Population Genomic Screening for Three Common Hereditary Conditions : A Cost-Effectiveness Analysis.

BACKGROUND: The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown. OBJECTIVE: To estimate the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH). DESIGN: Decision analytic Markov model. DATA SOURCES: Published literature. TARGET POPULATION: Separate age-based cohorts (ages 20 to 60 years at time of screening) of racially and ethnically representative U.S. adults. TIME HORIZON: Lifetime. PERSPECTIVE: U.S. health care payer. INTERVENTION: Population genomic screening using clinical sequencing with a restricted panel of high-evidence genes, cascade testing of first-degree relatives, and recommended preventive interventions for identified probands. OUTCOME MEASURES: Incident breast, ovarian, and colorectal cancer cases; incident cardiovascular events; quality-adjusted survival; and costs. RESULTS OF BASE-CASE ANALYSIS: Screening 100 000 unselected 30-year-olds resulted in 101 (95% uncertainty interval [UI], 77 to 127) fewer overall cancer cases and 15 (95% UI, 4 to 28) fewer cardiovascular events and an increase of 495 quality-adjusted life-years (QALYs) (95% UI, 401 to 757) at an incremental cost of $33.9 million (95% UI, $27.0 million to $41.1 million). The incremental cost-effectiveness ratio was $68 600 per QALY gained (95% UI, $41 800 to $88 900). RESULTS OF SENSITIVITY ANALYSIS: Screening 30-, 40-, and 50-year-old cohorts was cost-effective in 99%, 88%, and 19% of probabilistic simulations, respectively, at a $100 000-per-QALY threshold. The test costs at which screening 30-, 40-, and 50-year-olds reached the $100 000-per-QALY threshold were $413, $290, and $166, respectively. Variant prevalence and adherence to preventive interventions were also highly influential parameters. LIMITATIONS: Population averages for model inputs, which were derived predominantly from European populations, vary across ancestries and health care environments. CONCLUSION: Population genomic screening with a restricted panel of high-evidence genes associated with 3 CDC Tier 1 conditions is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions. PRIMARY FUNDING SOURCE: National Human Genome Research Institute.

Genetic Variants Associated With Systolic Blood Pressure in Children and Adolescents.

Background Genetics, along with lifestyle and behavioral characteristics, play an important role in hypertension in adults. Our aim was to identify genetic variants associated with blood pressure in childhood and adolescence. Methods and Results We conducted a candidate single-nucleotide polymorphism (SNP) analysis and genome-wide association study among 9778 participants aged <18 years in BioVU, the Vanderbilt University Medical Center biobank. The outcome was childhood blood pressure percentile from age 0 to 18 years. For the candidate SNP analysis, a total of 457 previously identified SNPs were examined. Linear regression was used to test the association between genetic variants and median systolic blood pressure (SBP) percentile. Adjusted models included median age, self-reported sex, race, the first 4 principal components of ancestry, and median body mass index Z score. Analyses were conducted in the overall cohort and stratified by age group. A polygenic risk score was calculated for each participant, and the association between polygenic risk score and median SBP percentile in childhood was examined using linear regression. In the overall candidate SNP analysis, 2 SNPs reached significance: rs1018148 (FBN1; P=1.0×10-4) and rs11105354 (ATP2B1; P=1.4×10-4). In the postpuberty age group, 1 SNP reached significance: rs1018148 (FBN1; P=2.2×10-5). In the genome-wide association study of all participants, no SNPs reached genome-wide significance. Higher polygenic risk score was associated with higher SBP percentile (ß, 0.35 [95% CI, 0.10-0.60)], and there was a significant interaction with age (P for interaction<0.01). Conclusions These findings suggest that genetic variants play an important role in SBP in childhood and adolescence and provide evidence for age-specific genetic associations with SBP.

Frequency of benign neutropenia among Black versus White individuals undergoing a bone marrow assessment.

