Christopher J. Pannucci

Identifying and avoiding bias in research.

Summary: This narrative review provides an overview on the topic of bias as part of a series of articles in Plastic and Reconstructive Surgery on evidence-based medicine. Bias can occur in the planning, data collection, analysis, and publication phases of research. Understanding research bias allows readers to critically and independently review the scientific literature and avoid treatments that are suboptimal or potentially harmful. A thorough understanding of bias and how it affects study results is essential for the practice of evidence-based medicine.

Validation of the Caprini Risk Assessment Model in Plastic and Reconstructive Surgery Patients

BACKGROUND The Venous Thromboembolism Prevention Study (VTEPS) Network is a consortium of 5 tertiary referral centers established to examine venous thromboembolism (VTE) in plastic surgery patients. We report our midterm analyses of the studys control group to evaluate the incidence of VTE in patients who receive no chemoprophylaxis, and validate the Caprini Risk Assessment Model (RAM) in plastic surgery patients. STUDY DESIGN Medical record review was performed at VTEPS centers for all eligible plastic surgery patients between March 2006 and June 2009. Inclusion criteria were Caprini score ≥3, surgery under general anesthesia, and postoperative hospital admission. Patients who received chemoprophylaxis were excluded. Dependent variables included symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) within the first 60 postoperative days and time to DVT or PE. RESULTS We identified 1,126 historic control patients. The overall VTE incidence was 1.69%. Approximately 1 in 9 (11.3%) patients with Caprini score >8 had a VTE event. Patients with Caprini score >8 were significantly more likely to develop VTE when compared with patients with Caprini score of 3 to 4 (odds ratio [OR] 20.9, p < 0.001), 5 to 6 (OR 9.9, p < 0.001), or 7 to 8 (OR 4.6, p = 0.015). Among patients with Caprini score 7 to 8 or Caprini score >8, VTE risk was not limited to the immediate postoperative period (postoperative days 1-14). In these high-risk patients, more than 50% of VTE events were diagnosed in the late (days 15-60) postoperative period. CONCLUSIONS The Caprini RAM effectively risk-stratifies plastic and reconstructive surgery patients for VTE risk. Among patients with Caprini score >8, 11.3% have a postoperative VTE when chemoprophylaxis is not provided. In higher risk patients, there was no evidence that VTE risk is limited to the immediate postoperative period.

Postoperative enoxaparin prevents symptomatic venous thromboembolism in high-risk plastic surgery patients.

Background: Venous thromboembolism is a major patient safety issue. The Plastic Surgery Foundation–sponsored Venous Thromboembolism Prevention Study examined whether postoperative enoxaparin prevents symptomatic venous thromboembolism in adult plastic surgery patients. Methods: In 2009, four sites uniformly adopted a clinical protocol. Patients with a Caprini score of 3 or higher received postoperative enoxaparin prophylaxis for the duration of inpatient stay. Venous Thromboembolism Prevention Study historical control patients had an operation between 2006 and 2008 but received no chemoprophylaxis for 60 days after surgery. The primary study outcome was symptomatic 60-day venous thromboembolism. Results: Three thousand three hundred thirty-four patients (1876 controls and 1458 enoxaparin patients) were included. Notable risk reduction was present in patients with a Caprini score greater than 8 (8.54 percent versus 4.07 percent; p = 0.182) and a Caprini score of 7 to 8 (2.55 percent versus 1.15 percent; p = 0.230) who received postoperative enoxaparin. Logistic regression was limited to highest risk patients (Caprini score ≥7) and demonstrated that length of stay greater than or equal to 4 days (adjusted odds ratio, 4.63; p = 0.007) and Caprini score greater than 8 (odds ratio, 2.71; p = 0.027) were independent predictors of venous thromboembolism. When controlling for length of stay and Caprini score, receipt of postoperative enoxaparin was protective against venous thromboembolism (odds ratio, 0.39; p = 0.042). Conclusions: In high-risk plastic surgery patients, postoperative enoxaparin prophylaxis is protective against 60-day venous thromboembolism when controlling for baseline risk and length of stay. Hospitalization for 4 or more days is an independent risk factor for venous thromboembolism. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Identifying patients at high risk for venous thromboembolism requiring treatment after outpatient surgery.

