It Is Time to Reconsider Factorial Designs: How Bradford Hill and R. A. Fisher Shaped the Standard of Clinical Evidence.

OBJECTIVES: Could medical research and quality improvement studies be more productive with greater use of multifactor study designs? METHODS: Drawing on new primary sources and the literature, we examine the roles of A. Bradford Hill and Ronald A. Fisher in introducing the design of experiments in medicine. RESULTS: Hill did not create the randomized controlled trial, but he popularized the idea. His choice to set aside Fisher's advanced study designs shaped the development of clinical research and helped the single-treatment trial to become a methodological standard. CONCLUSIONS: Multifactor designs are not widely used in medicine despite their potential to make improvement initiatives and health services research more efficient and effective. Quality managers, health system leaders, and directors of research institutes could increase productivity and gain important insights by promoting a broader use of factorial designs to study multiple interventions simultaneously and to learn from interactions.

Platelet count abnormalities and peri-operative outcomes in adults undergoing elective, non-cardiac surgery.

BACKGROUND: Anemia and transfusion of blood in the peri-operative period have been shown to be associated with increased morbidity and mortality across a wide variety of non-cardiac surgeries. While tests of coagulation, including the platelet count, have frequently been used to identify patients with an increased risk of peri-operative bleeding, results have been equivocal. The aim of this study was to assess the effect of platelet level on outcomes in patients undergoing elective surgery. MATERIALS AND METHODS: Retrospective cohort analysis of prospectively-collected clinical data from American College of Surgeons National Surgical Quality Improvement Program (NSQIP) between 2006-2016. RESULTS: We identified 3,884,400 adult patients who underwent elective, non-cardiac surgery from 2006-2016 at hospitals participating in NSQIP, a prospectively-collected, national clinical database with established reproducibility and validity. After controlling for all peri- and intraoperative factors by matching on propensity scores, patients with all levels of thrombocytopenia or thrombocytosis had higher odds for perioperative transfusion. All levels of thrombocytopenia were associated with higher mortality, but there was no association with complications or other morbidity after matching. On the other hand, thrombocytosis was not associated with mortality; but odds for postoperative complications and 30-day return to the operating room remained slightly increased after matching. CONCLUSIONS: These findings may guide surgeons in the appropriate use and appreciation of the utility of pre-operative screening of the platelet count prior to an elective, non-cardiac surgery.

Tutorial on Data Balancing: Application to Benchmarking Clinicians.

In this tutorial, we show how data balancing, in general, and stratified covariate balancing, in particular, can be used to benchmark clinicians. This tutorial aims to explain the concepts behind data balancing to readers who do not have a strong statistical background. Data balancing enables the analyst to compare the performance of clinicians with their peer groups on the same set of patients. The comparison is done in 3 steps. First, the patients are described in terms of their conditions/comorbidities. Each combination of comorbidities is treated as a separate type of patient. Second, the analyst measures the frequency of observing different types of patients. Third, expected outcomes are calculated for both the clinician and the peer group. The expected outcome for the clinician is calculated as the sum of product of 2 terms: probability of and the average outcome for different types of patients. The expected outcome for the peer group is calculated in the same way, with one difference: the distribution of peer group's patients is switched with the distribution of the clinician's patients. This allows us to simulate the performance of peer group on the clinician's patients. This switch in frequencies accomplishes the same goal as using propensity weights, or covariate balancing weights, but it avoids the cumbersome need to estimate the weights. In switching the distributions, a problem arises when the peer group does not see the same type of patients as the clinician. When the peer group's outcome for some patient types is missing, a synthetic case is organized. These synthetic cases are constructed from the peer group's experience with 2 complementary parts of the missing case. The reliance on synthetic cases allows one to have a match for every type of clinician's patients. Together, the synthetic case and the switch of distribution allow one to simulate the performance of the clinician and the peer group on same set of cases. The tutorial walks the reader through examples. The procedures described here can be applied to data in electronic health records. We present Standard Query Language for doing so.