Healthy individuals in the United States identified as having Black race have lower neutrophil counts, on average, than individuals identified as having White race, which could result in more negative diagnostic evaluations for neutropenia. To test this hypothesis, the proportion of evaluations where the final diagnosis was clinically insignificant neutropenia for Black and White individuals who underwent an evaluation by a haematologist that included a bone marrow (BM) biopsy to investigate neutropenia was assessed. 172 individuals without prior haematological diagnoses who underwent a haematological evaluation to investigate neutropenia. Individuals diagnosed with clinically insignificant neutropenia between Black and White individuals were compared using a propensity-score-adjusted logistic regression. Of 172 individuals, 42 (24%) were classified as Black race, 86 (50%) were males, and the 79 (46%) were over 18 years old. A BM biopsy did not identify pathology in 95% (40 of 42) of Black individuals and 68% (89 of 130) of White Individuals. Black individuals (25 of 42 [60%]) received a final diagnosis of clinically insignificant neutropenia, compared to White individuals (12 of 130 [9%]) (adjusted odds ratio =7.9, 95% CI: 3.1 - 21.1). We conclude that black individuals were more likely to receive a diagnosis of clinically insignificant neutropenia after haematological assessment.

Preoperative Predictors of Complex Regional Pain Syndrome Outcomes in the 6 Months Following Total Knee Arthroplasty.

This prospective observational study evaluated preoperative predictors of complex regional pain syndrome (CRPS) outcomes in the 6 months following total knee arthroplasty (TKA). Participants were n = 110 osteoarthritis patients (64.5% female) undergoing unilateral TKA with no prior CRPS history. Domains of negative affect (depression, anxiety, catastrophizing), pain (intensity, widespread pain, temporal summation of pain [TSP]), pain interference, sleep disturbance, and pro-inflammatory status (tumor necrosis factor-alpha [TNF-a]) were assessed preoperatively. CRPS outcomes at 6-week and 6-month follow-up included the continuous CRPS Severity Score (CSS) and dichotomous CRPS diagnoses (2012 IASP criteria). At 6 months, 12.7% of participants met CRPS criteria, exhibiting a "warm CRPS" phenotype. Six-week CSS scores were predicted by greater preoperative depression, anxiety, catastrophizing, TSP, pain intensity, sleep disturbance, and TNF-a (P's < .05). Provisional CRPS diagnosis at 6 weeks was predicted by higher preoperative TSP, sleep disturbance, and TNF-a (P's < .05). CSS scores at 6 months were predicted by more widespread and intense preoperative pain, and higher preoperative TSP, pain interference, and TNF-a (P's < .01). CRPS diagnosis at 6 months was predicted only by more widespread and intense pain preoperatively (P's < .05). Risk for CRPS following TKA appears to involve preoperative central sensitization and inflammatory mechanisms. Preoperative negative affect is unlikely to directly influence long-term CRPS risk. PERSPECTIVE: This article identifies preoperative predictors of CRPS features at 6 months following total knee arthroplasty, including more widespread pain and higher pain intensity, temporal summation of pain, pain interference, and tumor necrosis factor-alpha levels. Findings suggest the importance of central sensitization and inflammatory mechanisms in CRPS risk following tissue trauma.

Oxidative stress is associated with characteristic features of the dysfunctional chronic pain phenotype.

ABSTRACT: The dysfunctional chronic pain (Dysfunctional CP) phenotype is an empirically identifiable CP subtype with unclear pathophysiological mechanisms that cuts across specific medical CP diagnoses. This study tested whether the multidimensional pain and psychosocial features that characterize the dysfunctional CP phenotype are associated broadly with elevated oxidative stress (OS). Measures of pain intensity, bodily extent of pain, catastrophizing cognitions, depression, anxiety, sleep disturbance, pain interference, and function were completed by 84 patients with chronic osteoarthritis before undergoing total knee arthroplasty. Blood samples were obtained at the initiation of surgery before incision or tourniquet placement. Plasma levels of F2-isoprostanes and isofurans, the most highly specific measures of in vivo OS, were quantified using gas chromatography/negative ion chemical ionization mass spectrometry. The results indicated that controlling for differences in age, sex, and body mass index, higher overall OS (mean of isoprostanes and isofurans) was associated with significantly (P < 0.05) greater pain intensity, more widespread pain, greater depressive symptoms and pain catastrophizing, higher pain interference, and lower function. OS measures were not significantly associated with sleep disturbance or anxiety levels (P >0.10). The results build on prior case-control findings suggesting that presence of a CP diagnosis is associated with elevated OS, highlighting that it may specifically be individuals displaying characteristics of the dysfunctional CP phenotype who are characterized by elevated OS. Clinical implications of these findings remain to be determined.

