bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perioperative Epidural Use and Risk of Delirium in Surgical Patients: A Secondary Analysis of the PODCAST Trial
Authors: Vlisides Phillip E. , Thompson Aleda , Kunkler Bryan S. , Maybrier Hannah R. , Avidan Michael S. , Mashour George A. 
Published: March 2019

BACKGROUND:
Postoperative delirium is an important public health concern without effective prevention strategies. This study tested the hypothesis that perioperative epidural use would be associated with decreased risk of delirium through postoperative day 3.

METHODS:
This was a secondary, observational, nonrandomized analysis of data from The Prevention of Delirium and Complications Associated With Surgical Treatments Trial (PODCAST; NCT01690988). The primary outcome of the current study was the incidence of delirium (ie, any positive delirium screen, postanesthesia care unit through postoperative day 3) in surgical patients (gastrointestinal, hepatobiliary-pancreatic, gynecologic, and urologic) receiving postoperative epidural analgesia compared to those without an epidural. As a secondary outcome, all delirium assessments were then longitudinally analyzed in relation to epidural use throughout the follow-up period. Given the potential relevance to delirium, postoperative pain, opioid consumption, sleep disturbances, and symptoms of depression were also analyzed as secondary outcomes. A semiparsimonious multivariable logistic regression model was used to test the association between postoperative epidural use and delirium incidence, and generalized estimating equations were used to test associations with secondary outcomes described. Models included relevant covariates to adjust for confounding.

RESULTS:
In total, 263 patients were included for analysis. Epidural use was not independently associated with reduced delirium incidence (adjusted odds ratio, 0.65 [95% CI, 0.32–1.35]; P = .247). However, when analyzing all assessments over the follow-up period, epidural patients were 64% less likely to experience an episode of delirium (adjusted odds ratio, 0.36 [95% CI, 0.17–0.78]; P = .009). Adjusted pain scores (visual analog scale, 0–100 mm) were significantly lower in the epidural group on postoperative day 1 (morning, −16 [95% CI, −26 to −7], P < .001; afternoon, −15 [95% CI, −25 to −5], P < .01) and postoperative day 3 (morning, −13 [95% CI, −20 to −5], P < .01). Adjusted mean oral and IV morphine equivalents were also significantly lower on postoperative day 1 in the epidural group (74% lower [95% CI, 55%–85%]; P < .0001). Finally, postoperative epidural use was not significantly associated with new sleep disturbances or changes in depression symptoms.

CONCLUSIONS:
Postoperative epidural use was not associated with a reduced overall incidence of delirium. However, longitudinal analysis revealed reduced adjusted odds of experiencing an episode of delirium in the epidural group. Epidural use was also associated with reduced postoperative pain and opioid consumption. An appropriately designed follow-up study is warranted to further analyze the relationship among epidural use, postoperative delirium, and related outcomes.
Early Treatment With Metformin in a Mice Model of Complex Regional Pain Syndrome Reduces Pain and Edema
Authors: Das Vaskar , Kroin Jeffrey S. , Moric Mario , McCarthy Robert J. , Buvanendran Asokumar 
Published: March 2019

BACKGROUND:
Metformin, an adenosine monophosphate (AMP)–activated protein kinase activator, as well as a common drug for type 2 diabetes, has previously been shown to decrease mechanical allodynia in mice with neuropathic pain. The objective of this study is to determine if treatment with metformin during the first 3 weeks after fracture would produce a long-term decrease in mechanical allodynia and improve a complex behavioral task (burrowing) in a mouse tibia fracture model with signs of complex regional pain syndrome.

METHODS:
Mice were allocated into distal tibia fracture or nonfracture groups (n = 12 per group). The fracture was stabilized with intramedullary pinning and external casting for 21 days. Animals were then randomized into 4 groups (n = 6 per group): (1) fracture, metformin treated, (2) fracture, saline treated, (3) nonfracture, metformin treated, and (4) nonfracture, saline treated. Mice received daily intraperitoneal injections of metformin 200 mg/kg or saline between days 14 and 21. After cast removal, von Frey force withdrawal (every 3 days) and burrowing (every 7 days) were tested between 25 and 56 days. Paw width was measured for 14 days after cast removal. AMP-activated protein kinase downregulation at 4 weeks after tibia fracture in the dorsal root ganglia was examined by immunohistochemistry for changes in the AMP-activated protein kinase pathway.

