Machine learning based DNA melt curve profiling enables automated novel genotype detection.

Surveillance for genetic variation of microbial pathogens, both within and among species, plays an important role in informing research, diagnostic, prevention, and treatment activities for disease control. However, large-scale systematic screening for novel genotypes remains challenging in part due to technological limitations. Towards addressing this challenge, we present an advancement in universal microbial high resolution melting (HRM) analysis that is capable of accomplishing both known genotype identification and novel genotype detection. Specifically, this novel surveillance functionality is achieved through time-series modeling of sequence-defined HRM curves, which is uniquely enabled by the large-scale melt curve datasets generated using our high-throughput digital HRM platform. Taking the detection of bacterial genotypes as a model application, we demonstrate that our algorithms accomplish an overall classification accuracy over 99.7% and perform novelty detection with a sensitivity of 0.96, specificity of 0.96 and Youden index of 0.92. Since HRM-based DNA profiling is an inexpensive and rapid technique, our results add support for the feasibility of its use in surveillance applications.

Estimating the influence of maternal height on under-five mortality in Nigeria.

This study uses a nationally representative data sample to assess the effect of maternal height as an intergenerational influence on under-five mortality. Data from the 2003 and 2008 Nigerian Demographic Health Survey (NDHS) (n = 41,005) selecting women aged 15 to 49 yrs whose most recent births were within 5 years (n = 23,568), were analyzed. The outcome measure was under-five mortality. Independent variables included maternal height categorized as > or = 63 inch, 61-62.9 inch, 59.1-60.9 inch, < 59.1 inch. Confounding factors were controlled for. A multivariable logistic regression was used to obtain odds ratio estimates along with their respective confidence interval. After adjusting for confounding factors, we found that each 1 inch increase in maternal height, was associated with a decreased odds of mortality OR 0.98 (95% CI 0.97-0.99). The OR of under-five mortality when comparing women > or = 63 inch versus women < 59.1 inch was 1.13 (95% CI 0.98-1.31). The population attributable fraction of child death due to maternal short stature was 0.36.

Surgical management of esophageal diverticulum: a review of the Nationwide Inpatient Sample database.

BACKGROUND: Esophageal diverticulum is rare in the United States. The mainstay treatment of symptomatic esophageal diverticulum is surgical correction. Much of the available information regarding esophageal diverticulum and its surgical management has been derived from small studies and institutional reviews. Our study objective was to investigate the demographics, perioperative conditions, and predictors of outcomes after surgical treatment of acquired esophageal diverticulum using a nationally representative database. METHODS: A retrospective review using the Nationwide Inpatient Sample database from 2000-2009 was performed for patients with acquired esophageal diverticulum. The patients were stratified into Zenker's diverticulum (ZD) or non-Zenker's diverticulum (NZD) subgroups. The covariates retrieved included age, gender, ethnicity, insurance type, and Charlson comorbidity index. A multivariate analysis was performed to determine the predictors of postoperative morbidity. Discharge-level weights were applied. RESULTS: Overall, a total of 4253 patients met our inclusion criteria, 3197 (75%) with ZD and 1056 (25%) with NZD. In the ZD group, the mean age was 73 ± 12.3 y, and most were men (55%) and white (67%). The mean length of stay was 5.82 ± 8.08 d, and the mortality rate was 1.2%. The most common complication was septicemia or sepsis (2.0%). The black patients had higher odds of postoperative morbidity than the white patients (odds ratio [OR] 2.29, 95% confidence interval [CI] 1.02-5.17). The risk of overall postoperative morbidity was 52% greater for women (OR 1.52, 95% CI 1.01-2.29). An increasing Charlson comorbidity index was an independent predictor of morbidity. In the NZD group, the mean age was 69 ± 13.9 y, and most were also men (51%) and white (63%). The mean length of stay was 8.13 ± 10.56 d, and the mortality rate was 1.6%. The most common complication was air leak (3.1%). The black and Hispanic patients had higher odds of postoperative morbidity than the white patients (OR 1.97, 95% CI 1.05-3.72 and OR 2.37, 95% CI 1.06-5.30, respectively). An increasing Charlson comorbidity index was an independent predictor of morbidity. Compared with laparoscopy, the risk of developing postoperative morbidity was higher with the thoracotomy procedure (OR 7.45, 95% CI 1.11-50.18). CONCLUSIONS: Using a nationally representative database, our study found that female gender, black race, and the presence of comorbidities were associated with increased postoperative morbidity among patients with ZD. Among the patients with NZD, black and Hispanic patients had worse postoperative morbidity than the white patients, and the presence of comorbidities was associated with increased postoperative morbidity. Thoracotomy for the correction of NZD was associated with increased postoperative morbidity compared with the laparoscopic approach.

