Association of Laryngeal Botulinum Neurotoxin Injection With Work Productivity for Patients With Spasmodic Dysphonia.

Importance: A disordered voice can affect an individual across both work and non-work-related life domains. There is insufficient research on the effect of spasmodic dysphonia or its treatment with botulinum neurotoxin (BoNT) injections on work productivity. Objective: To assess whether employed patients with spasmodic dysphonia experience voice-related work productivity impairment before BoNT injection, and had a 10% or greater improvement in productivity 1 month after treatment with BoNT injection. Design, Setting, and Particpants: This prospective case series carried out in 2 laryngology outpatient clinics from November 1, 2015, to August 30, 2018 included a consecutive sample of adult employed patients diagnosed with spasmodic dysphonia. Analysis was conducted between November 1, 2015, to July 31, 2018. Exposures: Treatment with BoNT injection into the intrinsic laryngeal musculature. Main Outcomes and Measures: Eligible participants completed the following validated outcomes instruments immediately before and 1 month after outpatient laryngeal BoNT injection: the Work Productivity and Activity Impairment instrument (WPAI), Voice Handicap Index (VHI), and WorkHoarse. Demographic, comorbidity, and occupational voice use data were also collected at baseline. The changes in outcome measures (primary, WPAI Work Productivity Impairment domain) were tested using a paired 2-tailed t test. Exploratory subgroup analyses were analyzed with multivariable linear regression, adjusting for demographic, comorbidity, and voice use variables. Results: Of the 101 patients enrolled, 75 completed the study. The mean (SD) age of the 75 completing participants was 55.7 (11.8) years and 53 (71%) were women. The participants who completed the study had mean (SD) voice-related work productivity impairment of 43% (27%) at baseline and 22% (23%) at 1 month after BoNT injection (difference, 20% [27%] improvement; 95% CI, 14%-27%; effect size, 0.74). Conclusions and Relevance: This case series study found that employed patients with spasmodic dysphonia reported voice-related work productivity impairment, which improved significantly 1 month after treatment with BoNT injection. The association of spasmodic dysphonia with voice-related work productivity appeared greater in women than men with comparable outcomes with BoNT treatment, but this exploratory sex-associated difference requires independent validation.

Parents' Satisfaction with Silver Diamine Fluoride Treatment of Carious Lesions in Children.

Purpose: Current national evidence-based recommendations for treatment of carious lesions include the use of 38 percent silver diamine fluoride (SDF). The purpose of this study was to learn parents' opinions of esthetic changes to their children's teeth following treatment with SDF.
Methods: Three-hundred nineteen parents who had previously consented to SDF for caries arrest or caries prevention were asked if their child received SDF, if they noticed changes because of SDF, and how "bothered" they were by the changes.
Results: Two-hundred ten parents reported their child received SDF in the past 12 months, of whom 76 percent were confirmed by Codes on Dental Procedures and Nomenclature (CDT): 115 children received SDF for caries arrest and 45 received topical fluoride (SDF) for prevention. Of all 210 who reported SDF, 30 percent described discoloration of their child's teeth or gingiva. On a scale of zero (not bothered at all by changes due to SDF) to 10 (very bothered), parents' average rating was 1.2 ipoints; the average within the caries arrest group was 1.7.
Conclusion: Dental treatment requires a shared decision between parents and professionals, and follow-up regarding new procedures is warranted. In this study, treatment with SDF was well accepted by most parents.

Reliability of the conditioned pain modulation paradigm across three anatomical sites.

