To Scan or Not to Scan: Development of a Clinical Decision Support Tool to Determine if Imaging Would Aid in the Diagnosis of Appendicitis.

BACKGROUND: Appendicitis is one of the most common surgically treated diseases in the world. CT scans are often over-utilized and ordered before a surgeon has evaluated the patient. Our aim was to develop a tool using machine learning (ML) algorithms that would help determine if there would be benefit in obtaining a CT scan prior to surgeon consultation. METHODS: Retrospective chart review of 100 randomly selected cases who underwent appendectomy and 100 randomly selected controls was completed. Variables included components of the patient's history, laboratory values, CT readings, and pathology. Pathology was used as the gold standard for appendicitis diagnosis. All variables were then used to build the ML algorithms. Random Forest (RF), Support Vector Machine (SVM), and Bayesian Network Classifiers (BNC) models with and without CT scan results were trained and compared to CT scan results alone and the Alvarado score using area under the Receiver Operator Curve (ROC), sensitivity, and specificity measures as well as calibration indices from 500 bootstrapped samples. RESULTS: Among the cases that underwent appendectomy, 88% had pathology-confirmed appendicitis. All the ML algorithms had better sensitivity, specificity, and ROC than the Alvarado score. SVM with and without CT had the best indices and could predict if imaging would aid in appendicitis diagnosis. CONCLUSION: This study demonstrated that SVM with and without CT results can be used for selective imaging in the diagnosis of appendicitis. This study serves as the initial step and proof-of-concept to externally validate these results with larger and more diverse patient population.

Clinical risk factors and inflammatory biomarkers of post-traumatic acute kidney injury in combat patients.

BACKGROUND: Post-traumatic acute kidney injury has occurred in every major military conflict since its initial description during World War II. To ensure the proper treatment of combat casualties, early detection is critical. This study therefore aimed to investigate combat-related post-traumatic acute kidney injury in recent military conflicts, used machine learning algorithms to identify clinical and biomarker variables associated with the development of post-traumatic acute kidney injury, and evaluated the effects of post-traumatic acute kidney injury on wound healing and nosocomial infection. METHODS: We conducted a retrospective clinical cohort review of 73 critically injured US military service members who sustained major combat-related extremity wounds and had collected injury characteristics, assayed serum and tissue biopsy samples for the expression of protein and messenger ribonucleic acid biomarkers. Bivariate analyses and random forest recursive feature elimination classification algorithms were used to identify associated injury characteristics and biomarker variables. RESULTS: The incidence of post-traumatic acute kidney injury was 20.5%. Of that, 86% recovered baseline renal function and only 2 (15%) of the acute kidney injury group required renal replacement therapy. Random forest recursive feature elimination algorithms were able to estimate post-traumatic acute kidney injury with the area under the curve of 0.93, sensitivity of 0.91, and specificity of 0.91. Post-traumatic acute kidney injury was associated with injury severity score, serum epidermal growth factor, and tissue activin A type receptor 1, matrix metallopeptidase 10, and X-C motif chemokine ligand 1 expression. Patients with post-traumatic acute kidney injury exhibited poor wound healing and increased incidence of nosocomial infections. CONCLUSION: The occurrence of acute kidney injury in combat casualties may be estimated using injury characteristics and serum and tissue biomarkers. External validations of these models are necessary to generalize for all trauma patients.

Behavior Profiles at 2 Years for Children Born Extremely Preterm with Bronchopulmonary Dysplasia.

