A Machine Learning Approach to Identify Predictors of Severe COVID-19 Outcome in Patients With Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) patients have a lowered immune response to infection, potentially due to the use of corticosteroids and immunosuppressive drugs. Predictors of severe COVID-19 outcomes within the RA population have not yet been explored in a real-world setting. OBJECTIVES: To identify the most influential predictors of severe COVID-19 within the RA population. STUDY DESIGN: Retrospective cohort study. SETTING: Research was conducted using Optum's de-identified Clinformatics® Data Mart Database (2000-2021Q1), a US commercial claims database. METHODS: We identified adult patients with index COVID-19 (ICD-10-CM diagnosis code U07.1) between March 1, 2020, and December 31, 2020. Patients were required to have continuous enrollment and have evidence of one inpatient or 2 outpatient diagnoses of RA in the 365 days prior to index. RA patients with COVID-19 were stratified by outcome (mild vs severe), with severe cases defined as having one of the following within 60 days of COVID-19 diagnosis: death, treatment in the intensive care unit (ICU), or mechanical ventilation. Baseline demographics and clinical characteristics were extracted during the 365 days prior to index COVID-19 diagnosis. To control for improving treatment options, the month of index date was included as a potential independent variable in all models. Data were partitioned (80% train and 20% test), and a variety of machine learning algorithms (logistic regression, random forest, support vector machine [SVM], and XGBoost) were constructed to predict severe COVID-19, with model covariates ranked according to importance. RESULTS: Of 4,295 RA patients with COVID-19 included in the study, 990 (23.1%) were classified as severe. RA patients with severe COVID-19 had a higher mean age (mean [SD] = 71.6 [10.3] vs 63.4 [13.7] years, P < 0.001) and Charlson Comorbidity Index (CCI) (3.8 [2.4] vs 2.4 [1.8], P < 0.001) than those with mild cases. Males were more likely to be a severe case than mild (29.1% vs 18.5%, P < 0.001). The top 15 predictors from the best performing model (XGBoost, AUC = 75.64) were identified. While female gender, commercial insurance, and physical therapy were inversely associated with severe COVID-19 outcomes, top predictors included a March index date, older age, more inpatient visits at baseline, corticosteroid or gamma-aminobutyric acid analog (GABA) use at baseline or the need for durable medical equipment (i.e., wheelchairs), as well as comorbidities such as congestive heart failure, hypertension, fluid and electrolyte disorders, lower respiratory disease, chronic pulmonary disease, and diabetes with complication. LIMITATIONS: The cohort meeting our eligibility criteria is a relatively small sample in the context of machine learning. Additionally, diagnoses definitions rely solely on ICD-10-CM codes, and there may be unmeasured variables (such as labs and vitals) due to the nature of the data. These limitations were carefully considered when interpreting the results. CONCLUSIONS: Predictive baseline comorbidities and risk factors can be leveraged for early detection of RA patients at risk of severe COVID-19 outcomes. Further research should be conducted on modifiable factors in the RA population, such as physical therapy.

Labor prior to cesarean delivery associated with higher post-discharge opioid consumption.

BACKGROUND: Severe acute post-cesarean delivery (CD) pain has been associated with an increased risk for persistent pain and postpartum depression. Identification of women at increased risk for pain can be used to optimize post-cesarean analgesia. The impact of labor prior to CD (intrapartum CD) on acute post-operative pain and opioid use is unclear. We hypothesized that intrapartum CD, which has been associated with both increased inflammation and affective distress related to an unexpected surgical procedure, would result in higher postoperative pain scores and increased opioid intake. METHODS: This is a secondary analysis of a prospective cohort study examining opioid use up to 2 weeks following CD. Women undergoing CD at six academic medical centers in the United States 9/2014-3/2016 were contacted by phone two weeks following discharge. Participants completed a structured interview that included questions about postoperative pain scores and opioid utilization. They were asked to retrospectively estimate their maximal pain score on an 11-point numeric rating scale at multiple time points, including day of surgery, during hospitalization, immediately after discharge, 1st week, and 2nd week following discharge. Pain scores over time were assessed utilizing a generalized linear mixed-effects model with the patient identifier being a random effect, adjusting for an a priori defined set of confounders. A multivariate negative binomial model was utilized to assess the association between intrapartum CD and opioid utilization after discharge, also adjusting for the same confounders. In the context of non-random prescription distribution, this model was constructed with an offset for the number of tablets dispensed. RESULTS: A total of 720 women were enrolled, 392 with and 328 without labor prior to CD. Patients with intrapartum CD were younger, less likely to undergo repeat CD or additional surgical procedures, and more likely to experience a complication of CD. Women with intrapartum CD consumed more opioid tablets following discharge than women without labor (median 20, IQR 10-30 versus 17, IQR 6-30; p = 0.005). This association persisted after adjustment for confounders (incidence rate ratio 1.16, 95% CI 1.05-1.29; p = 0.004). Pain scores on the day of surgery were higher in women with intrapartum CD (difference 0.91, 95% CI 0.52-1.30; adj. p = <0.001) even after adjustment for confounders. Pain scores at other time points were not meaningfully different between the two groups. CONCLUSION: Intrapartum CD is associated with worse pain on the day of surgery but not other time points. Opioid requirements following discharge were modestly increased following intrapartum CD.