Association Between a Common, Benign Genotype and Unnecessary Bone Marrow Biopsies Among African American Patients.

Importance: Up to two-thirds of African American individuals carry the benign rs2814778-CC genotype that lowers total white blood cell (WBC) count. Objective: To examine whether the rs2814778-CC genotype is associated with an increased likelihood of receiving a bone marrow biopsy (BMB) for an isolated low WBC count. Design, Setting, and Participants: This retrospective genetic association study assessed African American patients younger than 90 years who underwent a BMB at Vanderbilt University Medical Center, Mount Sinai Health System, or Children's Hospital of Philadelphia from January 1, 1998, to December 31, 2020. Exposure: The rs2814778-CC genotype. Main Outcomes and Measures: The proportion of individuals with the CC genotype who underwent BMB for an isolated low WBC count and had a normal biopsy result compared with the proportion of individuals with the CC genotype who underwent BMB for other indications and had a normal biopsy result. Results: Among 399 individuals who underwent a BMB (mean [SD] age, 41.8 [22.5] years, 234 [59%] female), 277 (69%) had the CC genotype. A total of 35 patients (9%) had clinical histories of isolated low WBC counts, and 364 (91%) had other histories. Of those with a clinical history of isolated low WBC count, 34 of 35 (97%) had the CC genotype vs 243 of 364 (67%) of those without a low WBC count history. Among those with the CC genotype, 33 of 34 (97%) had normal results for biopsies performed for isolated low WBC counts compared with 134 of 243 individuals (55%) with biopsies performed for other histories (P < .001). Conclusions and Relevance: In this genetic association study, among patients of African American race who had a BMB with a clinical history of isolated low WBC counts, the rs2814778-CC genotype was highly prevalent, and 97% of these BMBs identified no hematologic abnormality. Accounting for the rs2814778-CC genotype in clinical decision-making could avoid unnecessary BMB procedures.

The Partnership to Improve Diabetes Education Trial: a Cluster Randomized Trial Addressing Health Communication in Diabetes Care.

BACKGROUND: Effective type 2 diabetes care remains a challenge for patients including those receiving primary care in safety net settings. OBJECTIVE: The Partnership to Improve Diabetes Education (PRIDE) trial team and leaders from a regional department of health evaluated approaches to improve care for vulnerable patients. DESIGN: Cluster randomized controlled trial. PATIENTS: Adults with uncontrolled type 2 diabetes seeking care across 10 unblinded, randomly assigned safety net clinics in Middle TN. INTERVENTIONS: A literacy-sensitive, provider-focused, health communication intervention (PRIDE; 5 clinics) vs. standard diabetes education (5 clinics). MAIN MEASURES: Participant-level primary outcome was glycemic control [A1c] at 12 months. Secondary outcomes included select health behaviors and psychosocial aspects of care at 12 and 24 months. Adjusted mixed effects regression models were used to examine the comparative effectiveness of each approach to care. KEY RESULTS: Of 410 patients enrolled, 364 (89%) were included in analyses. Median age was 51 years; Black and Hispanic patients represented 18% and 25%; 96% were uninsured, and 82% had low annual income level (< $20,000); adequate health literacy was seen in 83%, but numeracy deficits were common. At 12 months, significant within-group treatment effects occurred from baseline for both PRIDE and control sites: adjusted A1c (- 0.76 [95% CI, - 1.08 to - 0.44]; P < .001 vs - 0.54 [95% CI, - 0.86 to - 0.21]; P = .001), odds of poor eating (0.53 [95% CI, 0.33-0.83]; P = .01 vs 0.42 [95% CI, 0.26-0.68]; P < .001), treatment satisfaction (3.93 [95% CI, 2.48-6.21]; P < .001 vs 3.04 [95% CI, 1.93-4.77]; P < .001), and self-efficacy (2.97 [95% CI, 1.89-4.67]; P < .001 vs 1.81 [95% CI, 1.1-2.84]; P = .01). No significant difference was observed between study arms in adjusted analyses. CONCLUSIONS: Both interventions improved the participant's A1c and behavioral outcomes. PRIDE was not more effective than standard education. Further research may elucidate the added value of a focused health communication program in this setting.