Background and aims Conditioned Pain Modulation (CPM) is a measure of pain inhibition-facilitation in humans that may elucidate pain mechanisms and potentially serve as a diagnostic test. In laboratory settings, the difference between two pain measures [painful test stimulus (TS) without and with the conditioning stimulus (CS) application] reflects the CPM magnitude. Before the CPM test can be used as a diagnostic tool, its reliability on the same day (intra-session) and across multiple days (inter-session) needs to be known. Furthermore, it is important to determine the most reliable anatomical sites for both the TS and the CS. This study aimed to measure the intra-session and inter-session reliability of the CPM test paradigm in healthy subjects with the TS (pressure pain threshold-PPT) applied to three test sites: the face, hand, and dorsum of the foot, and the CS (cold pressor test-CPT) applied to the contralateral hand. Methods Sixty healthy participants aged 18-65 were tested by the same examiner on 3 separate days, with an interval of 2-7 days. On each day, testing was comprised of two identical experimental sessions in which the PPT test was performed on each of the three dominant anatomical sites in randomized order followed by the CPM test (repeating the PPT with CPT on the non-dominant hand). CPM magnitude was calculated as the percent change in PPT. The Intraclass Correlation Coefficient (ICC), Coefficient of Variation (CV), and Bland-Altman analyses were used to assess reliability. Results PPT relative reliability ranged from good to excellent at all three sites; the hand showed an intra-session ICC of 0.90 (0.84, 0.94) before CPT and ICC of 0.89 (0.83, 0.92) during CPT. The PPT absolute reliability was also high, showing a low bias and small variability when performed on all three sites; for example, CV of the hand intra-session was 8.0 before CPT and 8.1 during CPT. The relative reliability of the CPM test, although only fair, was most reliable when performed during the intra-session visits on the hand; ICC of 0.57 (0.37, 0.71) vs. 0.20 (0.03, 0.39) for the face, and 0.22 (0.01, 0.46) for the foot. The inter-session reliability was lower in all three anatomical sites, with the best reliability on the hand with an ICC of 0.40 (0.23, 0.55). The pattern of absolute reliability of CPM was similar to the relative reliability findings, with the reliability best on the hand, showing lower intra-session and inter-session variability (CV% = 43.5 and 51.5, vs. 70.1 and 73.1 for the face, and 75.9 and 78.9 for the foot). The CPM test was more reliable in women than in men, and in older vs. younger participants. Discussion The CPM test was most reliable when the TS was applied to the dominant hand and CS performed on the contralateral hand. These data indicate that using the CS and TS in the same but contralateral dermatome in CPM testing may create the most reliable results.

Survival of Zirconia Crowns in Primary Maxillary Incisors at 12-, 24- and 36-Month Follow-Up.

Purpose: The purpose of this study was to assess the survival probability of zirconia crowns (ZCs) on primary maxillary incisors placed in children diagnosed with severe early childhood caries at 12-, 24-, and 36-month follow-up visits in a university pediatric dental clinic. Methods: Ninety-four teeth in 30 healthy 24- to 60-month-olds who received ZCs under general anesthesia participated in this study (N equals 94). Data included children's demographics, dental-related variables, appointment dates, survival of crown, and type of failure (defined as replacement of lost ZCs or extraction of the treated tooth due to evidence of apical periodontitis prior to natural exfoliation). Descriptive statistics were performed to examine demographics, while Kaplan-Meier survival curves were used to estimate survival probabilities of ZCs over time. Unadjusted and adjusted hazard ratios (HR) from Cox proportional hazard regression with robust standard errors were used to compare risk of ZC failure by patient and tooth characteristics. Results: The overall survival probabilities for ZCs at 12, 24, and 36 months were 93 percent, 85 percent, and 76 percent, respectively. Conclusion: With esthetic characteristics and high survival probabilities, zirconia crowns present as a suitable alternative for reconstruction of primary maxillary incisors in young children. (Pediatr Dent 2019;41(5):385-90).

Nighttime Extubation Does Not Increase Risk of Reintubation, Length of Stay, or Mortality: Experience of a Large, Urban, Teaching Hospital.

