Citations

Purpose Multiple studies have found an association between the prompt initiation of empirically-appropriate antimicrobial therapy and improved patient outcomes. Such empiric-antimicrobial therapy is often broad; however, once the patient's infectious syndrome, microbiology, and susceptibilities are more defined, it is important to refine antimicrobial therapy. Despite the potential benefits of an “antimicrobial de-escalation” approach, it may be difficult to enforce in clinical practice. Mayo Clinic's Computer-Based Antimicrobial Monitoring System (CBAM) is a medical-informatics tool that was used to assist in this endeavor. This study evaluates the hypothesis that CBAM can enhance the de-escalation of vancomycin and broad-spectrum combination antimicrobial therapy. Methods Hospitalized patients at the Mayo Clinic were screened from January through June 2006 using rule-based algorithms incorporated by CBAM. Interventions were performed by physicians and pharmacists as pertinent. These patients were compared with a historical group of patients obtained by CBAM reporting capabilities. De-escalation rates and mean duration of antimicrobial therapy were compared between groups. Results Vancomycin de-escalation rates significantly improved from 33% to 68% with intervention ( P = 0.001). In addition, the average duration of therapy was decreased from 10.4 ± 7.3 days to 7.7 ± 2.4 days among patients who underwent vancomycin de-escalation per recommendation ( P = 0.014). Conclusions Utilizing the Mayo Clinic's CBAM system to identify potential patients for de-escalation is a unique approach and was successful at improving adherence to vancomycin de-escalation.

Object The aim of this study was to evaluate the outcomes of Gamma Knife surgery (GKS) when used for patients with intractable cluster headache (CH). Methods Four participating centers of the North American Gamma Knife Consortium identified 17 patients who underwent GKS for intractable CH between 1996 and 2008. The median patient age was 47 years (range 26–83 years). The median duration of pain before GKS was 10 years (range 1.3–40 years). Seven patients underwent unsuccessful prior surgical procedures, including microvascular decompression (2 patients), microvascular decompression with glycerol rhizotomy (2 patients), deep brain stimulation (1 patient), trigeminal ganglion stimulation (1 patient), and prior GKS (1 patient). Fourteen patients had associated autonomic symptoms. The radiosurgical target was the trigeminal nerve (TN) root and the sphenopalatine ganglion (SPG) in 8 patients, only the TN in 8 patients, and only the SPG in 1 patient. The median maximum TN and SPG dose was 80 Gy. Results Favorable pain relief (Barrow Neurological Institute Grades I–IIIb) was achieved and maintained in 10 (59%) of 17 patients at a median follow-up of 34 months. Three patients required additional procedures (repeat GKS in 2 patients, hypothalamic deep brain stimulation in 1 patient). Eight (50%) of 16 patients who had their TN irradiated developed facial sensory dysfunction after GKS. Conclusions Gamma Knife surgery for intractable, medically refractory CH provided lasting pain reduction in approximately 60% of patients, but was associated with a significantly greater chance of facial sensory disturbances than GKS used for trigeminal neuralgia.

Abstract Disparities in clinical outcomes of breast cancer have been described among different racial and ethnic groups in the U.S. Convincing data exist showing that Latina women have a lower incidence of breast cancer but a higher breast cancer–related mortality rate compared with white women. Noticeable differences in breast cancer incidence are present even within different Latina subsets with a higher incidence in second- and third-generation women compared with foreign born. An increasing amount of data exists pointing to significant differences in the genetics and biology of breast cancer in Latinas as a significant contributor to the higher mortality, including a higher incidence of triple-negative breast cancers (which do not overexpress HER-2 protein and are negative for estrogen receptors and progesterone receptors). Other social and environmental factors are likely to play a significant role as well, including a lower rate of screening mammography, variable access to medical care, among others. Recent data are inconclusive regarding differences among racial/ethnic groups in the response to chemotherapy. Data on racial/ethnic variations in the pharmacogenomics of chemotherapy, endocrine treatments, and toxicity are more limited, with some data suggesting differences in frequencies of polymorphisms of genes involved in the metabolism of some of these agents. Further studies are needed on this subject.

