Ivabradine: A Review of Labeled and Off-Label Uses.

Ivabradine is a unique medication recently approved in the USA for the treatment of select heart failure patients. It was first approved for use in several countries around the world over a decade ago as an anti-anginal agent, with subsequent approval for use in heart failure patients. Since ivabradine has selective activity blocking the I f currents in the sinus node, it can reduce heart rate without appreciable effects on blood pressure. Given this heart-rate-specific effect, it has been investigated in many off-label indications as an alternative to traditional heart-rate-reducing medications such as beta blockers and calcium channel blockers. We conducted searches of PubMed and Google Scholar for ivabradine, heart failure, HFrEF, HFpEF, angina, coronary artery disease, inappropriate sinus tachycardia, postural orthostatic hypotension, coronary computed tomography angiography and atrial fibrillation. We reviewed and included studies, case reports, and case series published between 1980 and June 2016 if they provided information relevant to the practicing clinician. In many cases, larger clinical trials are needed to solidify the benefit of ivabradine, although studies indicate benefit in most therapeutic areas explored to date. The purpose of this paper is to review the current labeled and off-label uses of ivabradine, with a focus on clinical trial data.

Disparities in Revascularization After ST Elevation Myocardial Infarction (STEMI) Before and After the 2002 IOM Report.

OBJECTIVES: To examine nationwide trends for racial disparities in Percutaneous Coronary Intervention after ST elevated Myocardial Infarction (STEMI). BACKGROUND: The Institute of Medicine (IOM) report published in 2002 showed that African Americans were less likely to receive coronary revascularization such as CABG and stents even after controlling for socioeconomics. It recommended increased awareness of these disparities among health professionals to reduce this. We hypothesized that increased awareness of disparities since this report would have translated to reduction in racial disparities in percutaneous coronary intervention. METHODS: A retrospective analysis was conducted using data from the Agency of Healthcare Research and Quality's (AHRQ) National Inpatient Sample (NIS) 1998-2007. All patients with STEMI during this period were identified. The proportion that received Percutaneous Coronary Intervention (PCI) during the incident admission was compared by different ethnicities over the time period. Multivariable regression for each year was conducted using Poisson regression with robust variances. The analysis controlled for gender, insurance status, co-morbidities, hospital bed size, location and teaching status. RESULTS: Based on the database, about 2.04 million patients were managed for acute Myocardial Infarction from 1998 to 2007, of these 938,176 had STEMI. The primary PCI rate after STEMI among Caucasians was 29.1%, African Americans-23.3% and Hispanics-28.3% [P < 0.001] On multivariate regression, compared to Caucasians, African Americans and Hispanics respectively were 26% (IRR = 0.74) and 16% (IRR = 0.84) less likely to receive PCI (both with P < 0.001) during the entire study period. CONCLUSION: Ethnic disparities in primary PCI after STEMI persist despite the 2002 IOM report.

Association Between Insurance Status and Hospital Length of Stay Following Trauma.

Previous research has demonstrated that nonclinical factors are associated with differences in clinical care, with uninsured patients receiving decreased resource use. Studies on trauma populations have also shown unclear relationships between insurance status and hospital length of stay (LOS), a commonly used metric for evaluating quality of care. The objective of this study is to define the relationship between insurance status and LOS after trauma using the largest available national trauma dataset and controlling for significant confounders. Data from 2007 to 2010 National Trauma Data Bank were used to compare differences in LOS among three insurance groups: privately insured, publically insured, and uninsured trauma patients. Multivariable regression models adjusted for potential confounding due to baseline differences in injury severity and demographic and clinical factors. A total of 884,493 patients met the inclusion criteria. After adjusting for the influence of covariates, uninsured patients had significantly shorter hospital stays (0.3 days) relative to privately insured patients. Publicly insured patients had longer risk-adjusted LOS (0.9 days). Stratified differences in discharge disposition and injury severity significantly altered the relationship between insurance status and LOS. In conclusion, this study elucidates the association between insurance status and hospital LOS, demonstrating that a patient's ability to pay could alter LOS in acute trauma patients. Additional research is needed to examine causes and outcomes from these differences to increase efficiency in the health care system, decrease costs, and shrink disparities in health outcomes.

Disparities in trauma care: are fewer diagnostic tests conducted for uninsured patients with pelvic fracture?

