Joshua S. Richman

Association Between Marijuana Exposure and Pulmonary Function Over 20 Years

CONTEXT Marijuana smoke contains many of the same constituents as tobacco smoke, but whether it has similar adverse effects on pulmonary function is unclear. OBJECTIVE To analyze associations between marijuana (both current and lifetime exposure) and pulmonary function. DESIGN, SETTING, AND PARTICIPANTS The Coronary Artery Risk Development in Young Adults (CARDIA) study, a longitudinal study collecting repeated measurements of pulmonary function and smoking over 20 years (March 26, 1985-August 19, 2006) in a cohort of 5115 men and women in 4 US cities. Mixed linear modeling was used to account for individual age-based trajectories of pulmonary function and other covariates including tobacco use, which was analyzed in parallel as a positive control. Lifetime exposure to marijuana joints was expressed in joint-years, with 1 joint-year of exposure equivalent to smoking 365 joints or filled pipe bowls. MAIN OUTCOME MEASURES Forced expiratory volume in the first second of expiration (FEV(1)) and forced vital capacity (FVC). RESULTS Marijuana exposure was nearly as common as tobacco exposure but was mostly light (median, 2-3 episodes per month). Tobacco exposure, both current and lifetime, was linearly associated with lower FEV(1) and FVC. In contrast, the association between marijuana exposure and pulmonary function was nonlinear (P < .001): at low levels of exposure, FEV(1) increased by 13 mL/joint-year (95% CI, 6.4 to 20; P < .001) and FVC by 20 mL/joint-year (95% CI, 12 to 27; P < .001), but at higher levels of exposure, these associations leveled or even reversed. The slope for FEV(1) was -2.2 mL/joint-year (95% CI, -4.6 to 0.3; P = .08) at more than 10 joint-years and -3.2 mL per marijuana smoking episode/mo (95% CI, -5.8 to -0.6; P = .02) at more than 20 episodes/mo. With very heavy marijuana use, the net association with FEV(1) was not significantly different from baseline, and the net association with FVC remained significantly greater than baseline (eg, at 20 joint-years, 76 mL [95% CI, 34 to 117]; P < .001). CONCLUSION Occasional and low cumulative marijuana use was not associated with adverse effects on pulmonary function.

Safety and Tumor-specificity of Cetuximab-IRDye800 for Surgical Navigation in Head and Neck Cancer

Purpose: Positive margins dominate clinical outcomes after surgical resections in most solid cancer types, including head and neck squamous cell carcinoma. Unfortunately, surgeons remove cancer in the same manner they have for a century with complete dependence on subjective tissue changes to identify cancer in the operating room. To effect change, we hypothesize that EGFR can be targeted for safe and specific real-time localization of cancer. Experimental Design: A dose escalation study of cetuximab conjugated to IRDye800 was performed in patients (n = 12) undergoing surgical resection of squamous cell carcinoma arising in the head and neck. Safety and pharmacokinetic data were obtained out to 30 days after infusion. Multi-instrument fluorescence imaging was performed in the operating room and in surgical pathology. Results: There were no grade 2 or higher adverse events attributable to cetuximab-IRDye800. Fluorescence imaging with an intraoperative, wide-field device successfully differentiated tumor from normal tissue during resection with an average tumor-to-background ratio of 5.2 in the highest dose range. Optical imaging identified opportunity for more precise identification of tumor during the surgical procedure and during the pathologic analysis of tissues ex vivo. Fluorescence levels positively correlated with EGFR levels. Conclusions: We demonstrate for the first time that commercially available antibodies can be fluorescently labeled and safely administered to humans to identify cancer with sub-millimeter resolution, which has the potential to improve outcomes in clinical oncology. Clin Cancer Res; 21(16); 3658–66. ©2015 AACR.

Association between Intraoperative Hypotension and Hypertension and 30-day Postoperative Mortality in Noncardiac Surgery.