A comparison of sex, morphology, physiology and behavior of black-capped chickadees trapped using two common capture methods.

Many biological studies require the capture of individuals for sampling, for example for measurement of morphological or physiological traits, or for marking individuals for later observations. Capture methods employed often vary both within and between studies, and these differing methods could be more or less effective in capture of different individuals based on their morphology or behavior. If individuals that are prone to capture by the selected method differ with respect to traits of interest, such sampling bias could generate misleading or simply inaccurate results. The selection of capture methods could introduce two different forms of sampling bias, with the individuals that are sampled differing from the population at large or with individuals sampled via one method differing from individuals that could be sampled using a different method. We investigated this latter form of sampling bias by comparing individual birds sampled using two common capture techniques. We caught free-ranging black-capped chickadees (Poecile atricapillus) using walk-in traps baited with seed and mist nets paired with playback of an audio stimulus (conspecific mobbing calls). We measured 18 traits that we expect might vary among birds that are trappable by these differing methods-one that targets birds that are food motivated and potentially less neophobic and another that targets birds that respond readily to a perceived predation risk. We found no differences in the sex, morphology, initial and stress-induced corticosterone concentrations, behavioral response to a novel object, or behavioral response to a predator between individuals captured by these two methods. Individual variation in the behavioral response to a novel object was greater among birds caught by mist nets, suggesting this method might provide a sample that better reflects population-level individual variation. We do not know if the birds caught by these two methods provide a representative sample of the population at large, but can conclude that selection of either of these two common capture methods can similarly sample mean trait values of a population of interest. To accurately assess individual variation, particularly in behavior, mist nets might be preferable.

An Analysis of Real-World Data on the Safety of Etanercept in Older Patients with Rheumatoid Arthritis.

OBJECTIVE: The aim of this study was to use real-world data to evaluate potential interactions between age, treatment, and the risk of developing four adverse events (AEs) common in the elderly: congestive heart failure, serious infections, non-melanoma skin cancer, and interstitial lung disease. These AEs were identified as important in a prior age-based analysis (≤ 65 vs > 65 years) of etanercept- or placebo-treated patients with rheumatoid arthritis (RA) in controlled clinical trials. METHODS: Real-world data (1 January 2013 to 31 January 2018) were obtained from the IBM Watson Health MarketScan® Database. Patients were included if aged ≥ 18 years, enrolled for ≥ 1 year prior to RA diagnosis, and without any of the four AEs of interest prior to RA diagnosis or between RA diagnosis and first etanercept exposure. Logistic regression analysis was applied following propensity matching of patients receiving or not receiving etanercept based on age at diagnosis, age status at the beginning of observation (> 65 years or not), sex, geographic region, and follow-up duration. RESULTS: The overall cohort comprised 403,689 patients. The absolute risk of each of the four AEs increased with age. In propensity-matched cohorts, etanercept was associated with significantly higher odds of developing each of the four AEs (p < 0.001 for all). However, the relative risk of experiencing the four AEs in patients who received etanercept versus those who did not was similar between patients ≤ 65 years of age and those > 65 years of age. CONCLUSIONS: In patients with RA, the relative increase in etanercept-associated risk of experiencing congestive heart failure, serious infection, non-melanoma skin cancer, or interstitial lung disease was similar between elderly and non-elderly.