BACKGROUND: In the intensive care unit (ICU), extubation failure has been associated with greater resource utilization and worsened clinical outcomes. Most recently, nighttime extubation (NTE) has been reported as a risk factor for increased ICU and hospital mortality. We hypothesized that, in a large, urban, university-affiliated hospital with multidisciplinary assessment for extubation, rigorously protocolized extubation algorithms, and expert airway managers available at all times of day for assessment of high-risk extubations, NTE would not confer additional risk of adverse clinical outcomes. METHODS: This was a retrospective cohort study of mechanically ventilated adults at a single university-affiliated hospital. NTE was defined as occurring between 7:00 PM and 6:59 AM the following day. All data were extracted from the institution's electronic medical record. Multivariable regression analyses were used to assess associations between NTE and reintubation, ICU and hospital length of stay (LOS), and mortality with adjustments for demographic and clinical covariates defined a priori. Palliative, unplanned, and routine postoperative extubations were excluded in sensitivity analyses. RESULTS: Of 2241 patients, 204 of 2241 (9.1%) underwent NTE. The rates of reintubation (NTE 6.9% versus daytime extubation [DTE] 12.4%; adjusted odds ratio [95% confidence interval {CI}], 0.78 [0.43-1.41]; P = .41) and in-hospital mortality (NTE 3.4% versus DTE 5.9%; adjusted odds ratio [95% CI], 0.72 [0.28-1.84]; P = .49) were not found to differ. NTE, compared to DTE, was associated with shorter duration of mechanical ventilation (median [interquartile range], 1 [0-1] days vs 2 [1-4] days; adjusted ratio of geometric means [RGMs] [95% CI], 0.64 [0.54-0.70]; P < .001), ICU (2 [1-5] days vs 4 [2-10] days; adjusted RGMs [95% CI], 0.65 [0.57-0.75]; P < .001), and hospital LOS (6 [3-18] days vs 13 [6-25] days; adjusted RGMs [95% CI], 0.64 [0.56-0.74]; P < .001). These results were unchanged in sensitivity analyses. CONCLUSIONS: Patients who underwent NTE were not at increased risk of reintubation or in-hospital mortality. In addition, NTE was associated with a shortened duration of mechanical ventilation and hospital LOS. In health care systems with similar critical care delivery models, NTE may coincide with reduced resource utilization in appropriately selected patients.

Process Optimization and Digital Quality Improvement to Enhance Timely Initiation of Epidural Infusions and Postoperative Pain Control.

BACKGROUND: Although intraoperative epidural analgesia improves postoperative pain control, a recent quality improvement project demonstrated that only 59% of epidural infusions are started in the operating room before patient arrival in the postanesthesia care unit. We evaluated the combined effect of process and digital quality improvement efforts on provider compliance with starting continuous epidural infusions during surgery. METHODS: In October 2014, we instituted 2 process improvement initiatives: (1) an electronic order queue to assist the operating room pharmacy with infusate preparation; and (2) a designated workspace for the storage of equipment related to epidural catheter placement and drug infusion delivery. In addition, we implemented a digital quality improvement initiative, an Anesthesia Information Management System-mediated clinical decision support, to prompt anesthesia providers to start and document epidural infusions in pertinent patients. We assessed anesthesia provider compliance with epidural infusion initiation in the operating room and postoperative pain-related outcomes before (PRE: October 1, 2012 to September 31, 2014) and after (POST: January 1, 2015 to December 31, 2016) implementation of the quality improvement initiatives. RESULTS: Compliance with starting intraoperative epidural infusions was 59% in the PRE group and 85% in the POST group. After adjustment for confounders and preintervention time trends, segmented regression analysis demonstrated a statistically significant increase in compliance with the intervention in the POST phase (odds ratio, 2.78; 95% confidence interval, 1.73-4.49; P < .001). In the PRE and POST groups, cumulative postoperative intravenous opioid use (geometric mean) was 62 and 34 mg oral morphine equivalents, respectively. A segmented regression analysis did not demonstrate a statistically significant difference (P = .38) after adjustment for preintervention time trends. CONCLUSIONS: Process workflow optimization along with Anesthesia Information Management System-mediated digital quality improvement efforts increased compliance to intraoperative epidural infusion initiation. Adjusted for preintervention time trends, these findings coincided with a statistically insignificant decrease in postoperative opioid use in the postanesthesia care unit during the POST phase.

Increased Hyaluronan and TSG-6 in Association with Neuropathologic Changes of Alzheimer's Disease.