As medical providers seek new ways to control costs, online visits have begun to receive serious consideration. The purpose of this study was to compare the odds of being a cost outlier during a 6-month period after either an online visit or a standard drop-in visit in a conventional medical office setting. Medical records of primary care patients (both adults and children) seen in a large group practice in Minnesota in 2008 were analyzed for this study. Two groups of patients were studied: those who had an online visit ( N = 390) and a comparison group who had regular office care for same-day, acute visits ( N = 376). Case types were classified as either complex or common, with common being defined as treatment for pinkeye, sore throat, viral illness, bronchitis, or cough. Outliers were defined as patients for whom standard costs exceeded the 75 th percentile during a 6-month period after the index visit. Multiple logistic regression analysis was used to adjust for differences between groups. The percentage of online visitors who were cost outliers was 21.2 (versus 28.5 in the standard visit group). Median standard costs were $161 for online visits and $219 for same-day acute visits. The adjusted odds of being a cost outlier was lower for the online visit group than for the standard visit group (odds ratio [OR] 0.52, 95% confidence interval [95% CI] 0.35–0.77) after adjusting for number of visits in the previous 6 months, age, sex, and case type. Outpatient visits in the previous 6 months were positively related to outlier status (OR 1.23, 95% CI 1.17–1.29). Online visits appeared to reduce medical costs for patients during a 6-month period after the visit. ( Population Health Management 2010;13:59–63)

ObjectiveTo investigate the manofluorographic and functional outcomes after endoscopic laser cricopharyngeal myotomy (ELCPM) for cricopharyngeal (CP) bar.Study DesignCase series with chart review.SettingAcademic medical center.Subjects and MethodsReview of patients undergoing ELCPM between 2001 and 2007 was undertaken to determine the demographic, clinical, and manofluorographic findings before and six months after surgery. Two groups were established according to pharyngeal driving pressures: normal pressure group (> 55 mm Hg) and low pressure group (< 55 mm Hg).ResultsFourteen patients underwent ELCPM for CP bar without a concomitant head and neck or Zenker's procedure. There were no major surgical complications. All 14 patients improved at least one stage on the Functional Outcome Swallowing Scale (FOSS) after surgery. There was a statistically significant decrease in the FOSS stages after surgery. Videofluoroscopy demonstrated a significant postoperative increase in the mean cross‐sectional CP opening (CP‐area) from 32.75 to 123.52 mm2. Manofluorographic pressure recordings showed a significant postoperative decrease in the intrabolus pressure gradient across the cricopharyngeal region (IB‐Gra) from 25.44 to 13.22 mm Hg. Despite significant overall results, the change in the IB‐Gra showed no difference between the patient groups.ConclusionSubjective (FOSS) and objective manofluorographic (CP‐area, IB‐Gra) improvement in CP bar patients occurred after ELCPM. We suggest IB‐Gra as a reliable objective indicator for patients who might benefit from ELCPM and as an appropriate parameter for follow‐up after surgery. However, continued research on a larger patient population is required to enhance our understanding of CP bar and predictors of outcome after treatment of CP bar dysphagia.

A recently identified variant within the fat mass and obesity-associated ( FTO ) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.

Abstract A common variant on chromosomal region 15q24-25.1, marked by rs1051730, was found to be associated with lung cancer risk. Here, we attempted to confirm the second variant on 15q24-25.1 in several large sporadic lung cancer populations and determined what percentage of additional risk for lung cancer is due to the genetic effect of the second variant. SNPs rs1051730 and rs481134 were genotyped in 2,818 lung cancer cases and 2,766 controls from four populations. Joint analysis of these two variants (rs1051730 and rs481134) on 15q24-25.1 identified three major haplotypes (G_T, A_C, and G_C) and provided stronger evidence for association of 15q24-25.1 with lung cancer (P = 9.72 × 10−9). These two variants represent three levels of risk associated with lung cancer. The most common haplotype G_T is neutral; the haplotype A_C is associated with increased risk for lung cancer with 5.0% higher frequency in cases than in controls [P = 1.68 × 10−7; odds ratio (OR), 1.24; 95% confidence interval (95% CI), 1.14–1.35]; whereas the haplotype G_C is associated with reduced risk for lung cancer with 4.4% lower frequency in cases than in controls (P = 7.39 × 10−7; OR, 0.80; 95% CI, 0.73–0.87). We further showed that these two genetic variants on 15q24-25.1 independently influence lung cancer risk (rs1051730: P = 4.42 × 10−11; OR, 1.60; 95% CI, 1.46–1.74; rs481134: P = 7.01 × 10−4; OR, 0.81; 95% CI, 0.72–0.92). The second variant on 15q24-25.1, marked by rs481134, explains an additional 13.2% of population attributable risk for lung cancer. Cancer Res; 70(8); 3128–35. ©2010 AACR.