Race/Ethnicity and Sex and Opioid Administration in the Emergency Room.

BACKGROUND: Although racial/ethnic and sex disparities have been examined in health care generally and pain management more specifically, the combined influence of these sociodemographic factors together has not been well documented. The aim of this study was to examine the association between administration of opioid analgesics in the emergency department (ED) and interaction of race/ethnicity and sex. METHODS: We conducted a retrospective cohort study using 2010-2014 Center for Disease Control-National Hospital Ambulatory Medical Care Survey data for patients 12-55 years of age presenting to EDs with a primary diagnosis of appendicitis or gallbladder disease as defined by International Classification of Diseases, Ninth Revision codes. The primary outcome was the receipt of opioid analgesic medications. Secondary outcomes included: receipt of nonopioids, receipt of antiemetic medications, wait time to see a provider, and length of visit in the ED. The association between sex and analgesic receipt within Caucasian non-Hispanic and non-Caucasian groups was evaluated adjusting for pain score on presentation, patient age, emergent status, number of comorbidities, time of visit (month, day of the week, standard versus nonstandard working hours, year), and US region. RESULTS: After exclusions, a weighted sample of 553 ED visits was identified, representing 2,622,926 unique visits. The sample population was comprised of 1,858,035 (70.8%) females and 1,535,794 (58.6%) Caucasian non-Hispanics. No interaction was found in adjusted sampling-weighted model between sex and race/ethnicity on the odds of receiving opioids (P = .74). There was no difference in opioid administration to males as compared to females (odds ratio [OR] = 0.96, 95% CI, 0.87-1.06; P = .42) or to non-Caucasians as compared to Caucasians (OR = 0.99, 95% CI, 0.89-1.10; P = .84). In adjusted weighted models, non-Caucasian males, 123,121/239,457 (51.4%) did not differ from Caucasian non-Hispanic males, 317,427/525,434 (60.4%), on odds of receiving opioids, aOR = 0.88, 95% CI, 0.39-1.99; P = .75. Non-Caucasian females, 547,709/847,675 (64.6%) also did not differ from Caucasian females, 621,638/1,010,360 (61.5%), on odds of receiving opioids, aOR = 1.01, 95% CI, 0.53-1.90; P = .98. Across both sexes, non-Caucasians did not differ from Caucasians on receipt of nonopioid analgesics or antiemetics. Neither wait time to see a provider nor the length of the hospital visit was significantly different between sexes or race/ethnicities. CONCLUSIONS: Based on National Hospital Ambulatory Medical Care Survey data from 2010 to 2014, there is no statistically significant interaction between race/ethnicity and sex for administration of opioid analgesia to people presenting to the ED with appendicitis or gallbladder disease. These results suggest that the joint effect of patient race/ethnicity and sex may not manifest in disparities in opioid management.

Patent foramen ovale and long-term risk of ischaemic stroke after surgery.

AIMS: Pre-operatively diagnosed patent foramen ovale (PFO) is associated with an increased risk of ischaemic stroke within 30 days after surgery. This study aimed to assess the PFO-attributable ischaemic stroke risk beyond the perioperative period. METHODS AND RESULTS: This observational study of adult patients without history of stroke undergoing non-cardiac surgery with general anaesthesia examined the association of PFO with ischaemic stroke 1 and 2 years after surgery using multivariable logistic regression. Of the 144 563 patients included, a total of 1642 (1.1%) and 2376 (1.6%) ischaemic strokes occurred within 1 and 2 years after surgery, 54 (4.7%) and 76 (6.6%) among patients with PFO, and 1588 (1.1%) and 2300 (1.6%) among patients without PFO, respectively. The odds of ischaemic stroke within 1 and 2 years after surgery were increased in patients with PFO: adjusted odds ratio (aOR) 2.01, 95% confidence interval (CI) 1.51-2.69; P < 0.001 and aOR 2.10, 95% CI 1.64-2.68; P < 0.001, respectively. Among patients who underwent contrast transoesophageal echocardiography, the frequency of PFO was 27%, and the increased stroke risk in patients with PFO was robust (aOR 3.80, 95% CI 1.76-8.23; P = 0.001 for year 1). The PFO-attributable risk was mitigated by post-operative prescription of combination antithrombotic therapy (odds ratio 0.41, 95% CI 0.22-0.75; P for interaction = 0.004). CONCLUSION: Patients with PFO are vulnerable to ischaemic stroke for an extended period of time after surgery. Physicians should consider implementing PFO screening protocols in patients scheduled for major non-cardiac surgery.