Provider Networks in the Neonatal Intensive Care Unit Associate with Length of Stay.

We strive to understand care coordination structures of multidisciplinary teams and to evaluate their effect on post-surgical length of stay (PSLOS) in the Neonatal Intensive Care Unit (NICU). Electronic health record (EHR) data were extracted for 18 neonates, who underwent gastrostomy tube placement surgery at the Vanderbilt University Medical Center NICU. Based on providers' interactions with the EHR (e.g. viewing, documenting, ordering), provider-provider relations were learned and used to build patient-specific provider networks representing the care coordination structure. We quantified the networks using standard network analysis metrics (e.g., in-degree, out-degree, betweenness centrality, and closeness centrality). Coordination structure effectiveness was measured as the association between the network metrics and PSLOS, as modeled by a proportional-odds, logistical regression model. The 18 provider networks exhibited various team compositions and various levels of structural complexity. Providers, whose patients had lower PSLOS, tended to disperse patient-related information to more colleagues within their network than those, who treated higher PSLOS patients (P = 0.0294). In the NICU, improved dissemination of information may be linked to reduced PSLOS. EHR data provides an efficient, accessible, and resource-friendly way to study care coordination using network analysis tools. This novel methodology offers an objective way to identify key performance and safety indicators of care coordination and to study dissemination of patient-related information within care provider networks and its effect on care. Findings should guide improvements in the EHR system design to facilitate effective clinical communications among providers.

Likelihood-based analysis of outcome-dependent sampling designs with longitudinal data.

The use of outcome-dependent sampling with longitudinal data analysis has previously been shown to improve efficiency in the estimation of regression parameters. The motivating scenario is when outcome data exist for all cohort members but key exposure variables will be gathered only on a subset. Inference with outcome-dependent sampling designs that also incorporates incomplete information from those individuals who did not have their exposure ascertained has been investigated for univariate but not longitudinal outcomes. Therefore, with a continuous longitudinal outcome, we explore the relative contributions of various sources of information toward the estimation of key regression parameters using a likelihood framework. We evaluate the efficiency gains that alternative estimators might offer over random sampling, and we offer insight into their relative merits in select practical scenarios. Finally, we illustrate the potential impact of design and analysis choices using data from the Cystic Fibrosis Foundation Patient Registry.

Extending the Case-Control Design to Longitudinal Data: Stratified Sampling Based on Repeated Binary Outcomes.

We detail study design options that generalize case-control sampling when longitudinal outcome data are already collected as part of a primary cohort study, but new exposure data must be retrospectively processed for a secondary analysis. Furthermore, we assume that cost will limit the size of the subsample that can be evaluated. We describe a novel class of stratified outcome-dependent sampling designs for longitudinal binary response data where distinct strata are created for subjects who never, sometimes, and always experienced the event of interest during longitudinal follow-up. Individual designs within this class are differentiated by the stratum-specific sampling probabilities. We show for parameters associated with time-varying exposures, subjects who experience the event/outcome at some but not at all of the follow-up times (i.e., those who exhibit response variation) are highly informative. If the time-varying exposure varies exclusively within individuals (i.e., intraclass correlation coefficient is 0), then sampling all subjects with response variability can yield highly precise parameter estimates even when compared with an analysis of the original cohort. The flexibility of the designs and analysis procedures also permits estimation of parameters that correspond to time-fixed covariates, and we show that with an imputation-based estimation procedure, baseline covariate associations can be estimated with very high precision irrespective of the design. We demonstrate features of the designs and analysis procedures via a plasmode simulation using data from the Lung Health Study.