Plasma Biomarker for Post-concussive Syndrome: A Pilot Study Using an Alternating Current Electro-Kinetic Platform.

Background: Technology platforms that afford biomarker discovery in patients suffering from traumatic brain injury (TBI) remain an unmet medical need. Here, we describe an observational pilot study to explore the utility of an alternating current electrokinetic (ACE) microchip device in this context. Methods: Blood samples were collected from participating subjects with and without minor TBI. Plasma levels of glial fibrillary acidic protein (GFAP), Tau, ubiquitin C-terminal hydrolase L1 (UCH-L1), and cell-free DNA (cfDNA) were determined in subjects with and without minor TBI using ACE microchip device followed by on-chip immunofluorescent analysis. Post-concussive symptoms were assessed using the Rivermead Post Concussion Symptoms Questionnaire (RPCSQ) at one-month follow-up. Results: Highest levels of GFAP, UCH-L1, and Tau were seen in two minor TBI subjects with abnormality on head computed tomography (CT). In patients without abnormal head CT, Tau and GFAP levels discriminated between plasma from minor-TBI and non-TBI patients, with sensitivity and specificity of 64-72 and 50%, respectively. Plasma GFAP, UCH-L1, and Tau strongly correlated with the cumulative RPCSQ score. Plasma UCH-L1 and GFAP exhibited highest correlation to sensitivity to noise and light (r = 0.96 and 0.91, respectively, p < 0.001). Plasma UCH-L1 and Tau showed highest correlation with headache (r = 0.74 and 0.78, respectively, p < 0.001), sleep disturbance (r = 0.69 and 0.84, respectively, p < 0.001), and cognitive symptoms, including forgetfulness (r = 0.76 and 0.74, respectively, p < 0.001), poor concentration (r = 0.68 and 0.76, respectively, p < 0.001), and time required for information processing (r = 0.77 and 0.81, respectively, p < 0.001). cfDNA exhibited a strong correlation with depression (r = 0.79, p < 0.01) and dizziness (r = 0.69, p < 0.01). While cfDNA demonstrated positive correlation with dizziness and depression (r = 0.69 and 0.79, respectively, p < 0.001), no significant correlation was observed between cumulative RPCSQ and cfDNA (r = 0.07, p = 0.81). Conclusion: We provide proof-of-principle results supporting the utility of ACE microchip for plasma biomarker analysis in patients with minor TBI.

An Age-Based Analysis of Pediatric Melanoma: Staging, Surgery, and Mortality in the Surveillance, Epidemiology, and End Results Database.