RESULTS:
Metformin injections elevated von Frey thresholds (reduced mechanical allodynia) in complex regional pain syndrome mice versus saline-treated fracture mice between days 25 and 56 (difference of mean area under the curve, 42.5 g·d; 95% CI of the difference, 21.0–63.9; P < .001). Metformin also reversed burrowing deficits compared to saline-treated tibial fracture mice (difference of mean area under the curve, 546 g·d; 95% CI of the difference, 68–1024; P < .022). Paw width (edema) was reduced in metformin-treated fracture mice. After tibia fracture, AMP-activated protein kinase was downregulated in dorsal root ganglia neurons, and mechanistic target of rapamycin, ribosomal S6 protein, and eukaryotic initiation factor 2α were upregulated.

CONCLUSIONS:
The important finding of this study was that early treatment with metformin reduces mechanical allodynia in a complex regional pain syndrome model in mice. Our findings suggest that AMP-activated protein kinase activators may be a viable therapeutic target for the treatment of pain associated with complex regional pain syndrome.
Randomized Trial Comparing Early and Late Administration of Rocuronium Before and After Checking Mask Ventilation in Patients With Normal Airways
Authors: Min Se-Hee , Im Hyunjae , Kim Bo Rim , Yoon Susie , Bahk Jae-Hyon , Seo Jeong-Hwa 
Published: March 2019

BACKGROUND:
During induction of general anesthesia, it is common practice to delay neuromuscular blockade until the ability to deliver mask ventilation has been confirmed. However, the benefits of this approach have never been scientifically validated. We thus compared the early and late administration of rocuronium before and after checking mask ventilation to investigate the efficiency of mask ventilation and the time to tracheal intubation in patients with normal airways.

METHODS:
Patients (n = 114) were randomized to receive IV rocuronium either before (early rocuronium group, n = 58) or after (late rocuronium group, n = 56) checking mask ventilation. Expiratory tidal volumes (VTs) were measured at 10, 20, 30, 40, 50, and 60 seconds after apnea during mask ventilation. We graded the ease of mask ventilation and measured the time from apnea to tracheal intubation. The primary outcome was the average of mask VTs measured at 10, 20, 30, 40, 50, and 60 seconds after apnea. The main secondary outcome was the time from apnea to tracheal intubation. STATA was used for statistical analysis.

RESULTS:
The average of mask VTs measured at 10, 20, 30, 40, 50, and 60 seconds after apnea was larger in the early rocuronium group than in the late rocuronium group (552 mL breath−1 [165 mL breath−1] vs 393 mL breath−1 [165 mL breath−1], mean difference, 160 mL breath−1; 95% CI, 98−221 mL breath−1; P < .001, unpaired t test). Because the interaction between time and group was significant in mask VTs measured at 10, 20, 30, 40, 50, and 60 seconds after apnea (P < .001, linear mixed effects model), pairwise comparisons were performed at the 6 time points. The differences in VTs between the groups were significant at 10, 20, 30, 40, and 50 seconds after apnea (P < .001 each, contrast statements in STATA). The time from apnea to tracheal intubation was shorter in the early rocuronium group than in the late rocuronium group (116 seconds [42 seconds] vs 195 seconds [41 seconds]; mean difference, −79 seconds; 95% CI, −96 to −64 seconds, P < .001).

CONCLUSIONS:
The early administration of rocuronium before checking mask ventilation resulted in a larger mask VT and earlier tracheal intubation than the late administration of rocuronium after checking mask ventilation in patients with normal airways.
Real-Time Ultrasound Improves Accuracy of Caudal Block in Children
Authors: Adler Adam C. , Belon Craig A. , Guffey Danielle M. , Minard Charles G. , Patel Nihar V. , Chandrakantan Arvind 
Published: March 2019