Surgeon specialty and patient outcomes in carotid endarterectomy.

OBJECTIVE: The goal of this study was to compare outcomes of carotid endarterectomy performed by neurological, general, and vascular surgeons. METHODS: The authors identified 80,475 patients who underwent carotid endarterectomy between 2006 and 2015 in the National Surgical Quality Improvement Program, a prospectively collected, national clinical database with established reproducibility and validity. Nine hundred forty-three patients were operated on by a neurosurgeon; 75,649 by a vascular surgeon; and 3734 by a general surgeon. Preoperative and intraoperative characteristics and 30-day outcomes were stratified by the surgeon's primary specialty. Using propensity scores, comprising pre- and intraoperative characteristics as well as procedure and diagnostic codes, the authors matched 203 neurosurgery (NS) patients to 203 vascular surgery (VS) patients and 203 NS patients to 203 general surgery (GS) patients. No pre- or intraoperative factors were significantly different between specialties in the matched sample. Regular logistic regression and conditional logistic regression were used to predict postoperative complications in the full sample and in the matched sample. RESULTS: In the complete population sample, NS patients, when compared to patients of general and vascular surgeons, were less likely to be admitted from home and more likely to have carotid artery occlusion or stenosis with cerebral infarction, to be a current smoker, to have had recent chemo- or radiotherapy, to have surgery under general anesthesia, to undergo multiple procedures, and to have longer surgery times. In unadjusted analyses, NS patients were more likely to experience major complications (NS vs VS: odds ratio 1.3, 95% CI 1.1-1.6; NS vs GS: odds ratio 1.3, 95% CI 1.0-1.7); minor complications (NS vs VS: odds ratio 2.9, 95% CI 2.0-4.1; NS vs GS: odds ratio 2.7, 95% CI 1.7-4.2); intra- or postoperative transfusions (NS vs VS: odds ratio 1.6, 95% CI 1.4-1.9; NS vs GS: odds ratio 1.9, 95% CI 1.6-2.3); prolonged hospitalization (NS vs VS: odds ratio 3.0, 95% CI 2.6-3.5; NS vs GS: odds ratio 2.6, 95% CI 2.2-3.0); and discharge to skilled care facilities (NS vs VS: odds ratio 2.8, 95% CI 2.3-3.4; NS vs GS: odds ratio 3.1, 95% CI 2.4-4.1). In adjusted, propensity-matched analyses, however, patients' outcome with carotid endarterectomy performed by NS was comparable with those completed by GS and VS. CONCLUSIONS: Patients who undergo carotid endarterectomy performed by a neurosurgeon tend to have a greater preoperative disease burden than do those treated by a general or vascular surgeon, which contributes significantly to more morbid postoperative courses. In patients matched carefully on the basis of health status at the time of surgery and intraoperative variables that affect results, patients' outcomes after carotid endarterectomy do not appear to depend on the attending surgeon's primary specialty.

Impact of Resident Involvement in Neurosurgery: An American College of Surgeons' National Surgical Quality Improvement Program Database Analysis of 33,977 Patients.

OBJECTIVE: There is conflicting and limited literature on the effect of intraoperative resident involvement on surgical outcomes. Our study assessed effects of resident involvement on outcomes in patients undergoing neurosurgery. METHODS: We identified 33,977 adult neurosurgical cases from 374 hospitals in the 2006-2012 National Surgical Quality Improvement Program, a prospectively collected national database with established reproducibility and validity. Outcomes were compared according to resident involvement before and after 1:1 matching on procedure and perioperative risk factors. RESULTS: Resident involvement was documented in 13,654 cases. We matched 10,170 resident-involved cases with 10,170 attending-alone. In the matched sample, resident involvement was associated with increased surgery duration (average, 34 minutes) and slight increases in odds for prolonged hospital stay (odds ratio, 1.2; 95% confidence interval [CI], 1.2-1.3) and complications (odds ratio, 1.2; 95% CI, 1.1-1.3) including infections (odds ratio, 1.4; 95% CI, 1.2-1.7). Increased risk for infections persisted after controlling for surgery duration (odds ratio, 1.3; 95% CI, 1.1-1.5). The majority of cases were spine surgeries, and resident involvement was not associated with morbidity or mortality for malignant tumor and aneurysm patients. Training level of residents was not associated with differences in outcomes. CONCLUSION: Resident involvement was more common in sicker patients undergoing complex procedures, consistent with academic centers undertaking more complex cases. After controlling for patient and intraoperative characteristics, resident involvement in neurosurgical cases continued to be associated with longer surgical duration and slightly higher infection rates. Longer surgery duration did not account for differences in infection rates.

