The Effect of Sedation on Diagnostic Lumbar Medial Branch Blocks for Facetogenic Low Back Pain: An Observational Study.

BACKGROUND: Lumbar medial branch blocks (MBB) are some of the most commonly performed pain procedures in the United States. Diagnostic MBBs are performed to confirm if the generator of low back pain is the facet joint. However, with diagnostic injections, false positive blocks may occur. OBJECTIVES:   Our prospective observational study aims to investigate the effects of midazolam sedation on patients' perceived intensity of pain relief following lumbar MBB. STUDY DESIGN: This is a single-center multi-site prospective observational study registered on clinicaltrials.gov (NCT04453449). SETTING: The study was approved by the Henry Ford Health System Institutional Review Board (IRB) in June 2020 (IRB# 14010) and registered on clinicaltrials.gov in July 2020 (NCT04453449). This manuscript adheres to the applicable EQUATOR STROBE guidelines for an observational cohort study. METHODS: Patients that underwent MBB without sedation were compared to sedated patients. Patients were asked to complete the Numeric Rating Scale (NRS) at baseline, one day after their diagnostic blocks, as well as 4 weeks and 8 weeks after their lumbar radiofrequency ablation (RFA). The primary outcome is the difference between baseline NRS pain scores and the lowest reported score in the 8 hours following MBB. For patients who proceed to RFA, the frequency of false positive blocks was evaluated. A patient was considered to have a false positive block when they failed to achieve 50% pain relief from RFA after 2 successful sequential MBBs. RESULTS: There was no significant difference in the NRS pain score change between the sedated and non-sedated groups for diagnostic block one (P = 0.167) and diagnostic block 2 (P = 0.6145). There was no significant difference of false positive rates between non-sedation and sedation patients at 4-weeks post-RFA (P = 0.7178) and at 8-weeks post-RFA (P = 1.000). LIMITATIONS: Some of the limitations of this study include its nonrandomized design, patient self-reported pain scores, as well as the small variability in the injection technique of proceduralists and in the anatomical location of the injection site. CONCLUSIONS: This study showed that midazolam did not change patients' perceived intensity of pain following MBB, as well as false positive rates after RFA. Larger studies are required to draw definitive conclusions.

Prehabilitation in Adults Undergoing Cancer Surgery: A Comprehensive Review on Rationale, Methodology, and Measures of Effectiveness.

Cancer surgery places a significant burden on a patients' functional status and quality of life. In addition, cancer surgery is fraught with postoperative complications, themselves influenced by a patient's functional status. Prehabilitation is a unimodal or multimodal strategy that aims to increase a patient's functional capacity to reduce postoperative complications and improve postoperative recovery and quality of life. In most cases, it involves exercise, nutrition, and anxiety-reducing interventions. The impact of prehabilitation has been explored in several types of cancer surgery, most commonly colorectal and thoracic. Overall, the existing evidence suggests prehabilitation improves physiological outcomes (e.g., lean body mass, maximal oxygen consumption) as well as clinical outcomes (e.g., postoperative complications, quality of life). Notably, the benefit of prehabilitation is additional to that of enhanced recovery after surgery (ERAS) programs. While safe, prehabilitation programs require multidisciplinary coordination preoperatively. Despite the existence of numerous systematic reviews and meta-analyses, the certainty of evidence demonstrating the efficacy and safety of prehabilitation is low to moderate, principally due to significant methodological heterogeneity and small sample sizes. There is a need for more large-scale multicenter randomized controlled trials to draw strong clinical recommendations.

Using Simulation Training to Reduce Skill Decay Among Certified Registered Nurse Anesthetists.

BACKGROUND: Skill decay refers to the loss of skills and knowledge resulting from lack of consistent use. Among certified registered nurse anesthetists (CRNAs), skill decay can lead to negative results. One method that has been shown to mitigate skill decay is low-dose, high-frequency (LDHF) simulation. There is a gap in the LDHF simulation literature regarding CRNAs to determine its effectiveness in reducing skill decay or increasing confidence levels. METHOD: This study used a quasi-experimental pretest-posttest follow-up design. The pretests and posttests were evaluated using a Wilcoxon signed rank test to determine CRNAs' proficiency and confidence in central venous catheter (CVC) insertion before and after a simulated refresher training course. RESULTS: The CRNAs showed a significant improvement in CVC insertion proficiency, from a 50% pretest average to a 94% posttest average (p < .0001), and they retained proficiency 6 months later (91%, p = .0109). There was no significant change in CRNAs' confidence level following the training (p = .4486). CONCLUSION: A program of LDHF simulation training is an important activity in meeting the continuing education/training needs of CRNAs in improving and retaining CVC insertion proficiency. This study demonstrates the efficacy of a LDHF simulation program for CRNAs and helps to bridge the gap in the literature on the use of LDHF simulation among CRNAs. [J Contin Educ Nurs. 2024;55(4):187-194.].

