David Childers

Maternal physiologic parameters in relationship to systemic inflammatory response syndrome criteria: a systematic review and meta-analysis.

OBJECTIVE: To establish the normal maternal range in healthy pregnant women for each component of the systemic inflammatory response syndrome (SIRS) criteria and compare these ranges with existing SIRS criteria. DATA SOURCES: PubMed, Embase, and ClinicalTrials.gov databases were searched to identify studies of healthy parturients from the first trimester through 12 weeks postpartum that reported maternal temperature, respiratory rate, PaCO2, heart rate, white blood cell count data, or a combination of these. METHODS OF STUDY SELECTION: Data were extracted from studies providing maternal values for components of SIRS criteria. The mean, standard deviation, and two standard deviations from the mean for all criteria parameters published in the literature were reported. TABULATION, INTEGRATION, AND RESULTS: Eighty-seven studies met inclusion criteria and included 8,834 patients and 15,237 data points: temperature (10 studies and 2,367 patients), respiratory rate (nine studies and 312 patients), PaCO2 (12 studies and 441 patients), heart rate (39 studies and 1,374 patients), and white blood cell count (23 studies and 4,553 patients). Overlap with SIRS criteria occurred in healthy pregnant women during the second trimester, third trimester, and labor for each of the SIRS criteria except temperature. Every mean value for PaCO2 during pregnancy (and up to 48 hours postpartum) was below 32 mm Hg. Two standard deviations above the mean for temperature, respiratory rate, and heart rate were 38.1°C, 25 breaths per minute, and 107 beats per minute, respectively. CONCLUSION: Current SIRS criteria often overlap with normal physiologic parameters during pregnancy and the immediate postpartum period; thus, alternative criteria must be developed to diagnose maternal sepsis.

Risk Factors for Developing Thyroid-Associated Ophthalmopathy Among Individuals With Graves Disease

IMPORTANCE Thyroid-associated ophthalmopathy (TAO) is a common and debilitating manifestation of Graves disease (GD). Presently little is known about factors that may increase the risk of developing TAO among patients with GD. OBJECTIVE To identify risk factors associated with the development of TAO among individuals with newly diagnosed GD. DESIGN, SETTING, AND PARTICIPANTS In this longitudinal cohort study, all beneficiaries 18 years of age or older with newly diagnosed GD who were continuously enrolled in a large nationwide US managed care network and who visited an eye care professional 1 or more times from 2001 to 2009 were identified. International Classification of Diseases, Ninth Revision, Clinical Modification billing codes were used to identify those who developed manifestations of TAO. Multivariable Cox regression was used to determine the hazard of developing TAO among persons with newly diagnosed GD, with adjustment for sociodemographic factors, systemic medical conditions, thyrotropin levels, and medical and surgical interventions for management of hyperthyroidism. MAIN OUTCOMES AND MEASURES Manifestations of TAO measured by hazard ratios (HRs) with 95% CIs. RESULTS Of 8404 patients with GD who met the inclusion criteria, 740 (8.8%) developed TAO (mean follow-up, 374 days since initial GD diagnosis). After adjustment for potential confounders, surgical thyroidectomy, alone or in combination with medical therapy, was associated with a 74% decreased hazard for TAO (adjusted HR, 0.26 [95% CI, 0.12-0.51]) compared with radioactive iodine therapy alone. Statin use (for ≥60 days in the past year vs <60 days or nonuse) was associated with a 40% decreased hazard (adjusted HR, 0.60 [CI, 0.37-0.93]). No significant association was found for the use of nonstatin cholesterol-lowering medications or cyclooxygenase 2 inhibitors and the development of TAO. CONCLUSIONS AND RELEVANCE If prospective studies can confirm our finding that a thyroidectomy and statin use are associated with substantially reduced hazards for TAO among patients with GD, preventive measures for this burdensome manifestation of GD may become a reality.

Association of Geroprotective Effects of Metformin and Risk of Open-Angle Glaucoma in Persons With Diabetes Mellitus