Association of Preoperatively Diagnosed Patent Foramen Ovale With Perioperative Ischemic Stroke.

Importance: Perioperative stroke is a major complication for patients undergoing surgery. Patent foramen ovale (PFO) represents a possible anatomical link between venous thrombosis and stroke. Objective: To determine whether a preoperatively diagnosed PFO is associated with increased risk of perioperative ischemic stroke. Design, Setting, and Participants: Retrospective cohort study from Massachusetts General Hospital and 2 affiliated community hospitals between January 1, 2007, and December 31, 2015. Participants were 182 393 consecutive adults undergoing noncardiac surgery with general anesthesia. Exposures: Preoperatively diagnosed PFO. Main Outcomes and Measures: Perioperative ischemic stroke occurring within 30 days of surgery; stroke subtype by Oxfordshire Community Stroke Project classification and stroke severity by National Institute of Health Stroke Scale (NIHSS). Results: Among the 150 198 patient cases analyzed (median [SD] age, 55 [16] years), 1540 (1.0%) had a diagnosis of PFO before surgery. A total of 850 (0.6%) ischemic strokes occurred within 30 days of surgery (49 [3.2%] among patients with PFO and 801 [0.5%] among patients without PFO). In adjusted analyses, patients with PFO had an increased risk of ischemic stroke compared with patients without PFO (odds ratio, 2.66 [95% CI, 1.96-3.63]; P < .001). The estimated risks of stroke were 5.9 for every 1000 patients with PFO and 2.2 for every 1000 patients without PFO (adjusted absolute risk difference, 0.4% [95% CI, 0.2%-0.6%). Patients with PFO also had an increased risk of large vessel territory stroke (relative risk ratio, 3.14 [95% CI, 2.21-4.48]; P < .001) and a more severe stroke-related neurologic deficit measured by NIHSS (median, 4 [interquartile range {IQR}, 2-10] vs median, 3 [IQR, 1-6] for those without PFO; P = .02). Conclusions and Relevance: Among adult patients undergoing noncardiac surgery at 3 hospitals, having a preoperatively diagnosed PFO was significantly associated with increased risk of perioperative ischemic stroke within 30 days after surgery. Further research is needed to confirm these findings and to determine whether interventions would decrease this risk.

Assessment of Tricuspid Annular Motion by Speckle Tracking in Anesthetized Patients Using Transesophageal Echocardiography.

BACKGROUND: The perioperative assessment of right ventricular (RV) function remains a challenge. Tricuspid annular plane systolic excursion (TAPSE) using M-mode is a widely used measure of RV function. However, accurate alignment of the ultrasound beam with the direction of annular movement can be difficult with transesophageal echocardiography (TEE) to measure TAPSE, precluding effective use of M-mode to measure annular excursion. Tracking of specular reflectors in the myocardium may provide an angle-independent method to assess annular motion with TEE. We hypothesized that TEE speckle tracking of the lateral tricuspid annular motion represents a comparable measurement to the well-validated M-mode TAPSE on transthoracic echocardiogram (TTE), and may be considered as a reasonable alternative to TAPSE. METHODS: This is a prospective, observational cohort study. We included all patients, who were in sinus rhythm, with a preoperative TTE within 3 months of scheduled cardiac surgery that required intraoperative TEE. Tissue motion annular displacements (TMAD) of the lateral (L), septal (S), and midpoint (M) tricuspid annulus were measured (QLAB Cardiac Motion Quantification; Philips Medical, Andover, MA) after induction of general anesthesia. This was compared to the preoperative M-mode TAPSE on TTE. RESULTS: Seventy-two consecutive patients who met eligibility requirements were enrolled from September to November 2016. Twelve were excluded due to poor image quality, allowing TMAD to be analyzed in 60 patients. TMAD was analyzed offline and TMAD analysis was able to track tricuspid annular motion in all patients. The mean TMAD (L), TMAD (S), and TMAD (M) were 17.4 ± 5.2, 10.2 ± 4.8, and 14.2 ± 4.8 mm, respectively. TMAD (L) showed close correlation with M-mode TAPSE on TTE (r = 0.87, 95% confidence interval, 0.79-0.92; P < .01). All patients with a preoperative TAPSE <17 mm had a TMAD (L) <17 mm, while 71% of those with a TAPSE ≥ 17 mm had a TMAD (L) ≥ 17 mm. There was strong positive correlation between TMAD (L) and intraoperative RV fractional area change (r = 0.86, 95% confidence interval, 0.77-0.91; P < .01). Reproducibility analysis of TMAD within and across observers showed excellent correlation. CONCLUSIONS: TMAD is a quick and angle-independent method to quantitatively assess RV longitudinal function by TEE. It correlates strongly with M-mode TAPSE on TTE. Because TMAD and TAPSE were not simultaneously measured in this study, their correlation is subject to differences in loading conditions, general anesthesia, and changes in the disease process. TMAD may be easily applied in routine clinical settings and its role in the perioperative environment deserves to be further explored.