BACKGROUND: Research from other medical specialties suggests that uninsured patients experience treatment delays, receive fewer diagnostic tests, and have reduced health literacy when compared with their insured counterparts. We hypothesized that these disparities in interventions would not be present among patients experiencing trauma. Our objective was to examine differences in diagnostic and therapeutic procedures administered to patients undergoing trauma with pelvic fractures using a national database. METHODS: A retrospective analysis was conducted using the National Trauma Data Bank (NTDB), 2002 to 2006. Patients aged 18 to 64 years who experienced blunt injuries with pelvic fractures were analyzed. Patients who were dead on arrival, those with an injury severity score (ISS) less than 9, those with traumatic brain injury, and patients with burns were excluded. The likelihood of the uninsured receiving select diagnostic and therapeutic procedures was compared with the same likelihood in the insured. Multivariate analysis for mortality was conducted, adjusting for age, sex, race, ISS, presence of shock, Glasgow Coma Scale (GCS) motor score, and mechanism of injury. RESULTS: Twenty-one thousand patients met the inclusion criteria: 82% of these patients were insured and 18% were uninsured. There was no clinical difference in ISSs (21 vs 20), but the uninsured were more likely to present in shock (P < .001). The mortality rate in the uninsured was 11.6% vs 5.0% in the insured (P < .001). The uninsured were less likely to receive vascular ultrasonography (P = .01) and computed tomography (CT) of the abdomen (P < .005). There was no difference in the rates of CT of the thorax and abdominal ultrasonography, but the uninsured were more likely to receive radiographs. There was no difference in exploratory laparotomy and fracture reduction, but uninsured patients were less likely to receive transfusions, central venous pressure (CVP) monitoring, or arterial catheterization for embolization. Insurance-based disparities were less evident in level 1 trauma centers. CONCLUSIONS: Uninsured patients with pelvic fractures get fewer diagnostic procedures compared with their insured counterparts; this disparity is much greater for more invasive and resource-intensive tests and is less apparent in level 1 trauma centers. Differences in care that patients receive after trauma may be 1 of the mechanisms that leads to insurance disparities in outcomes after trauma.

Pediatric negative appendectomy rate: trend, predictors, and differentials.

BACKGROUND: Appendectomy is one of the most commonly performed emergency operations in children. The diagnosis of appendicitis can be quite challenging, particularly in children. We set out to determine the accuracy of diagnosis of appendicitis by analyzing the trends in the negative appendectomy rate (NAR) using a national database. MATERIALS AND METHODS: Analysis of the Kids Inpatient Database (KID) was performed for the years 2000, 2003, and 2006 on children with appendectomy, excluding incidental appendectomies. Children (<18 y) without appendicitis but who underwent appendectomies were classified as negative appendectomies (NA), and those with appendicitis as positive appendectomies (PA). Comparisons were made between those with PA versus NA by demographic characteristics. The subset of patients with NA was then further analyzed. RESULTS: An estimated 250,783 appendectomies met the inclusion criteria. The NAR was 6.7%. Length of stay (LOS) was longer in NA versus PA (7 versus 3 d, P < 0.05). The NAR was increased in children under 5 y (21.1% versus 5.4% for among the 5-10 y versus 5.9% among the >10 y, P < 0.0001) and in females (9.3% versus 5.1%, P < 0.001). On multivariate analysis, increasing age was associated with lower odds of NA (OR = 0.92, P < 0.001). Females, rural hospitals, and Blacks were significantly more likely to experience NA. CONCLUSIONS: Younger age, female gender, Black ethnicity and rural hospitals are independent predictors of NA. These factors can be incorporated into diagnostic algorithms to improve the accuracy of diagnosis of appendicitis in children.

Epidemiologic trend in elderly domestic injury.

BACKGROUND: The elderly constitute about 12% of the American population, with a projected increase of up to 25% in 2050. Elderly domestic injuries have been recognized as a major cause of morbidity and mortality. The objective of this study is to determine the 4-y national trend in elderly domestic injury, and we hypothesize that the home remains a significant source of injury. METHODS: Data on elderly patients ≥ 65 y was extracted from the National Trauma Data Bank's National Sample Project (NSP). Elderly patients with home injuries were compared with non-home injuries. Subsets of hospitalized patients were analyzed for trends in injury site over a 4 y period. Multivariate analysis was performed to determine the predictors of hospitalization and in-hospital mortality. RESULTS: A total of 98,288 patients, representing a weighed estimate of 472,456 elderly patients were analyzed. Forty-two percent of all injuries in the study population occurred at home, followed by motor vehicle crashes (MVC) at 25%. Home injuries as a proportion of annual injuries increased from 37% in 2003 to 40% in 2006. Majority (57%) were admitted to the floor and 14% to the intensive care unit (ICU). On multivariate analysis, African-Americans and Asians were less likely to be hospitalized (odds ratio (OR) 0.57 and 0.50, respectively, with females 47% less likely than males to die after hospitalization (P < 0.001). CONCLUSIONS: Home injuries remain the most significant source of elderly hospitalizations after trauma. With a rapidly growing elderly population, there is a need to recognize this specific location of injury and create directed preventive measures to avert elderly domestic injuries.