OBJECTIVE: To characterize behavior of 2-year-old children based on the severity of bronchopulmonary dysplasia (BPD). STUDY DESIGN: We studied children born at 22-26 weeks of gestation and assessed at 22-26 months of corrected age with the Child Behavior Checklist (CBCL). BPD was classified by the level of respiratory support at 36 weeks of postmenstrual age. CBCL syndrome scales were the primary outcomes. The relationship between BPD grade and behavior was evaluated, adjusting for perinatal confounders. Mediation analysis was performed to evaluate whether cognitive, language, or motor skills mediated the effect of BPD grade on behavior. RESULTS: Of 2310 children, 1208 (52%) had no BPD, 806 (35%) had grade 1 BPD, 177 (8%) had grade 2 BPD, and 119 (5%) had grade 3 BPD. Withdrawn behavior (P < .001) and pervasive developmental problems (P < .001) increased with worsening BPD grade. Sleep problems (P = .008) and aggressive behavior (P = .023) decreased with worsening BPD grade. Children with grade 3 BPD scored 2 points worse for withdrawn behavior and pervasive developmental problems and 2 points better for externalizing problems, sleep problems, and aggressive behavior than children without BPD. Cognitive, language, and motor skills mediated the effect of BPD grade on the attention problems, emotionally reactive, somatic complaints, and withdrawn CBCL syndrome scales (P values < .05). CONCLUSIONS: BPD grade was associated with increased risk of withdrawn behavior and pervasive developmental problems but with decreased risk of sleep problems and aggressive behavior. The relationship between BPD and behavior is complex. Cognitive, language, and motor skills mediate the effects of BPD grade on some problem behaviors.

Association of Anemia With Outcomes in Patients Undergoing Percutaneous Peripheral Vascular Intervention: Insights From the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2 VIC).

OBJECTIVES: To evaluate the clinical features and outcomes of patients with anemia undergoing percutaneous peripheral vascular intervention (PVI) in a contemporary registry. METHODS: We evaluated the differences in the clinical features and outcomes of patients with and without anemia undergoing PVI in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2 VIC) registry. Anemia was defined using World Health Organization criteria. RESULTS: Baseline anemia was present in 42.3% of 15,683 patients undergoing PVI. Compared to patients without anemia, those with anemia were older (mean age, 67 years vs 71 years), were more often black (16% vs 29%), and had higher comorbidities. Anemic patients were twice as likely to present with acute limb ischemia (5% vs 11%) and undergo urgent PVI (6% vs 15%) or below-the-knee PVI (18% vs 35%). Many in-hospital adverse events were higher in anemic patients. In a propensity-matched cohort, any adverse outcome (3.4% vs 8.4%; odds ratio [OR], 2.58; 95% confidence interval [CI], 1.94-3.42) or major cardiovascular event, defined as death, myocardial infarction, stroke, or amputation (1.1% vs 3.2%; OR, 2.96; 95% CI, 1.83-4.79) was more likely in anemic patients. Of all adverse events, the highest odds were observed for post-PVI transfusions and amputations in anemic patients. Multivariable logistic regression showed that baseline hemoglobin (1 g/dL below the normal value) was associated with greater risk of any adverse event (OR, 1.57; 95% CI, 1.47-1.68). CONCLUSION: The prevalence of anemia was high among PVI patients and was associated with significantly greater likelihood of amputation, any adverse event, and major cardiovascular events. Whether preprocedure correction of anemia has the potential to decrease post-PVI adverse events remains to be studied.

The Clinical Impact of Cardiology Consultation Prior to Major Vascular Surgery.

OBJECTIVE: To understand statewide variation in preoperative cardiology consultation prior to major vascular surgery and to determine whether consultation was associated with differences in perioperative myocardial infarction (poMI). SUMMARY BACKGROUND DATA: Medical consultation prior to major vascular surgery is obtained to reduce perioperative risk. Despite perceived benefit of preoperative consultation, evidence is lacking specifically for major vascular surgery on the effect of preoperative cardiac consultation. METHODS: Patient and clinical data were obtained from a statewide vascular surgery registry between January 2012 and December 2014. Patients were risk stratified by revised cardiac risk index category and compared poMI between patients who did or did not receive a preoperative cardiology consultation. We then used logistic regression analysis to compare the rate of poMI across hospitals grouped into quartiles by rate of preoperative cardiology consultation. RESULTS: Our study population comprised 5191 patients undergoing open peripheral arterial bypass (n = 3037), open abdominal aortic aneurysm repair (n = 332), or endovascular aneurysm repair (n = 1822) at 29 hospitals. At the patient level, after risk-stratification by revised cardiac risk index category, there was no association between cardiac consultation and poMI. At the hospital level, preoperative cardiac consultation varied substantially between hospitals (6.9%-87.5%, P <0.001). High preoperative consulting hospitals (rate >66%) had a reduction in poMI (OR, 0.52; confidence interval: 0.28-0.98; P <0.05) compared with all other hospitals. These hospitals also had a statistically greater consultation rate with a variety of medical specialties. CONCLUSIONS: Preoperative cardiology consultation for vascular surgery varies greatly between institutions, and does not appear to impact poMI at the patient level. However, reduction of poMI was noted at the hospitals with the highest rate of preoperative cardiology consultation as well as a variety of medical services, suggesting that other hospital culture effects play a role.

