Effect of Best Practice Advisories on Sedation Protocol Compliance and Drug-Related Hazardous Condition Mitigation Among Critical Care Patients.

OBJECTIVES: To determine whether best practice advisories improved sedation protocol compliance and could mitigate potential propofol-related hazardous conditions. DESIGN: Retrospective observational cohort study. SETTING: Two adult ICUs at two academic medical centers that share the same sedation protocol. PATIENTS: Adults 18 years old or older admitted to the ICU between January 1, 2016, and January 31, 2018, who received a continuous infusion of propofol. INTERVENTIONS: Two concurrent best practice advisories built in the electronic health record as a clinical decision support tool to enforce protocol compliance with triglyceride and lipase level monitoring and mitigate propofol-related hazardous conditions. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were baseline and day 3 compliance with triglyceride and lipase laboratory monitoring per protocol and time to discontinuation of propofol in the setting of triglyceride and/or lipase levels exceeding protocol cutoffs. A total of 1,394 patients were included in the study cohort (n = 700 in the pre-best practice advisory group; n = 694 in the post-best practice advisory group). In inverse probability weighted regression analyses, implementing the best practice advisory was associated with a 56.6% (95% CI, 52.6-60.9) absolute increase and a 173% relative increase (risk ratio, 2.73; 95% CI, 2.45-3.04) in baseline laboratory monitoring. The best practice advisory was associated with a 34.0% (95% CI, 20.9-47.1) absolute increase and a 74% (95% CI, 1.39-2.19) relative increase in day 3 laboratory monitoring after inverse probability weighted analyses. Among patients with laboratory values exceeding protocol cutoffs, implementation of the best practice advisory resulted in providers discontinuing propofol an average of 16.6 hours (95% CI, 4.8-28.3) sooner than pre-best practice advisory. Findings from alternate analyses using interrupted time series were consistent with the inverse probability weighted analyses. CONCLUSIONS: Best practice advisories can be effectively used in ICUs to improve sedation protocol compliance and may mitigate potential propofol-related hazardous conditions. Best practice advisories should undergo continuous quality assurance and optimizations to maximize clinical utility and minimize alert fatigue.

The effects of different durations of static stretching within a comprehensive warm-up on voluntary and evoked contractile properties.

Evidence for performance decrements following prolonged static stretching (SS) has led to a paradigm shift in stretching routines within a warm-up. Rather than SS, dynamic stretching (DS) and dynamic activity (DA) have replaced SS within warm-up routines. The objective of the present study was to compare the effect of differing lower limb SS durations (30 [SS30s], 60 [SS60s] or 120 s [SS120s] of SS per muscle group or no-stretch control) within a comprehensive warm-up protocol consisting of aerobic activity, DS and DA. Sixteen male participants completed the four stretching conditions in a randomized order, after a 5-min low-intensity (cycle) warm-up and before a DS/DA component on separate days. Tests included passive hip and knee ranges of motion (ROM), maximum voluntary knee extensor/flexor force, force produced at 100 ms (F100), vertical jump height and evoked knee extensor contractile properties. For hip flexion (hamstrings) ROM, SS120s provided the largest increase (5.6-11.7%) followed by SS60s (4.3-11.4%), control (4.4-10.6%) and SS30s (3.6-11.1%). For knee flexion (quadriceps) ROM, SS30s provided the largest increase (9.3-18.2%) followed by SS120s (6.5-16.3%), SS60s (7.2-15.2%) and control (6.3-15.2%). There were decreases in quadriceps F100 following SS in SS120s (29.6%) only. There were increases in vertical jump performance in the control (6.2%), SS60s (4.6%) and SS30s (3.3%). While 120 s SS per muscle increased ROM, even within a comprehensive warm-up routine, it also elicited notable performance decrements. However, moderate durations of SS were observed to improve ROM whilst either having negligible or beneficial (but not detrimental) effects on specific aspects of athletic performance.

Neighborhood effects on use of African-American Vernacular English.