Little is known about the extracellular matrix (ECM) during progression of AD pathology. Brain ECM is abundant in hyaluronan (HA), a non-sulfated glycosaminoglycan synthesized by HA synthases (HAS) 1-3 in a high molecular weight (MW) form that is degraded into lower MW fragments. We hypothesized that pathologic severity of AD is associated with increases in HA and HA-associated ECM molecules. To test this hypothesis, we assessed HA accumulation and size; HA synthases (HAS) 1-3; and the HA-stabilizing hyaladherin, TSG-6 in parietal cortex samples from autopsied research subjects with not AD (CERAD = 0, Braak = 0- II, n = 12-21), intermediate AD (CERAD = 2, Braak = III-IV, n = 13-18), and high AD (CERAD = 3, Braak = V-VI, n = 32-40) neuropathologic change. By histochemistry, HA was associated with deposits of amyloid and tau, and was also found diffusely in brain parenchyma, with overall HA quantity (measured by ELSA) significantly greater in brains with high AD neuropathology. Mean HA MW was similar among the samples. HAS2 and TSG-6 mRNA expression, and TSG-6 protein levels were significantly increased in high AD and both molecules were present in vasculature, NeuN-positive neurons, and Iba1-positive microglia. These results did not change when accounting for gender, advanced age (≥ 90 years versus <90 years), or the clinical diagnosis of dementia. Collectively, our results indicate a positive correlation between HA accumulation and AD neuropathology, and suggest a possible role for HA synthesis and metabolism in AD progression.

Agreement of treatment recommendations based on digital vs plaster dental models.

INTRODUCTION: The purpose of this study was to investigate differences in orthodontists' treatment plans based on digital models compared with plaster models. Additionally, we assessed whether digital or plaster models influence the reliability of orthodontists' treatment plans, as well as the amount of time required to arrive at the plan. METHODS: Sixteen orthodontists planned treatment for 20 patients at 2 time points using either the same or different model formats (digital or plaster). The treatment plan decisions and time spent making the plans were recorded. The permutation test and a random effects model were used to analyze the data. RESULTS: The treatment plans arrived at with digital and plaster models were similar. With respect to extractions, the mean difference between digital and plaster formats was 11.9% (95% CI, 7.5%-16.3%). For surgery, the mean difference was 9.4% (95% CI, 5.0%-13.8%). There was no significant difference in the agreement rate between those who viewed models in different formats compared with those who viewed models twice in the same format (P >0.05). The time spent to plan treatment with plaster models was not significantly different from the time spent with digital models (P = 0.87). CONCLUSIONS: Based on this study, digital models can be substituted for plaster models with no significant differences in the final plans, the reliability of the plans, and the time required to create the plan.

Childbearing and maternity leave in residency: determinants and well-being outcomes.

PURPOSE: To characterise determinants of resident maternity leave and their effect on maternal and infant well-being. Among non-parents, to identify factors that influence the decision to delay childbearing STUDY DESIGN: In 2016, a survey was sent to female residents at a large academic medical centre on their experiences with maternity leave, the impact of personal and programme factors on length of leave, reasons for delaying childbearing and measures of well-being. RESULTS: Forty-four percent (214/481) of residents responded. Fifty (23%) residents were parents, and 25 (12%) took maternity leave during training. The average maternity leave length was 8.4 weeks and did not differ across programme type, size or programme director gender but was longer for programmes with fewer women than men. The most common self-reported determinant of leave was financial. Residents with >8 weeks of leave were less likely to have postpartum depression or burnout and more likely to breastfeed longer, perceive support from colleagues and programme directors, and be satisfied with resident parenthood. Among 104 non-parents who were married or partnered, 84 (81%) were delaying childbearing, citing busy work schedules, concern for burdening colleagues and finances. CONCLUSIONS: This study suggests that multiple aspects of resident wellbeing are associated with longer maternity leaves, yet finances and professional relationships hinder length of leave and lead to delayed childbearing. These issues could be addressed at a programme level with clear policies describing how work is redistributed during parental leave and at an institutional and state level through provision of paid family leave.

Recommendations for clear aligner therapy using digital or plaster study casts.