Applications of focused ultrasound-mediated blood-brain barrier opening.

The blood brain barrier (BBB) plays a critically important role in the regulation of central nervous system (CNS) homeostasis, but also represents a major limitation to treatments of brain pathologies. In recent years, focused ultrasound (FUS) in conjunction with gas-filled microbubble contrast agents has emerged as a powerful tool for transiently and non-invasively disrupting the BBB in a targeted and image-guided manner, allowing for localized delivery of drugs, genes, or other therapeutic agents. Beyond the delivery of known therapeutics, FUS-mediated BBB opening also demonstrates the potential for use in neuromodulation and the stimulation of a range of cell- and tissue-level physiological responses that may prove beneficial in disease contexts. Clinical trials investigating the safety and efficacy of FUS-mediated BBB opening are well underway, and offer promising non-surgical approaches to treatment of devastating pathologies. This article reviews a range of pre-clinical and clinical studies demonstrating the tremendous potential of FUS to fundamentally change the paradigm of treatment for CNS diseases.

Sequential Organ Failure Assessment (SOFA) Score and Mortality Prediction in Patients With Severe Respiratory Distress Secondary to COVID-19.

Background This study looks at the validity of the sequential organ failure assessment score (SOFA) in detecting mortality in patients with Coronavirus disease of 2019 (COVID-19) pneumonia. Also, it is looking to determine the optimal SOFA score that will discriminate between mortality and survival. Methods It is a retrospective chart review of the patients admitted to Henry Ford Hospital from March 2020 to December 2020 with COVID-19 pneumonia who developed severe respiratory distress. We collected the following information; patient demographics (age, sex, body mass index), co-morbidities (history of diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease, coronary artery disease, or cancer), SOFA scores (the ratio of arterial oxygen tension (PaO2) to the fraction of inspired oxygen, Glasgow Coma Scale (GCS) score, mean arterial pressure, serum creatinine level, bilirubin level, and platelet count) as well as inpatient mortality. Results There were 320 patients; out of these, 111 were intubated. The receiver operating characteristic (ROC) curve for SOFA at the moment of inclusion in the study had an area under the curve of 0.883. The optimal point for discrimination between mortality and survival is SOFA of 5. A SOFA score of less than two is associated with 100% survival, while a score of more than 11 is associated with 100% mortality. Conclusions SOFA score in COVID-19 patients with severe respiratory distress strongly correlates with the initial SOFA score. It is a valuable tool for predicting mortality in COVID-19 patients.

The Burnout Epidemic Within A Viral Pandemic: Impact of a Wellness Initiative.

Background: Anesthesiologists are at high risk of developing burnout, a condition which can lead to many deleterious effects for the physician, and far-reaching effects on their patients and hospital systems. The COVID-19 pandemic has presented new challenges that have further exacerbated the risk of burnout in anesthesiologists. It is critical to develop effective strategies to promote well-being and decrease burnout for physicians in this specialty. The purpose of this observational study was to evaluate the impact of a Physician Well-Being Initiative on distress and well-being in anesthesiologists. It was hypothesized that the wellness intervention would promote an improvement in well-being scores. Methods: The Physician Well-Being Initiative was launched in August 2019 in the Department of Anesthesiology, Pain Management and Perioperative Medicine at Henry Ford Hospital in Detroit, Michigan. The Physician Well-Being Initiative was designed to address several of the key factors that improve physician wellness, including 1) a sense of autonomy; 2) positive view of leadership; and 3) flexible schedule opportunities. To assess the impact of the Physician Well-Being Initiative on the well-being and distress scores of participating anesthesiologists, the physicians were emailed the validated Well-Being Index survey at baseline and 3, 6 and 12 months. The Well-Being Index evaluates multiple items of distress in the healthcare setting. The sample size was limited to the 54 anesthesiologists at Henry Ford Hospital. Results: Forty-four of the 54 anesthesiologists completed the baseline questionnaire. A total of 44 physicians answered the questionnaire at baseline, with more male than female physicians (35 males and 7 females) and the majority (17/44) in practice for 5-10 years. Thirty-two physicians completed the survey at 3 and 6 months, and 31 physicians at 12 months after the launch of the Physician Well-Being Initiative. Twenty-one physicians completed the questionnaire at all 4 time points. Although the COVID-19 pandemic started shortly after the 6-month surveys were submitted, results indicated that there was a 0.05 decrease in the Well-Being Index sum score for every 1-month of time (coefficient -0.05, 95% CI -0.01, -0.08, P = 0.013). This study shows that, with the wellness initiative in place, the department was able to maintain and potentially even reduce physician distress despite the concurrent onset of the pandemic. Conclusions: Following the launch of a sustained wellness initiative, this study demonstrates that physician wellness improved with time. This suggests that it takes time for a wellness initiative to have an effect on well-being and distress in anesthesiologists.