Predictors of surgical site infection after open lower extremity revascularization.

OBJECTIVE: Surgical site infection (SSI) after open lower extremity bypass (LEB) is a serious complication leading to an increased rate of graft failure, hospital readmission, and health care costs. This study sought to identify predictors of SSI after LEB for arterial occlusive disease and also potential modifiable factors to improve outcomes. METHODS: Data from a statewide cardiovascular consortium of 35 hospitals were used to obtain demographic, procedural, and hospital risk factors for patients undergoing elective or urgent open LEB between January 2012 and June 2015. Bivariate comparisons and targeted maximum likelihood estimation were used to identify independent risk factors of SSI. Adjusted odds ratios (ORs) were calculated for patient demographics, comorbidities, operative details, and hospital-level factors. RESULTS: Our study population included 3033 patients who underwent 703 femoral-femoral bypasses, 1431 femoral-popliteal bypasses, and 899 femoral-distal vessel bypasses. An SSI was diagnosed in 320 patients (10.6%) ≤30 days after the index operation. Adjusted patient and procedural predictors of SSI included renal failure currently requiring dialysis (OR, 4.35; 95% confidence interval [CI], 3.45-5.47; P < .001), hypertension (OR, 4.29; 95% CI, 2.74-6.72; P < .001), body mass index ≥25 kg/m2 (OR, 1.78; 95% CI, 1.23-2.57; P = .002), procedural time >240 minutes (OR, 2.95; 95% CI, 1.89-4.62; P < .001), and iodine-only skin preparation (OR, 1.73; 95% CI, 1.02-2.91; P = .04). Hospital factors associated with increased SSI included hospital size <500 beds (OR, 2.22; 95% CI, 1.09-4.55; P = .028) and major teaching hospital (OR, 1.66; 95% CI, 1.07-2.58; P = .024). SSI resulted in increased risk of major amputation and surgical reoperation (P < .01), but did not affect 30-day mortality. CONCLUSIONS: SSI after LEB is associated with an increase in rate of amputation and reoperation. Several patient, operative, and hospital-related risk factors that predict postoperative SSI were identified, suggesting that targeted improvements in perioperative care may decrease complications and improve vascular patient outcomes.

Antimicrobial effects of virgin coconut oil and its medium-chain fatty acids on Clostridium difficile.

Clostridium difficile is the leading cause of hospital-acquired antibiotic-associated diarrhea worldwide; in addition, the proliferation of antibiotic-resistant C. difficile is becoming a significant problem. Virgin coconut oil (VCO) has been shown previously to have the antimicrobial activity. This study evaluates the lipid components of VCO for the control of C. difficile. VCO and its most active individual fatty acids were tested to evaluate their antimicrobial effect on C. difficile in vitro. The data indicate that exposure to lauric acid (C12) was the most inhibitory to growth (P<.001), as determined by a reduction in colony-forming units per milliliter. Capric acid (C10) and caprylic acid (C8) were inhibitory to growth, but to a lesser degree. VCO did not inhibit the growth of C. difficile; however, growth was inhibited when bacterial cells were exposed to 0.15-1.2% lipolyzed coconut oil. Transmission electron microscopy (TEM) showed the disruption of both the cell membrane and the cytoplasm of cells exposed to 2 mg/mL of lauric acid. Changes in bacterial cell membrane integrity were additionally confirmed for VCO and select fatty acids using Live/Dead staining. This study demonstrates the growth inhibition of C. difficile mediated by medium-chain fatty acids derived from VCO.