Does this treatment work for me? The patient's role in assessing medical care.

Randomised clinical trials are designed to determine whether a particular treatment is appropriate to make a significant difference to the health of a defined population and to aid its approval for use. For an accurate, cheap and simple assessment to see if a treatment benefits an individual person, all that is needed is a pen, paper, simple pocket calculator and daily recording of a few variables. It requires the ability to read and write and to understand addition and division. Factorial design of experiments is used to show the impact of several variables and their interaction on the person's health status. An example of a 75-year-old man with an enlarged prostate is used here to illustrate this approach. This person was able to understand and reduce side effects, lower the costs of medication by 83% and improve measured health status by 28%. A multivariate model for this person was then created with about 450 person-days of data.

Autonomic components of Complex Regional Pain Syndrome (CRPS) are favourably affected by Electrical Twitch-Obtaining Intramuscular Stimulation (ETOIMS): effects on blood pressure and heart rate.

INTRODUCTION: Favourable pain relief results on evoking autonomous twitches at myofascial trigger points with Electrical Twitch Obtaining Intramuscular Stimulation (ETOIMS). AIM: To document autonomic nervous system (ANS) dysfunction in Complex Regional Pain Syndrome (CRPS) from blood pressure (BP) and pulse/heart rate changes with ETOIMS. METHODS AND MATERIALS: A patient with persistent pain regularly received serial ETOIMS sessions of 60, 90, 120 or ≥150 min over 24 months. Outcome measures include BP: systolic, diastolic, pulse pressure and pulse/heart rate, pre-session/immediate-post-session summed differences (SDPPP index), and pain reduction. His results were compared with that of two other patients and one normal control. Each individual represented the following maximal elicitable twitch forces (TWF) graded 1-5: maximum TWF2: control subject; maximum TWF3: CRPS patient with suspected ANS dysfunction; and maximum TWF4 and TWF5: two patients with respective slow-fatigue and fast-fatigue twitches who during ETOIMS had autonomous twitching at local and remote myotomes simultaneously from denervation supersensitivity. ETOIMS results between TWFs were compared using one-way analysis of variance test. RESULTS: The patients showed immediate significant pain reduction, BP and pulse/heart rate changes/reduction(s) except for diastolic BP in the TWF5 patient. TWF2 control subject had diastolic BP reduction with ETOIMS but not with rest. Linear regression showed TWF grade to be the most significant variable in pain reduction, more so than the number of treatments, session duration and treatment interval. TWF grade was the most important variable in significantly reducing outcome measures, especially pulse/heart rate. Unlike others, the TWF3 patient had distinctive reductions in SDPPP index. CONCLUSIONS: Measuring BP and pulse/heart rate is clinically practical for alerting ANS dysfunction maintained CRPS. SDPPP index (≥26) and pulse/heart rate (≥8) reductions with almost every ETOIMS treatment, plus inability to evoke autonomous twitches due to pain-induced muscle hypertonicity, are pathognomonic of this problem.

The Influence of Race on Short-term Outcomes After Laminectomy and/or Fusion Spine Surgery.