Emergent Surgical Airway Skills: Time to Re-evaluate the Competencies.

Introduction One of the most challenging scenarios an anesthesia provider can face is treating a can't intubate can't ventilate (CICV) patient. The incidence of CICV is estimated to be around one in 10,000 cases. According to the American Society of Anesthesiology Closed Claims Study, adverse respiratory events are the most common type of injury, with difficult intubation and ventilation contributing to the majority of these cases. The objective of this non-interventional quality improvement project was to evaluate the prior training, exposure, and self-reported confidence in handling the CICV scenario among anesthesia providers at Henry Ford Hospital in Detroit, MI. Methods An online questionnaire was distributed via email to all residents, certified registered nurse anesthetists (CRNAs), and attending anesthesiologists in March 2021. The email contained a link to an online questionnaire via Microsoft Forms (Microsoft Corporation, Redmond, WA). Univariate group comparisons were carried out between the respondents' role (attending, CRNA, or resident), as well as between the number of years that the respondents were in practice (< 5 years, 5-10 years, > 10 years). Results Out of the total 170 anesthesia providers, 119 participated in the study where 54 (45%) were attendings, 44 (37%) were residents, and 21 (18%) were CRNAs. The majority (75%) did not know the surgical airway kit location, and 87% had not performed the surgical airway procedure before. The vast majority (96.7%) recommended simulation training compared to online training or lecture series, and just over 50% recommended annual training frequency. When looking at the differences in responses based on years of experience as an anesthesia provider, the majority of those with > 10 years in practice knew how to perform the surgical airway technique while respondents with < 5 years did not know how to perform the technique, and 50% of those with five to 10 years experience knew how to perform the surgical airway procedure for a CICV scenario. Conclusion Although there were many significant differences observed between the various provider roles and years in practice, surprisingly, the responses revealed both a lack of experience and confidence in performing the surgical airway procedure in all provider roles. These findings highlight a need for better emergency airway teaching and training. These findings will be used to guide the design and implementation of improved surgical airway training for residents, CRNAs, and attending anesthesiologists with the goal of better preparedness for handling a CICV scenario.

Sonodynamic therapy: Rapid progress and new opportunities for non-invasive tumor cell killing with sound.

Solid tumor treatment relies heavily upon chemotherapies, radiation, surgical resection, and/or immunotherapies. Although many alternative non-invasive solid tumor therapies have been proposed through the years and continue to be tested in various contexts, tumor cell eradication remains a daunting task for the current cancer armamentarium. Indeed, solid tumors exhibit physically and biochemically heterogenous microenvironments, allowing them to easily acquire resistance mechanisms. Progress in sonodynamic therapy (SDT), a treatment modality capable of controlling tumor growth while limiting off-target effects and toxicities, has accelerated in recent years. SDT combines "sonosensitizing" agents with the non-invasive application of focused acoustic energy [i.e. focused ultrasound (FUS)] to drive highly localized formation of tumor cell-killing reactive oxygen species (ROS). Sonosensitizers selectively accumulate in tumor cells, after which FUS radiation eliminates the tumor by forcing the tumor cells to undergo cell death. In this article, we comprehensively review recent studies wherein SDT has been applied to treat primary and metastatic tumors. We discuss sonosensitizers, combination therapies with SDT, developments in defining the mechanism of SDT-induced cell cytotoxicity, and the promise SDT offers as a modulator of anti-tumor immunity.