African-American Vernacular English (AAVE) is systematic, rooted in history, and important as an identity marker and expressive resource for its speakers. In these respects, it resembles other vernacular or nonstandard varieties, like Cockney or Appalachian English. But like them, AAVE can trigger discrimination in the workplace, housing market, and schools. Understanding what shapes the relative use of AAVE vs. Standard American English (SAE) is important for policy and scientific reasons. This work presents, to our knowledge, the first experimental estimates of the effects of moving into lower-poverty neighborhoods on AAVE use. We use data on non-Hispanic African-American youth (n = 629) from a large-scale, randomized residential mobility experiment called Moving to Opportunity (MTO), which enrolled a sample of mostly minority families originally living in distressed public housing. Audio recordings of the youth were transcribed and coded for the use of five grammatical and five phonological AAVE features to construct a measure of the proportion of possible instances, or tokens, in which speakers use AAVE rather than SAE speech features. Random assignment to receive a housing voucher to move into a lower-poverty area (the intention-to-treat effect) led youth to live in neighborhoods (census tracts) with an 11 percentage point lower poverty rate on average over the next 10-15 y and reduced the share of AAVE tokens by ∼3 percentage points compared with the MTO control group youth. The MTO effect on AAVE use equals approximately half of the difference in AAVE frequency observed between youth whose parents have a high school diploma and those whose parents do not.

Knowledge of Repetition Range Does Not Affect Maximal Force Production Strategies of Adolescent Females.

PURPOSE: Contrary to adult force reserve strategies, it is not known whether adolescent females with less experience performing maximal voluntary contractions (MVC) have specific responses to a known or unknown fatigue endpoint. METHODS: Using a counterbalanced random crossover design, fourteen inexperienced female adolescents completed three elbow flexor (EF) fatiguing protocols. Participants were randomly assigned to a control (informed they would perform 12 MVCs), unknown (not informed of the number of MVCs to be completed, but stopped after 12) or deception condition (instructed to complete 6 MVCs, however, after the sixth repetition performed another 6 MVCs). Before and during the interventions, EF impulse, force, and biceps brachii (BB) and triceps brachii (TB) electromyography (EMG) activity were recorded. RESULTS: Participants exhibited decreases in impulse (10.9%; p < .05), force (7.5%; p = .001), BB (16.2%; p < .05) and TB (12.9%; p < .05) EMG activity between the pretest and the first repetition of all protocols. Knowledge of endpoint, or lack of it, did not change measures with the repeated MVCs. When informed about the final repetition, force remained depressed suggesting no physiological reserve. CONCLUSION: Adolescent females exhibited an anticipatory response to the task of performing repeated MVCs. A lack of change with knowledge of endpoint indicates that those lacking in MVC experience do not employ the same pacing strategies as in previous studies of participants with MVC experience.

Insights into the Affordable Medicines Facility-malaria in Ghana: the role of caregivers and licensed chemical sellers in four regions.

BACKGROUND: The Affordable Medicine Facility-malaria (AMFm) was an innovative global financing mechanism for the provision of quality-assured artemisinin-based combination therapy (ACT) across both the private and public health sectors in eight countries in sub-Saharan Africa. This study evaluated the effectiveness of AMFm subsidies in increasing access to ACT in Ghana and documented malaria management practices at the household and community levels during the implementation of the AMFm. METHODS: This study, conducted in four regions in Ghana between January, 2011 to December, 2012, employed cross-sectional mixed-methods design that included qualitative and quantitative elements, specifically household surveys, focus group discussions (FGD) and in-depth interviews. RESULTS: The study indicated high ACT availability, adequate provider knowledge and reasonably low quality-assured ACT use in the study areas, all of which are a reflection of a high market share of ACT in these hard-to-reach areas of the country. Adequate recognition of childhood malaria symptoms by licensed chemical seller (LCS) attendants was observed. A preference by caregivers for LCS over health facilities for seeking treatment solutions to childhood malaria was found. CONCLUSIONS: Artemisinin-based combination therapy with the AMFm logo was accessible and affordable for most people seeking treatment from health facilities and LCS shops in rural areas. Caregivers and LCS were seen to play key roles in the health of the community especially with children under 5 years of age.

LAPAROSCOPIC GASTROPEXY FOR CORRECTION OF A HIATAL HERNIA IN A NORTHERN ELEPHANT SEAL (MIROUNGA ANGUSTIROSTRIS).