STUDY DESIGN: A retrospective cohort analysis of prospectively collected clinical data. OBJECTIVE: The aim of this study was to assess the effect of race on outcomes in patients undergoing elective laminectomy and/or fusion spine surgery. SUMMARY OF BACKGROUND DATA: Studies that have looked at the effect of race on spine surgery outcomes have failed to take into account baseline risk factors that may influence peri-operative outcomes. METHODS: We identified 48,493 adult patients who underwent elective spine surgery consisting of elective laminectomy and/or fusion, from 2006 to 2012, at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP), a prospectively collected, national clinical database with established reproducibility and validity. Pre- and intraoperative characteristics and 30-day outcomes were stratified by race. We used propensity scores to match African-American and Caucasian patients on all pre- and intraoperative factors, including by principal diagnosis leading to surgery as well as surgery performed. We used regular and conditional logistic regression to predict the effect of race on adverse postoperative outcomes in the full sample and matched sample. RESULTS: Caucasians comprised 82% of our sample. We found no differences in the incidence of pre- and intraoperative factors when comparing Caucasian patients with all minority patients, and only minimal increased odds for prolonged length of length of hospitalization (LOS) and discharge with continued care. However, African-American patients, who comprised 39% of our minority sample, had more preoperative comorbidities than Caucasian patients. Even after eliminating all differences between pre- and intraoperative factors between Caucasian and African-American patients, African-American patients continued to have LOS that was, on average, one day longer than Caucasian patients. African-American patients also had higher odds for major complications [odds ratio (OR) = 1.3; 95% confidence interval (95% CI) 1.1-1.6], and to be discharged requiring continued care (OR = 2.3; 95% CI 1.8-2.8). CONCLUSION: African-American race is independently associated with prolonged LOS, major complications, and a need to be discharged with continued care in patients undergoing elective spine surgery. LEVEL OF EVIDENCE: 3.

Ethical, Legal, and Social Implications of Personalized Genomic Medicine Research: Current Literature and Suggestions for the Future.

PURPOSE: This review identifies the prominent topics in the literature pertaining to the ethical, legal, and social issues (ELSI) raised by research investigating personalized genomic medicine (PGM). METHODS: The abstracts of 953 articles extracted from scholarly databases and published during a 5-year period (2008-2012) were reviewed. A total of 299 articles met our research criteria and were organized thematically to assess the representation of ELSI issues for stakeholders, health specialties, journals, and empirical studies. RESULTS: ELSI analyses were published in both scientific and ethics journals. Investigational research comprised 45% of the literature reviewed (135 articles) and the remaining 55% (164 articles) comprised normative analyses. Traditional ELSI concerns dominated the discourse including discussions about disclosure of research results. In fact, there was a dramatic increase in the number of articles focused on the disclosure of research results and incidental findings to research participants. Few papers focused on particular disorders, the use of racial categories in research, international communities, or special populations (e.g., adolescents, elderly patients, or ethnic groups). CONCLUSION: Considering that strategies in personalized medicine increasingly target individuals' unique health conditions, environments, and ancestries, further analysis is needed on how ELSI scholarship can better serve the increasingly global, interdisciplinary, and diverse PGM research community.

Use and Utility of Hemostatic Screening in Adults Undergoing Elective, Non-Cardiac Surgery.

INTRODUCTION: One view of value in medicine is outcome relative to cost of care provided. With respect to operative care, increased attention has been placed on evaluation and optimization of patients prior to undergoing an elective surgery. We examined more than 2 million patients having elective, non-cardiac surgery to assess the incidence and utility of pre-operative hemostatic screening, compared with a composite of history variables that may indicate a propensity for bleeding, to assess several important outcomes of surgery. MATERIALS & METHODS: We queried the NSQIP database to identify 2,020,533 patients and compared hemostatic tests (PT, aPTT, platelet count) and history covariables indicative of potential for abnormal hemostasis. We compared outcomes across predictor values; used Person's chi-square tests to compare differences, and logistic regression to model outcomes. RESULTS: Approximately 36% of patients had all three tests pre-operatively while 16% had none of them; 11.2% had a history predictive of potential abnormal bleeding. Outcomes of interest across the cohort included death in 0.7%, unplanned return to the operating room or re-admission within 30 days in 3.8% and 6.2% of patients; 5.3% received a transfusion during or after surgery. Sub-analyses in each of the nine surgical specialties' most common procedures yielded similar results. CONCLUSION: The limited predictive value of each hemostatic screening test, as well as excess costs associated with them, across a broad spectrum of elective surgeries, suggests that limiting pre-operative testing to a more select group of patients may be reasonable, equally efficacious, efficient, and cost-effective.

