Paul J. Karanicolas

Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND VTE is a common cause of preventable death in surgical patients. METHODS We developed recommendations for thromboprophylaxis in nonorthopedic surgical patients by using systematic methods as described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS We describe several alternatives for stratifying the risk of VTE in general and abdominal-pelvic surgical patients. When the risk for VTE is very low (< 0.5%), we recommend that no specific pharmacologic (Grade 1B) or mechanical (Grade 2C) prophylaxis be used other than early ambulation. For patients at low risk for VTE (∼1.5%), we suggest mechanical prophylaxis, preferably with intermittent pneumatic compression (IPC), over no prophylaxis (Grade 2C). For patients at moderate risk for VTE (∼3%) who are not at high risk for major bleeding complications, we suggest low-molecular-weight heparin (LMWH) (Grade 2B), low-dose unfractionated heparin (Grade 2B), or mechanical prophylaxis with IPC (Grade 2C) over no prophylaxis. For patients at high risk for VTE (∼6%) who are not at high risk for major bleeding complications, we recommend pharmacologic prophylaxis with LMWH (Grade 1B) or low-dose unfractionated heparin (Grade 1B) over no prophylaxis. In these patients, we suggest adding mechanical prophylaxis with elastic stockings or IPC to pharmacologic prophylaxis (Grade 2C). For patients at high risk for VTE undergoing abdominal or pelvic surgery for cancer, we recommend extended-duration, postoperative, pharmacologic prophylaxis (4 weeks) with LMWH over limited-duration prophylaxis (Grade 1B). For patients at moderate to high risk for VTE who are at high risk for major bleeding complications or those in whom the consequences of bleeding are believed to be particularly severe, we suggest use of mechanical prophylaxis, preferably with IPC, over no prophylaxis until the risk of bleeding diminishes and pharmacologic prophylaxis may be initiated (Grade 2C). For patients in all risk groups, we suggest that an inferior vena cava filter not be used for primary VTE prevention (Grade 2C) and that surveillance with venous compression ultrasonography should not be performed (Grade 2C). We developed similar recommendations for other nonorthopedic surgical populations. CONCLUSIONS Optimal thromboprophylaxis in nonorthopedic surgical patients will consider the risks of VTE and bleeding complications as well as the values and preferences of individual patients.

Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis

Objective To investigate the association between treatment induced change in high density lipoprotein cholesterol and total death, coronary heart disease death, and coronary heart disease events (coronary heart disease death and non-fatal myocardial infarction) adjusted for changes in low density lipoprotein cholesterol and drug class in randomised trials of lipid modifying interventions. Design Systematic review and meta-regression analysis of randomised controlled trials. Data sources Medline, Embase, Central, CINAHL, and AMED to October 2006 supplemented by contact with experts in the field. Study selection In teams of two, reviewers independently determined eligibility of randomised trials that tested lipid modifying interventions to reduce cardiovascular risk, reported high density lipoprotein cholesterol and mortality or myocardial infarctions separately for treatment groups, and treated and followed participants for at least six months. Data extraction and synthesis Using standardised, pre-piloted forms, reviewers independently extracted relevant information from each article. The change in lipid concentrations for each trial and the weighted risk ratios for clinical outcomes were calculated. Results The meta-regression analysis included 108 randomised trials involving 299 310 participants at risk of cardiovascular events. All analyses that adjusted for changes in low density lipoprotein cholesterol showed no association between treatment induced change in high density lipoprotein cholesterol and risk ratios for coronary heart disease deaths, coronary heart disease events, or total deaths. With all trials included, change in high density lipoprotein cholesterol explained almost no variability (<1%) in any of the outcomes. The change in the quotient of low density lipoprotein cholesterol and high density lipoprotein cholesterol did not explain more of the variability in any of the outcomes than did the change in low density lipoprotein cholesterol alone. For a 10 mg/dl (0.26 mmol/l) reduction in low density lipoprotein cholesterol, the relative risk reduction was 7.2% (95% confidence interval 3.1% to 11%; P=0.001) for coronary heart disease deaths, 7.1% (4.5% to 9.8%; P<0.001) for coronary heart disease events, and 4.4% (1.6% to 7.2%; P=0.002) for total deaths, when adjusted for change in high density lipoprotein cholesterol and drug class. Conclusions Available data suggest that simply increasing the amount of circulating high density lipoprotein cholesterol does not reduce the risk of coronary heart disease events, coronary heart disease deaths, or total deaths. The results support reduction in low density lipoprotein cholesterol as the primary goal for lipid modifying interventions.

