Association Between Intraoperative Dexamethasone and Postoperative Mortality in Patients Undergoing Oncologic Surgery: A Multicentric Cohort Study.

OBJECTIVE: We examined the effects of dexamethasone on postoperative mortality, recurrence-free survival, and side effects in patients undergoing oncologic operations. BACKGROUND: Dexamethasone prevents nausea and vomiting after anesthesia and may affect cancer proliferation. METHODS: A total of 30,561 adult patients undergoing solid cancer resection between 2005 and 2020 were included. Multivariable logistic regression was applied to investigate the effect of dexamethasone on 1-year mortality and recurrence-free survival. Effect modification by the cancer's potential for immunogenicity, defined as a recommendation for checkpoint inhibitor therapy based on the National Comprehensive Cancer Network guidelines, was investigated through interaction term analysis. Key safety endpoints were dexamethasone-associated risk of hyperglycemia >180 mg/dL within 24 hours and surgical site infections within 30 days after surgery. RESULTS: Dexamethasone was administered to 38.2% (11,666/30,561) of patients (6.5±2.3 mg). Overall, 3.2% (n=980/30,561) died and 15.4% (n=4718/30,561) experienced cancer recurrence within 1 year of the operation. Dexamethasone was associated with a -0.6% (95% confidence interval: -1.1, -0.2, P =0.007) 1-year mortality risk reduction [adjusted odds ratio (OR adj ): 0.79 (0.67, 0.94), P =0.009; hazard ratio=0.82 (0.69, 0.96), P =0.016] and higher odds of recurrence-free survival [OR adj : 1.28 (1.18, 1.39), P <0.001]. This effect was only present in patients with solid cancers who were defined as not to respond to checkpoint inhibitor therapy [OR adj : 0.70 (0.57, 0.87), P =0.001 vs OR adj : 1.13 (0.85, 1.50), P =0.40]. A high (>0.09 mg/kg) dose of dexamethasone increased the risk of postoperative hyperglycemia [OR adj : 1.55 (1.32, 1.82), P <0.001], but not for surgical site infections [OR adj : 0.84 (0.42, 1.71), P =0.63]. CONCLUSIONS: Dexamethasone is associated with decreased 1-year mortality and cancer recurrence in patients undergoing surgical resection of cancers that are not candidates for immune modulators. Dexamethasone increased the risk of postoperative hyperglycemia, however, no increase in surgical site infections was identified.

Mindfulness-Based Interdisciplinary Pain Management Program for Complex Polymorbid Pain in Veterans: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effects of interdisciplinary pain management on pain-related disability and opioid reduction in polymorbid pain patients with 2 or more comorbid psychiatric conditions. DESIGN: Two-arm randomized controlled trial testing a 3-week intervention with assessments at pre-treatment, post-treatment, 6-month, and 12-month follow-up. SETTING: Department of Veterans Affairs medical facility. PARTICIPANTS: 103 military veterans (N=103) with moderate (or worse) levels of pain-related disability, depression, anxiety, and/or posttraumatic stress disorder randomly assigned to usual care (n=53) and interdisciplinary pain management (n=50). All participants reported recent persistent opioid use. Trial participants had high levels of comorbid medical and mental health conditions. INTERVENTIONS: Experimental arm-a 3-week, interdisciplinary pain management program guided by a structured manual; comparison arm-usual care in a large Department of Veterans Affairs medical facility. MAIN OUTCOME MEASURES: Oswestry Disability Index (pain disability); Timeline Followback Interview and Medication Event Monitoring System (opioid use). Analysis used generalized linear mixed model with all posttreatment observations (posttreatment, 6-month follow-up, 12-month follow-up) entered simultaneously to create a single posttreatment effect. RESULTS: Veterans with polymorbid pain randomized to the interdisciplinary pain program reported significantly greater decreases in pain-related disability compared to veterans randomized to treatment as usual (TAU) at posttreatment, 6-month, and 12-month follow-up. Aggregated mean pain disability scores (ie, a summary effect of all posttreatment observations) for the interdisciplinary pain program were -9.1 (95% CI: -14.4, -3.7, P=.001) points lower than TAU. There was no difference between groups in the proportion of participants who resumed opioid use during trial participation (32% in both arms). CONCLUSION: These findings offer the first evidence of short- and long-term interdisciplinary pain management efficacy in polymorbid pain patients, but more work is needed to examine how to effectively decrease opioid use in this population.

Trends in gender, race, and ethnic diversity among prospective physical medicine and rehabilitation physicians.