Preoperative steroid use and the incidence of perioperative complications in patients undergoing craniotomy for definitive resection of a malignant brain tumor.

We studied the impact of preoperative steroids on 30 day morbidity and mortality of craniotomy for definitive resection of malignant brain tumors. Glucocorticoids are used to treat peritumoral edema in patients with malignant brain tumors, however, prolonged (⩾ 10 days) use of preoperative steroids as a risk factor for perioperative complications following resection of brain tumors has not been studied comprehensively. Therefore, we identified 4407 patients who underwent craniotomy to resect a malignant brain tumor between 2007 and 2012, who were reported in the National Surgical Quality Improvement Program, a prospectively collected clinical database. Metastatic brain tumors constituted 37.5% (n=1611) and primary malignant gliomas 62.5% (n=2796) of the study population. We used logistic regression to assess the association between preoperative steroid use and perioperative complications before and after 1:1 propensity score matching. Patients who received steroids constituted 22.8% of the population (n=1009). In the unmatched cohort, steroid use was associated with decreased length of hospitalization (odds ratio [OR] 0.7; 95% confidence interval [CI] 0.6-0.8), however, the risk for readmission (OR 1.5; 95% CI 1.2-1.8) was increased. In the propensity score matched cohort (n=465), steroid use was not statistically associated with any adverse outcomes. Patients who received steroids were less likely to stay hospitalized for a protracted period of time, but were more likely to be readmitted after discharge following craniotomy. As an independent risk factor, preoperative steroid use was not associated with any observed perioperative complications. The findings of this study suggest that preoperative steroids do not independently compromise the short term outcome of craniotomy for resection of malignant brain tumors.

Risks associated with preoperative anemia and perioperative blood transfusion in open surgery for intracranial aneurysms.

OBJECT: Preoperative anemia may be treated with a blood transfusion. Both are associated with adverse outcomes in various surgical procedures, but this has not been clearly elucidated in surgery for cerebral aneurysms. In this study the authors assessed the association of preoperative anemia and perioperative blood transfusion, separately, on 30-day morbidity and mortality in patients undergoing open surgery for ruptured and unruptured intracranial aneurysms. METHODS: The authors identified 668 cases (including 400 unruptured and 268 unruptured intracranial aneurysms) of open surgery for treatment of intracranial aneurysms in the 2006-2012 National Surgical Quality Improvement Program, a validated and reproducible prospective clinical database. Anemia was defined as a hematocrit level less than 39% in males and less than 36% in females. Perioperative transfusion was defined as at least 1 unit of packed or whole red blood cells given at any point between the start of surgery to 72 hours postoperatively. The authors separately compared surgical outcome between patients with (n = 198) versus without (n = 470) anemia, and those who underwent (n = 78) versus those who did not receive (n = 521) a transfusion, using a 1:1 match on propensity score. RESULTS: In the matched cohorts, all observed covariates were comparable between anemic (n = 147) versus nonanemic (n = 147) and between transfused (n = 67) versus nontransfused patients (n = 67). Anemia was independently associated with prolonged hospital length of stay (LOS; odds ratio [OR] 2.5, 95% confidence interval [CI] 1.4-4.5), perioperative complications (OR 1.9, 95% CI 1.1-3.1), and return to the operating room (OR 2.1, 95% CI 1.1-4.5). Transfusion was also independently associated with perioperative complications (OR 2.4, 95% CI 1.1-5.3). CONCLUSIONS: Preoperative anemia and transfusion are each independent risk factors for perioperative complications in patients undergoing surgery for cerebral aneurysms. Perioperative anemia is also associated with prolonged hospital LOS and 30-day return to the operating room.