BACKGROUND:Caudal block, the most common regional anesthetic in children, is predominantly performed using palpation to determine placement. The efficacy of the palpation technique is unknown with respect to block success. While ultrasound has been suggested for use during caudal block, its use is infrequent.METHODS:A single-blinded prospective observational trial was performed evaluating provider success rate of caudal blocks placed by palpation alone. After needle insertion and partial local anesthetic injection, an ultrasound was performed to confirm correct location.RESULTS:A total of 109 caudal blocks were performed during the prospective observational study. Success rate for caudal blocks done by palpation alone was 78.9% as confirmed by ultrasound. In 21.1% of caudal blocks, the provider incorrectly judged the needle to be in the caudal space as confirmed with ultrasound.CONCLUSIONS:Real-time ultrasound visualization of local anesthetic injection provides reliable and immediate confirmation during caudal block in children.
Ultrasound-Guided Erector Spinae Plane Block in Patients Undergoing Open Epigastric Hernia Repair: A Prospective Randomized Controlled Study
Authors: Abu Elyazed Mohamed M. , Mostafa Shaimaa F. , Abdelghany Mohamed S. , Eid Gehan M. 
Published: March 2019

BACKGROUND:
Hernia repair is associated with considerable postoperative pain. We studied the analgesic efficacy of bilateral ultrasound-guided erector spinae plane block in patients undergoing open midline epigastric hernia repair (T6–T9).

METHODS:
Sixty patients 18–65 years of age were randomly allocated into 2 groups. Patients in the erector spinae plane block group received bilateral ultrasound-guided erector spinae plane block at the level of T7 transverse process using 20 mL of bupivacaine 0.25% on each side, while the control group received bilateral sham erector spinae plane block using 1 mL of normal saline. All patients underwent general anesthesia for surgery. Pain severity (visual analog scale), consumption of intraoperative fentanyl, time to first request of rescue analgesia, and postoperative pethidine consumption were recorded over the first 24 hours postoperatively.

RESULTS:
At 2 hours postoperatively, the visual analog scale pain score was significantly lower in the erector spinae plane block group compared to the control group (estimated main effect of 2.53; P < .001; 95% CI, 1.8–3.2) and remained lower until 12 hours postoperatively (P < .001 from postanesthesia care unit admission to 4 hours postoperatively, .001 at 6 hours, .025 at 8 hours, and .043 at 12 hours). At 18 and 24 hours, visual analog scale pain scores were not significantly different between both groups (P = .634 and .432, respectively). Four patients in the erector spinae plane block group required intraoperative fentanyl compared to 27 patients in control group. The median (quartiles) of intraoperative fentanyl consumption in the erector spinae plane block group was significantly lower (0 µg [0–0 µg]) compared to that of the control group (94 µg [74–130 µg]). Ten patients in the erector spinae plane block group required postoperative rescue pethidine compared to 25 patients in control group. The median [quartiles] of postoperative rescue pethidine consumption was significantly lower in the erector spinae plane block group (0 mg [0–33 mg]) compared to that of the control group (83 mg [64–109 mg]). Time to first rescue analgesic request was significantly prolonged in the erector spinae plane block group compared to control group (P < .001).

CONCLUSIONS:
Ultrasound-guided bilateral erector spinae plane block provided lower postoperative visual analog scale pain scores and decreased consumption of both intraoperative fentanyl and postoperative rescue analgesia for patients undergoing open epigastric hernia repair.
Proliferator-Activated Receptor-Gamma Coactivator-1α Haploinsufficiency Promotes Pain Chronification After Burn Injury
Authors: Miao Jiamin , Zhou Xue , Ding Weihua , You Zerong , Doheny Jason , Mei Wei , Chen Qian , Mao Jianren , Shen Shiqian 
Published: March 2019

BACKGROUND:
Tissue injuries such as surgery and trauma are usually accompanied by simultaneous development of acute pain, which typically resolves along with tissue healing. However, in many cases, acute pain does not resolve despite proper tissue repair; rather, it transitions to chronic pain. In this study, we examined whether proliferator-activated receptor-gamma coactivator-1α (PGC-1α), a master regulator of mitochondria biogenesis, is implicated in pain chronification after burn injury in mice.

METHODS:
We used PGC-1α+/+ and littermates PGC-1α+/− mice of both sex. Burn injury was induced on these mice. Hindpaw mechanical withdrawal thresholds and thermal withdrawal latency were examined.