A female northern elephant seal (Mirounga angustirostris) weaned pup presented with malnutrition. During rehabilitation, the seal developed regurgitation and reduced lung sounds on auscultation. Radiographs and endoscopy performed under sedation suggested a diaphragmatic hernia. A Type I (or sliding) hiatal hernia was confirmed with a positive contrast upper gastrointestinal study, revealing varying degrees of herniation of the gastric fundus through the diaphragm into the caudal thorax as well as esophageal reflux. The animal was treated preoperatively with an H2 antagonist and antinausea medication. A laparoscopic gastropexy was performed under general anesthesia. The animal recovered well postoperatively and resolution of clinical signs was achieved. The animal was released back into the wild 21 kg above admit weight. To our knowledge, we report here the first surgical correction of a hiatal hernia in a marine mammal.

Efficacy of Installation of Temporary Bathing Transfer Aids by Older Adults.

Grab bars facilitate bathing and reduce the risk of falls during bathing. Suction cup handholds and rim-mounted tub rails are an alternative to grab bars. The objective of this study was to determine whether older adults could install handholds and tub rails effectively to support bathing transfers. Participants installed rim-mounted tub rails and suction cup handholds in a simulated bathroom environment. Installation location and mechanical loading performance were evaluated. Participant perceptions during device installation and a bathing transfer were characterized. While 85% of suction cup handholds met loading requirements, more than half of participants installed the suction cup handhold in an unexpected location based on existing guidance documents. No rim-mounted tub rails were successfully installed. Participants were confident that the devices had been installed effectively. Suction cup handholds and rim mounted tub rails are easy to install, but clients may need additional guidance regarding where, and how to install them.

Biomechanical Demands and User Preference Associated with Wall-Mounted and Rim-Mounted Grab Bars.

Background. Grab bars are used to support bathing tasks. Sometimes, temporary rim-mounted grab bars may be preferred over permanent wall-mounted grab bars. Purpose. We compared postural requirements, applied loads, and user perceptions between two configurations of rim-mounted grab bars, a vertical wall-mounted grab bar, and a no-grab bar condition. Method. Ten adults entered and exited a simulated bathing environment. Trunk flexion was evaluated via 3D kinematics, while load cells mounted to the grab bars facilitated the evaluation of applied loads. Participants rated each condition on perceived safety, comfort, effectiveness, and ease of use. Findings. Rim-mounted grab bars resulted in greater trunk flexion and greater applied loads and were less favorably perceived. Implications. The rim-mounted grab bars included in this study may induce challenging postural demands and loading scenarios, and occupational therapists should consider whether they meet the needs of their clients.

Functionally Adaptive Myosite Selection Using High-Density sEMG for Upper Limb Myoelectric Prostheses.

OBJECTIVE: Our study defines a novel electrode placement method called Functionally Adaptive Myosite Selection (FAMS), as a tool for rapid and effective electrode placement during prosthesis fitting. We demonstrate a method for determining electrode placement that is adaptable towards individual patient anatomy and desired functional outcomes, agnostic to the type of classification model used, and provides insight into expected classifier performance without training multiple models. METHODS: FAMS relies on a separability metric to rapidly predict classifier performance during prosthesis fitting. RESULTS: The results show a predictable relationship between the FAMS metric and classifier accuracy (3.45%SE), allowing estimation of control performance with any given set of electrodes. Electrode configurations selected using the FAMS metric show improved control performance ( ) for target electrode counts compared to established methods when using an ANN classifier, and equivalent performance ( R2 ≥ .96) to previous top-performing methods on an LDA classifier, with faster convergence ( ). We used the FAMS method to determine electrode placement for two amputee subjects by using the heuristic to search through possible sets, and checking for saturation in performance vs electrode count. The resulting configurations that averaged 95.8% of the highest possible classification performance using a mean 25 number of electrodes (19.5% of the available sites). SIGNIFICANCE: FAMS can be used to rapidly approximate the tradeoffs between increased electrode count and classifier performance, a useful tool during prosthesis fitting.

Resilience and crime victimization.