BACKGROUND: Clear aligner therapy has evolved considerably since its introduction 20 years ago. Clinicians have become more experienced with aligner therapy, but little is known about the types of malocclusions that clinicians currently treat with aligners. Similarly, it is not known if viewing digital vs plaster models has any impact on the treatment planning process for aligners. The aim of this study was to assess which types of malocclusions are recommended for treatment with clear aligners, and also to determine if recommendations for aligner treatment differed when using digital versus plaster models. METHODS: Sixteen orthodontists treatment planned 20 cases at two time points with either the same or different model formats (digital versus plaster). As part of the treatment planning process, they were asked whether each patient was a good candidate for Invisalign® treatment, and if not, why. Generalized estimating equations regression (GEE), the permutation test, and a logistic regression model with GEE were used to analyze the data. RESULTS: No significant difference was found between the Invisalign® choices in the digital model group and those in the plaster model group at T1 (p = 0.59). There was no significant difference between the agreement rate of the different formats group and that of the same format group (p = 0.97). Cases with extractions had less Invisalign® recommendations (15%) compared to cases with no extractions (55%) (p = 0.0015). Cases with surgery had less Invisalign® recommendations (29%) compared to cases with no surgery (57%) (p = 0.035). CONCLUSIONS: In this study, viewing orthodontic records with digital versus plaster models did not influence decisions about Invisalign® recommendations. Additionally, the orthodontists in this study tended to not recommend Invisalign® for extraction cases, surgical cases, or difficult cases.

Effect of supplemental vibration on orthodontic treatment with aligners: A randomized trial.

INTRODUCTION: Supplemental vibration has been reported to accelerate orthodontic tooth movement and reduce discomfort. Our purpose was to investigate the effects of AcceleDent on Invisalign treatment. This randomized clinical trial was carried out in 2 orthodontic private practices with a 1:1 allocation ratio. METHODS: Adult patients who were beginning their orthodontic treatment were randomly allocated to either an active (A) or a sham (B) AcceleDent Aura device (OrthoAccel Technologies, Inc. Houston, TX). All patients were placed on a 1-week aligner change regimen, and fit was evaluated every 3 weeks. The outcomes were the ability to complete the initial set of aligners and the incisor irregularity measurements for those who completed their regimen of aligners. In addition, aligner compliance, pain levels, and oral health-related quality of life data were gathered from questionnaires. The subjects, investigators, and assessors were all blinded to the treatment arms. RESULTS: Twenty-seven subjects were randomized into 2 groups (A and B), 1 subject discontinued treatment, and 13 subjects were analyzed in each group. The Fisher exact test showed no significant difference in completion rates between the 2 groups (group A, 77%; group B, 85%; P = 1). Independent-sample t tests showed no significant difference between the final irregularity index or change in irregularity index between the 2 groups. Compliance was similar in both groups. The Wilcoxon rank sum test showed minimal differences in pain levels. Quality of life responses were similar in both groups. No serious harm was observed. CONCLUSIONS: We found no evidence that the AcceleDent Aura device impacts the ability to complete a series of aligners with a 1-week change regimen or the final alignment achieved in adult patients. It also had no significant effect on the reduction of orthodontic pain or oral health-related quality of life parameters when used with Invisalign.

Palliative Care Needs Assessment in the Neuro-ICU: Effect on Family.

BACKGROUND: Examine the association of a daily palliative care needs checklist on outcomes for family members of patients discharged from the neurosciences intensive care unit (neuro-ICU). METHODS: We conducted a prospective, longitudinal cohort study in a single, thirty-bed neuro-ICU in a regional comprehensive stroke and level 1 trauma center. One of two neuro-ICU services that admit patients to the same ICU on alternating days used a palliative care needs checklist during morning work rounds. Between March and October, 2015, surveys were mailed to family members of patients discharged from the neuro-ICU. RESULTS: Nearly half of surveys (n = 91, 48.1%) were returned at a median of 4.7 months. At the time of survey completion, mean Modified rankin scale score (mRS) of neuro-ICU patients was 3.1 (SD 2). Overall ratings of quality of care were relatively high (82.2 on a 0-100 scale) with 32% of family members meeting screening criteria for depressive syndrome. The primary outcome measuring family satisfaction, consisting of eight items from the Family Satisfaction in the ICU questionnaire, did not differ significantly between families of patients from either ICU service nor did family ratings of depression (PHQ-8) and post-traumatic stress (PCL-17). CONCLUSIONS: Among families of patients discharged from the neuro-ICU, the daily use of a palliative care needs checklist had no measurable effect on family satisfaction scores or long-term psychological outcomes. Further research is needed to identify optimal interventions to meet the palliative care needs specific to family members of patients treated in the neuro-ICU.