Outcome-related, Auxiliary Variable Sampling Designs for Longitudinal Binary Data.

BACKGROUND: Epidemiologists have long used case-control and related study designs to enhance variability of response and information available to estimate exposure-disease associations. Less has been done for longitudinal data. METHODS: We discuss an epidemiological study design and analysis approach for longitudinal binary response data. We seek to gain statistical efficiency by oversampling relatively informative subjects for inclusion into the sample. In this methodological demonstration, we develop this concept by sampling repeatedly from an existing cohort study to estimate the relationship of chronic obstructive pulmonary disease to past-year smoking in a panel of baseline smokers. To account for oversampling, we describe a sequential offsetted regressions approach for valid inferences in this setting. RESULTS: Targeted sampling can lead to increased statistical efficiency when combined with sequential offsetted regressions. Efficiency gains are degraded with increased prevalence of the disease response variable, with decreased association between the sampling variable and the response, and with other design and analysis parameters, providing guidance to those wishing to use these types of designs in the future. CONCLUSIONS: These designs hold promise for efficient use of resources in longitudinal cohort studies.

High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial.

IMPORTANCE: Statins affect several mechanisms underlying acute kidney injury (AKI). OBJECTIVE: To test the hypothesis that short-term high-dose perioperative atorvastatin would reduce AKI following cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS: Double-blinded, placebo-controlled, randomized clinical trial of adult cardiac surgery patients conducted from November 2009 to October 2014 at Vanderbilt University Medical Center. INTERVENTIONS: Patients naive to statin treatment (n = 199) were randomly assigned 80 mg of atorvastatin the day before surgery, 40 mg of atorvastatin the morning of surgery, and 40 mg of atorvastatin daily following surgery (n = 102) or matching placebo (n = 97). Patients already taking a statin prior to study enrollment (n = 416) continued taking the preenrollment statin until the day of surgery, were randomly assigned 80 mg of atorvastatin the morning of surgery and 40 mg of atorvastatin the morning after (n = 206) or matching placebo (n = 210), and resumed taking the previously prescribed statin on postoperative day 2. MAIN OUTCOMES AND MEASURES: Acute kidney injury defined as an increase of 0.3 mg/dL in serum creatinine concentration within 48 hours of surgery (Acute Kidney Injury Network criteria). RESULTS: The data and safety monitoring board recommended stopping the group naive to statin treatment due to increased AKI among these participants with chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2) receiving atorvastatin. The board later recommended stopping for futility after 615 participants (median age, 67 years; 188 [30.6%] were women; 202 [32.8%] had diabetes) completed the study. Among all participants (n = 615), AKI occurred in 64 of 308 (20.8%) in the atorvastatin group vs 60 of 307 (19.5%) in the placebo group (relative risk [RR], 1.06 [95% CI, 0.78 to 1.46]; P = .75). Among patients naive to statin treatment (n = 199), AKI occurred in 22 of 102 (21.6%) in the atorvastatin group vs 13 of 97 (13.4%) in the placebo group (RR, 1.61 [0.86 to 3.01]; P = .15) and serum creatinine concentration increased by a median of 0.11 mg/dL (10th-90th percentile, -0.11 to 0.56 mg/dL) in the atorvastatin group vs by a median of 0.05 mg/dL (10th-90th percentile, -0.12 to 0.33 mg/dL) in the placebo group (mean difference, 0.08 mg/dL [95% CI, 0.01 to 0.15 mg/dL]; P = .007). Among patients already taking a statin (n = 416), AKI occurred in 42 of 206 (20.4%) in the atorvastatin group vs 47 of 210 (22.4%) in the placebo group (RR, 0.91 [0.63 to 1.32]; P = .63). CONCLUSIONS AND RELEVANCE: Among patients undergoing cardiac surgery, high-dose perioperative atorvastatin treatment compared with placebo did not reduce the risk of AKI overall, among patients naive to treatment with statins, or in patients already taking a statin. These results do not support the initiation of statin therapy to prevent AKI following cardiac surgery. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00791648.