RESULTS:
Hindpaw mechanical withdrawal thresholds and thermal withdrawal latencies were comparable at baseline between PGC-1α+/− and PGC-1α+/+ mice. After burn injury, both PGC-1α+/+ and PGC-1α+/− mice exhibited an initial dramatic decrease of withdrawal parameters at days 3 and 5 after injury. While PGC-1α+/+ mice fully recovered their withdrawal parameters to preinjury levels by days 11–14, PGC-1α+/− mice failed to recover those parameters during the same time frame, regardless of sex. Moreover, we found that PGC-1α+/− mice resolved tissue inflammation in a similar fashion to PGC-1α+/+ mice using a chemiluminescence-based reactive oxygen species imaging technique.

CONCLUSIONS:
Taken together, our data suggest that PGC-1α haploinsufficiency promotes pain chronification after burn injury.
Dose–Response Study of 4 Weight-Based Phenylephrine Infusion Regimens for Preventing Hypotension During Cesarean Delivery Under Combined Spinal–Epidural Anesthesia
Authors: Xiao Fei , Shen Bei , Xu Wen-ping , Feng Ying , Ngan Kee Warwick D. , Chen Xin-zhong 
Published: March 2019

BACKGROUND:
Prophylactic IV infusion of phenylephrine has been recommended to prevent hypotension during spinal anesthesia for cesarean delivery. However, the optimal infusion dose is unknown. This study aimed to determine the infusion dose of phenylephrine that would be effective in preventing hypotension in 50% (ED50) and 90% (ED90) of patients when administered as a prophylactic infusion at a fixed rate based on the individual body weight.

METHODS:
Eighty parturients scheduled for elective cesarean delivery were randomly allocated to receive IV infusion of prophylactic phenylephrine at 0.25, 0.375, 0.5, or 0.625 µg/kg/min (n = 20 per group) started immediately after intrathecal injection of 10 mg hyperbaric bupivacaine and 5 µg sufentanil using a combined spinal–epidural technique. An effective dose was defined by the occurrence of no hypotension (defined as a decrease in systolic blood pressure by ≥20% below baseline and to <90 mm Hg) during the interval from the initiation of spinal anesthesia to delivery of the infant. Values for ED50 and ED90 of prophylactic phenylephrine were calculated using probit analysis.

RESULTS:
Hypotension occurred in 13/20, 8/20, 2/20, and 1/20 patients in the groups that received phenylephrine infusion at 0.25, 0.375, 0.5, or 0.625 µg/kg/min, respectively. The calculated values for ED50 and ED90 were 0.31 (95% CI, 0.24–0.36) and 0.54 (95% CI, 0.46–0.76) µg/kg/min, respectively. No difference was found in the incidence of adverse effects and neonatal outcomes among groups.

CONCLUSIONS:
Under the conditions of this study, when phenylephrine was given as a fixed-rate prophylactic infusion during spinal anesthesia for cesarean delivery to prevent hypotension, the values for ED50 and ED90 were 0.31 (95% CI, 0.24–0.36) and 0.54 (95% CI, 0.46–0.76) µg/kg/min, respectively.
Development and Testing of an Integrated Score for Physical Behaviors
Authors: KEADLE SARAH KOZEY , KRAVITZ ELI S. , MATTHEWS CHARLES E. , TSENG MARILYN , CARROLL RAYMOND J. 
Published: March 2019

ABSTRACT

Purpose
Interest in a variety of physical behaviors (e.g., exercise, sitting time, sleep) in relation to health outcomes creates a need for new statistical approaches to analyze the joint effects of these distinct but inter-related physical behaviors. We developed and tested an integrated physical behavior score (PBS).

Methods
National Institutes of Health-American Association of Retired Persons Diet and Health Study participants (N = 163,016) completed a questionnaire (2004–2006) asking about time spent in five exercise and nonexercise physical activities, two sedentary behaviors (television and nontelevision), and sleep. In half of the sample, we used shape-constrained additive regression to model the relationship between each behavior and survival. Maximum logit scores from each of the eight behavior-survival functions were summed to produce a PBS that was proportionally rescaled to range from 0 to 100. We examined predictive validity of the PBS in the other half-sample using Cox Proportional Hazards models after adjustment for covariates for all-cause and cause-specific mortality.

Results
In the testing sample, over an average of 6.6 yr of follow-up, 8732 deaths occurred. We found a strong graded decline in risk of all-cause mortality across quintiles of PBS (Q5 vs Q1 hazard ratio [95% CI] = 0.53 [0.49, 0.57]). Risk estimates for the PBS were higher than any of the components in isolation. Results were similar but stronger for cardiovascular disease (Q5 vs Q1 = 0.42 [0.39, 0.48]) and other mortality (Q5 vs Q1 = 0.42 [0.36, 0.48]). The relationship between PBS and mortality was observed in stratified analyses by median age, sex, body mass index, and health status.