Background:Although deviations in intraoperative blood pressure are assumed to be associated with postoperative mortality, critical blood pressure thresholds remain undefined. Therefore, the authors estimated the intraoperative thresholds of systolic blood pressure (SBP), mean blood pressure (MAP), and diastolic blood pressure (DBP) associated with increased risk-adjusted 30-day mortality. Methods:This retrospective cohort study combined intraoperative blood pressure data from six Veterans Affairs medical centers with 30-day outcomes to determine the risk-adjusted associations between intraoperative blood pressure and 30-day mortality. Deviations in blood pressure were assessed using three methods: (1) population thresholds (individual patient sum of area under threshold [AUT] or area over threshold 2 SDs from the mean of the population intraoperative blood pressure values), (2). absolute thresholds, and (3) percent change from baseline blood pressure. Results:Thirty-day mortality was associated with (1) population threshold: systolic AUT (odds ratio, 3.3; 95% CI, 2.2 to 4.8), mean AUT (2.8; 1.9 to 4.3), and diastolic AUT (2.4; 1.6 to 3.8). Approximate conversions of AUT into its separate components of pressure and time were SBP < 67 mmHg for more than 8.2 min, MAP < 49 mmHg for more than 3.9 min, DBP < 33 mmHg for more than 4.4 min. (2) Absolute threshold: SBP < 70 mmHg for more than or equal to 5 min (odds ratio, 2.9; 95% CI, 1.7 to 4.9), MAP < 49 mmHg for more than or equal to 5 min (2.4; 1.3 to 4.6), and DBP < 30 mmHg for more than or equal to 5 min (3.2; 1.8 to 5.5). (3) Percent change: MAP decreases to more than 50% from baseline for more than or equal to 5 min (2.7; 1.5 to 5.0). Intraoperative hypertension was not associated with 30-day mortality with any of these techniques. Conclusion:Intraoperative hypotension, but not hypertension, is associated with increased 30-day operative mortality.

Timing of Surgical Antibiotic Prophylaxis and the Risk of Surgical Site Infection

IMPORTANCE Timing of prophylactic antibiotic administration for surgical procedures is a nationally mandated and publicly reported quality metric sponsored by the Centers for Medicare and Medicaid Services Surgical Care Improvement Project. Numerous studies have failed to demonstrate that adherence to the Surgical Care Improvement Project prophylactic antibiotic timely administration measure is associated with decreased surgical site infection (SSI). OBJECTIVE; To determine whether prophylactic antibiotic timing is associated with SSI occurrence. DESIGN Retrospective cohort study using national Veterans Affairs patient-level data on prophylactic antibiotic timing for orthopedic, colorectal, vascular, and gynecologic procedures from 2005 through 2009. SETTING National Veterans Affairs Surgical Care Improvement Project data from 112 Veterans Affairs hospitals and matched Veterans Affairs Surgical Quality Improvement Program data. PATIENTS Patients undergoing hip or knee arthroplasty, colorectal surgical procedures, arterial vascular surgical procedures, and hysterectomy. INTERVENTION Timing of prophylactic antibiotic administration with respect to surgical incision time. MAIN OUTCOMES AND MEASURES Data for prophylactic antibiotic agent, prophylactic antibiotic timing with respect to surgical incision, and patient and procedure risk variables were assessed for their relationship with the occurrence of a composite superficial or deep incisional SSI within 30 days after the procedure. Nonlinear generalized additive models were used to examine the association between antibiotic timing and SSI. RESULTS Of the 32,459 operations, prophylactic antibiotics were administered at a median of 28 minutes (interquartile range, 17-39 minutes) prior to surgical incision, and 1497 cases (4.6%) developed an SSI. Compared with procedures with antibiotic administration within 60 minutes prior to incision, higher SSI rates were observed for timing more than 60 minutes prior to incision (unadjusted odds ratio [OR] = 1.34; 95% CI, 1.08-1.66) but not after incision (unadjusted OR = 1.26; 95% CI, 0.92-1.72). In unadjusted generalized additive models, we observed a significant nonlinear relationship between prophylactic antibiotic timing and SSI when considering timing as a continuous variable (P = .01). In generalized additive models adjusted for patient, procedure, and antibiotic variables, no significant association between prophylactic antibiotic timing and SSI was observed. Vancomycin hydrochloride was associated with higher SSI occurrence for orthopedic procedures (adjusted OR = 1.75; 95% CI, 1.16-2.65). Cefazolin sodium and quinolone in combination with an anaerobic agent were associated with fewer SSI events (cefazolin: adjusted OR = 0.49; 95% CI, 0.34-0.71; quinolone: adjusted OR = 0.55; 95% CI, 0.35-0.87) for colorectal procedures. CONCLUSIONS AND RELEVANCE The SSI risk varies by patient and procedure factors as well as antibiotic properties but is not significantly associated with prophylactic antibiotic timing. While adherence to the timely prophylactic antibiotic measure is not bad care, there is little evidence to suggest that it is better care.

Preoperative oral antibiotics reduce surgical site infection following elective colorectal resections.