Supervising anesthesiologists cannot be effectively compared according to their patients' postanesthesia care unit admission pain scores.

BACKGROUND: Measurement of postoperative pain scores on arrival to the postanesthesia care unit (PACU) is a potential quality metric for supervising anesthesiologists. Our goal in this study was to determine whether rank-ordering by initial PACU numeric rating scale (NRS) pain score, as collected by nurses in a nonresearch clinical setting, could be used to compare anesthesiologists after adjusting for confounding factors. METHODS: For a large population of adult patients, the admission PACU NRS pain scores (0-10) were evaluated using proportional odds mixed effects models. Fixed effects included age, gender, race, opioids in the preoperative medication list, American Society of Anesthesiologists (ASA) physical status classification, emergency surgery, laparoscopic approach, outpatient status, anesthesiologist, and PACU nurse; surgeon and surgical procedure were included as random effects. RESULTS: A total of 26,680 initial PACU pain scores were analyzed. The PACU nurse had the largest observed association with initial PACU pain score. Compared with the nurse with the median covariate adjusted NRS score, the odds ratio (OR) for an increased reported pain score ranged from 0.16 (95% confidence interval [CI] 0.11 to 0.24) to 2.95 (95% CI 2.43 to 3.59). For anesthesiologists, the ORs for an increase in reported pain ranged from 0.60 (95% CI 0.37 to 0.99) to 1.44 (95% CI 0.98 to 2.11). Factors associated with increased pain scores were preoperative opioids, female gender, and ASA physical status 2 and 3. Lower pain scores were associated with outpatient surgery, laparoscopy, African American race, and older patients. CONCLUSIONS: There is little to no evidence to suggest that supervising anesthesiologists can be compared with one another effectively using admission PACU NRS pain scores. The confounding association of the PACU nurse eliciting the admission pain score greatly exceeded the contribution by the anesthesiologist.

Etomidate use and postoperative outcomes among cardiac surgery patients.

BACKGROUND: Although a single dose of etomidate can cause relative adrenal insufficiency, the impact of etomidate exposure on postoperative outcomes is unknown. The objective of this study was to examine the association between a single induction dose of etomidate and clinically important postoperative outcomes after cardiac surgery. METHODS: The authors retrospectively examined the association between etomidate exposure during induction of anesthesia and postoperative outcomes in patients undergoing cardiac surgery from January 2007 to December 2009 by using multivariate logistic regression analyses and Cox proportional hazards regression analyses. Postoperative outcomes of interest were severe hypotension, mechanical ventilation hours, hospital length of stay, and in-hospital mortality. RESULTS: Sixty-two percent of 3,127 patients received etomidate. Etomidate recipients had a higher incidence of preoperative congestive heart failure (23.0 vs. 18.3%; P = 0.002) and a lower incidence of preoperative cardiogenic shock (1.3 vs. 4.0%; P < 0.001). The adjusted odds ratio for severe hypotension and in-hospital mortality associated with receiving etomidate was 0.80 (95% CI, 0.58-1.09) and 0.75 (95% CI, 0.45-1.24), respectively, and the adjusted hazard ratio for time to mechanical ventilation removal and time to hospital discharge was 1.10 (95% CI, 1.00-1.21) and 1.07 (95% CI, 0.97-1.18), respectively. Propensity score analysis did not change the association between etomidate use and postoperative outcomes. CONCLUSIONS: In this study, there was no evidence to suggest that etomidate exposure was associated with severe hypotension, longer mechanical ventilation hours, longer length of hospital stay, or in-hospital mortality. Etomidate should remain an option for induction of anesthesia in cardiac surgery patients.

Association of brief health literacy screening and blood pressure in primary care.