The pediatric melanoma population is not well described, and current guidelines for their management are not well defined. Our study aims to identify this population, treatment modalities, and outcomes using a national population-based database. We reviewed the Surveillance, Epidemiology, and End Results database (2004-2008). Patients ≤21 years old with melanoma were included and grouped into ≤12 years of age, 13 to 18 years, and 19 to 21 years. Clinical characteristics were analyzed across the groups. A total of 1255 patients were included: 52.7 per cent were 19 to 21 years of age, 36.3 per cent were 13 to 18 years of age, and 11.0 per cent were ≤12 years of age. The 19- to 21-year-olds had the highest proportion of stage I (50.5%) versus ≤12 years of age (31.9%); the ≤12-year-olds had the highest proportion of stage IV (3.6%) versus 19 to 21 years of age (0.9%), P < 0.001. The 19- to 21-year-olds had the highest proportion receiving wide local excisions only (34.8%) versus ≤12 years of age (26.4%); the ≤12-year-olds had the highest proportion of patients without any surgeries (16.0%) versus 13 to 18 years of age (9.4%), P = 0.169. On adjusted analysis, the 19- to 21-year-olds had worse survival compared with ≤12 years of age (hazard ratio: 5.26, P = 0.017, 95% confidence interval 1.34-20.65). Disparities were found in the ≤12-year-old melanoma population, as they had later stage melanomas, less invasive surgery, and lower survival. Clearer prognostic factors are needed to better elucidate their management.

Trauma associated splenic artery aneurysms: an analysis of the National Trauma Data Bank.

BACKGROUND: Trauma associated splenic artery aneurysm (SAA) is potentially life threatening and infrequently studied. We evaluated the subject using a large trauma database. METHODS: The National Trauma Data Bank (2002 to 2006) was queried. All patients aged greater than or equal to 18 years with a primary diagnosis of SAA (International Classification of Diseases: Ninth Revision code 442.83) were identified. Data on demographics, injury severity, pre-existing comorbidities, surgical interventions, complications, and mortality were analyzed. RESULTS: One hundred twenty-four patients were included with a mean age of 40 ± 13 years and 72% were male. Mean Injury Severity Score was 24 ± 12. All patients suffered blunt trauma, and 5% of the patients (n = 6) had systolic blood pressure less than 90 mm Hg on arrival. The most frequent interventions were surgical ligation of aneurysm (45%), bronchoscopy (35%), endovascular procedures (27%), splenectomy (27%), and thoracostomy tube (25%). About 1.7% developed pulmonary collapse. Mean length of stay was 13 days and mortality was 1.6%. CONCLUSIONS: Trauma associated SAA has low mortality and most patients require surgical intervention. Pulmonary dysfunction and invasive pulmonary procedures are frequent despite low rate of chest injuries possibly due to anatomic proximity of lung and spleen.

African-American Men with Low-Risk Prostate Cancer: Modern Treatment and Outcome Trends.

OBJECTIVE: To investigate the clinical characteristics and treatment patterns for African-American (AA) men with low-risk prostate cancer (PCa) using a national, population-based dataset. METHODS: We conducted a retrospective review of the Surveillance Epidemiology and End Results database 2004-2008. AA men aged ≥40 years with low-risk PCa were identified. For comparison, white men were selected using the same selection criteria. We reviewed all recorded treatment modalities. Definitive treatment (DT) was defined as undergoing radiotherapy or prostatectomy. RESULTS: Overall, 7246 AA men and 47,154 white men met the criteria. Most of the patients had PSA level between 4.1 and 6.9 ng/mL (56.2 %) and received DT (76 %). Black men were younger (mean age: 62(±8) vs. 65(±10) years), less likely to receive DT (adjusted odds ratio (AOR), 0.71 [0.67-0.76]), and of those receiving DT, less likely to undergo prostatectomy (AOR, 0.58 [0.54-0.62]). Patients receiving DT had lower crude cancer-specific and overall mortality (0.17 vs. 0.41 % and 2.9 vs. 7.8 %, p value < 0.001, respectively, among blacks). The difference in overall mortality was largest among ≥ 75 years (5.6 vs. 18.2 %). Across age groups, blacks had higher all-cause mortality (AOR, 1.45 [1.13-1.87] and 1.56[1.31-1.86] for <65 and ≥ 65 years, respectively). CONCLUSION: Our study of a large modern cohort of men with low-risk PCa demonstrates significant lower receipt of DT, lower receipt of prostatectomy among those receiving DT, and lower survival for black men compared to their white counterparts. Older men were less likely to receive DT. Patients who received DT had better survival. The survival difference was most striking among the elderly.