BACKGROUND: Surgical site infection is a major cause of morbidity after colorectal resections. Despite evidence that preoperative oral antibiotics with mechanical bowel preparation reduce surgical site infection rates, the use of oral antibiotics is decreasing. Currently, the administration of oral antibiotics is controversial and considered ineffective without mechanical bowel preparation. OBJECTIVE: The aim of this study is to examine the use of mechanical bowel preparation and oral antibiotics and their relationship to surgical site infection rates in a colorectal Surgical Care Improvement Project cohort. DESIGN: This retrospective study used Veterans Affairs Surgical Quality Improvement Program preoperative risk and surgical site infection outcome data linked to Veterans Affairs Surgical Care Improvement Project and Pharmacy Benefits Management data. Univariate and multivariable models were performed to identify factors associated with surgical site infection within 30 days of surgery. SETTINGS: This study was conducted in 112 Veterans Affairs hospitals. PATIENTS: Included were 9940 patients who underwent elective colorectal resections from 2005 to 2009. MAIN OUTCOME MEASURE: The primary outcome measured was the incidence of surgical site infection. RESULTS: Patients receiving oral antibiotics had significantly lower surgical site infection rates. Those receiving no bowel preparation had similar surgical site infection rates to those who had mechanical bowel preparation only (18.1% vs 20%). Those receiving oral antibiotics alone had an surgical site infection rate of 8.3%, and those receiving oral antibiotics plus mechanical bowel preparation had a rate of 9.2%. In adjusted analysis, the use of oral antibiotics alone was associated with a 67% decrease in surgical site infection occurrence (OR=0.33, 95% CI 0.21–0.50). Oral antibiotics plus mechanical bowel preparation was associated with a 57% decrease in surgical site infection occurrence (OR=0.43, 95% CI 0.34–0.55). Timely administration of parenteral antibiotics (Surgical Care Improvement Project-1) had a modest protective effect, with no effect observed for other Surgical Care Improvement Project measures. Hospitals with higher rates of oral antibiotics use had lower surgical site infection rates (R2 = 0.274, p < 0.0001). LIMITATIONS: Determination of the use of oral antibiotics and mechanical bowel preparation is based on retrospective prescription data, and timing of actual administration cannot be determined. CONCLUSIONS: Use and type of preoperative bowel preparation varied widely. These results strongly suggest that preoperative oral antibiotics should be administered for elective colorectal resections. The role of oral antibiotics independent of mechanical bowel preparation should be examined in a prospective randomized trial.

The Relationship Between Timing of Surgical Complications and Hospital Readmission

IMPORTANCE Readmissions after surgery are costly and may reflect quality of care in the index hospitalization. OBJECTIVES To determine the timing of postoperative complications with respect to hospital discharge and the frequency of readmission stratified by predischarge and postdischarge occurrence of complications. DESIGN, SETTING, AND PARTICIPANTS This is a retrospective cohort study of national Veterans Affairs Surgical Quality Improvement Program preoperative risk and outcome data on the Surgical Care Improvement Project cohort for operations performed from January 2005 to August 2009, including colorectal, arthroplasty, vascular, and gynecologic procedures. The association between timing of complication with respect to index hospitalization and 30-day readmission was modeled using generalized estimating equations. MAIN OUTCOME AND MEASURE All-cause readmission within 30 days of the index surgical hospitalization discharge. RESULTS Our study of 59 273 surgical procedures performed at 112 Department of Veterans Affairs (VA) hospitals found an overall complication rate of 22.6% (predischarge complications, 71.9%; postdischarge complications, 28.1%). The proportion of postdischarge complications varied significantly, from 8.7% for respiratory complications to 55.7% for surgical site infection (P < .001). The overall 30-day readmission rate was 11.9%, of which only 56.0% of readmissions were associated with a currently assessed complication. Readmission was predicted by patient comorbid conditions, procedure factors, and the occurrence of postoperative complications. Multivariable generalized estimating equation models of readmission adjusting for patient and procedure characteristics, hospital, and index length of stay found that the occurrence of postdischarge complications had the highest odds of readmission (odds ratio, 7.4-20.8) compared with predischarge complications (odds ratio, 0.9-1.48). CONCLUSIONS AND RELEVANCE More than one-quarter of assessed complications are diagnosed after hospital discharge and strongly predict readmission. Hospital discharge is an insufficient end point for quality assessment. Although readmission is associated with complications, almost half of readmissions are not associated with a complication currently assessed by the Veterans Affairs Surgical Quality Improvement Program.

Smoking as a risk factor for short-term outcomes following primary total hip and total knee replacement in veterans.

To assess the effect of smoking on postoperative complications following elective primary total hip replacement (THR) or primary total knee replacement (TKR).

