Opioid use disorder in adult burn patients: Implications for future mental health, behavioral and substance use patterns.

BACKGROUND: Burn patients continue to have a high opioid requirement, despite current national trends to decrease opioid prescribing. While effective, long-term opioid use results in opioid dependence and possibly other mental health comorbidities. This retrospective cohort study seeks to evaluate implications of diagnosed opioid use disorder in the development of subsequent psychiatric, behavioral and substance abuse patterns. METHODS: The TriNetX database was queried for patients 18 years and older with a diagnosis of thermal or chemical burn who developed opioid use disorder after their burn injury. Two matched cohorts were studied, opioid use disorder versus non-opioid use disorder, to evaluate risk of developing subsequent mental health and behavioral conditions, use of psychiatric health services, and future substance abuse. RESULTS: A total of 2020 patients were identified in each cohort, matched for demographics, external trauma, and burn size. Patients in the opioid use disorder group had a significantly higher incidence of mental health diagnoses (79.7 % versus 57.7 %, OR 1.973, CI 1.741-2.236, p < 0.0001), including major depressive disorder, generalized anxiety disorder, and post-traumatic stress disorder. This group was also more likely to utilize psychiatric services (16.0 % versus 10.3 %, OR 1.926, CI 1.595-2.326, p < 0.0001) and psychotherapy (12.6 % versus 7.2 %, OR 2.046, CI 1.650-2.536, p<0.0001). Furthermore, the opioid use disorder group had higher rates of polysubstance abuse (29.9 % versus 12.3 %, OR 3.048, CI 2.588-3.589, p<0.0001), suicidal / homicidal ideations (8.2 % versus 3.2 %, OR 3.057, CI 2.274-4.109, p<0.0001), and suicide attempts (2.0 % versus 0.7 %, OR 2.971, CI 1.611-5.478, p = 0.003). CONCLUSIONS: Burn patients who develop opioid use disorder have significantly higher rates of future psychiatric diagnoses, behavioral disturbances, and polysubstance abuse. A multidisciplinary team approach, including early involvement of pain and mental health services, could potentially reduce the development of opioid use disorder and its consequences.

The Immunologic Effect of Early Intravenous Two and Four Gram Bolus Dosing of Tranexamic Acid Compared to Placebo in Patients With Severe Traumatic Bleeding (TAMPITI): A Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial.

Background: The hemostatic properties of tranexamic acid (TXA) are well described, but the immunological effects of TXA administration after traumatic injury have not been thoroughly examined. We hypothesized TXA would reduce monocyte activation in bleeding trauma patients with severe injury. Methods: This was a single center, double-blinded, randomized controlled trial (RCT) comparing placebo to a 2 g or 4 g intravenous TXA bolus dose in trauma patients with severe injury. Fifty patients were randomized into each study group. The primary outcome was a reduction in monocyte activation as measured by human leukocyte antigen-DR isotype (HLA-DR) expression on monocytes 72 h after TXA administration. Secondary outcomes included kinetic assessment of immune and hemostatic phenotypes within the 72 h window post-TXA administration. Results: The trial occurred between March 2016 and September 2017, when data collection ended. 149 patients were analyzed (placebo, n = 50; 2 g TXA, n = 49; 4 g TXA, n = 50). The fold change in HLA-DR expression on monocytes [reported as median (Q1-Q3)] from pre-TXA to 72 h post-TXA was similar between placebo [0.61 (0.51-0.82)], 2 g TXA [0.57 (0.47-0.75)], and 4 g TXA [0.57 (0.44-0.89)] study groups (p = 0.82). Neutrophil CD62L expression was reduced in the 4 g TXA group [fold change: 0.73 (0.63-0.97)] compared to the placebo group [0.97 (0.78-1.10)] at 24 h post-TXA (p = 0.034). The fold decrease in plasma IL-6 was significantly less in the 4 g TXA group [1.36 (0.87-2.42)] compared to the placebo group [0.46 (0.19-1.69)] at 72 h post-TXA (p = 0.028). There were no differences in frequencies of myeloid or lymphoid populations or in classical complement activation at any of the study time points. Conclusion: In trauma patients with severe injury, 4 g intravenous bolus dosing of TXA has minimal immunomodulatory effects with respect to leukocyte phenotypes and circulating cytokine levels. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02535949.

Are Patients with Perforated Peptic Ulcers Who are Negative for Helicobacter pylori at a Greater Risk?

