Bayesian regularization to predict neuropsychiatric adverse events in smoking cessation with pharmacotherapy.

BACKGROUND: Research on risk factors for neuropsychiatric adverse events (NAEs) in smoking cessation with pharmacotherapy is scarce. We aimed to identify predictors and develop a prediction model for risk of NAEs in smoking cessation with medications using Bayesian regularization. METHODS: Bayesian regularization was implemented by applying two shrinkage priors, Horseshoe and Laplace, to generalized linear mixed models on data from 1203 patients treated with nicotine patch, varenicline or placebo. Two predictor models were considered to separate summary scores and item scores in the psychosocial instruments. The summary score model had 19 predictors or 26 dummy variables and the item score model 51 predictors or 58 dummy variables. A total of 18 models were investigated. RESULTS: An item score model with Horseshoe prior and 7 degrees of freedom was selected as the final model upon model comparison and assessment. At baseline, smokers reporting more abnormal dreams or nightmares had 16% greater odds of experiencing NAEs during treatment (regularized odds ratio (rOR) = 1.16, 95% credible interval (CrI) = 0.95 - 1.56, posterior probability P(rOR > 1) = 0.90) while those with more severe sleep problems had 9% greater odds (rOR = 1.09, 95% CrI = 0.95 - 1.37, P(rOR > 1) = 0.85). The prouder a person felt one week before baseline resulted in 13% smaller odds of having NAEs (rOR = 0.87, 95% CrI = 0.71 - 1.02, P(rOR < 1) = 0.94). Odds of NAEs were comparable across treatment groups. The final model did not perform well in the test set. CONCLUSIONS: Worse sleep-related symptoms reported at baseline resulted in 85%-90% probability of being more likely to experience NAEs during smoking cessation with pharmacotherapy. Treatment for sleep disturbance should be incorporated in smoking cessation program for smokers with sleep disturbance at baseline. Bayesian regularization with Horseshoe prior permits including more predictors in a regression model when there is a low number of events per variable.

Utility of Surveillance Angiography in Aneurysmal Subarachnoid Hemorrhage: A Retrospective Study of 223 Consecutive Patients.

BACKGROUND: Patients with aneurysmal subarachnoid hemorrhage (aSAH) who survive the rupture are at risk for delayed neurologic deficits and cerebral infarction. The ideal method(s) of surveillance for cerebral vasospasm, and the link between radiographic vasospasm and delayed neurologic deficits, remain controversial. We instituted a postbleed day 7 angiography protocol with the stated goals of identification of vasospasm, improving neurologic outcomes, and possibly lowering cost of care. METHODS: We conducted a quality improvement project in which we retrospectively analyzed consecutive cases of aSAH from a single institution over a 5-year period. Patients were excluded if they did not receive treatment for their aneurysm or were < 18 years of age. We analyzed demographic and outcome information for patients managed by protocolled angiography versus those who were managed by as-needed endovascular rescue therapy. Statistical tests were performed comparing means and proportions in both cohorts, as appropriate. RESULTS: In total, 223 patients were identified who met inclusion criteria. In total, 157 patients were identified in the protocolled day 7 angiography group, and 66 were in the nonprotocolled angiography group. Demographics were similar between the day 7 angiogram and medical management cohorts, except for a higher mean age among the latter group (p = 0.016). The protocolled angiography group underwent a significantly greater number of angiograms (p < 0.001) and had a significantly higher cost of hospitalization ($240,327 vs. $205,719, p = 0.03), with no significant difference in rate of cerebral infarction, length of intensive care unit stay, length of hospital stay, discharge location, or discharge modified Rankin Score. CONCLUSIONS: This cohort comparison analysis draws into question the practice of protocolized cerebral angiography in patients with aSAH.

Quantitative planar array screen of 1000 proteins uncovers novel urinary protein biomarkers of lupus nephritis.