What do we know about resilience in crime victimization? In this article, the authors discuss resilience defined as protective factors (e.g., personality characteristics, biological characteristics, social and cultural factors, and community characteristics); as a process of adaptation (e.g., self-enhancement, positive cognitive appraisals, coping styles, and spirituality), including an iterative perspective on resilience as a cascade of protective processes; and as positive outcomes (e.g., lack of symptoms) following exposure to adverse events. Within each of these definitional frameworks, they consider general conceptual issues pertaining to resilience and then the small body of research that has focused specifically on resilience and some type of crime victimization. Research and clinical implications are discussed.

Exogenous supplementation of antithrombin III in adult and pediatric patients receiving extracorporeal membrane oxygenation.

BACKGROUND: Antithrombin III deficiency can occur with heparin anticoagulation during extracorporeal membrane oxygenation leading to heparin resistance. Antithrombin III supplementation has been shown to improve anticoagulation; however, there is no consensus on appropriate administration. We described the effect of antithrombin III supplementation on coagulation parameters in adult and pediatric extracorporeal membrane oxygenation patients. METHODS: We conducted a retrospective cohort study using electronic medical records of patients who received ⩾1 dose of antithrombin III during extracorporeal membrane oxygenation while on continuous heparin. Endpoints included the change in anti-Xa levels and antithrombin III activity at -6 versus 6 h relative to antithrombin III supplementation, and heparin infusion rates at 6 versus 12 h after antithrombin III supplementation. RESULTS: Eighteen patients receiving 36 antithrombin III administrations were analyzed. Mean (standard deviation) anti-Xa values at -6 versus 6 h were 0.15 (0.07) versus 0.24 (0.15) IU/mL (p-value: 0.250) for pediatrics and 0.19 (0.22) versus 0.31 (0.27) IU/mL (p-value: 0.052) for adults. Mean (standard deviation) plasma antithrombin III activity at the same intervals were 32% (14.2%) versus 66.8% (25.1%; p-value: 0.062) for pediatrics and 30.3% (14%) versus 52.8% (8.1%; p-value: 0.094) for adults. Mean (standard deviation) heparin rates at 6 versus 12 h after antithrombin III for pediatrics were 23.6 (6) versus 23.5 (6.5) units/kg/h (p-value: 0.728), and 15.3 (6.6) versus 13.5 (8) units/kg/h (p-value: 0.188) for adults. CONCLUSION: Administration of antithrombin III improved anti-Xa levels in both populations, however, did not significantly reduce heparin rates. Our findings suggest that the use of antithrombin III restores heparin responsiveness in patients with low antithrombin III activity and low anti-Xa activity.

Pharmacokinetics of flucytosine in a critically ill patient on continuous venovenous hemodiafiltration.

PURPOSE: To describe the pharmacokinetics of flucytosine in a critically ill patient undergoing continuous venovenous hemodiafiltration (CVVHDF) treated for cryptococcal meningitis. SUMMARY: A 20-year-old female weighing 93.4 kg with a body mass index of 34.3 kg/m2 with a past medical history of systemic lupus erythematous with diffuse proliferative lupus nephritis (class IV) was admitted to the hospital after several months of worsening dyspnea, fatigue, myalgia, vomiting, and diarrhea. The patient developed worsening renal function and volume overload requiring CVVHDF on hospital day 7. She was diagnosed with cryptococcal meningitis on hospital day 8, and flucytosine 2,500 mg enterally every 12 hours and liposomal amphotericin B 500 mg intravenously every 24 hours were initiated. Flucytosine serum concentrations were collected on day 4 of therapy, and pharmacokinetics were performed on 2 sequential levels. Pharmacokinetic calculations displayed an elimination rate constant of 0.0338 h-1, a volume of distribution between 0.42 and 0.43 L/kg, a half-life of 20.5 hours, and a total drug clearance between 1.32 and 1.36 L/h while on CVVHDF. The nonsequential levels displayed good correlation, and no further monitoring or dosage adjustment was required. The patient completed therapy, with clinical resolution of her infection, and no toxicities due to flucytosine were noted. CONCLUSION: Flucytosine dosed at 25 mg/kg of actual body weight every 12 hours during CVVHDF conferred therapeutic levels with no appreciable toxicities. Because of its narrow therapeutic index and risk of toxicity, additional pharmacokinetic studies are needed to determine optimal drug dosing of this medication in patients requiring renal replacement therapy.

Disparities in the use of chemotherapy and monoclonal antibody therapy for elderly advanced colorectal cancer patients in the community oncology setting.