The most common cause of reoperation following repair of atrioventricular septal defect (AVSD) is left atrioventricular valve regurgitation. However, reoperation for subaortic obstruction is required in some, especially after initial repair of partial AVSD. Etiology of reoperation and late outcome were evaluated. Between 1962 and 2007, 146 patients (59 male) underwent reoperation at the authors' institution after prior repair of partial (n = 96) and complete (n = 50) AVSD. Median age at reoperation after repair of partial AVSD was 26 years (range, 10 months to 71 years) and 4.5 years (range, 53 days to 38 years) after repair of complete AVSD. The 3 most common indications for reoperation included left atrioventricular (AV) valve regurgitation in 105 patients, subaortic stenosis in 29, and right AV valve regurgitation in 21. The most common procedures performed included left AV valve repair in 59 (40%) patients, left AV valve replacement in 56 (38%), subaortic fibrous resection/myectomy in 24 (16%), and right AV valve surgery in 19 (13%). Freedom from subsequent reoperation at 10 years was 48% after initial repair of complete AVSD and 84% after initial repair of partial AVSD. During late follow-up, 10-year actuarial survival was 91% and 77% after initial repair of complete and partial AVSD, respectively. The most common indication for reoperation after initial repair of partial or complete AVSD is left AV valve pathology; left ventricular outflow tract obstruction was more common in partial AVSD. Although freedom from subsequent reoperations is higher after initial repair of partial AVSD, these patients have reduced long-term survival when compared with complete AVSD.

We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH ( P < 10 −75 ), ARMS2 ( P < 10 −59 ), C2/CFB ( P < 10 −20 ), C3 ( P < 10 −9 ), and CFI ( P < 10 −6 ). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 × 10 −11 ), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci ( LIPC , P = 1.3 × 10 −7 ; CETP , P = 7.4 × 10 −7 ) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c—associated alleles near LPL ( P = 3.0 × 10 −3 ) and ABCA1 ( P = 5.6 × 10 −4 ). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies.

The purpose of this study was to characterize the effect of TIEG1 on the molecular structure of collagen within tail tendon fibers using 3-mo-old female C57BL/6 wild-type (WT) and TIEG1 KO mice. Synchrotron X-ray microdiffraction experiments were carried out on single tendon fibers extracted from the WT and TIEG1 KO dorsal tail tendon. The fibers were scanned in the radial direction, and X-ray patterns were obtained. From these patterns, the meridional direction was analyzed through X-ray intensity profile. In addition, collagen content was investigated using hydroxyproline assays, and qualitative real-time PCR experiments were performed on RNA isolated from fibroblasts to examine specific gene expression changes. The results showed different X-ray diffraction patterns between WT and TIEG1 KO tendon fibers, indicating a disorganization of the collagen structure for the TIEG1 KO compared with WT mice. Furthermore, the analyses of the X-ray intensity profiles exhibited a higher (23 Å) period of collagen for the TIEG1 KO compared with the WT mice. The results of the hydroxyproline assays revealed a significant decrease in the TIEG1 KO compared with WT mice, leading to a decrease in the total amount of collagen present within the TIEG1 KO tendons. Moreover, qualitative real-time PCR results showed differences in the expression profiles of specific genes known to play important roles in tendon fiber development. These data further elucidate the role of TIEG1 on tendon structure and could explain the previous defects in the structure-function relationship found for TIEG1 KO tendon fibers.