Effect of Intubation Timing on the Outcome of Patients With Severe Respiratory Distress Secondary to COVID-19 Pneumonia.

Background The optimal timing of intubation for critically ill patients with severe respiratory illness remains controversial among healthcare providers. The coronavirus disease 2019 (COVID-19) pandemic has raised even more questions about when to implement this life-saving therapy. While one group of providers prefers early intubation for patients with respiratory distress because these patients may deteriorate rapidly without it, other providers believe that intubation should be delayed or avoided because of its associated risks including worse outcomes. Research question Our objective was to assess whether the timing of intubation in patients with severe COVID-19 pneumonia was associated with differences in mortality or other outcomes. Study design and methods This was a single-center retrospective observational cohort study. We analyzed outcomes of patients who were intubated secondary to COVID-19 pneumonia between March 13, 2020, and December 12, 2020, at Henry Ford Hospital in Detroit, Michigan. Patients were categorized into two groups: early intubated (intubated within 24 hours of the onset of severe respiratory distress) and late intubated (intubated after 24 hours of the onset of severe respiratory distress). Demographics, comorbidities, respiratory rate oxygenation (ROX) index, sequential organ failure assessment (SOFA) score, and treatment received were compared between groups. The primary outcome was mortality. Secondary outcomes were ventilation time, intensive care unit stay, hospital length of stay, and discharge disposition. Post hoc and Kaplan-Meier survival analyses were performed. Results A total of 110 patients were included: 55 early intubated and 55 late intubated. We did not observe a significant difference in overall mortality between the early intubated (43%) and the late intubated groups (53%) (p = 0.34). There was no statistically significant difference in patients' baseline characteristics including SOFA scores (the early intubation group had a mean score of 7.5 compared to 6.7 in the late intubation group). Based on the ROX index, the early intubation group had significantly more patients with a reduced risk of intubation (45%) than the late group (27%) (p = 0.029). The early intubation group was treated with a high-flow nasal cannula at a significantly lower rate (47%) than the late intubation group (83%) (p < 0.001). Significant differences in patient baseline characteristics, treatment received, and other outcomes were not observed. Post hoc analysis adjusting for SOFA score between 0 and 9 revealed significantly higher mortality in the late intubation group (49%) than in the early intubation group (26%) (p = 0.03). Patients in the 0 to 9 SOFA group who were intubated later had 2.7 times the odds of dying during hospital admission compared to patients who were intubated early (CI, 1.09-6.67). Interpretation The timing of intubation for patients with severe COVID-19 pneumonia was not significantly associated with overall mortality or other patient outcomes. However, within the subgroup of patients with SOFA scores of 9 or lower at the time of intubation, patients intubated after 24 hours of the onset of respiratory distress had a higher risk of death than those who were intubated within 24 hours of respiratory distress. Thus, patients with COVID-19 pneumonia who are not at a high level of organ dysfunction may benefit from early mechanical ventilation.

Targeting p130Cas- and microtubule-dependent MYC regulation sensitizes pancreatic cancer to ERK MAPK inhibition.

To identify therapeutic targets for KRAS mutant pancreatic cancer, we conduct a druggable genome small interfering RNA (siRNA) screen and determine that suppression of BCAR1 sensitizes pancreatic cancer cells to ERK inhibition. Integrative analysis of genome-scale CRISPR-Cas9 screens also identify BCAR1 as a top synthetic lethal interactor with mutant KRAS. BCAR1 encodes the SRC substrate p130Cas. We determine that SRC-inhibitor-mediated suppression of p130Cas phosphorylation impairs MYC transcription through a DOCK1-RAC1-ß-catenin-dependent mechanism. Additionally, genetic suppression of TUBB3, encoding the ßIII-tubulin subunit of microtubules, or pharmacological inhibition of microtubule function decreases levels of MYC protein in a calpain-dependent manner and potently sensitizes pancreatic cancer cells to ERK inhibition. Accordingly, the combination of a dual SRC/tubulin inhibitor with an ERK inhibitor cooperates to reduce MYC protein and synergistically suppress the growth of KRAS mutant pancreatic cancer. Thus, we demonstrate that mechanistically diverse combinations with ERK inhibition suppress MYC to impair pancreatic cancer proliferation.

Frequency and Analysis of Unplanned Extubation in Coronavirus Disease 2019 Patients.

