Introduction to Bayesian Analyses for Clinical Research.

Bayesian analyses are becoming more popular as a means of analyzing data, yet the Bayesian approach is novel to many members of the broad clinical audience. While Bayesian analyses are foundational to anesthesia pharmacokinetic/pharmacodynamic modeling, they also can be used for analyzing data from clinical trials or observational studies. The traditional null hypothesis significance testing (frequentist) approach uses only the data collected from the current study to make inferences. On the other hand, the Bayesian approach quantifies the external information or expert knowledge and combines the external information with the study data, then makes inference from this combined information. We introduce to the clinical and translational science researcher what it means to do Bayesian statistics, why a researcher would choose to perform their analyses using the Bayesian approach, when it would be advantageous to use a Bayesian instead of a frequentist approach, and how Bayesian analyses and interpretations differ from the more traditional frequentist methods. Throughout this paper, we use various pain- and anesthesia-related examples to highlight the ideas and statistical concepts that should be relatable to other areas of research as well.

AAAPT Diagnostic Criteria for Acute Thoracic Surgery Pain.

Patients undergoing thoracic surgery experience particular challenges for acute pain management. Availability of standardized diagnostic criteria for identification of acute pain after thoracotomy and video assisted thoracic surgery (VATS) would provide a foundation for evidence-based management and facilitate future research. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the United States Food and Drug Administration, the American Pain Society (APS), and the American Academy of Pain Medicine (AAPM) formed the ACTTION-APS-AAPM Pain Taxonomy (AAAPT) initiative to address absence of acute pain diagnostic criteria. A multidisciplinary working group of pain experts was invited to develop diagnostic criteria for acute thoracotomy and VATS pain. The working group used available studies and expert opinion to characterize acute pain after thoracotomy and VATS using the 5-dimension taxonomical structure proposed by AAAPT (i.e., core diagnostic criteria, common features, modulating factors, impact/functional consequences, and putative mechanisms). The resulting diagnostic criteria will serve as the starting point for subsequent empirically validated criteria. PERSPECTIVE ITEM: This article characterizes acute pain after thoracotomy and VATS using the 5-dimension taxonomical structure proposed by AAAPT (ie, core diagnostic criteria, common features, modulating factors, impact and/or functional consequences, and putative mechanisms).

Preoperative Patient Expectations of Postoperative Pain Are Associated with Moderate to Severe Acute Pain After VATS.

OBJECTIVE: The goal of this post hoc analysis of subjects from a prospective observational study was to identify the predictors of patients developing moderate to severe acute pain (mean numerical rating scale [NRS] ≥4, 0-10) during the first three days after video-assisted thoracoscopic surgery (VATS) from a comprehensive evaluation of demographic, psychosocial, and surgical factors. METHODS: Results from 82 patients who were enrolled one week before VATS and evaluated during the first three postoperative days are presented. The primary outcome variable of the current study was the presence of moderate to severe acute pain after VATS. RESULTS: Fifty-nine percent (95% confidence interval, 47-69%) of study subjects developed moderate to severe acute pain after VATS. Factors univariately associated with the presence of moderate to severe acute pain were greater average expected postoperative pain, greater pain to a suprathreshold cold stimulus, and longer durations of surgery and hospital stay (P < 0.05). When considered in the multiple logistic regression models, the patients' preoperative average intensity of expected postoperative pain (NRS, 0-10) was the only measure associated with the moderate to severe acute pain. Average intensity of postoperative pain expected by patients when questioned preoperatively mediated the effect of reported intensity of pain to the suprathreshold cold stimulus for moderate to severe acute pain levels. Preoperative patient expectations had greater predictive value than other assessed variables including psychosocial factors such as catastrophizing or anxiety assessed one week before surgery. CONCLUSIONS: None of the preoperative psychosocial measures were associated with the moderate to severe acute pain after VATS. Average expected postoperative pain was the only measure associated with the development of moderate to severe acute pain after VATS.

A Prospective Study of Chronic Pain after Thoracic Surgery.