OBJECTIVE: The goal of these studies is to discover novel urinary biomarkers of lupus nephritis (LN). METHODS: Urine from systemic lupus erythematosus (SLE) patients was interrogated for 1000 proteins using a novel, quantitative planar protein microarray. Hits were validated in an independent SLE cohort with inactive, active non-renal (ANR) and active renal (AR) patients, in a cohort with concurrent renal biopsies, and in a longitudinal cohort. Single-cell renal RNA sequencing data from LN kidneys were examined to deduce the cellular origin of each biomarker. RESULTS: Screening of 1000 proteins revealed 64 proteins to be significantly elevated in SLE urine, of which 17 were ELISA validated in independent cohorts. Urine Angptl4 (area under the curve (AUC)=0.96), L-selectin (AUC=0.86), TPP1 (AUC=0.84), transforming growth factor-ß1 (TGFß1) (AUC=0.78), thrombospondin-1 (AUC=0.73), FOLR2 (AUC=0.72), platelet-derived growth factor receptor-ß (AUC=0.67) and PRX2 (AUC=0.65) distinguished AR from ANR SLE, outperforming anti-dsDNA, C3 and C4, in terms of specificity, sensitivity and positive predictive value. In multivariate regression analysis, urine Angptl4, L-selectin, TPP1 and TGFß1 were highly associated with disease activity, even after correction for demographic variables. In SLE patients with serial follow-up, urine L-selectin (followed by urine Angptl4 and TGFß1) were best at tracking concurrent or pending disease flares. Importantly, several proteins elevated in LN urine were also expressed within the kidneys in LN, either within resident renal cells or infiltrating immune cells, based on single-cell RNA sequencing analysis. CONCLUSION: Unbiased planar array screening of 1000 proteins has led to the discovery of urine Angptl4, L-selectin and TGFß1 as potential biomarker candidates for tracking disease activity in LN.

Elicitation of prior probability distributions for a proposed Bayesian randomized clinical trial of whole blood for trauma resuscitation.

BACKGROUND: Whole blood trauma resuscitation is conceptually appealing and increasingly used but lacks evidence. A randomized controlled trial is needed but challenging to design. A Bayesian approach might be more efficient and more interpretable than a conventional frequentist design. We report the results on an elicitation meeting to create prior probability distributions to help develop such a trial. METHODS: In-person expert elicitation meeting, based on Sheffield Elicitation Framework methodology. We used an interactive graphical tool to elicit the quantities of interest (24-hour mortality and certainty required). Two rounds were conducted, with an intervening discussion of deidentified responses. Individual responses were aggregated into probability distributions. RESULTS: Fifteen experts participated. The pooled belief was that the median 24-hour mortality of trauma patients with hemorrhagic shock treated with component therapy (the current standard of care) was 19% (95% credible interval [CrI], 6%-45%), and the median 24-hour mortality of those treated with whole blood, 16% (95% CrI, 5%-39%). The pooled prior distribution for the relative risk had a median of 0.84 (95% CrI, 0.26-3.1), indicating that the expert group had a 64% prior belief that whole blood decreases 24-hour mortality compared to component therapy. CONCLUSIONS: Experts had moderately strong beliefs that whole blood reduces the 24-hour mortality of trauma patients with hemorrhagic shock. These data will assist with the design and planning of a Bayesian trial of whole blood resuscitation, which will help to answer a key question in contemporary transfusion practice.

Clinical Characteristics and Long-Term Outcomes of Midaortic Syndrome.