GRADE guidelines: 13. Preparing Summary of Findings tables and evidence profiles—continuous outcomes

Presenting continuous outcomes in Summary of Findings tables presents particular challenges to interpretation. When each study uses the same outcome measure, and the units of that measure are intuitively interpretable (e.g., duration of hospitalization, duration of symptoms), presenting differences in means is usually desirable. When the natural units of the outcome measure are not easily interpretable, choosing a threshold to create a binary outcome and presenting relative and absolute effects become a more attractive alternative. When studies use different measures of the same construct, calculating summary measures requires converting to the same units of measurement for each study. The longest standing and most widely used approach is to divide the difference in means in each study by its standard deviation and present pooled results in standard deviation units (standardized mean difference). Disadvantages of this approach include vulnerability to varying degrees of heterogeneity in the underlying populations and difficulties in interpretation. Alternatives include presenting results in the units of the most popular or interpretable measure, converting to dichotomous measures and presenting relative and absolute effects, presenting the ratio of the means of intervention and control groups, and presenting the results in minimally important difference units. We outline the merits and limitations of each alternative and provide guidance for meta-analysts and guideline developers.

Prevention of VTE in nonorthopedic surgical patients. Antithrombotic therapy and prevention of thrombosis, 9th ed

BACKGROUND VTE is a common cause of preventable death in surgical patients. METHODS We developed recommendations for thromboprophylaxis in nonorthopedic surgical patients by using systematic methods as described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS We describe several alternatives for stratifying the risk of VTE in general and abdominal-pelvic surgical patients. When the risk for VTE is very low (< 0.5%), we recommend that no specific pharmacologic (Grade 1B) or mechanical (Grade 2C) prophylaxis be used other than early ambulation. For patients at low risk for VTE (∼1.5%), we suggest mechanical prophylaxis, preferably with intermittent pneumatic compression (IPC), over no prophylaxis (Grade 2C). For patients at moderate risk for VTE (∼3%) who are not at high risk for major bleeding complications, we suggest low-molecular-weight heparin (LMWH) (Grade 2B), low-dose unfractionated heparin (Grade 2B), or mechanical prophylaxis with IPC (Grade 2C) over no prophylaxis. For patients at high risk for VTE (∼6%) who are not at high risk for major bleeding complications, we recommend pharmacologic prophylaxis with LMWH (Grade 1B) or low-dose unfractionated heparin (Grade 1B) over no prophylaxis. In these patients, we suggest adding mechanical prophylaxis with elastic stockings or IPC to pharmacologic prophylaxis (Grade 2C). For patients at high risk for VTE undergoing abdominal or pelvic surgery for cancer, we recommend extended-duration, postoperative, pharmacologic prophylaxis (4 weeks) with LMWH over limited-duration prophylaxis (Grade 1B). For patients at moderate to high risk for VTE who are at high risk for major bleeding complications or those in whom the consequences of bleeding are believed to be particularly severe, we suggest use of mechanical prophylaxis, preferably with IPC, over no prophylaxis until the risk of bleeding diminishes and pharmacologic prophylaxis may be initiated (Grade 2C). For patients in all risk groups, we suggest that an inferior vena cava filter not be used for primary VTE prevention (Grade 2C) and that surveillance with venous compression ultrasonography should not be performed (Grade 2C). We developed similar recommendations for other nonorthopedic surgical populations. CONCLUSIONS Optimal thromboprophylaxis in nonorthopedic surgical patients will consider the risks of VTE and bleeding complications as well as the values and preferences of individual patients.

Randomized Controlled Trials of Surgical Interventions

Background and Objectives:Surgical trials pose many methodological challenges often not present in trials of medical interventions. If not properly accounted for, these challenges may introduce significant biases and threaten the validity of the results. Methods:We systematically reviewed the significance of randomized controlled trials in the evaluation of surgical interventions, discussed the methodological challenges encountered in designing and conducting randomized controlled trials of surgical treatments, and proposed possible solutions to overcome these challenges. Conclusions:Many barriers and issues of surgical trials affecting internal validity can be overcome with proper methodology, and in most cases these issues do not restrict their conduct. Researchers should consider their research question carefully and design a surgical trial that contains features appropriate for the question. In doing so, they must ensure that the trial is valid, feasible, and affordable—a difficult feat, but one well worth the challenge.