BACKGROUND: The goal of this study was to detect the predictors of chronic pain at 6 months after thoracic surgery from a comprehensive evaluation of demographic, psychosocial, and surgical factors. METHODS: Thoracic surgery patients were enrolled 1 week before surgery and followed up 6 months postsurgery in this prospective, observational study. Comprehensive psychosocial measurements were assessed before surgery. The presence and severity of pain were assessed at 3 and 6 months after surgery. One hundred seven patients were assessed during the first 3 days after surgery, and 99 (30 thoracotomy and 69 video-assisted thoracoscopic surgery, thoracoscopy) patients completed the 6-month follow-up. Patients with versus without chronic pain related to thoracic surgery at 6 months were compared. RESULTS: Both incidence (P = 0.37) and severity (P = 0.97) of surgery-related chronic pain at 6 months were similar after thoracotomy (33%; 95% CI, 17 to 53%; 3.3 ± 2.1) and thoracoscopy (25%; 95% CI, 15 to 36%; 3.3 ± 1.7). Both frequentist and Bayesian multivariate models revealed that the severity of acute pain (numerical rating scale, 0 to 10) is the measure associated with chronic pain related to thoracic surgery. Psychosocial factors and quantitative sensory testing were not predictive. CONCLUSIONS: There was no difference in the incidence and severity of chronic pain at 6 months in patients undergoing thoracotomy versus thoracoscopy. Unlike other postsurgical pain conditions, none of the preoperative psychosocial measurements were associated with chronic pain after thoracic surgery.

Prolonged Operative Time to Extubation Is Not a Useful Metric for Comparing the Performance of Individual Anesthesia Providers.

BACKGROUND: One anesthesiologist performance metric is the incidence of "prolonged" (15 min or longer after dressing complete) times to extubation. The authors used several methods to identify the performance outliers and assess whether targeting these outliers for reduction could improve operating room workflow. METHODS: Time to extubation data were retrieved for 27,757 anesthetics and 81 faculty anesthesiologists. Provider-specific incidences of prolonged extubation were assessed by using unadjusted frequentist statistics and a Bayesian model adjusted for prone positioning, American Society of Anesthesiologist's base units, and case duration. RESULTS: 20.31% of extubations were "prolonged," and 40% of anesthesiologists were identified as outliers using a frequentist approach, that is, incidence greater than upper 95% CI (20.71%). With an adjusted Bayesian model, only one anesthesiologist was deemed an outlier. If an average anesthesiologist performed all extubations, the incidence of prolonged extubations would change negligibly (to 20.67%). If the anesthesiologist with the highest incidence of prolonged extubations was replaced with an average anesthesiologist, the change was also negligible (20.01%). Variability among anesthesiologists in the incidence of prolonged extubations was significantly less than among other providers. CONCLUSIONS: Bayesian methodology with covariate adjustment is better suited to performance monitoring than an unadjusted, nonhierarchical frequentist approach because it is less likely to identify individuals spuriously as outliers. Targeting outliers in an effort to alter operating room activities is unlikely to have an operational impact (although monitoring may serve other purposes). If change is deemed necessary, it must be made by improving the average behavior of everyone and by focusing on anesthesia providers rather than on faculty.

Assessing and Comparing Anesthesiologists' Performance on Mandated Metrics Using a Bayesian Approach.

BACKGROUND: Periodic assessment of performance by anesthesiologists is required by The Joint Commission Ongoing Professional Performance Evaluation program. METHODS: The metrics used in this study were the (1) measurement of blood pressure and (2) oxygen saturation (SpO2) either before or less than 5 min after anesthesia induction. Noncompliance was defined as no measurement within this time interval. The authors assessed the frequency of noncompliance using information from 63,913 cases drawn from the anesthesia information management system. To adjust for differences in patient and procedural characteristics, 135 preoperative variables were analyzed with decision trees. The retained covariate for the blood pressure metric was patient's age and, for SpO2 metric, was American Society of Anesthesiologist's physical status, whether the patient was coming from an intensive care unit, and whether induction occurred within 5 min of the start of the scheduled workday. A Bayesian hierarchical model, designed to identify anesthesiologists as "performance outliers," after adjustment for covariates, was developed and was compared with frequentist methods. RESULTS: The global incidences of noncompliance (with frequentist 95% CI) were 5.35% (5.17 to 5.53%) for blood pressure and 1.22% (1.14 to 1.30%) for SpO2 metrics. By using unadjusted rates and frequentist statistics, it was found that up to 43% of anesthesiologists would be deemed noncompliant for the blood pressure metric and 70% of anesthesiologists for the SpO2 metric. By using Bayesian analyses with covariate adjustment, only 2.44% (1.28 to 3.60%) and 0.00% of the anesthesiologists would be deemed "noncompliant" for blood pressure and SpO2, respectively. CONCLUSION: Bayesian hierarchical multivariate methodology with covariate adjustment is better suited to faculty monitoring than the nonhierarchical frequentist approach.

Incidence and severity of chronic pain at 3 and 6 months after thoracotomy: meta-analysis.

