Association of Patient Belief About Success of Antibiotics for Appendicitis and Outcomes: A Secondary Analysis of the CODA Randomized Clinical Trial.

Importance: A patient's belief in the likely success of a treatment may influence outcomes, but this has been understudied in surgical trials. Objective: To examine the association between patients' baseline beliefs about the likelihood of treatment success with outcomes of antibiotics for appendicitis in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial. Design, Setting, and Participants: This was a secondary analysis of the CODA randomized clinical trial. Participants from 25 US medical centers were enrolled between May 3, 2016, and February 5, 2020. Included in the analysis were participants with appendicitis who were randomly assigned to receive antibiotics in the CODA trial. After informed consent but before randomization, participants who were assigned to receive antibiotics responded to a baseline survey including a question about how successful they believed antibiotics could be in treating their appendicitis. Interventions: Participants were categorized based on baseline survey responses into 1 of 3 belief groups: unsuccessful/unsure, intermediate, and completely successful. Main Outcomes and Measures: Three outcomes were assigned at 30 days: (1) appendectomy, (2) high decisional regret or dissatisfaction with treatment, and (3) persistent signs and symptoms (abdominal pain, tenderness, fever, or chills). Outcomes were compared across groups using adjusted risk differences (aRDs), with propensity score adjustment for sociodemographic and clinical factors. Results: Of the 776 study participants who were assigned antibiotic treatment in CODA, a total of 425 (mean [SD] age, 38.5 [13.6] years; 277 male [65%]) completed the baseline belief survey before knowing their treatment assignment. Baseline beliefs were as follows: 22% of participants (92 of 415) had an unsuccessful/unsure response, 51% (212 of 415) had an intermediate response, and 27% (111 of 415) had a completely successful response. Compared with the unsuccessful/unsure group, those who believed antibiotics could be completely successful had a 13-percentage point lower risk of appendectomy (aRD, -13.49; 95% CI, -24.57 to -2.40). The aRD between those with intermediate vs unsuccessful/unsure beliefs was -5.68 (95% CI, -16.57 to 5.20). Compared with the unsuccessful/unsure group, those with intermediate beliefs had a lower risk of persistent signs and symptoms (aRD, -15.72; 95% CI, -29.71 to -1.72), with directionally similar results for the completely successful group (aRD, -15.14; 95% CI, -30.56 to 0.28). Conclusions and Relevance: Positive patient beliefs about the likely success of antibiotics for appendicitis were associated with a lower risk of appendectomy and with resolution of signs and symptoms by 30 days. Pathways relating beliefs to outcomes and the potential modifiability of beliefs to improve outcomes merit further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Applying Behavioral Nudges in a Dietary Comparator for Surgical Trials: Developing the MediDiet.

INTRODUCTION: Dietary interventions are increasingly being proposed as alternatives to surgery for common gastrointestinal conditions. Integrating aspects of cognitive psychology (e.g., behavioral nudges) into dietary interventions is becoming popular, but evidence is lacking on their effectiveness and unintended effects. We assessed the effects of including nudges in the development of a dietary intervention based on the Mediterranean diet. METHODS: We conducted two-arm randomized surveys of United States adults. After a validated dietary questionnaire, participants received feedback about dietary consistency with a Mediterranean diet with (A) no nudge versus (B) one of several nudges: peer comparison, positive affect induction + peer comparison, or defaults. Participants rated their negative and positive emotions, motivation for dietary change, and interest in recipes. Responses were analyzed using baseline covariate-adjusted regression. RESULTS: Among 1709 participants, 56% were men and the median age was 36 y. Nudges as a class did not significantly affect the extent of negative or positive emotions, motivation, or interest. However, specific nudges had different effects: compared to no nudge, peer comparison blunted negative emotions and increased motivation, although decreased interest in recipes, while defaults increased interest in recipes but reduced motivation. CONCLUSIONS: In this pilot, behavioral nudges as a class of strategies did not improve participants' reactions to dietary feedback nor did they promote negative reactions. However, specific nudges may be better considered separately in their effects. Future testing should explore whether specific nudges including peer comparison and defaults improve dietary intervention effectiveness, especially in people with the specific gastrointestinal conditions of interest.

Long-Term Prescription Opioid Use After Injury in Washington State 2015-2018.