Beyond incidence: Costs of complications in trauma and what it means for those who pay.

INTRODUCTION: Trauma patients have greater rates of complications than general surgery patients; however, existing surgical pay-for-performance (P4P) guidelines have yet to be adapted for trauma care. To better understand whether current P4P measures are applicable to trauma, this study used nationally representative data to determine the mortality and attributable costs associated with the presence or absence of both Centers for Medicare and Medicaid Services-recognized complications (urinary tract infections, surgical site infections [SSIs], and pneumonia) and other major trauma-related complications. METHODS: Trauma admissions were extracted from the 2008 National Inpatient Sample using primary ICD-9-CM diagnosis codes (range, 800-905, 910-939, 950-958). Patients aged 18-65 years with a duration of hospital stay of >3 days and isolated complications were included. To account for differences in patient factors, coarsened-exact matching was used to create comparable cohorts of adult patients with and without complications. Multivariable regression was then performed within matched groups to determine differences in cost and mortality, controlling for hospital characteristics and wage index. RESULTS: Of 493,372 trauma patients, 78,156 met inclusion criteria, of whom 24.4% had an isolated complication. Consistent with surgical P4P guidelines, SSI, urinary tract infections, and pneumonia had the greatest incidence (8.0%, 5.2%, and 4.4%, respectively); however, mortality in matched patients with complications was greatest for sepsis (odds ratio [OR], 9.76; 95% CI, 3.84-24.80), myocardial infarction (MI; OR, 4.21; 95% CI, 1.70-10.44) and stroke (OR, 3.02; 95% CI, 1.40-6.52). Excess costs associated with a complication were similarly greatest for sepsis (relative cost, 1.84; 95% CI, 1.57-2.17), followed by acute respiratory distress syndrome (ARDS; relative cost, 1.84; 95% CI, 1.7-1.99) and MI (relative cost, 1.73; 95% CI, 1.51-1.99). CONCLUSION: Consideration of attributable costs and mortality suggest that additional complications have a substantial impact among trauma patients, beyond the conditions used in general surgery P4P guidelines. These aspects of trauma should be prioritized to capture the influence of complications in trauma that the incidence of frequent but less costly conditions overlooks.

Body mass index in blunt trauma patients with hemorrhagic shock: opposite ends of the body mass index spectrum portend poor outcome.

BACKGROUND: There are controversial data on the relationship between trauma and body mass index. We investigated this relationship in traumatic hemorrhagic shock. METHODS: The "Glue Grant" database was analyzed, stratifying patients into underweight, normal weight (NW), overweight, Class I obesity, Class II obesity, and Class III obesity. Predictors of mortality and surgical interventions were statistically determined. RESULTS: One thousand nine hundred seventy-six patients were included with no difference in injury severity between groups. Marshall's score was elevated in overweight (5.3 ± 2.7, P = .016), Class I obesity (5.8 ± 2.7, P < .001), Class II obesity (5.9 ± 2.8, P < .001), and Class III obesity (6.3 ± 3.0, P < .001) compared with NW (4.8 ± 2.6). Underweight had higher lactate (4.8 ± 4.2 vs 3.3 ± 2.5, P = .04), were 4 times more likely to die (odds ratio 3.87, confidence interval 2.22 to 6.72), and were more likely to undergo a laparotomy (odds ratio 2.06, confidence interval 1.31 to 3.26) than NW. CONCLUSION: Early assessment of body mass index, with active management of complications in each class, may reduce mortality in traumatic hemorrhagic shock.

Epidemiology of 577 pediatric firearm fatalities: a 2-year review of the National Trauma Data Bank.