Profiling adult intussusception patients: comparing colonic versus enteric intussusception.

BACKGROUND: Adult intussusception is a rare entity representing 1% of all adult bowel obstruction, hospital admissions secondary to intussusception historically has ranged between .003% and .02%. There is limited knowledge regarding enteric and colonic surgical intussusception patients and their associated conditions. METHODS: A retrospective study was conducted using data from the National Inpatient Sample from 1998 to 2006. The inclusion criteria were surgical patients with intussusception. RESULTS: A total of 1,178 cases of intussusception requiring surgery were isolated from the database. The mean patient age was 49.57 years, about 58% were females, 99.43% of this population was insured, and the overall mortality rate was 1.70%. Colonic resection was associated with greater mortality compared with the enteric resection group (P = .018). CONCLUSIONS: This was a large study on surgical adult intussusception patients conducted in the United States. We show differences in demography, comorbidities, and potential causes between colonic and enteric intussusception.

Differential trends in racial preferences for cosmetic surgery procedures.

There appears to be an increasing acceptance of cosmetic surgery procedures among minority populations in America. Our objective was to determine trends in elective cosmetic procedure utilization as they apply to racial/ethnic differences. A retrospective analysis was performed using the Nationwide Inpatient Sample. Adult patients undergoing elective cosmetic procedures defined by the appropriate International Classification of Disease 9 Clinical Modification procedure codes were included. Demographic characteristics and hospital course particulars were evaluated. There were 71,775 patients meeting the inclusion criteria. Median age was 48 years. The majority were female (90%), and white (65%). The median household income for the patient's zip code was most commonly in the highest economic quartile (4th quartile, 40%). The most common cosmetic procedure was liposuction (67%). The overall mean percentage change in the frequency of these procedures showed a 1.8 per cent decline among white patients, whereas Black, Hispanic, Asian, and Native American patients had an increase of 7.5 per cent, 4.7 per cent, 14.5 per cent, and 105.5 per cent, respectively. We conclude that there is an identified increasing trend in the proportion of racial/ethnic minorities represented among the recipients of cosmetic surgery procedures.

Negative appendectomy: a 10-year review of a nationally representative sample.

BACKGROUND: Appendectomy remains one of the most common emergency surgical procedures encountered throughout the United States. With improvements in diagnostic techniques, the efficiency of diagnosis has increased over the years. However, the entity of negative appendectomies still poses a dilemma because these are associated with unnecessary risks and costs to both patients and institutions. This study was conducted to show current statistics and trends in negative appendectomy rates in the United States. METHODS: A retrospective analysis was conducted using data from the National Inpatient Sample from 1998 to 2007. Adult patients (>18 y) having undergone appendectomies were identified by the appropriate International Classification of Diseases 9th revision codes. Patients with incidental appendectomy and those with appendiceal pathologies, also identified by relevant International Classification of Diseases 9th revision codes, were excluded. The remaining patients represent those who underwent an appendectomy without appendiceal disease. The patients then were stratified according to sex, women were classified further into younger (18-45 y) and older (>45 y) based on child-bearing age. The primary diagnoses subsequently were categorized by sex to identify the most common conditions mistaken for appendiceal disease in the 2 groups. RESULTS: Between 1998 and 2007, there were 475,651 cases of appendectomy that were isolated. Of these, 56,252 were negative appendectomies (11.83%). There was a consistent decrease in the negative appendectomy rates from 14.7% in 1998 to 8.47% in 2007. Women accounted for 71.6% of cases of negative appendectomy, and men accounted for 28.4%. The mortality rate was 1.07%, men were associated with a higher rate of mortality (1.93% vs .74%; P < .001). Ovarian cyst was the most common diagnosis mistaken for appendicitis in younger women, whereas malignant disease of the ovary was the most common condition mistaken for appendiceal disease in women ages 45 and older. The most common misdiagnosis in men was diverticulitis of the colon. CONCLUSIONS: There has been a consistent decline in the rates of negative appendectomy. This trend may be attributed to better diagnostics. Gynecologic conditions involving the ovary are the most common to be misdiagnosed as appendiceal disease in women.