Intraoperative Esmolol as an Adjunct for Perioperative Opioid and Postoperative Pain Reduction: A Systematic Review, Meta-analysis, and Meta-regression.

BACKGROUND: Esmolol is an ultrashort ß-1 receptor antagonist. Recent studies suggest a role for esmolol in pain response modulation. The authors performed a meta-analysis to determine if the intraoperative use of esmolol reduces opioid consumption or pain scores. METHODS: PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, pubget, and Google Scholar were searched. Studies were included if they were randomized, placebo- or opioid-controlled trials written in English, and performed on patients 18 years of age or older. For comparison of opioid use, included studies tracked opioid consumption intraoperatively and/or in the postanesthesia care unit. Pain score comparisons were performed during the first hour after surgery. RESULTS: Seventy-three studies were identified, 23 were included in the systematic review, and 19 were eligible for 1 or more comparisons. In 433 patients from 7 trials, intraoperative esmolol decreased intraoperative opioid consumption (Standard Mean Difference [SMD], -1.60; 95% confidence interval [CI], -2.25 to -0.96; P ≤ .001). In 659 patients from 12 trials, intraoperative esmolol decreased postanesthesia care unit opioid consumption (SMD, -1.21; 95% CI, -1.66 to -0.77; P ≤ .001). In 688 patients from 11 trials, there was insufficient evidence of change in postoperative 1 hour pain scores (SMD, -0.60; 95% CI, -1.44 to 0.24; P = .163). CONCLUSIONS: This meta-analysis demonstrates that intraoperative esmolol use reduces both intraoperative and postoperative opioid consumption, with no change in postoperative pain scores.

Dexmedetomidine promotes biomimetic non-rapid eye movement stage 3 sleep in humans: A pilot study.

OBJECTIVES: Sleep, which comprises of rapid eye movement (REM) and non-REM stages 1-3 (N1-N3), is a natural occurring state of decreased arousal that is crucial for normal cardiovascular, immune and cognitive function. The principal sedative drugs produce electroencephalogram beta oscillations, which have been associated with neurocognitive dysfunction. Pharmacological induction of altered arousal states that neurophysiologically approximate natural sleep, termed biomimetic sleep, may eliminate drug-induced neurocognitive dysfunction. METHODS: We performed a prospective, single-site, three-arm, randomized-controlled, crossover polysomnography pilot study (n = 10) comparing natural, intravenous dexmedetomidine- (1-µg/kg over 10 min [n = 7] or 0.5-µg/kg over 10 min [n = 3]), and zolpidem-induced sleep in healthy volunteers. Sleep quality and psychomotor performance were assessed with polysomnography and the psychomotor vigilance test, respectively. Sleep quality questionnaires were also administered. RESULTS: We found that dexmedetomidine promoted N3 sleep in a dose dependent manner, and did not impair performance on the psychomotor vigilance test. In contrast, zolpidem extended release was associated with decreased theta (∼5-8 Hz; N2 and N3) and increased beta oscillations (∼13-25 Hz; N2 and REM). Zolpidem extended release was also associated with increased lapses on the psychomotor vigilance test. No serious adverse events occurred. CONCLUSIONS: Pharmacological induction of biomimetic N3 sleep with psychomotor sparing benefits is feasible. SIGNIFICANCE: These results suggest that α2a adrenergic agonists may be developed as a new class of sleep enhancing medications with neurocognitive sparing benefits.