IMPORTANCE Caloric restriction mimetic drugs have geroprotective effects that delay or reduce risks for a variety of age-associated systemic diseases, suggesting that such drugs might also have the potential to reduce risks of blinding ophthalmologic conditions for which age is a major risk factor. OBJECTIVE To determine whether the caloric restriction mimetic drug metformin hydrochloride is associated with reduced risk of open-angle glaucoma (OAG) in persons with diabetes mellitus. DESIGN, SETTING, AND PATIENTS Retrospective cohort study of patients aged 40 years or older with diabetes mellitus and no preexisting record of OAG in a large US managed care network from January 1, 2001, through December 31, 2010. EXPOSURES Quantity of metformin and other prescribed diabetes medications as captured from outpatient pharmacy records. MAIN OUTCOMES AND MEASURES Risk of developing OAG. RESULTS Of 150 016 patients with diabetes mellitus, 5893 (3.9%) developed OAG. After adjusting for confounding factors, those prescribed the highest quartile of metformin hydrochloride (>1110 g in 2 years) had a 25% reduced OAG risk relative to those who took no metformin (hazard ratio = 0.75; 95% CI, 0.59-0.95; P = .02). Every 1-g increase in metformin hydrochloride use was associated with a 0.16% reduction in OAG risk (adjusted hazard ratio = 0.99984; 95% CI, 0.99969-0.99999; P = .04), which predicts that taking a standard dose of 2 g of metformin hydrochloride per day for 2 years would result in a 20.8% reduction in risk of OAG. After accounting for potential confounders, including metformin and diabetic medications, the risk of developing OAG was increased by 8% (hazard ratio = 1.08; 95% CI, 1.03-1.13; P = .003) for each unit of increase in glycated hemoglobin level. CONCLUSIONS AND RELEVANCE Metformin use is associated with reduction in risk of developing OAG, and risk is reduced even when accounting for glycemic control in the form of glycated hemoglobin level. Other diabetes medications did not confer a similar OAG risk reduction. This study suggests that metformin may be affecting OAG risk on multiple levels, some involving improved glycemic control and some involving mechanisms outside glycemic control such as neurogenesis, inflammatory systems, or longevity pathways targeted by caloric restriction mimetic drugs. If confirmed by prospective clinical trials, these findings could lead to novel treatments for this sight-threatening disease.

Postoperative spine and VEPTR infections in children: a case-control study.

Background: Surgical site infection (SSI) after pediatric scoliosis surgery is a major cause of morbidity. We compared the odds ratios of various potential risk factors for infection among patients who developed a deep SSI following spinal deformity surgery and those who remained infection free. Methods: This was a case-control study, not a matched study. More noninfection cases (50) than infection cases (20) were selected because more were available. Twenty children with a deep SSI after scoliosis surgery were compared with 50 similar children who did not develop a deep SSI. Fourteen perioperative factors were examined in both the groups. Results: Of the 20 patients who had a deep SSI, 14 had neuromuscular scoliosis. In the infected group, 6 patients had undergone vertical expandable prosthetic titanium rib placement, 2 had undergone growing rod insertion, and 12 had undergone posterior spinal fusion. Eighteen patients developed a SSI within 1 year of the operation and 2 patients presented with a SSI >1 year after surgery. Sixteen patients had positive cultures. Majority were skin flora: coagulase-negative Staphylococcus (8) and Propionibacterium acnes (4). Both patients with tracheostomies had Enterococcus faecalis infections. When comparing the 20 patients with deep SSI to the 50 controls, increased preoperative Cobb angle (P=0.011), increased postoperative Cobb angle (P=0.0043), nonambulatory status (P=0.0002), and increased length of stay (P=0.015) were associated with significantly increased odds of infection. Conclusions: Our study shows that patients with neuromuscular scoliosis are at higher risk of developing a deep SSI after spinal deformity surgery. Skin flora is a common cause of deep SSI. We have now instituted a standard skin preparation protocol to include alcohol and chlorhexidine washes the night before and the morning of surgery. We have altered our prophylactic antibiotic regimen to cover skin flora in all patients and gastrointestinal flora in patients with a tracheostomy. We have counseled the families of nonambulatory children with large neuromuscular curves regarding the significantly increased odds of postoperative deep SSI. Level of Evidence: Level III.

Characteristics and In-Hospital Outcomes of Peripartum Cardiomyopathy Diagnosed During Delivery in the United States From the Nationwide Inpatient Sample (NIS) Database

BACKGROUND Peripartum cardiomyopathy (PPCM) is associated with advanced maternal age, African-American race, hypertensive disorders of pregnancy, and multiple-gestation pregnancies. Less is known regarding racial differences in risk factors and predictors of adverse in-hospital outcomes. METHODS AND RESULTS A total of 1,337 women with PPCM were identified with the use of the Nationwide Inpatient Sample (2004-2011). Clinical profiles and maternal outcomes in delivering mothers with and without PPCM were compared and stratified by race. In multivariate analysis, established risk factors for PPCM were confirmed. Anemia (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.6-2.5; P < .0001), asthma (OR 2.2, 95% CI 1.5-3.2; P = .0002), smoking (OR 33.6, 95% CI 9.3-159.4; P < .0001), and thyroid disease (OR 5.9; 95% CI 1.5-21.3; P = .01) were associated with PPCM. Risk factors significant in whites, African Americans, and Hispanics were hypertension during pregnancy and anemia. Patients with PPCM had higher rates of in-hospital adverse outcomes (P < .0001), but no differences in race or comorbidities predicted adverse events. CONCLUSIONS Hypertensive disorders during pregnancy and anemia were associated with PPCM in whites, African Americans, and Hispanics, providing further evidence that vascular stress may play a role in the pathogenesis of PPCM. Thyroid disorders may represent a novel risk factor for PPCM.

Gauging interest of the general public in laser-assisted in situ keratomileusis eye surgery.