Idiopathic Interstitial Pneumonia Associated With Autoantibodies: A Large Case Series Followed Over 1 Year.

BACKGROUND: Some patients with autoimmune characteristics and idiopathic interstitial pneumonia, particularly usual interstitial pneumonia (UIP), do not fit neatly into the category of connective tissue disease-associated interstitial lung disease (CTD-ILD), idiopathic pulmonary fibrosis (IPF), or recently proposed yet to be validated criteria for interstitial pneumonia with autoimmune features (IPAF). Outcomes of these patients are unknown. METHODS: This was a retrospective single-center study. Analyses of variance compared differences in mean change in FVC and diffusion capacity (Dlco) over 1 year among 124 well-defined patients (20 patients with positive autoantibodies with or without symptoms of connective tissue disease [AI-ILD], 15 patients with IPAF, 36 patients with CTD-ILD, and 53 patients with IPF with negative CTD serologies [Lone-IPF]). RESULTS: Of the patients, 75% with AI-ILD, 33% with IPAF, and 33% with CTD-ILD had UIP. Initial FVC and Dlco were similarly moderately reduced across groups. Mean change in FVC over 12 months was as follows: -60 mL (IPAF), -110 mL (AI-ILD), -10 mL (CTD-ILD), and -90 mL (Lone-IPF) (P = .52). Mean change in Dlco was as follows: 2.39 mL/mm Hg/min (IPAF), -1.15 mL/mm Hg/min (AI-ILD), -0.27 mL/mm Hg/min (CTD-ILD), and -1.05 mL/mm Hg/min (Lone-IPF) (P < .001). By pattern of disease, the mean change in FVC was as follows: -140 mL (UIP), 10 mL (nonspecific interstitial pneumonia), and 12 mL (unclassifiable/other) (P = .001). CONCLUSIONS: No clinically significant differences in pulmonary function to distinguish between patients with AI-ILD, IPAF, CTD-ILD, and Lone-IPF were observed after 1 year. Longer periods of follow-up are needed to understand the outcomes of these patients. It is not yet clear whether AI-ILD is a distinct phenotype or a variant of the newly proposed entity IPAF.

Continuous intraoperative epidural infusions affect recovery room length of stay and analgesic requirements: a single-center observational study.

PURPOSE: Continuous intraoperative epidural analgesia may improve post-operative pain control and decrease opioid requirements. We investigate the effect of epidural infusion initiation before or after arrival in the post-anesthesia care unit on recovery room duration and post-operative opioid use. METHODS: We performed a retrospective chart review of abdominal, thoracic and orthopedic surgeries where an epidural catheter was placed prior to surgery at the University of Washington Medical Center during a 24 month period. RESULTS: Patients whose epidural infusions were started prior to PACU arrival (Group 2: n = 540) exhibited a shorter PACU length of stay (p = .004) and were less likely to receive intravenous opioids in the recovery room (34 vs. 48%; p < .001) compared to patients whose infusions were started after surgery (Group 1: n = 374). Although the highest patient-reported pain scores were lower in Group 2 (5.3 vs. 6.0; p = .030), no differences in the pain scores prior to PACU discharge were observed. CONCLUSION: Intraoperative continuous epidural infusions decrease PACU LOS as discharge criteria for patient-reported NRS pain scores are met earlier.