Surgeon specialty and outcomes after elective spine surgery.

STUDY DESIGN: Retrospective cohort analysis of prospectively collected clinical data. OBJECTIVE: To compare outcomes of elective spine fusion and laminectomy when performed by neurological and orthopedic surgeons. SUMMARY OF BACKGROUND DATA: The relationship between primary specialty training and outcome of spinal surgery is unknown. METHODS: We analyzed the 2006 to 2012 American College of Surgeons National Surgical Quality Improvement Project database of 50,361 patients, 33,235 (66%) of which were operated on by a neurosurgeon. We eliminated all differences in preoperative and intraoperative risk factors between surgical specialties by matching 17,126 patients who underwent orthopedic surgery (OS) to 17,126 patients who underwent neurosurgery (NS) on propensity scores. Regular and conditional logistic regressions were used to predict adverse postoperative outcomes in the full sample and matched sample, respectively. The effect of perioperative transfusion on outcomes was further assessed in the matched sample. RESULTS: Diagnosis and procedure were the only factors that were found to be significantly different between surgical subspecialties in the full sample. We found that compared with patients who underwent NS, patients who underwent OS were more than twice as likely to experience prolonged length of stay (LOS) (odds ratio: 2.6, 95% confidence interval: 2.4-2.8), and significantly more likely to receive a transfusion perioperatively, have complications, and to require discharge with continued care. After matching, patients who underwent OS continued to have slightly higher odds for prolonged LOS, and twice the odds for receiving perioperative transfusion compared with patients who underwent NS. Taking into account perioperative transfusion did not eliminate the difference in LOS between patients who underwent OS and those who underwent NS. CONCLUSION: Patients operated on by OS have twice the odds for undergoing perioperative transfusion and slightly increased odds for prolonged LOS. Other differences between surgical specialties in 30-day postoperative outcomes were minimal. Analysis of a large, multi-institutional sample of prospectively collected clinical data suggests that surgeon specialty has limited influence on short-term outcomes after elective spine surgery. LEVEL OF EVIDENCE: 3.

Impact of increased body mass index on outcomes of elective spinal surgery.

STUDY DESIGN: Observational retrospective cohort study of prospectively collected database. OBJECTIVE: To determine whether overweight body mass index (BMI) influences 30-day outcomes of elective spine surgery. SUMMARY OF BACKGROUND DATA: Obesity is prevalent in the United States, but its impact on the outcome of elective spine surgery remains controversial. METHODS: We used National Surgical Quality Improvement Program, a prospective clinical database with proven validity and reproducibility consisting of 256 perioperative standardized variables from surgical patients at nearly 400 academic and nonacademic hospitals nationwide. We identified 49,314 patients who underwent elective fusion, laminectomy or both between 2006 and 2012. We divided patients according to BMI (kg/m2) as normal (18.5-24.9), preobese (25.0-29.9), obese I (30.0-34.9), obese II (35.0-39.9), and obese III (≥40). Relationship between increased BMI and outcome of surgery measured as prolonged hospitalization, complications, return to the operating room, discharged with continued care requirement, readmission, and death was determined using logistic regression before and after propensity score matching. RESULTS: All overweight patients (BMI ≥25 kg/m2) showed increased odds of an adverse outcome compared with normal patients in unmatched analyses, with maximal effect seen in obese III group. In the propensity-matched sample, obese III patients continued to show increased odds for complications (odds ratio, 1.6; 95% confidence interval, 1.1-2.3), readmission (odds ratio, 2.3; 95% confidence interval, 1.1-4.9), and return to the operating room (odds ratio, 1.8; 95% confidence interval, 1.1-3.1). CONCLUSION: Impact of obesity on elective spine surgery outcome is mediated, at least in part, by comorbidities in patients with BMI between 25.0 and 39.9 kg/m2. However, BMI itself is an independent risk factor for adverse outcomes in morbidly obese patients. LEVEL OF EVIDENCE: 3.

The effect of blood transfusion on short-term, perioperative outcomes in elective spine surgery.