UNLABELLED: This systematic review was performed to determine the incidence and the severity of chronic pain at 3 and 6 months after thoracotomy based on meta-analyses. We conducted MEDLINE, Web of Science, and Google Scholar searches of databases and references for English articles; 858 articles were reviewed. Meta-regression analysis based on the publication year was used to examine if the chronic pain rates changed over time. Event rates and confidence intervals with random effect models and Freeman-Tukey double arcsine variance-stabilizing transformation were obtained separately for the incidence of chronic pain based on 1,439 patients from 17 studies at 3 months and 1,354 patients from 15 studies at 6 months. The incidences of chronic pain at 3 and 6 months after thoracotomy were 57% (95% confidence interval [CI], 51-64%) and 47% (95% CI, 39-56%), respectively. The average severity of pain ratings on a 0 to 100 scale at these times were 30 ± 2 (95% CI, 26-35) and 32 ± 7 (95% CI, 17-46), respectively. Reported chronic pain rates have been largely stable at both 3 and 6 months from the 1990s to the present. PERSPECTIVE: This systematic review's findings suggest that reported chronic pain rates are approximately 50% at 3 and 6 months and have been largely stable from the 1990s to the present. The severity of this pain is not consistently reported. Chronic pain after thoracotomy continues to be a significant problem despite advancing perioperative care.

Staff training makes a difference: improvements in neonatal illicit drug testing and intervention at a tertiary hospital.

OBJECTIVE: This project explored the impact of staff training on the rates of perinatal maternal and neonatal illicit drug testing. METHODS: Controlled, retrospective chart review on 1186 newborn and mother dyads from 2006 (pre-training control group) and on 1861 dyads from 2009 (post-training study group) was completed. Differences between rates of infant and mother drug testing were compared. RESULTS: Increased drug testing rates for the mothers and infants led to increased case finding that tripled both for the mothers (13-3.7%, p < 0.001) and for the infants (0.9-2.9%, p < 0.001). Missed opportunities for newborn testing was reduced by 35 times (20.9-0.6%, p < 0.001). CONCLUSION: This retrospective study led to an increase in the number of documented drug-exposed newborns. This research emphasizes the importance of and encourages other hospitals to analyze the efficacy of their current protocol and staff training practices in place to ensure the best child protection services.

Triple-blind randomized clinical trial of time until sensory change using 1.5% mepivacaine with epinephrine, 0.5% bupivacaine, or an equal mixture of both for infraclavicular block.

BACKGROUND AND OBJECTIVES: Practitioners mix faster-onset, intermediate-duration local anesthetics (LAs) with slower-onset, long-duration LAs to get fast peripheral nerve block (PNB) onset and long duration. We hypothesized that 1.5% mepivacaine (with epinephrine) (mepivacaine) or 1.5% mepivacaine (with epinephrine) mixed with 0.5% bupivacaine (mixed) would reduce PNB sensory onset by 20% or more versus 0.5% bupivacaine alone (bupivacaine). METHODS: Patients (n = 93) having arm surgery were randomized to 1 of the 3 LA groups. Infraclavicular PNB was administered using 1 of 3 LAs; afterward, PNB sensory (motor) onset, duration, and other outcomes were assessed. Subjects, physicians, and the biostatistician were blinded until study completion. RESULTS: Median (interquartile range) PNB sensory onset (in minutes) was as follows: mepivacaine, 3 (3-6); mixed, 6 (3-6); and bupivacaine, 6 (3-12) (P = 0.0085). Mepivacaine PNB sensory onset was not faster than mixed (P = 0.57), but mixed was faster than bupivacaine (P = 0.0035). More mixed group patients achieved PNB sensory onset (0.81) versus the bupivacaine group (0.54) at 6 mins. Median (interquartile range) PNB motor onset (in minutes) was as follows: mepivacaine, 15 (12-18); mixed, 17 (12-21); and bupivacaine, 21 (12-24) (P < 0.0001). Median sensory and motor PNB duration (in minutes) was as follows: mepivacaine, 281 and 320; mixed, 439 and 556; and bupivacaine, 850 and 1109. Sensory (motor) PNB duration was shorter with mepivacaine versus mixed (P < 0.0001, P = 0.034), and mixed was shorter versus bupivacaine (P = 0.0243, P = 0.034). CONCLUSIONS: Mixing 1.5% mepivacaine (with epinephrine) with 0.5% bupivacaine speeds up PNB sensory (motor) onset compared with 0.5% bupivacaine alone.

Detecting qualitative interaction: a Bayesian approach.