Objective:To identify independent predictors of 30-day venous thromboembolism (VTE) events requiring treatment after outpatient surgery. Background:An increasing proportion of surgical procedures are performed in the outpatient setting. The incidence of VTE requiring treatment after outpatient surgery is unknown. Methods:Prospective observational cohort study using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2005 to 2009. Adult patients who had outpatient surgery or surgery with subsequent 23-hour observation were included. The main outcome measure was 30-day VTE requiring treatment. Patients were randomly assigned to derivation (N = 173,501) or validation (N = 85,730) cohorts. Logistic regression examined independent risk factors for 30-day VTE. A weighted risk index was created and applied to the validation cohort. Stratified analyses examined 30-day VTE by risk level. Results:Thirty-day incidence of VTE for the overall cohort was 0.15%. Independent risk factors included current pregnancy (adjusted odds ratio [OR] = 7.80, P = 0.044), active cancer (OR = 3.66, P = 0.005), age 41 to 59 years (OR = 1.72, P = 0.008), age 60 years or more (OR = 2.48, P < 0.001), body mass index 40 kg/m2 or higher (OR = 1.81, P = 0.015), operative time 120 minutes or more (OR = 1.69, P = 0.027), arthroscopic surgery (OR = 5.16, P < 0.001), saphenofemoral junction surgery (OR = 13.20, P < 0.001), and venous surgery not involving the great saphenous vein (OR = 15.61, P < 0.001). The weighted risk index identified a 20-fold variation in 30-day VTE between low (0.06%) and highest risk (1.18%) patients. Conclusions:Thirty-day VTE risk after outpatient surgery can be quantified using a weighted risk index. The risk index identifies a high-risk subgroup of patients with 30-day VTE rates of 1.18%.

Stratifying the Risk of Venous Thromboembolism in Otolaryngology

Objective. The consequences of perioperative venous thromboembolism (VTE) are devastating; identifying patients at risk is an essential step in reducing morbidity and mortality. The utility of perioperative VTE risk assessment in otolaryngology is unknown. This study was designed to risk-stratify a diverse population of otolaryngology patients for VTE events. Study Design. Retrospective cohort study. Setting. Single-institution academic tertiary care medical center. Subjects and Methods. Adult patients presenting for otolaryngologic surgery requiring hospital admission from 2003 to 2010 who did not receive VTE chemoprophylaxis were included. The Caprini risk assessment was retrospectively scored via a validated method of electronic chart abstraction. Primary study variables were Caprini risk scores and the incidence of perioperative venous thromboembolic outcomes. Results. A total of 2016 patients were identified. The overall 30-day rate of VTE was 1.3%. The incidence of VTE in patients with a Caprini risk score of 6 or less was 0.5%. For patients with scores of 7 or 8, the incidence was 2.4%. Patients with a Caprini risk score greater than 8 had an 18.3% incidence of VTE and were significantly more likely to develop a VTE when compared to patients with a Caprini risk score less than 8 (P < .001). The mean risk score for patients with VTE (7.4) was significantly higher than the risk score for patients without VTE (4.8) (P < .001). Conclusion. The Caprini risk assessment model effectively risk-stratifies otolaryngology patients for 30-day VTE events and allows otolaryngologists to identify patient subgroups who have a higher risk of VTE in the absence of chemoprophylaxis.

Patient selection for day case-eligible surgery: identifying those at high risk for major complications.