BACKGROUND: Midaortic syndrome (MAS) is a rare congenital or acquired condition marked by segmental or diffuse stenosis of the distal thoracic and/or abdominal aorta and its branches. The optimal approach to medical or interventional management of MAS and long-term outcomes in adults are not well defined. We reviewed MAS cases to characterize the natural history of aortic disease, identify prognostic factors, and evaluate the durability of invasive interventions. METHODS: We conducted a retrospective review of patients with MAS who presented to Memorial Hermann Hospital and Baylor College of Medicine between 1997 and 2018. We categorized cases according to demographic and clinical manifestations, etiologies, the extent of aortic involvement, interventions, and vascular outcomes. RESULTS: We identified a cohort of 13 patients with MAS. The etiology of MAS was identified in 6 cases, including genetic syndromes (neurofibromatosis type 1 (2/13), Williams syndrome (1/13), fibromuscular dysplasia (2/13), and Takayasu arteritis (1/13)). Mean age at first documented clinical event was 25.2 (2-67) years, but cases with genetic etiologies presented significantly younger (18.2 years). The most common primary anatomic site was the suprarenal and infrarenal aorta (zones 5-8). Extra-aortic locations involved the renal (4/13), celiac (3/13), and superior mesenteric (3/13) arteries. Clinical manifestations included hypertension (13/13), claudication (9/13), and postprandial abdominal pain (5/13). All patients with available follow-up data underwent at least one surgical or endovascular intervention (range: 1-8). Postoperative complications included renal failure requiring postdischarge hemodialysis and respiratory failure. There were no deaths in long-term follow-up. CONCLUSIONS: MAS is a complex vasculopathy with substantial variability in clinical presentation and anatomic distribution. Extensive disease frequently requires multiple invasive interventions and results in refractory hypertension, which may predict subsequent clinical events. A multidisciplinary approach with long-term monitoring is essential for preservation of end-organ function and quality of life in this debilitating disease.

Population versus Customized Growth Curves: Prediction of Composite Neonatal Morbidity.

OBJECTIVE: To assess the ability of customized and population growth nomograms in identifying newborns with composite neonatal morbidity (CNM). STUDY DESIGN: This study included women who participated in the 10 Maternal-Fetal Medicine Units (MFMU) trials and delivered a nonanomalous singleton with a known gestational age (GA) of 24 weeks or more and documented birthweight. Population nomograms were based on Alexander's nomogram, whereas customized nomograms used publicly available softwares. Random-effect logistic regression was used to estimate the adjusted odds ratio (aOR). Positive and negative likelihood ratios (LRs) were calculated to assess nomogram performance. RESULTS: Of 92,225 women, 85% met the inclusion criteria. Using the population nomogram, 12% were small for gestational age (SGA) and 10% were large for gestational age (LGA), and using customized nomograms, 15% were SGA and 16% LGA. SGA newborns had a higher likelihood of CNM (aOR: 2.62; 95% confidence interval [CI]: 2.48-2.76) for population nomograms and 3.22 (95% CI: 3.07-3.39) for customized nomograms. LGA newborns had a similar CNM with population nomogram but significantly higher with customized nomogram (aOR: 1.42; 95% CI: 1.34-1.50). For the adverse outcomes among SGA and LGA, the positive LRs for the two nomograms were similar with overlapping 95% CI. CONCLUSION: Though both SGA and LGA are associated with adverse perinatal outcomes, the detection using both nomograms was similar.

Growth among Twins: Use of Singleton versus Twin-Specific Growth Nomograms.

OBJECTIVE: We hypothesized that utilization of a twin-specific nomograms, when compared with one based on singleton data, is less likely to classify twins as having abnormal growth and more likely to identify perinatal morbidity and mortality. MATERIALS AND METHODS: Data were culled from seven Maternal-Fetal Medicine Units (MFMU) studies, the included twin gestations in their study population. Each newborn twin's birth weight percentile was categorized using Alexander et al (singleton data) and Ananth et al (twin data) nomogram. Logistic regression models were adjusted for maternal race and body mass index, neonatal sex, study, and twin correlation. RESULTS: More twins were categorized as small for gestational age (SGA) when singleton nomogram was used (33%) compared with twin nomogram (4%). The use of singleton nomogram revealed a higher composite neonatal morbidity (CNM) and stillbirth rates among SGA twins but a similar neonatal mortality rate when compared with appropriate for gestational age. Correspondingly, when twin-specific nomogram was utilized, the CNM, odds of stillbirth, and neonatal mortality were higher among SGA twins. The rate of large for gestational age among twins was increased with the use of twin-specific nomograms. CONCLUSION: Utilization of twin-specific nomogram is less likely to categorize twins as SGA and more likely to identify those at risk for stillbirth and neonatal mortality.

Large for Gestational Age Infants and Adverse Outcomes among Uncomplicated Pregnancies at Term.