BACKGROUND: As the proportion of women and individuals who are underrepresented in medicine slowly rises, disparities persist in numerous arenas and specialties. In physical medicine and rehabilitation (PM&R), there is a continued need to focus on diversity among trainees. This study aims to evaluate diversity among PM&R applicants and residents over the past 6 years. OBJECTIVE: To describe the demographic trends in PM&R over the last 6 years and compare those findings with trends in other specialties. DESIGN: Surveillance. SETTING: Analyses of national databases from self-reported questionnaires. PARTICIPANTS: The study consists of 126,833 medical school matriculants, 374,185 resident applicants, and 326,134 resident trainees over the last 6 years. MAIN OUTCOME MEASURES: Self-reported demographic data from the Association of American Medical Colleges and the Accreditation Council for Graduate Medical Education were analyzed for medical school matriculants, PM&R applicants, and current residents for the cycles of 2014-2015 to 2019-2020. The data were then comparatively reviewed between PM&R and other medical specialties. RESULTS: In the 6 cycles evaluated, women accounted for 36%-39% of PM&R residents, but 47%-48% in non-PM&R specialties. Women applicants to the PM&R specialty averaged 34.4% over the 6 years analyzed, which was the fourth lowest of the 11 specialties examined. Black or African American and Hispanic, Latino, or of Spanish Origin populations each accounted for only 6% of PM&R residents. PM&R demonstrated a noticeably higher proportion of White (62.1% vs. 60.3%) and an observably lower proportion of Black or African American (6.0% vs. 7.1%) and Hispanic, Latino, or of Spanish Origin (6.3% vs. 7.9%) residents compared with non-PM&R specialties. CONCLUSION: There is underrepresentation of women and multiple racial and ethnic minority groups in the field of PM&R from applicants to trainees demonstrating a need to improve recruitment efforts.

Statistical evaluation of a biomarker.

A biomarker may provide a diagnosis, assess disease severity or risk, or guide other clinical interventions such as the use of drugs. Although considerable progress has been made in standardizing the methodology and reporting of randomized trials, less has been accomplished concerning the assessment of biomarkers. Biomarker studies are often presented with poor biostatistics and methodologic flaws that precludes them from providing a reliable and reproducible scientific message. A host of issues are discussed that can improve the statistical evaluation and reporting of biomarker studies. Investigators should be aware of these issues when designing their studies, editors and reviewers when analyzing a manuscript, and readers when interpreting results.

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.

Open label, randomized, crossover pilot trial of high-resolution, relational, resonance-based, electroencephalic mirroring to relieve insomnia.

Effective noninvasive interventions for insomnia are needed. High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM™) is a noninvasive, electroencephalography (EEG)-based method to facilitate greater client-unique, autocalibrated improvements of balance and harmony in cortical neural oscillations. This study explores using HIRREM for insomnia. Twenty subjects, with an Insomnia Severity Index (ISI) score of ≥15 (14 women, mean age 45.4, mean ISI 18.6), were enrolled in this randomized, unblinded, wait-list control, crossover, superiority study. Subjects were randomized to receive 8-12 HIRREM sessions over 3 weeks, plus usual care (HUC), or usual care alone (UC). Pre- and post-HIRREM data collection included ISI (primary outcome), and many secondary, exploratory measures (CES-D, SF-36, HR, BP, neurocognitive testing, and VAS scales). The UC group later crossed over to receive HIRREM. ISI was also repeated 4-6 weeks post-HIRREM. All subjects completed the primary intervention period. Analysis for differential change of ISI in the initial intervention period for HUC versus UC showed a drop of 10.3 points (95% CI: -13.7 to -6.9, P < 0.0001, standardized effect size of 2.68). Key secondary outcomes included statistically identical differential change for the crossed-over UC group, and persistence of the effect on the ISI up to > 4 weeks post-HIRREM. Differential change in the HUC group was also statistically significant for CES-D (-8.8, 95% CI: -17.5 to -0.1, P = 0.047), but other exploratory outcomes were not statistically significant. For all receiving HIRREM (n = 19), decreased high-frequency total power was seen in the bilateral temporal lobes. No adverse events were seen. This pilot clinical trial, the first using HIRREM as an intervention, suggests that HIRREM is feasible and effective for individuals having moderate-to-severe insomnia, with clinically relevant, statistically significant benefits based on differential change in the ISI. Effects persisted for 4 weeks after completion of HIRREM. Larger controlled clinical trials are warranted.

Topiramate for phantom limb pain: a time-series analysis.

There is growing evidence of topiramate's efficacy in treating neuropathic pain. This article reports a detailed analysis of the response of four amputee subjects with phantom limb pain. Individual time-series analyses revealed that three out of four amputee participants receiving topiramate had statistically significant decreases in pain, with the peak effect noted at 800 mg daily. This analysis supports a hypothesis that topiramate may be effective in reducing phantom limb pain, and suggests a definitive study is indicated.