Background:Due to economic pressures and improvements in perioperative care, outpatient surgical procedures have become commonplace. However, risk factors for outpatient surgical morbidity and mortality remain unclear. There are no multicenter clinical data guiding patient selection for outpatient surgery. The authors hypothesize that specific risk factors increase the likelihood of day case-eligible surgical morbidity or mortality. Methods:The authors analyzed adults undergoing common day case-eligible surgical procedures by using the American College of Surgeons’ National Surgical Quality Improvement Program database from 2005 to 2010. Common day case-eligible surgical procedures were identified as the most common outpatient surgical Current Procedural Terminology codes provided by Blue Cross Blue Shield of Michigan and Medicare publications. Study variables included anthropometric data and relevant medical comorbidities. The primary outcome was morbidity or mortality within 72 h. Intraoperative complications included adverse cardiovascular events; postoperative complications included surgical, anesthetic, and medical adverse events. Results:Of 244,397 surgeries studied, 232 (0.1%) experienced early perioperative morbidity or mortality. Seven independent risk factors were identified while controlling for surgical complexity: overweight body mass index, obese body mass index, chronic obstructive pulmonary disease, history of transient ischemic attack/stroke, hypertension, previous cardiac surgical intervention, and prolonged operative time. Conclusions:The demonstrated low rate of perioperative morbidity and mortality confirms the safety of current day case-eligible surgeries. The authors obtained the first prospectively collected data identifying risk factors for morbidity and mortality with day case-eligible surgery. The results of the study provide new data to advance patient-selection processes for outpatient surgery.

Assessment of postoperative venous thromboembolism risk in plastic surgery patients using the 2005 and 2010 Caprini Risk score.

Background: Venous thromboembolism is an important patient safety issue. The authors sought to compare the predictive capacity of the 2005 and 2010 Caprini Risk Assessment Models for perioperative venous thromboembolism risk. Methods: The authors performed a retrospective, observational, crossover study using an established surgical outcomes database. A total of 3334 adult plastic surgery patients were identified. Patients were risk-stratified using both the 2005 and 2010 Caprini Risk Assessment Models. Each patient served as his or her own control, resulting in precise matching for identified and unidentified confounders. The outcome of interest was 60-day, symptomatic venous thromboembolism. The predictive capacities of the 2005 and 2010 Caprini risk scores were compared. Results: Use of the 2010 Caprini Risk Assessment Model resulted in a systematic increase in the aggregate risk score. The median 2010 Caprini score was significantly higher than the median 2005 Caprini score (6 versus 5, p < 0.001). When compared with the 2010 model, the 2005 Caprini Risk Assessment Model was able to better separate the lowest and highest risk patients from one another. Patients classified as “super-high” risk (Caprini score >8) using the 2005 Caprini Risk Assessment Model were significantly more likely to have a 60-day venous thromboembolism event when compared with patients classified as super-high risk using the 2010 guidelines (5.85 percent versus 2.52 percent, p = 0.021). Conclusions: When compared with the 2010 Caprini Risk Assessment Model, the 2005 Caprini Risk Assessment Model provides superior risk stratification. The 2005 Caprini Risk Assessment Model is the more appropriate method to risk-stratify plastic surgery patients for perioperative venous thromboembolism risk. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

The effect of postoperative enoxaparin on risk for reoperative hematoma.

Background: The risk of postoperative bleeding is the chief concern expressed by plastic surgeons who do not use pharmacologic prophylaxis against venous thromboembolism. The Plastic Surgery Foundation–funded Venous Thromboembolism Prevention Study examined whether receipt of postoperative enoxaparin prophylaxis changed 60-day reoperative hematoma rates. Methods: In 2009, the studys network sites uniformly adopted a “best practice” clinical protocol to provide postoperative enoxaparin to adult plastic surgery patients at risk for perioperative venous thromboembolism. Historical control patients (2006 to 2008) received no chemoprophylaxis for 60 days after surgery. Retrospective chart review identified demographic and surgery-specific risk factors that potentially contributed to bleeding risk. The primary study outcome was 60-day reoperative hematoma. Stratified analyses examined reoperative hematoma in the overall population and among high-risk patients. Multivariable logistic regression controlled for identified confounders. Results: Complete data were available for 3681 patients (2114 controls and 1567 enoxaparin patients). Overall, postoperative enoxaparin did not change the reoperative hematoma rate when compared with controls (3.38 percent versus 2.65 percent, p = 0.169). Similar results were seen in subgroup analyses for breast reconstruction (5.25 percent versus 4.21 percent, p = 0.737), breast reduction (7.04 percent versus 8.29 percent, p = 0.194), and nonbreast plastic surgery (2.20 percent versus 1.46 percent, p = 0.465). In the regression model, independent predictors of reoperative hematoma included breast surgery, microsurgical procedure, and post–bariatric surgery body contouring. Receipt of postoperative enoxaparin was not an independent predictor (odds ratio, 1.16; 95 percent CI, 0.77 to 1.76). Conclusion: Postoperative enoxaparin does not produce a clinically relevant or statistically significant increase in observed rates of reoperative hematoma. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk: II