Health literacy impacts health outcomes. However, the relationship to blood pressure is inconsistent. This study aimed to determine whether health literacy, assessed by clinic staff, is associated with blood pressure among patients with hypertension. The design was a cross-sectional study of a large sample of primary care patient encounters in 3 academic medical center clinics in Nashville, Tennessee. Health literacy was assessed using the Brief Health Literacy Screen, with higher scores indicating higher health literacy. Blood pressure was extracted from the electronic health record. Using 23,483 encounters in 10,644 patients, the authors examined the association of health literacy with blood pressure in multivariable analyses, adjusting for age, gender, race, education, and clinic location. Independent of educational attainment, 3-point increases in health literacy scores were associated with 0.74 mmHg higher systolic blood pressure (95% CI [0.38, 1.09]) and 0.30 mmHg higher diastolic blood pressure (95% CI [0.08, 0.51]). No interaction between education and health literacy was observed (p = .91). In this large primary care population of patients with hypertension, higher health literacy, as screened in clinical practice, was associated with a small increase in blood pressures. Future research is needed to explore this unexpected finding.

Duration of upper and lower extremity peripheral nerve blockade is prolonged with dexamethasone when added to ropivacaine: a retrospective database analysis.

BACKGROUND: Dexamethasone, when added to local anesthetics, has been shown to prolong the duration of peripheral nerve blocks; however, there are limited studies utilizing large numbers of patients. The purpose of this study was to examine the effect of adding dexamethasone to ropivacaine on duration of nerve blocks of the upper and lower extremity. METHODS: We reviewed 1,040 patient records collected in an orthopedic outpatient surgery center that had received an upper or lower extremity peripheral nerve block with ropivacaine 0.5% with or without dexamethasone and/or epinephrine. The primary outcome was duration of analgesia in upper or lower extremity blocks containing dexamethasone as an adjunct. Secondary outcomes included postoperative patient pain scores, satisfaction, and the incidence of block related complications. Linear and ordinal logistic regression models were used to examine the independent effect of dexamethasone on outcomes. RESULTS: Dexamethasone was observed to increase median block duration by 37% (95% confidence interval: 31-43%). The increased block duration persisted within body regions (upper and lower) and across a range of block types. Dexamethasone was also observed to reduce pain scores on the day of surgery (P = 0.001) and postoperative day 1 (P < 0.001). There was no significant difference in duration of nerve blocks when epinephrine (1:400,000) was added to 0.5% ropivacaine with or without dexamethasone. CONCLUSION: The addition of dexamethasone to 0.5% ropivacaine prolongs the duration of peripheral nerve blocks of both the upper and lower extremity.

An analysis of risk factors for patient complaints about ambulatory anesthesiology care.

BACKGROUND: Anesthesiology groups continually seek data sources and evaluation metrics for ongoing professional practice evaluation, credentialing, and other quality initiatives. The analysis of patient complaints associated with physicians has been previously shown to be a marker for patient dissatisfaction and a predictor of malpractice claims. Additionally, previous studies in other specialties have revealed a nonuniform distribution of complaints among professionals. In this study, we describe the distribution of complaints among anesthesia providers and identify factors associated with complaint risk in pediatric and adult populations. METHODS: We performed an analysis of a complaint database for an academic medical center. Complaints were recorded as comments during postoperative telephone calls to ambulatory surgery patients regarding the quality of their anesthesiology care. Calls between July 1, 2006 and June 30, 2010 were included. Risk factors were grouped into 3 categories: patient demographics, procedural, and provider characteristics. RESULTS: A total of 22,871 calls placed on behalf of 120 anesthesiologists were evaluated, of which 307 yielded a complaint. There was no evidence of provider-to-provider heterogeneity in complaint risk in the pediatric population. In the adult population, an unadjusted test for the random intercept variance component in the mixed effects model pointed toward significant heterogeneity (P = 0.01); however, after adjusting for a prespecified set of risk factors, provider-to-provider heterogeneity was no longer observed (P = 0.20). Several risk factors exhibited evidence for complaint risk. In the pediatric patient model, risk factors associated with complaint risk included a 10-year change in age, the use of general anesthesia (versus not), and a 1-hour change in the actual minus scheduled start times. Odds ratios were 1.47 (95% confidence interval (CI), 1.04-2.08), 0.22 (95% CI, 0.07-0.62), and 1.27 (95% CI, 1.10-1.47), respectively. In the adult patient model, risk factors associated with complaint risk included male gender, general anesthesia, a 10-year change in provider experience, and speaking with the patient (rather than a family member). Odd ratios were 0.66 (95% CI, 0.47-0.92), 0.67 (95% CI, 0.47-0.95), 1.18 (95% CI, 1.01-1.38), and 1.96 (95% CI, 1.17-3.29), respectively. CONCLUSIONS: There was apparent evidence in adult patients to suggest heterogeneity in provider risk for a patient complaint. However, once patient, procedural, and provider factors were acknowledged in analyses, such evidence for heterogeneity is diminished substantially. Further study into how and why these factors are associated with greater complaint risk may reveal potential interventions to decrease complaints.