Studies in various surgical procedures have shown that transfusion of red blood cells (RBC) increases the risk of postoperative morbidity and mortality. Impact of blood transfusion in patients undergoing spine surgery is not well-described. We assessed the impact of intra and postoperative transfusion on postoperative morbidity and mortality in patients undergoing elective spine surgery. We used the American College of Surgeons' National Surgical Quality Improvement Program to identify a retrospective cohort of 36,901 adult patients who underwent elective spine surgery between 2006 and 2011. Patients who received intra or postoperative transfusion (n=3262) were matched to those who did not using propensity scores. Logistic regression predicted adverse postoperative outcomes. We conducted sensitivity analysis in a subset of patients in whom the number of intraoperatively transfused units of RBC or whole blood was known. Upon matching, preoperative hematocrit, length of surgery, and percentage of spinal fusion surgery were not significantly different between transfused and non-transfused patients. After matching, transfusion remained adversely associated with prolonged length of stay (LOS) in hospital (odds ratio [OR] 2.6, 95% confidence interval [CI] 2.3-2.9), postoperative complications (OR 1.6, 95% CI 1.4-1.9), and an increased 30 day return to operation room (OR 1.7, 95% CI 1.3-2.2). Transfusion of even one unit of blood intraoperatively was associated with prolonged LOS (OR 2.0, 95% CI 1.5-2.6) and minor complications (OR 2.4, 95% CI 1.3-4.3). Therefore, transfusion of RBC or whole blood, even a single unit, increased LOS and postoperative morbidity in patients undergoing elective spine surgery, independent of preoperative hematocrit level and patient comorbidities.

Indices to measure risk of HIV acquisition in Rakai, Uganda.

INTRODUCTION: Targeting most-at-risk individuals with HIV preventive interventions is cost-effective. We developed gender-specific indices to measure risk of HIV among sexually active individuals in Rakai, Uganda. METHODS: We used multivariable Cox proportional hazards models to estimate time-to-HIV infection associated with candidate predictors. Reduced models were determined using backward selection procedures with Akaike's information criterion (AIC) as the stopping rule. Model discrimination was determined using Harrell's concordance index (c index). Model calibration was determined graphically. Nomograms were used to present the final prediction models. RESULTS: We used samples of 7,497 women and 5,783 men. 342 new infections occurred among females (incidence 1.11/100 person years,) and 225 among the males (incidence 1.00/100 person years). The final model for men included age, education, circumcision status, number of sexual partners, genital ulcer disease symptoms, alcohol use before sex, partner in high risk employment, community type, being unaware of a partner's HIV status and community HIV prevalence. The Model's optimism-corrected c index was 69.1 percent (95% CI = 0.66, 0.73). The final women's model included age, marital status, education, number of sex partners, new sex partner, alcohol consumption by self or partner before sex, concurrent sexual partners, being employed in a high-risk occupation, having genital ulcer disease symptoms, community HIV prevalence, and perceiving oneself or partner to be exposed to HIV. The models optimism-corrected c index was 0.67 (95% CI = 0.64, 0.70). Both models were well calibrated. CONCLUSION: These indices were discriminative and well calibrated. This provides proof-of-concept that population-based HIV risk indices can be developed. Further research to validate these indices for other populations is needed.

Smoking and postoperative outcomes in elective cranial surgery.

OBJECT: The goal in this study was to assess whether a current or prior history of smoking and the number of smoking pack years affect the risk for adverse outcomes in the 30-day postoperative period in patients who undergo elective cranial surgery. METHODS: Data from the 2006-2011 American College of Surgeons' National Surgical Quality Improvement Project were used in this study. The authors identified 8296 patients who underwent elective cranial surgery, of whom 1718 were current smokers, 854 were prior smokers, and 5724 were never smokers. Using propensity scores and age, the authors matched current and prior smokers to never smokers. Odds ratios for adverse postoperative outcomes were predicted with logistic regression. The relationship between number of pack years and poor outcomes was also examined. RESULTS: In unadjusted analyses, prior and current smokers did not differ from never smokers for having poor outcomes postoperatively. Similarly, in matched analyses, no association was found between smoking and adverse outcomes. Number of pack years in propensity-matched analyses did not predict worse outcomes in prior or current smokers versus never smokers. CONCLUSIONS: The authors did not find smoking to be associated with 30-day postoperative morbidity or mortality. Although smoking cessation is beneficial for overall health, it may not improve the short-term (≤ 30 days) outcome of elective cranial surgery. Thus postponement of elective cranial cases only for smoking cessation may not be necessary.