Cardiovascular oscillations at the bedside: early diagnosis of neonatal sepsis using heart rate characteristics monitoring

We have applied principles of statistical signal processing and nonlinear dynamics to analyze heart rate time series from premature newborn infants in order to assist in the early diagnosis of sepsis, a common and potentially deadly bacterial infection of the bloodstream. We began with the observation of reduced variability and transient decelerations in heart rate interval time series for hours up to days prior to clinical signs of illness. We find that measurements of standard deviation, sample asymmetry and sample entropy are highly related to imminent clinical illness. We developed multivariable statistical predictive models, and an interface to display the real-time results to clinicians. Using this approach, we have observed numerous cases in which incipient neonatal sepsis was diagnosed and treated without any clinical illness at all. This review focuses on the mathematical and statistical time series approaches used to detect these abnormal heart rate characteristics and present predictive monitoring information to the clinician.

Oral antibiotic bowel preparation reduces length of stay and readmissions after colorectal surgery.

BACKGROUND Oral antibiotic bowel preparation (OABP) before colorectal resection has been shown to reduce surgical site infections. We examined whether OABP decreases length of stay (LOS) and readmissions for colorectal surgery. STUDY DESIGN This retrospective study used national Veterans Affairs Surgical Quality Improvement Program preoperative risk and outcomes data linked to Veterans Affairs Administrative and Pharmacy Benefits Management data on patients undergoing elective colorectal resections from 2005 to 2009. Exclusion criteria were preoperative LOS >2 days, American Society of Anesthesiologists class 5, or death before discharge. Patient and surgery characteristics, bowel preparation use, presence of an ostomy, indication for surgery, and indication for readmission using ICD-9 codes were determined. Negative binomial regression was used to model LOS. Logistic regression analyses modeled 30-day readmission. RESULTS Of the 8,180 patients, 1,161 (14.2%) were readmitted within 30 days. Length of stay and readmissions varied significantly by bowel preparation, procedure, presence of an ostomy, and American Society of Anesthesiologists class. Oral antibiotic bowel preparation was associated with a below-median postoperative LOS (negative binomial regression estimate = -0.1159; p < 0.0001) and fewer 30-day readmissions (adjusted odds ratio = 0.81; 95% CI, 0.68-0.97). Overall, 4.9% were readmitted for infections (ICD-9 codes) and this varied by bowel preparation (no preparation 6.1%, mechanical 5.4%, OABP 3.9%; p = 0.001). The readmission rate for noninfectious reasons was 9.3% and did not differ significantly by bowel preparation (no preparation 9.9%, mechanical 9.6%, OABP 8.8%; p = 0.38). CONCLUSIONS Oral antibiotic bowel preparation before elective colorectal surgery is associated with shorter postoperative LOS and lower 30-day readmission rates, primarily due to fewer readmissions for infections. Prospective studies are needed to verify these results.

Perceived Stress Is Associated With Incident Coronary Heart Disease and All‐Cause Mortality in Low‐ but Not High‐Income Participants in the Reasons for Geographic And Racial Differences in Stroke Study

Background Perceived stress may increase risk for coronary heart disease (CHD) and death, but few studies have examined these relationships longitudinally. We sought to determine the association of perceived stress with incident CHD and all‐cause mortality. Methods and Results Data were from a prospective study of 24 443 participants without CHD at baseline from the national Reasons for Geographic And Racial Differences in Stroke (REGARDS) study cohort. Outcomes were expert‐adjudicated acute CHD and all‐cause mortality. Over a mean follow‐up of 4.2 (maximum 6.9) years, there were 659 incident CHD events and 1320 deaths. Analyses were stratified by income level because of significant interactions with stress. For individuals with low income, 3529 (35.4%) reported high stress, and for those with high income, 2524 (22.1%) did so. Compared with reporting no stress, those reporting the highest stress had higher risk for incident CHD if they reported low income (sociodemographic‐adjusted HR 1.36, 95% CI: 1.04, 1.78) but not high income (sociodemographic‐adjusted HR 0.82, 95% CI: 0.57, 1.16); the finding in low income individuals attenuated with adjustment for clinical and behavioral factors (HR 1.29, 95% CI: 0.99, 1.69, P=0.06). After full adjustment, the highest stress category was associated with higher risk for death among those with low income (HR 1.55, 95% CI: 1.31, 1.82) but not high income (HR 1.13, 95% CI: 0.88, 1.46). Conclusions High stress was associated with greater risks of CHD and death for individuals with low but not high income.