Background: The link between Helicobacter pylori infection and peptic ulceration is well established. Recent studies have reported a decrease of H. pylori-related peptic ulcer disease; Helicobacter pylori eradication is likely the cause of this decrease. We hypothesized that patients with H. pylori-positive perforated peptic ulcer disease (PPUD) requiring surgical intervention had worse outcomes than patients with H. pylori-negative PPUD. Patients and Methods: A prospectively collected Acute and Critical Care Surgery registry spanning the years 2008 to 2015 was searched for patients with PPUD and tested for H. pylori serum immunoglobulin G (IgG) test. Patients were divided into two cohorts: H. pylori positive (HPP) and H. pylori negative (HPN). Demographics, laboratory values, medication history, social history, and esophagogastroduodenoscopy were collected. Student t-test was used for continuous variables and χ2 test was used for categorical variables. Linear regression was applied as appropriate. Results: We identified 107 patients diagnosed with PPUD, of whom 79 (74%) patients had H. pylori serum IgG testing. Forty-two (53.2%) tested positive and 37 (46.8%) tested negative. Helicobacter pylori-negative PPUD was more frequent in females (70.27%, p = 0.004), whites (83.78%, p = 0.001) and patients with higher body mass index (BMI) 28.81 ± 8.8 (p = 0.033). The HPN group had a lower serum albumin level (2.97 ± 0.96 vs. 3.86 ± 0.91 p = 0.0001), higher American Society of Anesthesiologists (ASA; 3.11 ± 0.85 vs. 2.60 ± 0.73; p = 0.005), and Charlson comorbidity index (4.81 ± 2.74 vs. 2.98 ± 2.71; p = 0.004). On unadjusted analysis the HPN cohort had a longer hospital length of stay (LOS; 20.20 ± 13.82 vs. 8.48 ± 7.24; p = 0.0001), intensive care unit (ICU) LOS (10.97 ± 11.60 vs. 1.95 ± 4.59; p = 0.0001), increased ventilator days (4.54 ± 6.74 vs. 0.98 ± 2.85; p = 0.004), and higher rates of 30-day re-admission (11; 29.73% vs. 5; 11.91%; p = 0.049). Regression models showed that HPN PPUD patients had longer hospital and ICU LOS by 11 days (p = 0.002) and 8 days (p = 0.002), respectively, compared with HPP PPUD. Conclusion: In contrast to our hypothesis, HPN patients had clinically worse outcomes than HPP patients. These findings may represent a difference in the baseline pathophysiology of the peptic ulcer disease process. Further investigation is warranted.

Early Emergency General Surgery Is Associated with a Higher Incidence of Clostridium difficile Infection.

BACKGROUND: Clostridium difficile infection (CDI) is an important surgical complication. Emergency general surgery (EGS) is a developing area of the acute care surgical practice. Few studies evaluating the incidence and risk factors of CDI in this patient population are available. PATIENTS AND METHODS: A prospectively maintained Acute and Critical Care Surgery registry spanning from 2008 to 2015 was queried for cases of operative EGS with clinical suspicion of CDI post-operatively. Diagnosis of CDI was made using toxin A/B assay in stools. Demographics, co-morbidities, surgical procedures, length of stay (LOS), intensive care unit LOS, antibiotic use, and death were obtained. The patients positive and negative for CDI were compared using chi-squared and Student's t-test. Multi-variable logistic regression was used to determine risk factors for CDI. RESULTS: A total of 550 patients were identified. The total incidence of CDI was 12.7%. There was no significant difference in demographics between CDI positive and negative patients. Average time to CDI diagnosis was 10.1 ± 8.5 days post-operatively. Patients who received three or more antibiotic classes were at higher risk of CDI developing post-operatively (83% vs. 75%, p = 0.04). The CDI positive patients underwent an EGS significantly earlier than CDI negative patients (0.9 ± 2.3 vs. 3.2 ± 9.2 days, p < 0.001). The most common procedures were partial colectomies (21.4%); small bowel resections/repairs (12.9%); gastric repair for perforated peptic ulcer (10%); skin and soft tissue procedure (7.1%), and laparotomies (5.7%). There was no difference in outcomes between the groups. On linear regression, an EGS performed later after admission was an independent risk factor for lower CDI (OR 0.87; CI 95% [0.79-0.96], p < 0.01). CONCLUSION: Patients undergoing an early EGS have a high incidence of CDI. The number of antibiotic classes administered post-operatively affects CDI status. Bowel resections appear to be at increased risk for CDI. Clinicians should have a high index of suspicion and low threshold for testing C. difficile in high-risk EGS patients.

Pre-Operative Anti-Fungal Therapy Does Not Improve Outcomes in Perforated Peptic Ulcers.