A Validated Risk Model to Predict 90-Day VTE Events in Postsurgical Patients

BACKGROUND VTE is the proximate cause of 100,000 deaths in the United States each year. Perioperative VTE risk among surgical patients varies by 20-fold, which highlights the importance of risk stratification to identify high-risk patients, in whom chemoprophylaxis can decrease VTE risk, and low-risk patients, for whom the risk-benefit relationship of prophylaxis may be unfavorable. METHODS We used data from a statewide surgical quality collaborative for surgical procedures performed between 2010 and 2012. Regression-based techniques identified predictors of 90-day VTE while adjusting for procedural complexity and comorbid conditions. A weighted risk index was created and was validated subsequently in a separate, independent dataset. RESULTS Data were available for 10,344 patients, who were allocated randomly to a derivation or validation cohort. The 90-day VTE rate was 1.4%; 66.2% of the derivation cohort and 65.5% of the validation cohort received chemoprophylaxis. Seven risk factors were incorporated into a weighted risk index: personal history of VTE, current cancer, sepsis/septic shock/systemic inflammatory response syndrome, age≥60 years, BMI≥40 kg/m2, male sex, and family history of VTE. Prediction for 90-day VTE was similar in the derivation and validation cohorts (areas under the receiver operator curve, 0.72 and 0.70, respectively). An 18-fold variation in 90-day VTE rate was identified. CONCLUSIONS A weighted risk index quantifies 90-day VTE risk among surgical patients and identifies an 18-fold variation in VTE risk among the overall surgical population.

The impact of acellular dermal matrix on tissue expander/implant loss in breast reconstruction: an analysis of the tracking outcomes and operations in plastic surgery database.

Background: Use of acellular dermal matrix in breast reconstruction has been associated with increased complications. However, existing studies are generally small, from single centers, and underpowered to control for confounding using regression techniques. Here, the Tracking Outcomes and Operations in Plastic Surgery database was used to examine the effect of acellular dermal matrix on expander/implant loss when controlling for other confounders. Methods: Analysis was limited to patients having tissue expander or implant-based breast reconstruction. Surgeon-reported data, International Classification of Diseases, Ninth Edition codes, and Current Procedural Terminology codes were used to identify independent variables. The dependent variable of interest was 30-day rates of tissue expander or implant loss. Bivariate statistics were performed. Multivariable logistic regression identified independent predictors of expander/implant loss when controlling for other confounders. Results: Data were available for 14,249 patients. The overall rate of expander/implant loss was 2.05 percent. Bivariate analysis demonstrated acellular dermal matrix was associated with an absolute increase in expander/implant loss of 0.7 percent (1.88 percent versus 2.58 percent, p = 0.012). The regression model demonstrated that rising body mass index, current smoking, and presence of diabetes were each independent predictors of expander/implant loss. When controlling for all other identified confounders, use of acellular dermal matrix was associated with a significant increase in expander/implant loss (odds ratio, 1.42; 95 percent confidence interval, 1.04 to 1.94; p = 0.026). Conclusions: Thirty-day risk for expander/implant loss after tissue expander or implant-based breast reconstruction was 2.05 percent. Use of acellular dermal matrix was associated with a 0.7 percent absolute risk increase for expander/implant loss. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.