Impact of preoperative anemia on outcomes in patients undergoing elective cranial surgery.

OBJECT: The objective of this study was to assess whether preoperative anemia in patients undergoing elective cranial surgery influences outcomes in the immediate perioperative period (≤ 30 days). METHODS: The National Surgical Quality Improvement Program (NSQIP) was used to identify 6576 patients undergoing elective cranial surgery between 2006 and 2011. Propensity scores were used to match patients with moderate to severe anemia (moderate-severe) or mild anemia with patients without anemia. Logistic regression analysis was used to predict the outcomes of interest. Sensitivity analyses were used to limit the sample to patients without perioperative transfusion as well as those who underwent craniotomy for definitive resection of a malignant brain tumor. RESULTS: A total of 6576 patients underwent elective cranial surgery, of whom 175 had moderate-severe anemia and 1868 had mild anemia. Patients with moderate-severe (odds ratio 1.8, 95% CI 1.1-2.8) and mild (odds ratio 1.5, 95% CI 1.3-1.7) anemia were more likely to have prolonged length of stay (LOS) in the hospital compared to those with no anemia. Similarly, in patients who underwent craniotomy for a malignant tumor resection (n = 2537), anemia of any severity was associated with prolonged LOS, but not postoperative complications nor death. CONCLUSIONS: Anemia is not associated with an overall increased risk for adverse outcomes in patients undergoing elective cranial surgery. However, patients with anemia are more likely to experience prolonged hospitalization postoperatively, resulting in increased resource utilization.

Effect of smoking on the perioperative outcomes of patients who undergo elective spine surgery.

STUDY DESIGN: Retrospective analysis of the prospectively collected American College of Surgeons National Surgical Quality Improvement database. OBJECTIVE: We assessed whether preoperative cigarette smoking and smoking duration predicted adverse, early, perioperative outcomes in patients undergoing elective spine surgery. SUMMARY OF BACKGROUND DATA: Prior studies have assessed the association of smoking and long-term outcomes for a number of spine surgery procedures, with conflicting findings. The association between smoking and 30-day outcomes for spine surgery is unknown. METHODS: A total 14,500 adults, classified as current (N = 3914), prior (N = 2057), and never smokers. Using propensity scores, current and prior smokers were matched to never smokers. Logistic regression was used to predict adverse postoperative outcomes. The relationship between pack-years and adverse outcomes was tested. Sensitivity analyses were conducted limiting the study sample to patients who underwent spine fusion (N = 4663), and using patient subgroups by procedure. RESULTS: In unadjusted analyses, prior smokers were significantly more likely to have prolonged hospitalization (1.2, 95% confidence interval [CI]: 1.1-1.3) and major complications (1.3, 95% CI: 1.1-1.6) compared with never smokers. No association was found between smoking status and adverse outcomes in adjusted, matched patient models. Current smokers with more than 60 pack-years were more likely to die within 30 days of surgery (3.0, 95% CI, 1.1-7.8), compared with never smokers. Sensitivity analyses confirmed these findings. CONCLUSION: The large National Surgical Quality Improvement population was carefully matched for a wide range of baseline comorbidities, including 29 variables previously suggested to influence perioperative outcomes. Although previous studies conducted in subgroups of spine surgery patients have suggested a deleterious effect for smoking on long-term outcomes in patients undergoing spine surgery, our analysis did not find smoking to be associated with early (30 d) perioperative morbidity or mortality.