The Adolescent Substance Abuse Prevention Study: A randomized field trial of a universal substance abuse prevention program.

OBJECTIVES: The purpose of the study was to determine whether a universal school-based substance abuse prevention program, Take Charge of Your Life (TCYL), prevents or reduces the use of tobacco, alcohol, or marijuana. METHODS: Eighty-three school clusters (representing school districts) from six metropolitan areas were randomized to treatment (41) or control (42) conditions. Using active consenting procedures, 19,529 seventh graders were enrolled in the 5-year study. Self-administered surveys were completed by the students annually. Trained Drug Abuse Resistance Education (D.A.R.E.) police officers presented TCYL in seventh and ninth grades in treatment schools. Analyses were conducted with data from 17,320 students who completed a baseline survey. Intervention outcomes were measured using self-reported past-month and past-year use of tobacco, alcohol, and marijuana when students were in the 11th grade. RESULTS: Main effect analyses show a negative program effect for use of alcohol and cigarettes and no effect for marijuana use. Subgroup analyses indicated that the negative effect occurred among nonusers at baseline, and mostly among white students of both genders. A positive program effect was found for students who used marijuana at baseline. Two complementary papers explore the relationship of the targeted program mediators to the use of alcohol, tobacco, and marijuana and specifically for students who were substance-free or who used substances at baseline. CONCLUSIONS: The negative impact of the program on baseline nonusers of alcohol and tobacco indicate that TCYL should not be delivered as a universal prevention intervention. The finding of a beneficial effect for baseline marijuana users further supports this conclusion. The programmatic and methodological challenges faced by the Adolescent Substance Abuse Prevention Study (ASAPS) and lessons learned offer insights for prevention researchers who will be designing similar randomized field trials in the future.

The influence of program mediators on eleventh grade outcomes for seventh grade substance users and nonusers.

OBJECTIVES: In their work examining the effects of the Take Charge of Your Life (TCYL) program, Sloboda and colleagues (This Issue) found that the TCYL program had significant positive effects on baseline marijuana users and significant negative effects on baseline nonusers of cigarettes and alcohol. METHODS: Mediational analyses were used to understand why the program had these differential impacts on baseline users and nonusers. RESULTS: Path models for binary outcomes revealed significant program impacts on marijuana normative beliefs and refusal skills. The treatment impacts were between 1.5 and 3 times larger for the baseline users than for nonusers. These direct effects of the program on normative beliefs and refusal skills mediated the treatment impact on use for baseline marijuana users. In contrast, the negative treatment effects on alcohol and cigarette use could not be explained by the program's targeted mediators (normative beliefs, refusal skills, consequences, attitudes and intentions). The direct effects of treatment on use for the baseline nonusers of cigarettes and alcohol remain unexplained. CONCLUSIONS: Possible explanations for this pattern and implications for strengthening universal prevention programs that are delivered to both users and nonusers are discussed. The importance of mediational analyses for programs that show negative impacts, as well as for those that show positive impacts is stressed.

Universal school-based substance abuse prevention programs: Modeling targeted mediators and outcomes for adolescent cigarette, alcohol and marijuana use.

OBJECTIVE: We examined the relationships among targeted constructs of social influences and competence enhancement prevention curricula and cigarette, alcohol and marijuana use outcomes in a diverse sample of high school students. We tested the causal relationships of normative beliefs, perceptions of harm, attitudes toward use of these substances and refusal, communication, and decision-making skills predicting the self-reported use of each substance. In addition, we modeled the meditation of these constructs through the intentions to use each substance and tested the moderating effects of the skills variables on the relationships between intentions to use and self-reported use of each of these substances. METHODS: Logistic regression path models were constructed for each of the drug use outcomes. Models were run using the Mplus 5.0 statistical application using the complex sample function to control for the sampling design of students nested within schools; full information maximum likelihood estimates (FIML) were utilized to address missing data. RESULTS: Relationships among targeted constructs and outcomes differed for each of the drugs with communication skills having a potentially iatrogenic effect on alcohol use. Program targets were mediated through the intentions to use these substances. Finally, we found evidence of a moderating effect of decision-making skills on perceptions of harm and attitudes toward use, depending upon the outcome. CONCLUSIONS: Prevention curricula may need to target specific drugs. In addition to normative beliefs, perceptions of harm, and refusal and decision-making skills, programs should directly target constructs proximal to behavioral outcomes such as attitudes and intentions. Finally, more research on the effects of communication skills on adolescent substance use should be examined.