The Effect of Hyponatremia and Sodium Variability on Outcomes in Adults with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Hyponatremia is common in patients with subarachnoid hemorrhage, but its effect on outcomes remains contentious. Fluctuation in sodium has been reported to negatively affect perioperative outcomes in general surgical patients, but not specifically in patients with a subarachnoid hemorrhage. The primary aim was to describe the relationship between 1) hyponatremia and 2) sodium fluctuations during intensive care and neurologic outcome at hospital discharge. METHODS: Adults with aneurysmal subarachnoid hemorrhage between January 2012 and September 2013 were retrospectively reviewed. Data were collected for admission to day 14 of intensive care or death. Severity of illness was assessed by Hunt and Hess grade and simplified acute physiology score. Hyponatremia was defined as any measurement <135 mEq/L. Sodium variability was categorized as a maximum change of <6, 6-12, or >12 mEq/L during intensive care. Neurologic outcomes at discharge were assessed by modified Rankin Scale. The relationship between sodium and outcome was assessed by ordinal logistic regression. RESULTS: A total of 198 patients were included. After adjustment for Hunt and Hess grade, severity of systemic illness, patient age, surgical intervention, and whether or not the hyponatremia was treated with additional sodium, hyponatremia was not associated with worse neurologic outcomes. More patients with sodium variability of 6-12 and >12 mEq/L had cerebral infarction than those with variability <6 mEq/L and had modified Rankin Scale scores of 2-3 and 4-6, respectively (P = 0.001). CONCLUSIONS: Sodium fluctuation, not hyponatremia, is associated with worse neurologic outcome in patients with aneurysmal subarachnoid hemorrhage. This is in contradistinction to current teaching and warrants further examination.

Lidocaine Impairs Proliferative and Biosynthetic Functions of Aged Human Dermal Fibroblasts.

BACKGROUND: The aged are at increased risk of postoperative wound healing complications. Because local anesthetics are infiltrated commonly into the dermis of surgical wounds, we sought to determine whether local anesthetics adversely affect proliferative and biosynthetic functions of dermal fibroblasts. We also evaluated the effect of local anesthetics on insulin-like growth factor-1 (IGF-1) and transforming growth factor-ß1 (TGF-ß1), growth factors that are important regulators of wound healing. METHODS: Human dermal fibroblasts (HFB) from aged and young donors were exposed to local anesthetic agents at clinically relevant concentrations. We screened the effects of lidocaine, bupivacaine, mepivacaine, and ropivacaine on proliferation of HFB. Lidocaine was most detrimental to proliferation in HFB. We then evaluated the effect of lidocaine on expression and function of the growth factors, IGF-1 and TGF-ß1. Lastly, concurrent exposure to lidocaine and IGF-1 or TGF-ß1 was evaluated for their effects on proliferation and expression of dermal collagens, respectively. RESULTS: Lidocaine and mepivacaine inhibited proliferation in aged HFB (for lidocaine 88% of control, 95% confidence interval [CI], 80%-98%, P = .009 and for mepivacaine 90% of control, 95% CI, 81%-99%, P = .032) but not in young HFB. Ropivacaine and bupivacaine did not inhibit proliferation. Because of the clinical utility of lidocaine relative to mepivacaine, we focused on lidocaine. Lidocaine decreased proliferation in aged HFB, which was abrogated by IGF-1. Lidocaine inhibited transcripts for IGF-1 and insulin-like growth factor-1 receptor (IGF1R) in fibroblasts from aged donors (IGF-1, log2 fold-change -1.25 [42% of control, 95% CI, 19%-92%, P = .035] and IGF1R, log2 fold-change -1.00 [50% of control, 95% CI, 31%-81%, P = .014]). In contrast, lidocaine did not affect the expression of IGF-1 or IGF1R transcripts in the young HFB. Transcripts for collagen III were decreased after lidocaine exposure in aged and young HFB (log2 fold-change -1.28 [41% of control, 95% CI, 20%-83%, P = .022] in aged HFB and log2 fold-change -1.60 [33% of control, 95% CI, 15%-73%, P = .019] in young HFB). Transcripts for collagen I were decreased in aged HFB (log2 fold-change -1.82 [28% of control, 95% CI, 14%-58%, P = .006]) but not in the young HFB. Similar to the transcripts, lidocaine also inhibited the protein expression of collagen III in young and aged HFB (log2 fold-change -1.79 [29% of control, 95% CI, 18%-47%, P = .003] in young HFB and log2 fold-change -1.76 [30% of control, 95% CI, 9%-93%, P = .043] in aged HFB). The effect of lidocaine on the expression of collagen III protein was obviated by TGF-ß1 in both young and aged HFB. CONCLUSIONS: Our results show that lidocaine inhibits processes relevant to dermal repair in aged HFB. The detrimental responses to lidocaine are due, in part, to interactions with IGF-1 and TGF-ß1.