Treatment outcomes of injured children at adult level 1 trauma centers: are there benefits from added specialized care?

BACKGROUND: Accidental traumatic injury is the leading cause of morbidity and mortality in children. The authors hypothesized that no mortality difference should exist between children seen at ATC (adult trauma centers) versus ATC with added qualifications in pediatrics (ATC-AQ). METHODS: The National Trauma Data Bank, version 7.1, was analyzed for patients aged <18 years seen at level 1 trauma centers. Bivariate analysis compared patients by ATC versus ATC-AQ using demographic and injury characteristics. Multivariate analysis adjusting for injury and demographic factors was then performed. RESULTS: A total sample of 53,702 children was analyzed, with an overall mortality of 3.9%. The adjusted odds of mortality was 20% lower for children seen at ATC-AQ (odds ratio, .80; 95% confidence interval, .68-.94). Children aged 3 to 12 years, those with injury severity scores > 25, and those with Glasgow Coma Scale scores < 8 all had significant reductions in the odds of death at ATC-AQ. CONCLUSIONS: Improved overall survival is associated with pediatric trauma patients treated at ATC-AQ.

Does the pattern of injury in elderly pedestrian trauma mirror that of the younger pedestrian?

BACKGROUND: Walking is the primary mode of transportation for people aged 65 y and over; hence pedestrian injuries are a substantial source of morbidity and mortality among elderly patients in the United States. This study is aimed at evaluating the pattern of injury in the elderly pedestrians and how it differs from younger patients. METHODS: Retrospective analysis of the National Trauma Data Bank (2002-2006) was performed, with inclusion criteria defined as pedestrian injuries based on ICD-9 codes, excluding age < 15 y. The following age categories in years were created: 15-24 (reference group), 25-34, 35-44, 45-54, 55-64, 65-74, 75-84, and 85-89. The injury prevalence was compared, and multivariate regression for mortality was conducted adjusting for demographic and injury characteristics. RESULTS: A total of 79,307 patients were analyzed. Superficial injuries were the most common at 29.1%, with lower extremity fractures and intracranial injuries following at 25.1% and 21.4% respectively. The very elderly (75-84 and 85-89) had significantly higher rates of fractures of the pelvis(16.2% and 16.8% versus 8.1% in the youngest group), upper (19.3% and 18.4% versus 9.8%), lower extremities (31.1% and 31.9% versus 22.5%) and intracranial injuries (25.5% and 28.7% versus 22.4%), but sustained lower rates of hepatic (2.3% and 1.7% versus 3.0%) injuries, with no difference seen in pancreatic, splenic, and genitourinary injuries. On multivariate analysis, very elderly patients were six to eight times more likely to die (OR 6.24 and 8.27, P < 0.001). CONCLUSION: Elderly patients have higher rates of fractures and intracranial injuries with an extremely worse mortality after pedestrian trauma.

Pediatric trauma at an adult trauma center.

BACKGROUND: Accidental traumatic injury is the number 1 cause of morbidity and mortality in the pediatric population. In this study, we aim to prove that certain pediatric patients can be treated with good outcomes at an adult level 1 trauma center. METHODS: Retrospective analysis using the Howard University Hospital trauma registry identified 71 patients treated at Howard University Hospital between the ages of 1 and 17 years old. Specific variables were identified and collected for each patient. RESULTS: The majority of pediatric traumas treated at Howard University Hospital between June 2004 and May 2005 had high survival rates (93%). The patients who did not survive (7%) included 3 patients who were dead on arrival and 2 who died shortly after arrival to the hospital. CONCLUSIONS: Certain pediatric populations who present with minor and/or isolated injuries can be treated in an adult level 1 trauma center with similar outcomes to treatment in a pediatric level 1 trauma center.

Laparoscopic versus open appendectomy in complicated appendicitis: a review of the NSQIP database.