Purpose: To assess interest among members of the general public in laser-assisted in situ keratomileusis (LASIK) surgery and how levels of interest in this procedure have changed over time in the United States and other countries. Methods: Using the Google Trends Web site, we determined the weekly frequency of queries involving the term “LASIK” from January 1, 2007, through January 1, 2011, in the United States, United Kingdom, Canada, and India. We fit separate regression models for each of the countries to assess whether residents of these countries differed in their querying rates on specific dates and over time. Similar analyses were performed to compare 4 US states. Additional regression models compared general public interest in LASIK surgery before and after the release of a 2008 Food and Drug Administration report describing complaints associated with this procedure. Results: During 2007 to 2011, the Google query rate for “LASIK” was highest among persons residing in India, followed by the United Kingdom, Canada, and the United States. During this time period, the query rate declined by 40% in the United States, 24% in India, and 22% in the United Kingdom, and it increased by 8% in Canada. In all 4 of the US states examined, the query rate declined—by 52% in Florida, 56% in New York, 54% in Texas, and 42% in California. Interest in LASIK declined further among US citizens after the Food and Drug Administration report release. Conclusions: Interest among the general public in LASIK surgery has been waning in recent years.

Congenital scoliosis SRS-22 outcomes in children treated with observation, surgery, and VEPTR.

Study Design. Prospective, nonrandomized study of children with congenital scoliosis. Objective. To determine the outcomes of children with congenital scoliosis using SRS-22. Summary of Background Data. Outcome measures in children with congenital scoliosis are unreported. Novel treatments such as VEPTR (vertical expandable prosthetic titanium rib) must show positive patient-reported outcomes during treatment because improvement in pulmonary function has not been demonstrated. Methods. Patients with congenital scoliosis were prospectively enrolled and divided into 3 groups: children under observation (OBSERVATION), children who had surgery (SURGICAL), and children treated with VEPTR (VEPTR). The SRS-22 questionnaire reports 6 domains: Total, Function, Mental Health, Image, Satisfaction, and Pain. SRS-22 questionnaires were prospectively collected from 184 OBSERVATION patients, 27 SURGICAL patients, and 22 VEPTR patients. Because of repeated measurement on each patient, the observations cannot be assumed to be independent. To account for this dependence, linear mixed models were used. Results. OBSERVATION scores were near normal in all domains. Initial postoperative scores for Function and Pain decreased for the SURGICAL group and subsequently Total, Function, Image, and Satisfaction scores increased. Initial postoperative VEPTR scores in Mental Health and Pain decreased and Total, Function, and Image scores increased during subsequent visits. Conclusion. Children with congenital scoliosis had SRS-22 scores that compare favorably with scores reported in the literature for adolescent idiopathic scoliosis. For SURGICAL and VEPTR patients with congenital scoliosis, SRS-22 Total, Function, and Image scores increased over time. Function, Image, and Pain require focus in children with congenital scoliosis. This is the first study that documents improvement in outcomes of VEPTR patients while in treatment. Level of Evidence: 2

Functional Data Analysis for Biomechanics

The application of nonlinear tools and advanced statistical methods is becoming more prevalent in biomechanical analyses. In a traditional biomechanics laboratory with motion analysis equipment, large amounts of kinematic data can be collected relatively easily. However, a significant gap exists between all the data that are collected and the data that are actually analyzed. Because movements occur over a period of time, whether seconds or minutes, each movement is represented by a continuous series of kinematic data (e.g., 60 or 120 observations per second). Using standard analytic methods, the continuous data associated with each movement are often reduced to a single discrete number. This reduction to a single summary value, such as a peak flexion, extension, or range of motion, excludes potentially valuable information. Reducing a curve representing hip motion during gait to a single range of motion value, for example, precludes the analysis of the entire movement pattern or the timing of the movement. A handful of investigations have recognized this limitation and have begun using functions to maintain the shape and timing of the movement in the analysis. The primary purpose of this chapter is to introduce an emerging collection of statistical methods called Functional Data Analysis (FDA). FDA is distinct from traditional analytic methods because how data changes continuously over time can be assessed. Therefore, information in continuous signals can be retained, such as changes in joint angles or in landmark positions during a movement task. FDA can be used for both exploratory and hypothesis driven analyses with traditional multivariate statistical methods that have been modified for functional predictor and response variables. Although representing motion data as a set of functions is not new to biomechanics analyses (Chester & Wrigley, 2008; Deluzio & Astephen, 2007; Landry et al., 2007; Lee et al., 2009; Sadeghi et al., 2002; 2000), statistical methods developed specifically for analyzing these functions have not been available. More recently, FDAmethods have been usedwithin biomechanics to studymastication (Crane et al., 2010), back pain (Page et al., 2006), as well as age, gender, and speed effects on walking (Roislien et al., 2009). Given the interest in and need for treating motion data as functions, it is important that methods for analyzing a set a functions using emerging statistical methods are brought to the attention of those in the biomechanics community. Although several excellent references exist for Functional Data Analysis (Ramsay, 2000; Ramsay et al., 2009; Ramsay & Silverman, 2002; 2005) there are important issues for biomechanists to be aware of when implementing this set of statistical tools. Therefore, the aims of this chapter are to provide an overview of the steps associated with FDA, to focus on 4

Reliable Exclusion of Acute Coronary Syndrome Among Hospitalized Patients With Elevated Troponin

Elevated cardiac troponin I (cTnI) occurs in acute coronary syndrome (ACS) as well as various scenarios not associated with ACS.