BACKGROUND: Patients with injury may be at high risk of long-term opioid use due to the specific features of injury (e.g., injury severity), as well as patient, treatment, and provider characteristics that may influence their injury-related pain management. OBJECTIVES: Inform prescribing practices and identify high-risk populations through studying chronic prescription opioid use in the trauma population. METHODS: Using the Washington State All-Payer Claims Database (WA-APCD) data, we included adults aged 18-65 years with an incident injury from October 1, 2015-December 31, 2017. We compared patient, injury, treatment, and provider characteristics by whether or not the patients had long-term (≥ 90 days continuous prescription opioid use), or no opioid use after injury. RESULTS: We identified 191,130 patients who met eligibility criteria and were included in our cohort; 5822 met criteria for long-term use. Most had minor injuries, with a median Injury Severity Score = 1, with no difference between groups. Almost all patients with long-term opioid use had filled an opioid prescription in the year prior to their injury (95.3%), vs. 31.3% in the no-use group (p < 0.001). Comorbidities associated with chronic pain, mental health, and substance use conditions were more common in the long-term than the no-use group. CONCLUSION: Across this large cohort of multiple, mostly minor, injury types, long-term opioid use was relatively uncommon, but almost all patients with chronic use post injury had preinjury opioid use. Long-term opioid use after injury may be more closely tied to preinjury chronic pain and pain management than acute care pain management.

Association Between Statewide Medicaid Opioid Policy and Postoperative Opioid Prescribing among Surgeons at a Large Safety-Net Hospital.

BACKGROUND: Restrictive state and payer policies may be effective in reducing opioid prescribing by surgeons, but their impact has not been well studied. In 2017, Washington Medicaid implemented an opiod prescribing limit of 42 pills, prompting a large regional safety-net hospital to implement a decision support intervention in response. We aimed to evaluate the effects on surgeons' prescribing. STUDY DESIGN: We retrospectively studied postoperative opioid prescribing (quantity of pills prescribed at discharge) to opioid-naïve surgical patients at a regional safety-net hospital from 2016 to 2020. We investigated associations between the policy and opioid prescribing by using interrupted time series analysis, adjusting for clinical and sociodemographic factors. RESULTS: A total of 12,799 surgical encounters involving opioid-naïve patients (59% male, mean age 52) were analyzed. Opioids were prescribed for 75%. From 2016 to 2020, the mean prescribed opioid quantity decreased from 36 pills to 17 pills. In interrupted time series analysis, the Medicaid policy implementation was associated with an immediate change of -8.4 pills (95% CI -12 to -4.7; p < 0.001) per prescription and a subsequent rate of decrease similar to that prepolicy. In a comparison of changes between patients insured through Medicaid vs Medicare, Medicaid patients had an immediate change of -9.8 pills (95% CI -19 to -0.76; p = 0.03) after policy implementation and continued decreases similar to those prepolicy. No immediate or subsequent policy-related changes were observed among Medicare patients. CONCLUSION: In a large regional safety-net institution, postoperative opioid prescriptions decreased in size over time, with immediate changes associated with a state Medicaid policy and corresponding decision support intervention. These findings pose implications for surgeons, hospital leaders, and payers seeking to address opioid use via judicious prescribing.

Effects of opioid addiction risk information on Americans' agreement with postoperative opioid minimization and perceptions of quality.

BACKGROUND: Judicious opioid prescribing and patient counseling, including in the postoperative context, are important efforts to address the U.S. opioid crisis. In discussions with patients and loved ones, there is commonly an emphasis on addiction risk. From a behavioral science standpoint, presenting addiction risk information represents a fear appeal. Clinicians may also seek to build trust and confidence by presenting balanced views of benefits and risks. However, little is known about if and how addiction risk information evokes negative emotions, affects perceptions of quality, and influences perspectives on judicious opioid prescribing. METHODS: We conducted a four-arm, randomized survey of U.S. adults involving a vignette about post-appendectomy pain management for a friend, including the quantity of opioids commonly prescribed. Participants were given either no additional information (control), addiction risk information, addiction plus health risk information, or addiction plus death risk information. We compared evoked affect, agreement with a reduced opioid prescription compared to common practice, and perceptions of quality. RESULTS: Among 1,546 participants (56% men, mean age 39), 78% agreed with reducing the quantity of opioids prescribed, relative to common practices. Compared to the control, providing addiction risk information did not impact the degree of evoked negative emotions or the likelihood of agreement with reduced opioid prescriptions. Providing opioid risk information increased the likelihood of high surgeon quality ratings. CONCLUSIONS: Among a sample of U.S. adults, presenting addiction risk did not effectively appeal to fear, nor increase agreement with judicious opioid prescribing. Alternative communication strategies may be needed for those purposes.

Incorporating emotions into clinical decision-making solutions.

Health and emotions are inexorably connected. Yet there is still little emphasis on emotions in many clinical decision-making tools and interventions. Instead, existing solutions have tended to target cognition - how people comprehend and act on information about health and disease. While clear thinking contributes to better choices, a potential consequence of heavily targeting cognition is an under-emphasis on emotions - a tendency to work on improving how people think about health care choices without addressing how they feel about them. Several solutions can help clinicians and behavioral scientists address these dynamics: critically evaluating current decision-making conceptual frameworks and strategies, searching for areas where emotions may play a role and where they may have been overlooked; and filling any identified gaps by drawing on insights from affective science. Clinical decision-making solutions should address how individuals feel, not just how they think.