Background While traumatic delivery with large for gestational age (LGA; birth weight above 90%) is acknowledged, there is paucity of data regarding other morbidity and mortality associated with LGA. Our hypothesis was that compared with appropriate for gestational age (AGA), LGA have a significantly higher rate of composite neonatal morbidity (CNM). Objective Our objective was to compare the CNM among uncomplicated LGA versus AGA at term (37 weeks or more) among all available Maternal-Fetal Medicine Units (MFMU) databases. We excluded women who delivered before 37 weeks, those with hypertension or diabetes, multiple gestations, and known anomalies, and those with birth weight less than 10% for GA. Using multivariable analysis, we compared the CNM between LGA and AGA. Random-effect logistic regressions were used to account for study heterogeneity, with adjustment for potential confounders. We calculated adjusted odds ratio (aOR) and 95% confidence intervals (CI). Results Approximately 60% (n = 50,734) of all participants met inclusion criteria. Among uncomplicated pregnancies, the rate of LGA was 12.1%. The rate of CNM was 15% in LGA and 10% in AGA (aOR: 1.58; 95% CI: 1.46-1.70). The likelihood of stillbirth and neonatal mortality was similar among both groups. Subgroup analysis revealed that CNM was increased among both birth weight > 95% and birth weight 90 to 95% and at different GA at delivery. Conclusion Among uncomplicated pregnancies at term, LGA newborns, compared with AGA, have a significantly higher likelihood of CNM but similar stillbirth and neonatal death risk. Trials are warranted to determine appropriate management of LGA to decrease these risks.

Morbidity and Mortality in Small-for-Gestational-Age Infants: A Secondary Analysis of Nine MFMU Network Studies.

Objective To compare the neonatal morbidity and mortality among small-for-gestational-age (SGA; birth weight < 10% for estimated gestational age [EGA]) versus appropriate-for-gestational-age (AGA; birth weight at 10-89%) newborns. Methods Data from nine Maternal-Fetal Medicine Units Network studies were used and included nonanomalous singletons at 24 weeks or more and birth weight < 90% for EGA. Using multivariable analysis, we compared the morbidity and mortality between SGA and AGA. Random-effect logistic regressions were utilized with adjustment for 10 variables. Results Among the nine studies 71,744 singletons met the inclusion criteria, with 13% (n = 9,415) SGA and 87% (n = 62,329) AGA. Among SGA, the likelihood of stillbirth (8.8 vs. 2.5 per 1,000 births; adjusted odds ratio [aOR] 3.98, 95% confidence interval [CI]: 2.92-5.42) and neonatal mortality (14.0 vs. 5.5 per 1,000 births; aOR 3.18, 95% CI: 2.55-3.95) was threefold higher compared with AGA. For the subgroup of newborns of EGA of 32 weeks or more, SGA, compared with AGA, had significantly higher risk of stillbirth (aOR 3.32, 95% CI: 2.16-5.12) and neonatal mortality (aOR 2.50; 95% CI: 1.38-4.54). From 35 weeks onward, the risk of stillbirth among SGA is almost four times higher than for AGA. Conclusion The risk of stillbirth and neonatal mortality is significantly higher with SGA than with AGA. Modification in practice or new management schema may be warranted.

Small-for-gestational-age infants among uncomplicated pregnancies at term: a secondary analysis of 9 Maternal-Fetal Medicine Units Network studies.