Obesity and oxidative stress predict AKI after cardiac surgery.

Obesity increases oxidative stress, endothelial dysfunction, and inflammation, but the effect of obesity on postoperative AKI is not known. We examined the relationship between body mass index (BMI) and AKI in 445 patients undergoing cardiac surgery and whether oxidative stress (F(2)-isoprostanes), inflammation (IL-6), or antifibrinolysis (plasminogen activator inhibitor-1 [PAI-1]) contribute to any identified relationship. Overall, 112 (25%) of the 445 patients developed AKI. Higher BMI was independently associated with increased odds of AKI (26.5% increase per 5 kg/m(2) [95% confidence interval, 4.3%-53.4%]; P=0.02). Baseline F(2)-isoprostane (P=0.04), intraoperative F(2)-isoprostane (P=0.003), and intraoperative PAI-1 (P=0.04) concentrations also independently predicted AKI. BMI no longer predicted AKI after adjustment for the effect of F(2)-isoprostanes, suggesting that obesity may affect AKI via effects on oxidative stress. In contrast, adjustment for IL-6 or PAI-1 did not substantially alter the association between BMI and AKI. Further, deconstruction of the obesity-AKI relationship into direct (i.e., independent of candidate pathways) and indirect (i.e., effect of BMI on AKI via each candidate pathway) effects indicated that F(2)-isoprostanes, but not IL-6 or PAI-1, partially mediate the relationship between obesity and AKI (P=0.001). In conclusion, obesity independently predicts AKI after cardiac surgery, and oxidative stress may partially mediate this association.

The impact of peripheral nerve techniques on hospital stay following major orthopedic surgery.

OBJECTIVE: To determine the impact of regional anesthesia on hospital stay for selected orthopedic procedures compared with traditional pain control modalities. DESIGN: In an era of an increasing volume of orthopedic surgeries, pain modalities that can optimize patient care while minimizing hospital length of stay can have an impact on reducing hospital costs as well as increasing patient satisfaction and improving patient outcomes. Previous studies have shown the potential benefits of regional anesthesia over traditional intravenous (IV) narcotics in meeting these goals in selected orthopedic procedures. METHODS: We retrospectively analyzed the medical records of 494 patients who underwent major orthopedic procedures performed with traditional postoperative pain management alone (IV patient-controlled analgesia and oral narcotics), single injection peripheral nerve block (PNB), and continuous peripheral nerve block (CPNB) in order to determine the impact that different pain modalities might have on hospital length of stay. RESULTS: When compared with traditional pain control modalities, single PNB and CPNB were associated with decreased length of hospital stay, though results for specific surgeries varied. The hazard ratios for hospital discharge from a Current Procedural Terminology code-stratified, covariate (age, gender, and ASA status) adjusted Cox proportional hazards model for single PNB vs no PNB and for CPNB vs no PNB were 1.35 (95% confidence interval: 1.02-1.79) and 1.91 (95% confidence interval: 1.42-2.57), respectively, pointing toward earlier hospital discharge when PNBs were used. CONCLUSIONS Our retrospective case review showed that, overall, hospital lengths of stay tended to be shorter for orthopedic surgery patients receiving single PNB and CPNB than for those receiving no block and traditional pain management.