OBJECTIVES: To determine if patients with coronavirus disease 2019 had a greater number of unplanned extubations resulting in reintubations than in patients without coronavirus disease 2019. DESIGN: Retrospective cohort study comparing the frequency of unplanned extubations resulting in reintubations in a group of coronavirus disease 2019 patients to a historical (noncoronavirus disease 2019) control group. SETTING: This study was conducted at Henry Ford Hospital, an academic medical center in Detroit, MI. The historical noncoronavirus disease 2019 patients were treated in the 68 bed medical ICU. The coronavirus disease 2019 patients were treated in the coronavirus disease ICU, which included the 68 medical ICU beds, 18 neuro-ICU beds, 32 surgical ICU beds, and 40 cardiovascular ICU beds, as the medical ICU was expanded to these units at the peak of the pandemic in Detroit, MI. PATIENTS: The coronavirus disease 2019 cohort included patients diagnosed with coronavirus disease 2019 who were intubated for respiratory failure from March 12, 2020, to April 13, 2020. The historic control (noncoronavirus disease 2019) group consisted of patients who were admitted to the medical ICU in the year spanning from November 1, 2018 to October 31, 2019, with a need for mechanical ventilation that was not related to surgery or a neurologic reason. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: To identify how many patients in each cohort had unplanned extubations, an electronic medical records query for patients with two intubations within 30 days was performed, in addition to a review of our institutional quality and safety database of reported self-extubations. Medical charts were manually reviewed by board-certified anesthesiologists to confirm each event was an unplanned extubation followed by a reintubation within 24 hours. There was a significantly greater incidence of unplanned extubations resulting in reintubation events in the coronavirus disease 2019 cohort than in the noncoronavirus disease 2019 cohort (coronavirus disease 2019 cohort: 167 total admissions with 22 events-13.2%; noncoronavirus disease 2019 cohort: 326 total admissions with 14 events-4.3%; p < 0.001). When the rate of unplanned extubations was expressed per 100 intubated days, there was not a significant difference between the groups (0.88 and 0.57, respectively; p = 0.269). CONCLUSIONS: Coronavirus disease 2019 patients have a higher incidence of unplanned extubation that requires reintubation than noncoronavirus disease 2019 patients. Further study is necessary to evaluate the variables that contribute to this higher incidence and clinical strategies that can reduce it.

Increased clinical failures when treating acute otitis media with macrolides: a meta-analysis.

BACKGROUND: Macrolide antibiotics are often used to treat children with acute otitis media (AOM); however, the 2004 American Academy of Pediatrics (AAP) and American Academy of Family Physicians guidelines recommend against their use in patients without history of a type I allergic reaction to penicillins. OBJECTIVE: To evaluate via meta-analysis the comparative efficacy of amoxicillin or amoxicillin/clavulanate to that of macrolide antibiotics in the treatment of children with AOM. METHODS: A systematic literature search of MEDLINE, EMBASE, and International Pharmaceutical Abstracts was conducted from the earliest available date through September 2008. We used the following MeSH and key words: amoxicillin, amoxicillin/clavulanate, Augmentin, azithromycin, ceftriaxone, clarithromycin, macrolides, AND media, otitis media, and effusion. Included studies were randomized, blinded, and controlled trials evaluating guideline-recommended antibiotics (amoxicillin or amoxicillin/clavulanate) compared to macrolide antibiotics (azithromycin or clarithromycin) in AOM in children. The primary outcome assessed was clinical failure measured between days 10 and 16 after starting antibiotic therapy. Results are reported as relative risks (RRs) with 95% confidence intervals and were calculated using a random-effects model. RESULTS: A total of 10 trials (N = 2766) evaluating children 6 months-15 years old were included in the meta-analysis. Upon meta-analysis, the use of macrolide antibiotics was associated with an increased risk of clinical failure (RR 1.31 [95% CI 1.07 to 1.60]; p = 0.008) corresponding to a number needed to harm of 32. Upon safety analysis, rates of any adverse reaction (RR 0.74 [95% CI 0.60 to 0.90]; p = 0.003) and diarrhea (RR 0.41 [95% CI 0.32 to 0.52]; p < 0.0001) were significantly lower in the macrolide group. CONCLUSIONS: The meta-analysis suggests that patients treated with macrolides for AOM may be more likely to have clinical failures. As such, it supports the current AAP AOM recommendation that macrolides be reserved for patients who can not receive amoxicillin or amoxicillin/clavulanate.