BACKGROUND: Most small (birthweight <10%) for-gestational-age cases occur at term, in uncomplicated pregnancies, and are not identified during prenatal visits as having fetal growth restriction. Hence, they do not benefit from antepartum surveillance and timed delivery. There is dismissive and disquieting opinion that small for gestational age among uncomplicated pregnancies is not associated with increased morbidities and, therefore, does not warrant improved detection. Our hypothesis was that among uncomplicated pregnancies at term, small for gestational age have significantly higher morbidity and mortality than appropriate (birthweight 10-89%) for gestational age. OBJECTIVE: We sought to compare composite neonatal morbidity among uncomplicated term singleton pregnancies with small vs appropriate for gestational age. STUDY DESIGN: We culled collected data from 9 completed Maternal-Fetal Medicine Units studies conducted from 1989 through 2004. All data were collected prospectively by trained staff. We excluded women who delivered <37 weeks and those with hypertension or diabetes, multiple gestation, known anomalies, and birthweight of ≥90% for gestational age. Using multivariable analysis, we compared composite neonatal morbidity, which included stillbirth and neonatal mortality between small and appropriate for gestational age. Random effect logistic regressions were used to account for study heterogeneity, with adjustment for potential confounders. We calculated adjusted odds ratios and 95% confidence intervals. RESULTS: Of the >91,000 women enrolled in the studies, 60% (n = 50,011) met the inclusion criteria. Among the uncomplicated pregnancies, 10.8% (n = 5416) were small for gestational age. The rate of composite neonatal morbidity of 16% in small for gestational age and 10% in appropriate for gestational age persisted (adjusted odds ratio, 1.75; 95% confidence interval, 1.71-1.78). After adjustment for confounders, the following neonatal morbidities were significantly more common among term small than appropriate for gestational age: Apgar <4 at 5 minutes, respiratory distress syndrome, mechanical ventilation, necrotizing enterocolitis grade 2 or 3, and neonatal sepsis. Lastly, rate of stillbirths (3.5 vs 0.9/1000 births; adjusted odds ratio, 3.49; 95% confidence interval, 1.83-6.67) and neonatal mortality (1.1 vs 0.4/1000 births; adjusted odds ratio, 2.56; 95% confidence interval, 1.83-3.57) were significantly more common with small than appropriate for gestational age. In secondary analyses the composite neonatal morbidity among newborns at <5% and at 5-9% was significantly higher than appropriate for gestational age. Lastly, in subgroup analyses of women who delivered at 37.0-38.6 weeks or at ≥39.0 weeks, the increased rate of composite neonatal morbidity, stillbirth, and neonatal mortality among small for gestational age persisted. CONCLUSION: Among uncomplicated pregnancies at term, small- compared to appropriate-for-gestational-age newborns have a significantly higher likelihood of composite neonatal morbidity, stillbirth, and neonatal mortality. A large multicenter trial is warranted to determine if improved detection of small for gestational age among uncomplicated pregnancies can mitigate morbidities and mortality, without disproportionate interventions and iatrogenic complications.

The Effect of Ascending Aortic Repair on Left Ventricular Remodeling.

Left ventricular (LV) hypertrophy is common in patients with thoracic aortic diseases and is associated with increased long-term mortality. Thoracic aortic aneurysms are reported to increase LV afterload because of kinetic energy loss within the aneurysm sac, which may improve after surgical repair. However, LV afterload may also increase because of the stiffness of prosthetics used for aortic repair. We sought to investigate the long-term effect of surgical aortic repair with prostheses on postsurgical LV mass. We reviewed patients who underwent ascending aortic replacement with a prosthesis at our institution from January 2008 to December 2018. We calculated the LV mass index based on pre- and postoperative echocardiogram measurements. The primary outcome was the change in LV mass index 6 months after aortic repair. Patients aged <18 years and those who had concomitant cardiac operations, severe aortic valve disease, or who had no echocardiographic data were excluded. Of 1,008 patients who underwent ascending aortic replacement, 134 (51 with acute aortic dissections) were included. The median baseline and follow-up LV mass index were 107 (90 to 135) g/m2 and 101 (83 to 123) g/m2, respectively. Overall, there was a significant reduction of LV mass index over time (p = 0.03). LV mass index decreased in 77 patients (59%). Presentation due to acute aortic dissection (p = 0.03) and baseline LV mass index (p <0.001) were significant predictors of LV mass reduction. In conclusion, LV mass index may significantly decrease over time after the aortic repair, but the course is highly variable. The largest decrease occurred in patients who presented because of aortic dissections rather than for elective repair of aneurysms.

Venous Sinus Stenting for Low Pressure Gradient Stenoses in Idiopathic Intracranial Hypertension.

