia, Infection, Restriction of growth, Adrenal insufficiency, Genital phenotypes, and Enteropathy. Here, we describe two additional patients currently living with the syndrome, including one patient with a novel de novo variant for which we provide functional data supporting its pathogenicity. We discuss features of dysmorphology, contrasting with previously described patients as well as drawing attention to additional clinical features, dysautonomia and hearing loss that have not previously been reported. We detail both patients' courses following diagnosis, with attention to treatment plans and recommended specialist care. Our patients are the oldest known with arginine-substituting amino acid variants, and we conclude that early diagnosis and multidisciplinary management may positively impact outcomes for this vulnerable group of patients.

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Emotional imagery and pupil diameter

Abstract

Pupil diameter is enhanced in a variety of emotional contexts, including viewing pictures, listening to sounds, and during threat of shock. In this study, we investigated pupil diameter changes during emotional imagery. Participants imagined scenes describing pleasant, unpleasant, or neutral events while pupil diameter was continuously recorded. Second by second changes in pupil diameter were analyzed to determine whether, and when, modulation of the pupil as a function of hedonic content is found. Results indicated a significant effect of hedonic content beginning shortly after script onset, with enhanced pupil diameter when imagining emotional (pleasant or unpleasant), compared to neutral, scenes. Pupil diameter during imagery covaried with rated emotional arousal, consistent with an interpretation that changes in pupil diameter during emotional imagery reflect sympathetic nervous system activity. Because emotional imagery is a key element in clinical assessment and treatment, pupil diameter could prove a useful index of emotional engagement in a variety of clinically pertinent contexts.

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Perioperative experiences of anesthesia reported by children and parents

Summary

Background

The Sprint National Anaesthesia Project reported feedback from adults but not from children. We developed questionnaires for children and parents, and conducted a survey of perioperative anesthetic experiences in a large pediatric hospital.

Methods

Patients undergoing elective general anesthesia were selected randomly each weekday over 10 weeks. Parents and children were approached within 4 hours after awakening, and were asked to complete a short questionnaire. Personal or patient identifiable data were not collected. Questionnaires were processed by optical mark reading technology and descriptive data analysis was performed.

Results

Seven hundred and forty parents and 250 children completed questionnaires. The most common symptoms reported by parents were thirst and hunger (76%), drowsiness (75%), sore throat (41%), and pain of the surgery (38%). Sixty-four percent of children felt worried or scared about something before the procedure: common worries were about the "anesthetic," "procedure," or "needles/cannula." Fifty-five percent reported postoperative pain. Thirty-nine children (15.6%) remembered something between going to sleep and waking up although distress was not reported; of these, the most common experiences remembered included hearing voices (34%), feeling sore (20%), and being worried (14%). Twenty-two parents (2.9%) had any complaint and most were about fasting instructions. Only 3 parents would not recommend the anesthetic service.

Conclusion

This study shows that the experiences of children and their parents are similar to those of adults reported by the Sprint National Anaesthesia Project. Thirst (and hunger), anxiety, and pain continue to be common problems for many children. This feedback may help direct interventions and research to improve the pediatric patient and parent experience with anesthesia.

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The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years: A population analysis

Summary

Background

Intravenous ketorolac is commonly administered to children for the control of postoperative pain. An effect site EC₅₀ for analgesia of 0.37 mg^.L⁻¹ is described in adults.

Aims

The aim of this study was to review age- and weight-related effects on ketorolac pharmacokinetic parameters in children and current dosing schedules.

Methods

Pooled intravenous ketorolac (0.5 mg^.kg⁻¹) concentration-time data in children aged 2 months to 16 years were analyzed using nonlinear mixed-effects models. Allometry was used to scale to a 70 kg person.

Results

There were 64 children aged 2 months to 16 years (641 plasma concentrations) available for analysis. A two-compartment mammillary model was used to describe pharmacokinetics. Clearance was 2.53 (CV 45.9%) L^.h^−1.70 kg⁻¹ and intercompartment clearance was 4.43 (CV 95.6%) L^.h^−1.70 kg⁻¹. Both central (V1) and peripheral (V2) volumes of distribution decreased with age over the first few years of postnatal life to reach V1 6.89 (CV 30.3%) L^.70 kg⁻¹ and V2 5.53 (CV 47.6%) L^.70 kg⁻¹.

Conclusion

Clearance, expressed as L^.h^−1.kg⁻¹, decreased with age from infancy. A dosing regimen of 0.5 mg^.kg⁻¹ every 6 hours maintains a trough concentration larger than 0.37 mg^.L⁻¹ in children 9 months to 16 years of age. This dosing regimen is consistent with current recommendations.

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