The impact of prophylactic dexamethasone on nausea and vomiting after laparoscopic cholecystectomy: a systematic review and meta-analysis.

Objective:To determine the impact of prophylactic corticosteroid administration on postoperative nausea, vomiting, pain and complications in patients undergoing laparoscopic cholecystectomy. Data Sources:We searched 4 bibliographic databases, conference proceedings, reference lists of articles and textbooks, and contacted experts in the field of anesthesia and hepatobiliary surgery. Review Methods:We evaluated the methodologic quality of trials and extracted data regarding baseline characteristics, interventions, and outcomes. We pooled results from the studies using a random-effects model, evaluated the degree of heterogeneity, and explored potential explanations for heterogeneity. Results:Seventeen trials met eligibility criteria and provided high quality evidence regarding steroid effectiveness. Irrespective of the co-interventions (other antiemetic medications), dexamethasone reduced the incidence of nausea (RR 0.59, 95% CI, 0.48–0.72), vomiting (RR 0.41, 95% CI, 0.30–0.55), and postoperative nausea or vomiting (RR 0.55, 95% CI, 0.44–0.67) relative to placebo. Dexamethasone also seemed to reduce the severity of postoperative pain (Ratio of Means 0.87, 95% CI, 0.78–0.98), although substantial unexplained heterogeneity was present (I2 90.4%). The incidence of headache and dizziness was similar between groups. Conclusions:Prophylactic dexamethasone decreases the incidence of nausea and vomiting after LC relative to placebo and may decrease the severity of postoperative pain. Dexamethasone does not increase the incidence of headaches or dizziness. Surgeons should consider administering prophylactic corticosteroids to patients undergoing laparoscopic cholecystectomy, particularly those at high risk of postoperative nausea and vomiting.

Evaluating Agreement: Conducting a Reliability Study

Instruments that are useful in clinical or research practice will, when the object of measurement is stable, yield similar results when applied at different times, in different situations, or by different users. Studies that measure the relation of differences between patients or subjects and measurement error (reliability studies) are becoming increasingly common in the orthopaedic literature. In this paper, we identify common aspects of reliability studies and suggest features that improve the readers confidence in the results. One concept serves as the foundation for all further consideration: in order for a reliability study to be relevant, the patients, raters, and test administration in the study must be similar to the clinical or research context in which the instrument will be used. We introduce the statistical measures that readers will most commonly encounter in reliability studies, and we suggest an approach to sample-size estimation. Readers interested in critically appraising reliability studies or in developing their own reliability studies may find this review helpful.

The more the better?: the impact of surgeon and hospital volume on in-hospital mortality following colorectal resection.

Objective:To determine the in-hospital mortality rates for patients undergoing colorectal resection for malignant or benign conditions, and to identify risk factors for in-hospital death, particularly the relationships with surgeon and hospital volume. Background:Although there is strong evidence that complex cancer operations are best performed at specialized high-volume centers and by high-volume surgeons, the relationship between surgeon and hospital volume and perioperative outcomes is less well defined for more common procedures such as colorectal resections, particularly for benign diseases. Methods:We obtained data from the Canadian Institute for Health Information Discharge Abstract Database on all adult patients who underwent colorectal resection between April 1, 2005 and March 31, 2006. We performed a logistic regression to identify variables associated with a higher likelihood of in-hospital death. Results:Twenty-one thousand seventy-four patients underwent colorectal resection, with the majority being elective (59.4%). Malignancy represented the most common indication for resection (56.8%), followed by diverticular disease (16.2%) and inflammatory bowel disease (7.1%). The overall in-hospital mortality rate among patients undergoing colorectal resection was 5.3%. Increased age (adjusted Odds Ratio [OR]: 1.97 per 10 years, P < 0.001), urgent operation (OR: 2.63, P < 0.001), indication for resection (P < 0.001), nature of the surgery (P < 0.001), and several comorbidities were all independently associated with an increased risk of death. Surgeons with higher volumes of colorectal resections achieved significantly lower mortality rates (OR: 0.92 per 20 cases/y, P = 0.003), corresponding to an adjusted mortality rate of 5.6% for surgeons in the bottom decile (1 case per year) compared with 4.5% for surgeons in the top decile (greater than 43 cases per year). Hospital volume was not associated with mortality (OR: 1.00 per 10 cases, P = 0.504). Conclusions:This large, population-based study suggests that surgeons who perform high volumes of colorectal resections achieve lower in-hospital mortality rates than surgeons with low volumes, whereas the hospital volume does not influence mortality.