The purpose of this study was to delineate the epidemiology of pediatric firearm injuries, including ethno-demographic patterns with impact on years of potential life lost (YPLL). A 2-year review of the National Trauma Data Bank (2007 to 2008) was conducted. Firearm fatalities in records of patients younger than 18 years were identified. Data were analyzed by demographic and injury characteristics and YPLL was calculated by ethnicity. A total of 577 deaths were identified in the pediatric group. Blacks accounted for 49.7 per cent of the fatalities; Hispanics, 19.2 per cent; whites, 17.7 per cent, and other ethnicity, 13.4 per cent. Median Injury Severity Score was 25 with a median Glasgow Coma Scale score of 3. Traumatic brain injury was present in 84.2 per cent of the records. Assault accounted for 72.8 per cent, self-inflicted injury 12.7 per cent, and unintentional injuries were 8.2 per cent. Most firearm fatalities occurred at home (33.6%). By emergency department (ED) disposition, 29.3 per cent died in the ED, 32.9 per cent were admitted to the intensive care unit, and 30.0 per cent taken to the operating room. Blacks had a total of 17,446 YPLL, Hispanics 6,776 YPLL, and whites 6,718 YPLL. Pediatric firearm fatalities still remain an important public health concern. Inclusive gun control policies focused on primary prevention of accidental injuries may be more effective in mitigating its impact.

Surgical management of complicated diverticulitis: a comparison of the laparoscopic and open approaches.

BACKGROUND: Laparoscopy has become a commonly used method of performing colectomies, but the outcomes associated with laparoscopy in the emergency setting have not been well studied. STUDY DESIGN: The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database was queried for patients with diverticulitis without hemorrhage who underwent a colectomy. Patient data retrieved included demographics and preoperative comorbidities. Each member of the cohort received either a primary anastomosis (PA) or a colostomy. Open and laparoscopic procedures were compared within these subgroups. Multivariate logistic regression analyses were performed to compare the risk-adjusted odds of postoperative morbidity and mortality for laparoscopic and open procedures. The risk-adjusted impact of preoperative comorbidities was also assessed. RESULTS: A total of 11,981 patients in the database met the study criteria. The majority were female (53%) and Caucasian (82%), and the mean age was 58 (±13) years. Comorbidities of the cardiovascular, pulmonary, or renal systems were present in 47%, 5%, and 1% of the cohort, respectively. On bivariate analysis, patients undergoing laparoscopy experienced lower rates of complications with both PA (14% vs 26%, p < 0.001) and colostomy (30% vs 37%, p = 0.02). The laparoscopic approach was associated with decreased mortality rates for patients undergoing PA (0.24% vs 0.79%, p < 0.001). Multivariate analysis revealed that preoperative cardiovascular and pulmonary comorbidities were each associated with increased postoperative morbidity, and that the laparoscopic approach was associated with lower postoperative morbidity for patients undergoing PA. The reduced risk of death for patients undergoing laparoscopic PA (vs open approach) did not achieve statistical significance (odds ratio 0.68, p = 0.3). A small number of patients underwent laparoscopic colostomy (n = 237, 2.4%), and they did not have a significantly different risk of death. CONCLUSIONS: The laparoscopic approach is associated with lower complication rates compared with the open approach for the surgical treatment of diverticulitis with a primary anastomosis.

Associated injuries in traumatic sternal fractures: a review of the National Trauma Data Bank.

Sternal fractures occur infrequently with blunt force trauma. The demographics and epidemiology of associated injuries have not been well characterized from a national trauma database. The National Trauma Data Bank was queried for patients with closed sternal fractures. The demographics were analyzed by age, gender, mechanism and indicators of anatomic and physiologic injuries. Types of commonly associated injuries were also determined. A total of 23,985 records were analyzed. Males accounted for 68.3 per cent and whites 70.9 per cent. Motor vehicle crash was the leading mechanism. More than 56 per cent had severe injuries based on Injury Severity Score (greater than 15) and 17 per cent with Glasgow Coma Score 8 or less. Crude mortality was 7.9 per cent. The majority (57.8%) and approximately one-third (33.7%) of the patients had rib fractures and lung contusions, respectively, 22.0 per cent with closed pneumothorax, 21.6 per cent had a closed thoracic vertebra fracture, 16.9 per cent with lumbar spine fracture, 3.9 per cent with concussion, and blunt cardiac injury in 3.6 per cent. Sternal fractures are usually associated with severe blunt trauma. Lung contusion remains the leading associated injury followed by vertebral spine fractures. Cardiac injuries are less frequent and vascular injuries less so. Mechanism of injury and presence of sternal fractures should alert providers to these potential associated injuries.