Loss of Efficacy to Spinal Cord Stimulator Therapy: Clinical Evidence and Possible Causes.

BACKGROUND: Although spinal cord stimulation (SCS) therapy has been shown to be efficacious in various pain conditions, the ability for SCS therapy to maintain long-term efficacy has been questioned. OBJECTIVE: The purpose of this study was to investigate whether a loss of efficacy (LOE) phenomenon exists with SCS therapy and to investigate if this phenomenon is more apparent in any specific patient population. STUDY DESIGN: A retrospective, observation chart review was conducted to evaluate the patient response to SCS therapy over time. SETTING: Massachusetts General Hospital, Boston, Massachusetts. METHODS: Patients who received a SCS at the Massachusetts General Hospital, between January 1, 2002 and December 31, 2012, were invited to participate. A total of 62 patients were included in this study. Various models were created to analyze pain score changes over time using 2-tailed statistical analysis. Additionally, one-way ANOVA and Pearson's chi-square tests were used to determine if certain patient characteristics were associated with LOE. RESULTS: Compared to the visual analog scale (VAS) score at one month after device implantation, pain scores increased 1.95 points after 2 years (95% CI: 1.06 to 2.84, P = < 0.001). There were no significant differences in baseline characteristics between the groups of patients who did and did not lose efficacy of their therapy. However, those who experienced LOE had a baseline SCS therapy VAS score 3.09 points lower than those who did not (95% CI: 1.69 to 4.48, P = < 0.001). LIMITATIONS: This study had several limitations including the retrospective nature of its design, confounders to VAS scores, small sample size, missing data points, and the evaluation of only conventional, low-frequency SCS therapy. CONCLUSIONS: Patients who received a SCS had a significant increase in VAS scores over time. Our data did not show any baseline patient characteristic that helped predict LOE. However, patients who have significant baseline response to therapy may be more likely to experience LOE. KEY WORDS: Spinal cord stimulation, chronic pain, retrospective study, low frequency electrical stimulation, efficacy, chronic pain therapy.

Changing Resident Physician Studying Behaviors: A Randomized, Comparative Effectiveness Trial of Goal Setting Versus Use of WOOP.

BACKGROUND: Following through on one's goals to study is essential for effective, self-regulated learning. This can be difficult for residents because of clinical demands and limited personal time. WOOP (Wish, Outcome, Obstacle, Plan) is a self-regulation strategy, also known as mental contrasting with implementation intentions. WOOP increases follow-through on goals in many domains, although it has not, to our knowledge, been evaluated in medical education. OBJECTIVE: We compared the effect of WOOP versus goal setting on time residents spent studying. METHODS: Through a prospective, randomized, comparative effectiveness study, during a 1-month, intensive care unit rotation, we clustered anesthesiology residents in single-blind fashion to WOOP versus goal setting. Both groups received organized study materials. The intervention group performed WOOP to study more; the comparison group set goals to study more. Residents tracked studying with daily diaries. The primary outcome was total time spent studying toward stated goals. Time spent studying "non-goal" medical material was a secondary outcome. RESULTS: Of 34 eligible residents, 100% participated. Sixteen residents were randomized to the WOOP group and 18 to the goal-setting group. The WOOP group spent significantly more time studying toward their goals compared with the goal-setting group (median = 4.3 hours versus 1.5 hours; P = .021; g = 0.66). There was no significant difference in time spent studying non-goal medical material between groups (median = 5.5 hours versus 5.0 hours, P = .99). CONCLUSIONS: WOOP increased the time residents spent studying toward their goals as compared with setting goals alone.

Sensitivity to Sevoflurane anesthesia is decreased in mice with a congenital deletion of Guanylyl Cyclase-1 alpha.