BACKGROUND: Medically refractory idiopathic intracranial hypertension (IIH) is frequently treated with venous sinus stenosis stenting with high success rates. Patient selection has been driven almost exclusively by identification of supraphysiological venous pressure gradients across stenotic regions based on theoretical assessment of likelihood of response. OBJECTIVE: To explore the possibility of benefit in low venous pressure gradient patients. METHODS: Using a single-center, prospectively maintained registry of patients with IIH undergoing venous stenting, we defined treatment groups by gradient pressures of ≤4, 5 to 8, and >8 mmHg based on the most frequently previously published thresholds for stenting. Baseline demographics, clinical, and neuro-ophthalmological outcomes (including optical coherence tomography and Humphrey visual fields) were compared. RESULTS: Among 53 patients, the mean age was 32 years and 70% female with a mean body mass index was 36 kg/m 2 . Baseline characteristics were similar between groups. The mean change in lumbar puncture opening pressure at 6 months poststenting was similar between the 3 groups (≤4, 5-8, and >8 mmHg; 13.4, 12.9, and 12.4 cmH 2 O, P = .47). Papilledema improvement was observed across groups at 6 months (100, 93, and 86, P = .7) as were all clinical symptoms. The mean changes in optical coherence tomography retinal nerve fiber layer (-30, -54, and -104, P = .5) and mean deviation in Humphrey visual fields (60, 64, and 67, P = .5) at 6 weeks were not significantly different. CONCLUSION: Patients with IH with low venous pressure gradient venous sinus stenosis seem to benefit equally from venous stenting compared with their higher gradient counterparts. Re-evaluation of our restrictive criteria for this potentially vision sparing intervention is warranted. Future prospective confirmatory studies are needed.

Multi-Modal Analgesic Strategy for Trauma: A Pragmatic Randomized Clinical Trial.

BACKGROUND: An effective strategy to manage acute pain and minimize opioid exposure is needed for injured patients. In this trial, we aimed to compare 2 multimodal pain regimens (MMPRs) for minimizing opioid exposure and relieving acute pain in a busy, urban trauma center. METHODS: This was an unblinded, pragmatic, randomized, comparative effectiveness trial of all adult trauma admissions except vulnerable patient populations and readmissions. The original MMPR (IV administration, followed by oral, acetaminophen, 48 hours of celecoxib and pregabalin, followed by naproxen and gabapentin, scheduled tramadol, and as-needed oxycodone) was compared with an MMPR of generic medications, termed the Multi-Modal Analgesic Strategies for Trauma (MAST) MMPR (ie oral acetaminophen, naproxen, gabapentin, lidocaine patches, and as-needed opioids). The primary endpoint was oral morphine milligram equivalents (MMEs) per day and secondary outcomes included total MMEs during hospitalization, opioid prescribing at discharge, and pain scores. RESULTS: During the trial, 1,561 patients were randomized, 787 to receive the original MMPR and 774 to receive the MAST MMPR. There were no differences in demographic characteristics, injury characteristics, or operations performed. Patients randomized to receive the MAST MMPR had lower MMEs per day (34 MMEs/d; interquartile range 15 to 61 MMEs/d vs 48 MMEs/d; interquartile range 22 to 74 MMEs/d; p < 0.001) and fewer were prescribed opioids at discharge (62% vs 67%; p = 0.029; relative risk 0.92; 95% credible interval, 0.86 to 0.99; posterior probability relative risk <1 = 0.99). No clinically significant difference in pain scores were seen. CONCLUSIONS: The MAST MMPR was a generalizable and widely available approach that reduced opioid exposure after trauma and achieved adequate acute pain control.

Risk Stratification for Superficial Surgical Site Infection after Emergency Trauma Laparotomy.