Differences in treatment effects between centers in a multi-center trial may be important. These differences represent treatment by subgroup interaction. Peto defines qualitative interaction (QI) to occur when the simple treatment effect in one subgroup has a different sign than in another subgroup: this interaction is important. Interaction where the treatment effects are of the same sign in all subgroups is called quantitative and is often not important because the treatment recommendation is identical in all cases. A hierarchical model is used here with exchangeable mean responses to each treatment between subgroups. The posterior probability of QI and the corresponding Bayes factor are proposed as a diagnostic and as a test statistic. The model is motivated by two multi-center trials with binary responses. The frequentist power and size of the test using the Bayes factor are examined and compared with two other commonly used tests. The impact of imbalance between the sample sizes in each subgroup on power is examined, and the test based on the Bayes factor typically has better power for unbalanced designs, especially for small sample sizes. An exact test based on the Bayes factor is also suggested assuming the hierarchical model. The Bayes factor provides a concise summary of the evidence for or against QI. It is shown by example that it is easily adapted to summarize the evidence for 'clinically meaningful QI,' defined as the simple effects being of opposite signs and larger in absolute value than a minimal clinically meaningful effect.

Effect of nitrous oxide on neurologic and neuropsychological function after intracranial aneurysm surgery.

BACKGROUND: Laboratory studies suggest that nitrous oxide augments brain injury after ischemia or hypoxia. The authors examined the relation between nitrous oxide use and outcomes using data from the Intraoperative Hypothermia for Aneurysm Surgery Trial. METHODS: The Intraoperative Hypothermia for Aneurysm Surgery Trial was a prospective randomized study of the impact of intraoperative hypothermia (temperature = 33 degrees C) versus normothermia (temperature = 36.5 degrees C) in patients with aneurysmal subarachnoid hemorrhage undergoing surgical clipping. Anesthesia was dictated by a limited-options protocol with the use of nitrous oxide determined by individual anesthesiologists. All patients were assessed daily for 14 days after surgery or until hospital discharge. Neurologic and neuropsychological testing were conducted at 3 months after surgery. Outcome data were analyzed via both univariate tests and multivariate logistic regression analysis correcting for factors thought to influence outcome. An odds ratio (OR) greater than 1.0 denotes a worse outcome in patients receiving nitrous oxide. RESULTS: Outcome data were available for 1,000 patients, of which 373 received nitrous oxide. There was no difference between groups in the development of delayed ischemic neurologic deficit. At 3 months after surgery, there were no significant differences between groups in any outcome variable: Glasgow Outcome Score (OR, 0.84; 95% confidence interval [CI], 0.63-1.14; P = 0.268), National Institutes of Health Stroke Scale (OR, 1.29; 95% CI, 0.96-1.73; P = 0.087), Rankin Disability Score (OR, 0.84; 95% CI, 0.61-1.15; P = 0.284), Barthel Activities of Daily Living Index (OR, 1.01; 95% CI, 0.68-1.51; P = 0.961), or neuropsychological testing (OR, 1.26; 95% CI, 0.85-1.87; P = 0.252). CONCLUSIONS: In a population of patients at risk for ischemic brain injury, nitrous oxide use had no overall beneficial or detrimental impact on neurologic or neuropsychological outcomes.

Sexual problems in male ankylosing spondylitis patients: relationship with functionality, disease activity, quality of life, and emotional status.

This study has focused on sexual problems of male ankylosing spondylitis (AS) patients. Initially, patients' perceptions about the effects of disease on sexual intercourse were assessed. Secondly, we investigated the factors that relate to the disease and affect sexual intercourse negatively. Thirdly, we compared data from the patients whose sexual intercourse were affected negatively with of those whose sexual intercourse were unaffected. This is a cross-sectional and double-centered study. A total of 53 married or sexually active male patients, who were certainly diagnosed with AS according to modified New York criteria, were assessed. Twenty seven patients (50.94%) expressed that their sexual life was affected negatively by the AS in general (affected patients), and 26 patients (49.06%) expressed no negative effect (unaffected patients). Both affected and unaffected patients were compared with each other with regard to educational level, joint involvement, functionality, disease activity, quality of life, and depression status. Mean BASFI, BASDAI scores were worse in the affected group, and the difference was statistically significant (p = 0.012, p = 0.039, respectively). There were statistically significant differences between the groups with regard to lumbar column and hip involvement (p = 0.035, p = 0.021; respectively). The physical functioning, role limitations due to physical problems, vitality/energy/fatigue, general mental health, and general health perception subscale scores of SF-36 were worse in the affected group, and the differences were statistically significant (p = 0.027, p = 0.023, p = 0,013, p = 0.005, p = 0.045, respectively). Affected patients' Beck Depression Inventory scores were worse than those of unaffected patients, and the difference between the groups was statistically significant (p = 0.039). Sexual problems are common in AS patients and might usually be associated with joint involvement, decreased functionality, increased disease activity, decreased health quality, and depression. Therefore, while examining AS patients and managing their treatments, special attention must be given to all domains of life instead of only physical problems.