State-by-state variation in emergency versus elective colon resections: room for improvement.

BACKGROUND: Compared with elective surgical procedures, emergency procedures are associated with higher cost, morbidity, and mortality. This study seeks to investigate potential state-by-state variations in the incidence of emergent versus elective colon resections. METHODS: A retrospective analysis of all adult patients (aged ≥18 years) included in the Nationwide Inpatient Sample from 2005 to 2009 who underwent hemicolectomy (right or left) or sigmoidectomy was conducted. Discharge-level weights were applied, and generalized linear models were used to assess the odds of a patient undergoing emergent versus elective colon surgery nationally and for each state after adjusting for patient and hospital factors. Odds ratios (ORs) were estimated with the national average as the reference. RESULTS: The final study cohort included 203,050 observations composed of 83,090 emergent and 119,960 elective colectomies. The state with the highest unadjusted proportion of emergent procedures was Nevada (53.6%), whereas Texas had the lowest (22.8%) [corrected]. Compared with the national average, the adjusted odds of undergoing emergency colectomy remained highest in Nevada (OR, 1.70; 95% confidence interval, 1.54-1.87) and lowest in Texas (OR, 0.43; 95% confidence interval, 0.36-0.51). CONCLUSION: Substantial state variations exist in rates of emergency colon surgery within the United States. Identification of these differences suggests significant variations in practice and a potential to decrease the number of emergent colon operations.

Regional variations in cost of trauma care in the United States: who is paying more?

BACKGROUND: The study of regional variations in costs of care has been used to identify areas of savings for several diseases and conditions. This study investigates similar potential regional differences in the cost of adult trauma care using an all-payer, nationally representative sample. METHODS: Trauma patients aged 18 to 64 years in the 2006-2008 Nationwide Inpatient Sample were identified using International Classification of Diseases, 9th Revision, Clinical Modification codes. Those with isolated diagnoses for five index conditions (ICs): blunt splenic injury, liver injury, tibia fracture, moderate traumatic brain injury, and pneumothorax/hemothorax were selected. Cost was estimated from charges using a cost-to-charge ratio. Generalized linear modeling was used to compare the mean cost for treating these ICs between US regions (Northeast, South, Midwest, and West), adjusting for hospital factors (size, teaching status, and location), patient demographics, injury severity, length of stay, Charlson comorbidity index, local wage index, and payer. Relative mean cost (RC) was calculated using Northeast as the reference, and sampling weights were applied to obtain regional estimates. Differences in adjusted mortality between regions were also assessed. RESULTS: Adjusted relative costs were estimated for 62,678 patients (South: 28,536; West: 12,975; Midwest: 11,450; and Northeast: 9,717). Mean costs for liver injury were 22%higher in the Midwest compared with the Northeast (RC: 1.22; 95%confidence interval [CI]: 1.10-1.35). Similarly higher costs were seen with other regions and ICs (RC for blunt splenic injury in the South: 1.18; 95% CI: 1.07-1.31; RC for pneumothorax/hemothorax in the West: 1.31; 95% CI: 1.22-1.41). No differences in adjusted mortality by region were noted overall. CONCLUSION: Even after controlling for factors known to influence medical care cost, as well as controlling for geographic differences in pricing, significant regional differences exist in the cost of trauma care. Exploring these variations may assist in identifying potential areas for cost savings.