Tramadol versus buprenorphine for the management of acute heroin withdrawal: a retrospective matched cohort controlled study.

Many medications have been used over the past thirty years for the treatment of opioid withdrawal, including propoxyphene, methadone, clonidine, parenteral buprenorphine, and, more recently, sublingual buprenorphine. Each has been found to have clinical strengths and limitations. Tramadol is a centrally acting synthetic analgesic with opiate activity primarily due to the binding of a metabolite to the micro receptor. Despite this micro receptor activity, tramadol appears to have low abuse potential and is a non-scheduled analgesic. The pharmacologic profile of tramadol makes it a candidate for opiate withdrawal treatment. A chart review was undertaken to retrospectively compare treatment outcomes of heroin-dependent patients when detoxified with parenteral buprenorphine (1996-1997) versus tramadol (1999-2000). Inclusion criteria for this study were heroin as drug of choice, current opioid physical dependence (ie, withdrawal symptoms), no current abuse of oral opioid analgesics, and no alcohol or benzodiazepine withdrawal symptoms. Patient cases that met inclusion criteria were group-matched between buprenorphine and tramadol on the basis of age, sex, and amount of heroin used (bags/day). Charts were audited for patient demographics, daily heroin use at admission, withdrawal symptoms, and discharge status. In total, 129 patient charts were reviewed, and 115 met all inclusion criteria and were group-matched (45 patients in the buprenorphine group, seventy in the tramadol group). There were no differences in demographics between the two groups of patients. Fifty-six percent of the buprenorphine group and 71% of the tramadol group completed detoxification; tramadol-treated patients had significantly higher average withdrawal symptoms when compared to the buprenorphine group and a greater reduction in withdrawal symptoms over time. Finally, the number of side effects was small and did not differ between the groups. The results of this study are consistent with previous pilot reports that indicated few clinical differences between parenteral buprenorphine and oral tramadol protocols when used in the management of acute heroin withdrawal. As a consequence, tramadol shows some promise as an opioid withdrawal management medication.

Is screening and brief advice for problem drinkers by clergy feasible? A survey of clergy.

Routine screening for alcohol abuse in primary care, with brief advice to stop drinking for those screening positive, can detect individuals with alcohol problems and reduce alcohol use and alcohol induced problems in those detected. Not everyone with alcohol problems sees a physician regularly, however, and not all respond to a physician's brief advice. To explore the feasibility of expanding screening for alcohol problems to clergy, we did a mailed survey to 315 clergy at Christian churches in Cleveland, Ohio. Clergy reported a variety of views about alcohol use and abuse, but most agreed that alcoholism is a disease. They indicated counseling a significant number of parishioners, and were receptive to learning brief screening questions to detect alcohol problems. We conclude that many clergy would be interested in a strategy of screening and then giving brief advice or referral to individuals found to have alcohol problems.

The use of tramadol for acute heroin withdrawal: a comparison to clonidine.

Using a retrospective chart review, 59 patients detoxified with tramadol were compared to 85 patients detoxified with clonidine on rates of leaving against medical advice (AMA) and control of withdrawal symptoms. Patients detoxified with tramadol had 23% (95% CI, 0.09-0.59; P < .01) the risk of leaving AMA and scored an average of 0.24 points lower (95% CI, 0.08-0.41; P < .01) on a 0-3 point withdrawal symptom scale compared to patients detoxified with clonidine. This preliminary study indicates that tramadol is more effective in managing withdrawal than clonidine, and may be especially useful in outpatient detoxification.