BACKGROUND: The clinical trials on which the treatment of advanced colorectal (CRC) is based enroll few elderly patients. Furthermore, few investigations have determined the use and outcomes of the treatment of advanced CRC in practice. This study evaluated the treatment of advanced CRC in community oncology practices, focusing on age-related differences in treatment and outcome. METHODS: A national, retrospective chart review was conducted to evaluate the management of advanced CRC in 10 community practices across the U.S. All medical records of patients diagnosed with advanced CRC initiating chemotherapy treatment after January 1, 2003 through 2006 were included. The primary aim was to compare the proportion receiving doublet chemotherapy (irinotecan or oxaliplatin with a fluoropyrimidine) as initial therapy in young (age 65 years) patients. Additional aims included age-based comparisons of the addition of bevacizumab to chemotherapy, overall chemotherapy use, all-cause mortality, and toxicity-related events. RESULTS: Overall, 520 patients (56% elderly) received 6,253 cycles of chemotherapy. Of the younger patients, 84% received doublet chemotherapy first-line, compared with 58% of elderly patients (p < .001). The use of each of the medications--irinotecan, oxaliplatin, and bevacizumab--was lower in elderly patients (p < .001). Independent predictors of a higher risk for mortality were age >65 (adjusted hazards ratio [HR],1.19; 95% confidence interval [CI], 1.02-1.39) and performance status score >or=2 (HR, 1.65; 95% CI, 1.41-1.91). CONCLUSION: Elderly patients are less likely to receive first-line doublet chemotherapy than younger patients. Age and performance status are independent predictors of treatment and overall survival.

The effect of rolling massage on the excitability of the corticospinal pathway.

The aim of the present study was to investigate the alterations of corticospinal excitability (motor evoked potential, MEP) and inhibition (silent period, SP) following rolling massage of the quadriceps muscles. Transcranial magnetic and femoral nerve electrical stimuli were used to elicit MEPs and compound muscle action potential (Mmax) in the vastus lateralis and vastus medialis muscles prior to and following either (i) 4 sets of 90-s rolling massage (ROLLING) or (ii) rest (CONTROL). One series of neuromuscular evaluations, performed after each set of ROLLING or CONTROL, included 3 MEPs and 1 Mmax elicited every 4 s during 15-s submaximal contractions at 10% (experiment 1, n = 16) and 50% (experiment 2, n = 10) of maximal voluntary knee extensions (MVC). The MEP/Mmax ratio and electromyographic activity recorded from vastus lateralis at 10% MVC demonstrated significantly lower values during ROLLING than CONTROL (P < 0.05). The ROLLING did not elicit any significant changes in muscle excitability (Mmax area) and duration of transcranial magnetic stimulation-induced SP recorded from any muscle or level of contraction (P > 0.05). The findings suggest that rolling massage can modulate the central excitability of the circuitries innervating the knee extensors; however, the observed effects are dependent on the background contraction intensity during which the neuromuscular measurements are recorded.

Paclitaxel and filgrastim for hematopoietic progenitor cell mobilization in patients with hematologic malignancies after failure of a prior mobilization regimen.

Paclitaxel and G-CSF have been evaluated for HPC mobilization in breast cancer and found to have tolerable toxicity with a predictable time to initiate leukapheresis. However, this approach has not been reported in patients with hematologic malignancies failing prior mobilization. We report a case-series of 26 adults given paclitaxel and G-CSF for HPC mobilization after failure of an initial mobilization. Patients received paclitaxel 250 mg/m(2) followed by G-CSF 10-16 mcg/kg/day. Compared to the initial regimen, paclitaxel mobilization produced greater CD34+ cell yields (median 1.53 x 10(6) CD34+ cells/kg vs. 0.79 x 10(6) CD34+ cells/kg, p = 0.004). Seventy-six percent of patients initiated leukapheresis on day 8, the remainder on day 9 or 10. Three patients developed febrile neutropenia resulting in one death prior to leukapheresis. Overall, 73% of patients proceeded with autologous HPC transplant. This case-series suggests paclitaxel may be an option for HPC mobilization in patients failing prior regimens.

Knockdown of Inner Arm Protein IC138 in Trypanosoma brucei Causes Defective Motility and Flagellar Detachment.