Staging Laparoscopy in the Management of Gastric Cancer: A Population-Based Analysis

BACKGROUND Staging laparoscopy can detect radiographically occult peritoneal metastases and prevent futile laparotomy in patients with gastric adenocarcinoma. We sought to assess the use of staging laparoscopy for gastric adenocarcinoma in a cohort of older patients and to compare outcomes after laparoscopy alone with nontherapeutic laparotomy. STUDY DESIGN Using Surveillance, Epidemiology and End Results (SEER) population-based cancer registry data linked with Medicare claims, we identified patients aged 65 or older diagnosed with gastric adenocarcinoma between 1998 and 2005. We defined staging laparoscopy as a laparoscopic procedure from 1 month before the date of diagnosis until death and futile laparotomy as a laparotomy in the absence of a therapeutic intervention. We examined trends in the use of staging laparoscopy and compared outcomes between patients who underwent staging laparoscopy alone and those who had a futile laparotomy. RESULTS Of 11,759 patients with gastric adenocarcinoma, 6,388 (54.3%) had at least 1 surgical procedure. Staging laparoscopy was performed in 506 (7.9%) patients who had any surgery, and 151 (29.8%) of these patients did not have a subsequent therapeutic intervention. Patients who underwent staging laparoscopy alone had a significantly lower rate of in-hospital mortality (5.3% vs 13.1%, p < 0.001) and shorter length of hospitalization (2 vs 10 days, p < 0.001) than patients who had futile laparotomy. CONCLUSIONS Our findings in this large, population-based cohort suggest that staging laparoscopy is used infrequently in the management of older patients with gastric adenocarcinoma. Increased use of staging laparoscopy could reduce the substantial morbidity and mortality associated with nontherapeutic laparotomy.

Long-term Outcomes Following Tumor Ablation for Treatment of Bilateral Colorectal Liver Metastases

IMPORTANCE Ablative therapies extend the capability of delivering potentially curative treatment for bilateral hepatic colorectal metastases. OBJECTIVE To compare the long-term effectiveness of ablation with that of resection in patients with bilateral hepatic colorectal metastases. DESIGN Review of a prospective database of 2123 operative cases of hepatic colorectal metastases. SETTING A large institution with expertise in ablation and resection. PATIENTS Patients with bilateral colorectal liver metastases undergoing operation with a curative intent. A total of 141 patients had been treated with bilateral resection (BR) and 95 had undergone ablation. INTERVENTIONS Radiofrequency or microwave ablation alone or in combination with resection (A/R) compared with BR. MAIN OUTCOMES AND MEASURES We compared tumor characteristics and operative and postoperative outcomes using χ2 or Wilcoxon tests as appropriate and assessed overall survival differences between the 2 groups using the log-rank test. RESULTS During the study, 141 patients were treated with BR and 95 patients with A/R. The A/R group was a significantly poorer prognostic group than the BR group as judged by the Clinical Risk Score (P < .01). There was no difference in median operative time (A/R: 280 minutes, BR: 282 minutes; P = .52), but a lower blood loss (A/R: 300 mL, BR: 500 mL; P < .01) and a shorter length of stay (A/R: 7 days, BR: 9 days; P < .01) was achieved in the A/R group. Long-term outcome was not significantly different between the groups (5-year overall survival, A/R: 56%, BR: 49%; P = .16). CONCLUSIONS AND RELEVANCE Treatment of bilateral, multiple hepatic metastases with combined resection and ablation was associated with improved perioperative outcomes without compromising long-term survival compared with bilateral resection. Ablative therapies extend the capability of delivering potentially curative treatment for bilateral hepatic colorectal metastases.