Conclusions
We developed a novel statistical method generated a composite physical behavior that is predictive of mortality outcomes. Future research is needed to test this approach in an independent sample.
Loading Behaviors Do Not Match Loading Abilities Postanterior Cruciate Ligament Reconstruction
Authors: CHAN MING-SHENG , SIGWARD SUSAN M. 
Published: March 2019

ABSTRACT

Purpose
Strategies that underload the surgical limb after anterior cruciate ligament reconstruction (ACLr) are observed in submaximal tasks. It is not known what underlies these strategies in early rehabilitation. The purpose of this study was to determine if underloading can be attributed to the inability to meet task demands with and without attention to limb loading or learned behavior.

Methods
Twenty individuals (110.6 [18.1] days) post-ACLr and 20 healthy individuals (CTRL) participated in this study. Participants performed standing, sit-to-stand, and squat tasks under natural, instructed, and feedback conditions. Limb-loading symmetry was calculated as the between-limb ratio of vertical ground reaction force impulse during each task. General Linear Model repeated-measures analysis, 2 (group) × 3 (condition), determined the effects of group and condition on limb-loading symmetry for each task.

Results
Significant interactions were observed for each task (all P < 0.001). Compared with CTRL, ACLr exhibited greater asymmetry during natural (deficits: standing, 10%, P = 0.001; sit-to-stand, 25%, P < 0.001; squat, 15%, P < 0.001) and instructed (deficits: sit-to-stand, 13%, P = 0.001; squat, 8%, P = 0.04), but not feedback conditions. The CTRL maintained symmetry across conditions and tasks. Anterior cruciate ligament reconstruction exhibited greater asymmetry in natural compared with instructed (deficits: standing, 11%, P < 0.001; sit-to-stand, 14%, P < 0.001; squat, 8%, P = 0.001) and feedback (deficits: standing, 10%, P = 0.001; sit-to-stand, 21%, P < 0.001; squat, 15%, P < 0.001) conditions.

Conclusions
The presence of loading asymmetries in natural but not feedback conditions indicates that individuals 3 months post-ACLr shift loading away from surgical limb despite the ability to meet task demands which may be suggestive of nonuse behavior. Even when instructed to load symmetrically, individuals continued to exhibit some degree of asymmetry.
Objectively Measured Physical Activity Is Associated with Vertebral Size in Midlife
Authors: MODARRESS-SADEGHI MAHSA , OURA PETTERI , JUNNO JUHO-ANTTI , NIEMELÄ MAISA , NIINIMÄKI JAAKKO , JÄMSÄ TIMO , KORPELAINEN RAIJA , KARPPINEN JARO 
Published: March 2019

ABSTRACTBackgroundVertebral fractures reduce the quality of life and are a major burden to the health care sector. Small vertebral size is associated with increased vertebral fracture risk. Previous studies have investigated the relationship between physical activity (PA) and vertebral size, but their results seem somewhat contradictory. In this population-based birth cohort study, we aimed to evaluate the relationship between objectively measured PA and vertebral size.MethodsThe study population consisted of 1202 cohort participants who underwent PA and vertebral size measurements at the age of 46 to 48 yr. Moderate-to-vigorous PA (MVPA, ≥3.5 METs) was measured by a wrist-worn accelerometer (Polar Active; Polar Electro, Finland) for 14 d. The vertebral axial cross-sectional area (CSA) of the L4 vertebra was measured and calculated from lumbar magnetic resonance imaging scans at 46 to 48 yr. We analyzed the association between the daily amount of MVPA (min·d−1) and vertebral CSA using multivariable linear regression analysis.ResultsThe daily amount of MVPA was significantly and positively associated with CSA in both sexes. For every minute per day of MVPA, men had 0.71 mm2(95% confidence interval, 0.36–1.06) and women 0.90 mm2(95% confidence interval, 0.58–1.21) larger CSA.ConclusionsPhysical activity of at least moderate intensity is positively associated with vertebral size and may thus prevent future vertebral fractures.