Background: Superficial surgical site infections (S-SSIs) are common after trauma laparotomy, leading to morbidity, increased costs, and prolonged length of stay (LOS). Opportunities to mitigate S-SSI risks are limited to the intra-operative and post-operative periods. Accurate S-SSI risk stratification is paramount at the time of operation to inform immediate management. We aimed to develop a risk calculator to aid in surgical decision-making at the time of emergency laparotomy. Methods: A retrospective cohort study of patients requiring emergency trauma laparotomy between 2011 and 2017 at a single, level 1 trauma center was performed. Operative factors, skin management strategy, and outcomes were determined by chart review. Bayesian multilevel logistic regression was utilized to create a risk calculator with variables available upon closure of the laparotomy. Models were validated on a 30% test cohort and discrimination reported as an area under the receiver operating characteristics curve (AUROC). Results: Of 1,322 patients, the majority were male (77%) with median age of 33 years, injured by blunt mechanism (54%), and median injury severity score of 19. Eighty-eight (7%) patients developed an S-SSI. Patients who developed S-SSI had higher final lactate, blood loss, transfusion requirements, and wound classification. Patients with S-SSI more frequently had mesenteric or large bowel injury than those without S-SSI. Superficial SSI was associated with increased complications and prolonged length of stay (LOS). The S-SSI predictive model demonstrated moderate discrimination with an AUROC of 0.69 (95% confidence interval [CI], 0.56-0.81). Parameters contributing the most to the model were damage control laparotomy, full-thickness large bowel injury, and large bowel resection. Conclusion: A predictive model for S-SSI was built using factors available to the surgeon upon index emergency trauma laparotomy closure. This calculator may be used to standardize intra- and post-operative care and to identify high-risk patients in whom to test novel preventative strategies and improve overall outcomes for patients requiring emergency trauma laparotomy.

Impact of Opioid-Minimizing Pain Protocols After Burn Injury.

In 2019, we implemented a pill-based, opioid-minimizing pain protocol and protocolized moderate sedation for dressing changes in order to decrease opioid exposure in burn patients. We hypothesized that these interventions would reduce inpatient opioid exposure without increasing acute pain scores. Two groups of consecutive patients admitted to the burn service were compared: Pre-group (from January 1, 2018 to July 31, 2019) and Post-group (from January 1, 2020 to June 30, 2020) from before and after the implementation of the protocols (from August 1, 2019 to December 31, 2019). We abstracted patient demographics and burn injury characteristics from the burn registry. We obtained opioid exposure and pain scale scores from the electronic medical record. The primary outcome was total morphine milligram equivalents (MMEs). Secondary outcomes included MMEs/day, pain domain-specific MMEs, and pain scores. Pain was estimated by creating a normalized pain score (range 0-1), which incorporated three different pain scales (Numeric Rating Scale, Behavioral Pain Scale, and Behavioral Pain Assessment Scale). Groups were compared using Wilcoxon rank-sum and chi-square tests. Treatment effects were estimated using Bayesian generalized linear models. There were no differences in demographics or burn characteristics between the Pre-group (n = 495) and Post-group (n = 174). The Post-group had significantly lower total MMEs (Post-group 110 MMEs [32, 325] vs Pre-group 230 [60, 840], P < .001), MMEs/day (Post-group 33 MMEs/day [15, 54] vs Pre-group 52 [27, 80], P < .001), and domain-specific total MMEs. No difference in average normalized pain scores was seen. Implementation of opioid-minimizing protocols for acute burn pain was associated with a significant reduction in inpatient opioid exposure without an increase in pain scores.

Surgical repair of bicuspid aortopathy at small diameters: Clinical and institutional factors.