BACKGROUND: Volatile anesthetics increase levels of the neurotransmitter nitric oxide (NO) and the secondary messenger molecule cyclic guanosine monophosphate (cGMP) in the brain. NO activates the enzyme guanylyl cyclase (GC) to produce cGMP. We hypothesized that the NO-GC-cGMP pathway contributes to anesthesia-induced unconsciousness. METHODS: Sevoflurane-induced loss and return of righting reflex (LORR and RORR, respectively) were studied in wild-type mice (WT) and in mice congenitally deficient in the GC-1α subunit (GC-1-/- mice). Spatial distributions of GC-1α and the GC-2α subunit in the brain were visualized by in situ hybridization. Brain cGMP levels were measured in WT and GC-1-/- mice after inhaling oxygen with or without 1.2% sevoflurane for 20 min. RESULTS: Higher concentrations of sevoflurane were required to induce LORR in GC-1-/- mice than in WT mice (1.5 ± 0.1 vs. 1.1 ± 0.2%, respectively, n = 14 and 14, P < 0.0001). Similarly, RORR occurred at higher concentrations of sevoflurane in GC-1-/- mice than in WT mice (1.0 ± 0.1 vs. 0.8 ± 0.1%, respectively, n = 14 and 14, P < 0.0001). Abundant GC-1α and GC-2α mRNA expression was detected in the cerebral cortex, medial habenula, hippocampus, and cerebellum. Inhaling 1.2% sevoflurane for 20 min increased cGMP levels in the brains of WT mice from 2.6 ± 2.0 to 5.5 ± 3.7 pmol/mg protein (n = 13 and 10, respectively, P = 0.0355) but not in GC-1-/- mice. CONCLUSION: Congenital deficiency of GC-1α abolished the ability of sevoflurane anesthesia to increase cGMP levels in the whole brain, and increased the concentration of sevoflurane required to induce LORR. Impaired NO-cGMP signaling raises the threshold for producing sevoflurane-induced unconsciousness in mice.

A Shared Decision-Making Intervention to Guide Opioid Prescribing After Cesarean Delivery.

OBJECTIVE: To assess whether a shared decision-making intervention decreases the quantity of oxycodone tablets prescribed after cesarean delivery. TECHNIQUE: A tablet computer-based decision aid formed the basis of a shared decision-making session to guide opioid prescribing after cesarean delivery. Women first received information on typical trajectories of pain resolution and expected opioid use after cesarean delivery and then chose the number of tablets of 5 mg oxycodone they would be prescribed up to the institutional standard prescription of 40 tablets. EXPERIENCE: From April 11, 2016, to June 10, 2016, 105 women were screened, 75 were eligible, and 51 consented to participate; one patient was excluded after enrollment as a result of prolonged hospitalization. The median number of tablets (5 mg oxycodone) women chose for their prescription was 20.0 (interquartile range 15.0-25.0), which was less than the standard 40-tablet prescription (P<.001). CONCLUSION: A shared decision-making approach to opioid prescribing after cesarean delivery was associated with approximately a 50% decrease in the number of opioids prescribed postoperatively in this cohort compared with our institutional standard prescription. This approach is a promising strategy to reduce the amount of leftover opioid medication after treatment of acute postcesarean pain. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02770612.

Patterns of Opioid Prescription and Use After Cesarean Delivery.

OBJECTIVE: To define the amount of opioid analgesics prescribed and consumed after discharge after cesarean delivery. METHODS: We conducted a survey at six academic medical centers in the United States from September 2014 to March 2016. Women who had undergone a cesarean delivery were contacted by phone 2 weeks after discharge and participated in a structured interview about the opioid prescription they received on discharge and their oral opioid intake while at home. RESULTS: A total of 720 women were enrolled; of these, 615 (85.4%) filled an opioid prescription. The median number of dispensed opioid tablets was 40 (interquartile range 30-40), the median number consumed was 20 (interquartile range 8-30), and leftover was 15 (interquartile range 3-26). Of those with leftover opioids, 95.3% had not disposed of the excess medication at the time of the interview. There was an association between a larger number of tablets dispensed and the number consumed independent of patient characteristics. The amount of opioids dispensed did not correlate with patient satisfaction, pain control, or the need to refill the opioid prescription. CONCLUSION: The amount of opioid prescribed after cesarean delivery generally exceeds the amount consumed by a significant margin, leading to substantial amounts of leftover opioid medication. Lower opioid prescription correlates with lower consumption without a concomitant increase in pain scores or satisfaction.

Using Search Engines to Investigate Shared Migraine Experiences.