BACKGROUND: Laparoscopic appendectomy (LA) has been an established treatment method for uncomplicated acute appendicitis. Controversy still exits regarding the superiority of either laparoscopic or open technique for the treatment of complicated appendicitis. OBJECTIVE: To examine for benefits in postoperative morbidity comparing laparoscopic versus open appendectomy for complicated appendicitis. METHODS: A retrospective analysis was performed using the American College of Surgeon's National Surgical Quality Improvement Project (ACS-NSQIP) dataset between 2005 and 2007. Inclusion criteria were patients undergoing either open or laparoscopic appendectomy, and had complicated appendicitis. Patients with negative appendectomies and age less than 18 y old were excluded. The primary outcome variable was postoperative complications. Multivariate analysis was performed adjusting for demographics and standard NSQIP comorbidities. RESULTS: We identified 2,790 complicated appendicitis cases treated with laparoscopic or open appendectomy. The majority were male (56.6%), White (70.3%), and 39.1% were younger than 40 y of age. On unadjusted analyses, the mean length of stay was significantly shorter for LA cases (3.97 d) than OA cases (5.13 d) (P < 0.001). On multivariate analysis, superficial surgical site infection was 70% less likely to occur in LA (OR 0.304 P = 0.000), organ space infection was 2-fold more likely to occur in LA (OR 2.19 P = 0.003), and dehiscence was 78% less likely to occur in LA (OR 0.22 P = 0.015). CONCLUSION: In cases of complicated appendicitis, laparoscopic appendectomy is superior in terms of superficial and deep wound infections; however, it is associated with an increased incidence of postoperative intra-abdominal abscess.

Pedestrians struck by motor vehicles further worsen race- and insurance-based disparities in trauma outcomes: the case for inner-city pedestrian injury prevention programs.

BACKGROUND: Pedestrian trauma is the most lethal blunt trauma mechanism, and the rate of mortality in African Americans and Hispanics is twice that compared with whites. Whether insurance status and differential survival contribute to this disparity is unknown. METHODS: This study is a review of vehicle-struck pedestrians in the National Trauma Data Bank, v7.0. Patients <16 years and > or =65 years, as well as patients with Injury Severity Score (ISS) <9, were excluded. Patients were categorized as white, African American, or Hispanic, and as privately insured, government insured, or uninsured. With white and privately insured patients as reference, logistic regression was used to evaluate mortality by race and insurance status after adjusting for patient and injury characteristics. RESULTS: In all, 26,404 patients met inclusion criteria. On logistic regression, African Americans had 22% greater odds of mortality (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.06-1.41) and Hispanics had 33% greater odds of mortality (OR, 1.33; 95% CI, 1.14-1.54) compared with whites. Uninsured patients had 77% greater odds of mortality (OR, 1.77; 95% CI, 1.52-2.06) compared with privately insured patients. CONCLUSION: African American and Hispanic race, as well as uninsured status, increase the risk of mortality after pedestrian crashes. Given the greater incidence of pedestrian crashes in minorities, this compounded burden of injury mandates pedestrian trauma prevention efforts in inner cities to decrease health disparities.

The number of lymph nodes examined debate in colon cancer: how much is enough?

BACKGROUND: Much debate exists over the significance of the number of lymph nodes (LN) examined after colon resection. MATERIALS AND METHODS: The Surveillance, Epidemiology and End Results (SEER) database was queried for patients who presented with colonic adenocarcinoma. Multiple Cox proportional hazard regressions were run using successive LN cut-offs (6-26), first controlling for and then stratifying by T-stage. This was repeated in subsets of patients delineated by LN status. Additional variables controlled for in every regression were age, gender, ethnicity, marital status, number of positive LN, grade, metastases, and extent of surgery. After each regression, a Harrell's C statistic and an Akaike's information criterion (AIC) were performed to test the predictive capacity and fit of the model, respectively. RESULTS: 128,071 patients met selection criteria. The highest Harrell's C statistics among all patients were the cutoffs at 14 LN and 15 LN. Between those, the AIC shows that the cutoff at 15 LN fit the data more closely than the 14 LN cutoff. The models with the best predictive ability and best fit by T-stage were T1, 14 LN; T2, 10 LN; T3, 10 LN; T4, 12 LN. CONCLUSIONS: Using a population-based dataset, we show the optimal number of LN examined is dependent upon the patient's tumor stage. Across all T-stages, the highest optimal number of LN resected was 15. Since it is possible to estimate but not perfectly predict the stage of a patient's tumor preoperatively, we believe the recommendation should be based on the most conservative measure.