BACKGROUND: With the advent of anti-Helicobacter pylori therapy, hospital admissions for peptic ulcer disease (PUD) have declined significantly since the 1990s. Despite this, operative treatment of PUD still is common. Although previous papers suggest that Candida in peritoneal fluid cultures may be associated with worse outcomes in patients with perforated peptic ulcers (PPUs), post-operative anti-fungal therapy has not been effective. We hypothesized that pre-operative anti-fungal drugs improve outcomes in patients with PPUs undergoing operative management. PATIENTS AND METHODS: A prospectively maintained Acute and Critical Care Surgery (ACCS) database spanning 2008-2015 and including more than 7,000 patients was queried for patients with PPUs. Demographics and clinical outcomes were abstracted. Pre-operative anti-fungal use, intra-operative peritoneal fluid cultures, and infectious outcomes were abstracted manually. We compared outcomes and the presence of fungal infections in patients receiving peri-operative anti-fungal drugs in the entire cohort and in patients with intra-operative peritoneal fluid cultures. Frequencies were compared by the Fisher exact or χ2 test as appropriate. The Student's t-test was used for continuous variables. RESULTS: There were 107 patients with PPUs who received operative management; 27 (25.2%) received pre-operative anti-fungal therapy; 33 (30.8%) received peritoneal fluid culture, and 17 cultures (51.5%) were positive for fungus. The presence of fungus in the cultures did not affect the outcomes. There were no differences in length of stay (LOS), intensive care unit (ICU) LOS, ventilator days, 30-day re-admission rates, or rates of intra-abdominal abscess formation or fungemia in patients who received pre-operative anti-fungal drugs regardless of the presence of fungi in the peritoneal fluid. CONCLUSION: Candida has been recovered in 29%-57% of peritoneal fluid cultures in patients with PPUs. However, no studies have evaluated pre-operative anti-fungal therapy in PPUs. Our data suggest that pre-operative anti-fungal drugs are unnecessary in patients undergoing operative management for PPU.

Femoral Osteomyelitis Caused by Cladophialophora in a Patient without Known Immunocompromise.

BACKGROUND: Chronic osteomyelitis associated with a stage IV decubitus ulcer is a challenging condition to manage, characterized by frequent relapses and need for long-term anti-microbial therapy. Although gram-positive cocci are the most common causes, fungal infections have been reported, usually in immunocompromised hosts. We present a case of Cladophialophora osteomyelitis in a patient without known immunocompromised that was managed with a Girdlestone pseudoarthroplasty. CASE REPORT: A 70-year-old male presented to our emergency room with fever, right hip pain, and purulent drainage from a right greater trochanter stage IV decubitus ulcer. His medical history was significant for T10 paraplegia secondary to spinal ependymomas and multiple spinal procedures, as well as significant recent weight loss. Past operations included multiple spinal procedures and repair of a right intertrochanteric femoral fracture with a plate and lateral compression screws. This led to post-operative decubitus ulcer formation over the right greater trochanter, requiring a gracilis flap. The flap remained intact for three years, then re-ulcerated. He subsequently developed femoral head osteomyelitis. To facilitate the treatment, the hardware was removed three weeks prior to presentation. With evidence of worsening osteomyelitis and a new soft-tissue infection, a Girdlestone procedure was performed. Intra-operatively, he was noted to have a pathological intertrochanteric fracture. Soft-tissue cultures yielded Pseudomonas aeruginosa; bone cultures grew Streptococcus dysgalactiae and Cladophialophora spp. Post-operatively, his wound was managed with negative pressure wound therapy with instillation and dwell (NPWTi-d). Delayed primary closure over a drain and topical negative pressure was done four days later. His course was uneventful, and he was discharged six days later. At his four-month follow-up, the wound was completely healed. CONCLUSION: Invasive fungal infections are rare in immunocompetent individuals. Cladophialophora osteomyelitis has been found in immunocompromised individuals with concomitant cerebral abscesses. To our knowledge, this is the first case of osteomyelitis without previously known immunocompromise.

Drain Failure in Intra-Abdominal Abscesses Associated with Appendicitis.

BACKGROUND: Previous studies have suggested that percutaneous drainage and interval appendectomy is an effective treatment for appendicitis with associated abscess. Few studies to date have analyzed risk factors for failed drain management. We hypothesized that older patients with more co-morbidities would be at higher risk for failing conservative treatment. METHODS: The 2010-2014 editions of the National Inpatient Sample (NIS) were queried for patients with diagnoses of peri-appendiceal abscesses. Minors and elective admissions were excluded. We identified patients who underwent percutaneous drainage and defined drain failure as undergoing a surgical operation after drainage but during the same inpatient visit to assess for factors associated with failure of drainage alone as a treatment. After univariable analysis, binomial logistic regression was used to assess for independent risk factors. Frequencies were analyzed by χ2 and continuous variables by Student's t-test. RESULTS: A total of 2,209 patients with appendiceal abscesses received drains; 561 patients (25.4%) failed conservative management and underwent operative intervention. On univariable analysis, patients who failed conservative management were younger, more likely to be Hispanic, have more inpatient diagnoses, and to have undergone drainage earlier in the hospital course. Multivariable regression demonstrated that the number of diagnoses, female sex, and Hispanic race were predictive of failure of drainage alone. Older age, West and Midwest census regions, and later drain placement were predictive of successful treatment with drainage alone. Failure was associated with more charges and longer hospital stay but not with a higher mortality rate. CONCLUSION: Approximately a quarter of patients will fail management of appendiceal abscess with percutaneous drain placement alone. Risk factors for failure are patient complexity, female sex, earlier drainage, and Hispanic race. Failure of drainage is associated with higher total charges and longer hospital stay; however, no change in the mortality rate was noted.