Validation of a low-cost simulation strategy for burn escharotomy training.

BACKGROUND: Escharotomy is the primary effective intervention to relieve constriction and impending vascular compromise in deep, circumferential or near-circumferential burns of the extremities and trunk. Training on escharotomy indications, technique and pitfalls is essential, as escharotomy is both an infrequent and high-risk procedure in civilian and military medical environments, including low-resource settings. Therefore, we aimed to validate an educational strategy that combines video-based instruction with a low-cost, low-fidelity simulation model for teaching burn escharotomy. METHODS: Pre-hospital and hospital-based medical personnel, with varying degrees of burn care-related experience, participated in a one-hour training session. The first part of the training consisted of video-based instruction that described the indications, preparation, steps, pitfalls and complications associated with escharotomy. The second part of the training consisted of a supervised, hands-on simulation with a previously described low-cost, low-fidelity escharotomy model. Participants were then offered two psychometrically validated instruments to assess their learning experience. RESULTS: 40 participants were grouped according to prior burn care and surgical experience: attending surgeons (6), surgery and emergency medicine residents and fellows (26), medical students (5), and pre-hospital personnel (3). On two psychometrically validated questionnaires, participants at both the attending and trainee levels overwhelmingly confirmed that our educational strategy met best educational practices on the criteria of active learning, collaboration, diverse ways of learning, and high expectations; they also highly rated their satisfaction with and self-confidence under this learning strategy. DISCUSSION: An educational strategy that combines video-based instruction and a low-cost, low-fidelity escharotomy simulation model was successfully demonstrated with participants across a broad range of prior burn care experience levels. This strategy is easily reproducible and broadly applicable to increase the knowledge and confidence of medical personnel before they are called to perform escharotomy. Important applications include resource-limited environments and deployed military settings.

Operative Versus Nonoperative Management of Nonfunctioning Pancreatic Neuroendocrine Tumors.

INTRODUCTION: Surgical resection is the only curative treatment for pancreatic neuroendocrine tumors (PNETs), but pancreatic operations carry a significant morbidity. We investigated whether the resection of small, asymptomatic nonfunctioning PNETs is beneficial. Clinicopathologic factors were retrospectively reviewed for all PNET cases from 1998 to 2014. METHODS: Kaplan-Meier survival and multivariable regression analyses were performed. A total of 249 patients had nonfunctioning PNETs with adequate follow-up, of whom 193 were resected and 56 were observed. Median age was 56 years, and 48 % of the patients were female. RESULTS: Overall, the resected patients had a significantly longer survival (OS) (p = 0.001). However, for the patients with PNETs ≤2.5 cm in size and without metastasis at presentation, tumor size significantly modified the effect of resection on overall survival (p < 0.05). The protective effect of resection increased as tumor size increased. An operation became a significant predictor of overall survival for tumors >1.5 cm (p = 0.050 or less for larger tumors) but was not significant for tumors <1.5 cm (p = 0.317 or more for smaller tumors), controlling for age-adjusted Charlson comorbidity index. CONCLUSION: Resection of nonfunctioning PNETs over 1.5 cm is independently and significantly associated with a longer survival. However, the benefit of resection for tumors under 1.5 cm is unclear.

Aurora B-dependent regulation of class IIa histone deacetylases by mitotic nuclear localization signal phosphorylation.

Class IIa histone deacetylases (HDACs 4/5/7/9) are transcriptional regulators with critical roles in cardiac disease and cancer. HDAC inhibitors are promising anticancer agents, and although they are known to disrupt mitotic progression, the underlying mechanisms of mitotic regulation by HDACs are not fully understood. Here we provide the first identification of histone deacetylases as substrates of Aurora B kinase (AurB). Our study identifies class IIa HDACs as a novel family of AurB targets and provides the first evidence that HDACs are temporally and spatially regulated by phosphorylation during the cell cycle. We define the precise site of AurB-mediated phosphorylation as a conserved serine within the nuclear localization signals of HDAC4, HDAC5, and HDAC9 at Ser265, Ser278, and Ser242, respectively. We establish that AurB interacts with these HDACs in vivo, and that this association increases upon disruption of 14-3-3 binding. We observe colocalization of endogenous, phosphorylated HDACs with AurB at the mitotic midzone in late anaphase and the midbody during cytokinesis, complemented by a reduction in HDAC interactions with components of the nuclear corepressor complex. We propose that AurB-dependent phosphorylation of HDACs induces sequestration within a phosphorylation gradient at the midzone, maintaining separation from re-forming nuclei and contributing to transcriptional control.