OBJECTIVE: Bicuspid aortic valve is a common risk factor for thoracic aortic aneurysm and dissection. Guidelines for elective ascending aortic intervention (AAI) in bicuspid aortic valve are derived from limited evidence, and the extent of practice variation due to patient and provider characteristics is unknown. Using data from 2 large cardiovascular registries, we investigated factors that influence decisions for AAI. METHODS: All bicuspid aortic valve cases with known aortic diameters and surgical status were included. We used multivariable logistic regression to profile predictors of isolated aortic valve replacement (AVR) or AVR+AAI, stratified by patient characteristics, surgical indications, and institution. RESULTS: We studied 2861 subjects at 18 institutions from 1996 to 2015. The median aortic diameter of patients who underwent AVR+AAI varied widely across institutions (39-52 mm). Aortic diameters were <45 mm in 38% of patients undergoing AVR+AAI. Patients who underwent AAI at <45 mm, compared with those managed nonoperatively, were younger (54 ± 13 vs 61 ± 15 years; P < .001) with more frequent aortic stenosis (53% vs 28%; P < .001) and regurgitation (52% vs 18%; P < .001). CONCLUSIONS: Clinical and institutional factors influence the timing of AAI and are associated with significant variability in ascending aortic diameter at AAI across institutions. More than one third of patients with a bicuspid aortic valve undergo AAI at aortic diameters <45 mm. Long-term outcomes of this subgroup of patients, who may manifest earlier and more severe disease, are needed to determine the risk-benefit ratio of routine aortic interventions at smaller diameters.

Opioid exposure after injury in United States trauma centers: A prospective, multicenter observational study.

BACKGROUND: Efforts to reduce opioid use in trauma patients are currently hampered by an incomplete understanding of the baseline opioid exposure and variation in United States. The purpose of this project was to obtain a global estimate of opioid exposure following injury and to quantify the variability of opioid exposure between and within United States trauma centers. STUDY DESIGN: Prospective observational study was performed to calculate opioid exposure by converting all sources of opioids to oral morphine milligram equivalents (MMEs). To estimate variation, an intraclass correlation was calculated from a multilevel generalized linear model adjusting for the a priori selected variables Injury Severity Score and prior opioid use. RESULTS: The centers enrolled 1,731 patients. The median opioid exposure among all sites was 45 MMEs per day, equivalent to 30 mg of oxycodone or 45 mg of hydrocodone per day. Variation in opioid exposure was identified both between and within trauma centers with the vast majority of variation (93%) occurring within trauma centers. Opioid exposure increased with injury severity, in male patients, and patients suffering penetrating trauma. CONCLUSION: The overall median opioid exposure was 45 MMEs per day. Despite significant differences in opioid exposure between trauma centers, the majority of variation was actually within centers. This suggests that efforts to minimize opioid exposure after injury should focus within trauma centers and not on high-level efforts to affect all trauma centers. LEVEL OF EVIDENCE: Epidemiological, level III.

Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis.

OBJECTIVE: This study evaluates the utility of urinary pro-thrombotic molecules such as tissue factor (TF), anti-thrombotic molecules such as tissue factor pathway inhibitor (TFPI), and fibrinolytic molecules such as plasmin and d-dimer as biomarkers of lupus nephritis (LN). METHODS: Urine samples from 113 biopsy-proven LN patients (89 active LN and 24 inactive LN), 45 chronic kidney disease patients, and 41 healthy controls were examined for d-dimer, plasmin, TF, and TFPI levels by ELISA. The area under the receiver operating characteristic curve (AUC) analysis, multivariate regression analysis, and Bayesian network analysis were performed to assess the diagnostic value of the assayed molecules in LN. RESULTS: Although urinary d-dimer, plasmin, TF, and TFPI were all elevated in active LN compared to all control groups, and correlated with rSLEDAI and SLICC RAS disease activity indices, urine plasmin emerged as the strongest independent predictor of eGFR and renal disease status, by multivariate regression analysis and Bayesian network analysis. Whereas urine plasmin discriminated active LN from inactive disease with an AUC of 0.84, the combination of urine plasmin and TFPI discriminated ALN from ILN with an AUC of 0.86, with both surpassing the specificity and positive predictive value of traditional markers such as anti-dsDNA and complement C3. CONCLUSION: Both thrombogenic and thrombolytic cascades appear to be upregulated in lupus nephritis, with proteins from both cascades appearing in the urine. Of the coagulation cascade proteins surveyed, urine plasmin emerges as the strongest predictor of eGFR and clinical renal disease in patients with LN.

Correction to: Urinary pro-thrombotic, anti-thrombotic, and fibrinolytic molecules as biomarkers of lupus nephritis.

Following publication of the original article [1], it was brought to our attention that the fifth author's name was incorrectly published. The original article [1] is corrected.