OBJECTIVES: To investigate migraine patterns in the United States using Google search data and utilize this information to better understand societal-level trends. Additionally, we aimed to evaluate time-series relationships between migraines and social factors. BACKGROUND: Extensive research has been done on clinical factors associated with migraines, yet population-level social factors have not been widely explored. Migraine internet search data may provide insight into migraine trends beyond information that can be gleaned from other sources. METHODS: In this longitudinal analysis of open access data, we performed a time-series analysis in which about 12 years of Google Trends data (January 1, 2004 to August 15, 2016) were assessed. Data points were captured at a daily level and Google's 0-100 adjusted scale was used as the primary outcome to enable the comparison of relative popularity in the migraine search term. We hypothesized that the volume of relative migraine Google searches would be affected by societal aspects such as day of the week, holidays, and novel social events. RESULTS: Several recurrent social factors that drive migraine searches were identified. Of these, day of the week had the most significant impact on the volume of Google migraine searches. On average, Mondays accumulated 13.31 higher relative search volume than Fridays (95% CI: 11.12-15.51, P ≤ .001). Surprisingly, holidays were associated with lower relative migraine search volumes. Christmas Day had 13.84 lower relative search volumes (95% CI: 6.26-21.43, P ≤ .001) and Thanks giving had 20.18 lower relative search volumes (95% CI: 12.55-27.82, P ≤ .001) than days that were not holidays. Certain novel social events and extreme weather also appear to be associated with relative migraine Google search volume. CONCLUSIONS: Social factors play a crucial role in explaining population level migraine patterns, and thus, warrant further exploration.

The effect of head rotation on efficiency of face mask ventilation in anaesthetised apnoeic adults: A randomised, crossover study.

BACKGROUND: Upper airway obstruction occurs commonly after induction of general anaesthesia. It is the major cause of difficult mask ventilation. OBJECTIVES: The aim of this study was to determine whether head rotation improves the efficiency of mask ventilation of anaesthetised apnoeic adults. DESIGN: A randomised, crossover study. SETTING: Single university teaching hospital. PATIENTS: Forty patients, aged 18 to 75 years with a BMI 18.5 to 35.0 kg m requiring general anaesthesia for elective surgery were recruited and randomised into two groups. INTERVENTIONS: Once apnoeic after induction of general anaesthesia, face mask ventilation began with pressure controlled ventilation, at a peak inspiratory pressure of 15 cmH2O. Each patient was ventilated for three 1-min intervals with the head position alternated every minute: group A, mask ventilation was performed with a neutral head position for 1 min, followed by an axial head position rotated 45° to the right for 1 min and then returned to the neutral position for another 1 min. In group B, the sequence of head positioning was rotated → neutral → rotated. MAIN OUTCOME MEASURES: Expiratory tidal volume, measured with a respiratory inductive plethysmograph. RESULTS: Two patients were excluded due to protocol violation; thus, data from 38 patients were analysed. The mean expiratory tidal volume was significantly higher in the rotated head position than in the neutral position (612.6 vs. 544.0 ml: difference [95% confidence interval], 68.6 [46.8 to 90.4] ml, P < 0.0001). CONCLUSION: Head rotation of 45° in anaesthetised apnoeic adults significantly increases the efficiency of mask ventilation compared with the neutral head position. Head rotation is an effective alternative to improve mask ventilation if airway obstruction is encountered. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02755077.

Comparison of the carbon dioxide laser and the radiofrequency unit for feline onychectomies.

This study compared the collateral tissue damage and incisional bridging with granulation tissue via histopathological examination following feline onychectomy performed by radiofrequency (RF) and carbon dioxide (CO(2)) laser. Two cats were euthanized, and their digits were harvested for histopathological evaluation on days 1, 3, and 7 post-onychectomy. Each digit was evaluated for total lesion width, total necrosis width, and degree of edema, hemorrhage, and inflammation. This study found few significant differences in collateral tissue damage between RF and CO(2) laser, but more incisional bridging by granulation tissue was noted with RF for feline onychectomies. These results indicate that RF for feline onychectomy is a reasonable alternative to CO(2) laser in regard to collateral tissue damage and bridging of the incision by granulation tissue. In addition, RF is not accompanied by the strict safety considerations and initial expense of acquisition of a CO(2) laser.