Ventilation by mask before and after the administration of neuromuscular blockade: a pragmatic non-inferiority trial.

BACKGROUND: Test ventilating prior to administration of neuromuscular blockade (NMB) in order to avoid a cannot intubate-cannot ventilate situation is a classic anesthesia teaching. The primary aim of our study was to show that facemask ventilation (FMV) after NMB was not inferior to FMV prior to NMB with respect to exhaled gas volumes before and after their administration. METHODS: This study was approved by the University of Washington Human Subjects Division (Seattle, Washington, USA). Written informed consent was obtained from all patients. Measurements of tidal volume (Vte) as well as other respiratory parameters during FMV were made for 60 s after induction of anesthesia and again after NMB. Difficult, impossible, inadequate, and dead-space only mask ventilation was graded using published definitions. Difficult intubation was defined as >2 attempts at intubation. The primary outcome was non-inferiority in Vte during both study periods defined as a mean difference of <50 mL. Multivariate analysis was performed to assess for interaction between operator experience, patient risk factors for difficult mask ventilation, exhaled volumes, and use of airway adjuncts. RESULTS: Two-hundred and ten patients were studied. Overall, FMV improved after NMBD. The mean (SD) Vte in mL/breath increased from 399 (169) to 428 (166) (mean dif. 30 mL, p = 0.001) and the minute ventilation in L/min from 5.6 (2.5) to 6.3 (2.5) (mean dif. 0.6, p < 0.001). No patient who was difficult to ventilate after induction became impossible after NMB. DISCUSSION: In patients at risk for or judged to be a difficult FMV by clinical grading scales, tidal volumes improved after administration of NMBDs. None of these patients exhibited a decline in ventilation or became impossible to ventilate after NMBDs. Several limitations are noted, including the use of hand-delivered breaths and inability to account for time-related changes in ventilation conditions independent of NMBDs. CONCLUSION: We conclude that FMV is no worse after NMB than before and is likely to improve airway conditions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02237443 . Registered August 28, 2014.

Modulation of P-glycoprotein at the Human Blood-Brain Barrier by Quinidine or Rifampin Treatment: A Positron Emission Tomography Imaging Study.

Permeability-glycoprotein (P-glycoprotein, P-gp), an efflux transporter at the human blood-brain barrier (BBB), is a significant obstacle to central nervous system (CNS) delivery of P-gp substrate drugs. Using positron emission tomography imaging, we investigated P-gp modulation at the human BBB by an approved P-gp inhibitor, quinidine, or the P-gp inducer, rifampin. Cerebral blood flow (CBF) and BBB P-gp activity were respectively measured by administration of (15)O-water followed by (11)C-verapamil. In a crossover design, healthy volunteers received quinidine and 11-29 days of rifampin treatment during different study periods. CBF and P-gp activity was measured in the absence (control; prior to quinidine treatment) and presence of P-gp modulation. At clinically relevant quinidine plasma concentrations, P-gp inhibition resulted in a 60% increase in (11)C-radioactivity distribution across the human BBB as measured by the brain extraction ratio (ER) of (11)C-radioactivity. Furthermore, the magnitude of BBB P-gp inhibition by quinidine was successfully predicted by a combination of in vitro and macaque data, but not by rat data. Although our findings demonstrated that quinidine did not completely inhibit P-gp at the human BBB, it has the potential to produce clinically significant CNS drug interactions with P-gp substrate drugs that exhibit a narrow therapeutic window and are significantly excluded from the brain by P-gp. Rifampin treatment induced systemic CYP3A metabolism of (11)C-verapamil; however, it reduced the ER by 6%. Therefore, we conclude that rifampin, at its usual clinical dose, cannot be used to induce P-gp at the human BBB to a clinically meaningful extent and is unlikely to cause inadvertent BBB-inductive drug interactions.