Motility in the protozoan parasite Trypanosoma brucei is conferred by a single flagellum, attached alongside the cell, which moves the cell forward using a beat that is generated from tip-to-base. We are interested in characterizing components that regulate flagellar beating, in this study we extend the characterization of TbIC138, the ortholog of a dynein intermediate chain that regulates axonemal inner arm dynein f/I1. TbIC138 was tagged In situ-and shown to fractionate with the inner arm components of the flagellum. RNAi knockdown of TbIC138 resulted in significantly reduced protein levels, mild growth defect and significant motility defects. These cells tended to cluster, exhibited slow and abnormal motility and some cells had partially or fully detached flagella. Slight but significant increases were observed in the incidence of mis-localized or missing kinetoplasts. To document development of the TbIC138 knockdown phenotype over time, we performed a detailed analysis of flagellar detachment and motility changes over 108 hours following induction of RNAi. Abnormal motility, such as slow twitching or irregular beating, was observed early, and became progressively more severe such that by 72 hours-post-induction, approximately 80% of the cells were immotile. Progressively more cells exhibited flagellar detachment over time, but this phenotype was not as prevalent as immotility, affecting less than 60% of the population. Detached flagella had abnormal beating, but abnormal beating was also observed in cells with no flagellar detachment, suggesting that TbIC138 has a direct, or primary, effect on the flagellar beat, whereas detachment is a secondary phenotype of TbIC138 knockdown. Our results are consistent with the role of TbIC138 as a regulator of motility, and has a phenotype amenable to more extensive structure-function analyses to further elucidate its role in the control of flagellar beat in T. brucei.

Endoscopic components separation for abdominal compartment syndrome.

BACKGROUND: Sustained intraabdominal pressures of 14 to 20 mm Hg have significant pathophysiological consequences, but there is currently no satisfactory low-morbidity procedure appropriate for intervention early in the disease process of abdominal compartment syndrome (ACS). The anatomical principles of abdominal wall components separation were used to develop a percutaneous procedure that increased abdominal capacity and decreased abdominal pressure. METHODS: Using a porcine model, we determined abdominal capacity changes by helium insufflation. Corn oil was then used to create an episode of sustained intraabdominal hypertension and changes in intraabdominal pressure and intestinal mucosal oxygenation were determined. RESULTS: Endoscopic abdominal wall components separation (EACS) increased abdominal capacity by 1 L (from 0.89 +/- 0.39 L to 1.95 +/- 0.48 L; P <0.001). During intraabdominal hypertension, EACS decreased abdominal pressure by 31.6% (from 15.9 +/- 2.1 to 11.0 +/- 1.5 mm Hg; P <0.001). Intestinal PO(2) was increased by 61% (18.8 +/- 11.4 to 30.3 +/- 11.7; P = 0.012) CONCLUSIONS: A minimally invasive procedure (EACS) is feasible and has demonstrated effectiveness in a porcine model of ACS.

Robotically assisted laparoscopic Roux-en-Y hepaticojejunostomy.

INTRODUCTION: This study evaluates the feasibility and safety of using robotically assisted laparoscopy to perform a Roux-en-Y hepaticojejunostomy. This new method was compared with the open and standard laparoscopic approaches. METHODS: Eighteen pigs underwent a needlescopic common bile duct ligation to create a jaundice model. Three to 5 days later, transabdominal ultrasound was performed, and the common bile duct diameter was documented. For the Roux-en-Y hepaticojejunostomy, the pigs were randomly assigned to the open group (n=6), standard laparoscopy group (n=6), or robotically assisted laparoscopy group (Zeus) (n=6). One surgeon performed all 3 approaches with 1 assistant. Operative times, techniques, and complication rates were documented. RESULTS: The open approach was faster in all instances. At the hepaticojejunostomy, no difference was noted between the groups with the total number of stitches used. The robot required fewer stitches and less time in the posterior wall of the hepaticojejunostomy (P=-0.0083 and P=0.02049, respectively). The hepaticojejunostomy time was similar for the laparoscopy and robotically assisted groups. CONCLUSION: Robotically assisted laparoscopic Roux-en-Y hepaticojejunostomy is a feasible procedure. When compared with standard laparoscopy, operating time is similar.