Are anatomic brain locations important in determining the clinical outcomes in acute ischemic stroke? --- An exploratory analysis of the NINDS Stroke Trial data

Background and purpose. Brain lesions in acute ischemic stroke measured by imaging tools provide important clinical information for diagnosis and final infarct volume has been considered as a potential surrogate marker for clinical outcomes. Strong correlations have been found between lesion volume and clinical outcomes in the NINDS t-PA Stroke Trial but little has been published about lesion location and clinical outcomes. Studies of the National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Trial data found the direction of the t-PA treatment effect on a decrease in CT lesion volume was consistent with the observed clinical effects at 3 months, but measure of t-PA treatment benefits using CT lesion volumes showed a diminished statistical significance, as compared to using clinical scales. ^ Methods. We used the global test to evaluate the hypothesis that lesion locations were strongly associated with clinical outcomes within each treatment group at 3 months after stroke. The anatomic locations of CT scans were used for analysis. We also assessed the effect of t-PA on lesion location using a global statistical test. ^ Results. In the t-PA group, patients with frontal lesions had larger infarct volumes and worse NIHSS score at 3 months after stroke. The clinical status of patients with frontal lesions in t-PA group was less likely to be affected by lesion volume, as compared to those who had no frontal lesions in at 3 months. For patients within the placebo group, both brain stem and internal capsule locations were significantly associated with a lower odd of having favorable outcomes at 3 months. Using a global test we could not detect a significant effect of t-PA treatment on lesion location although differences between two treatment groups in the proportion of lesion findings in each location were found. ^ Conclusions. Frontal, brain stem, and internal capsule locations were significantly related to clinical status at 3 months after stroke onset. We detect no significant t-PA effect on all 9 locations although proportion of lesion findings in differed among locations between the two treatment groups.^

STUDY OF THE EFFECTS OF TOTAL MODULATION TRANSFER FUNCTION CHANGES ON OBSERVER PERFORMANCE USING CLINICAL MAMMOGRAMS

The main goal of this study was to relate physical changes in image quality measured by Modulation Transfer Function (MTF) to diagnostic accuracy.^ One Hundred and Fifty Kodak Min-R screen/film combination conventional craniocaudal mammograms obtained with the Pfizer Microfocus Mammographic system were selected from the files of the Department of Radiology, at M.D. Anderson Hospital and Tumor Institute.^ The mammograms included 88 cases with a variety of benign diagnosis and 62 cases with a variety of malignant biopsy diagnosis. The average age of the patient population was 55 years old. 70 cases presented calcifications with 30 cases having calcifications smaller than 0.5mm. 46 cases presented irregular bordered masses larger than 1 cm. 30 cases presented smooth bordered masses with 20 larger than 1 cm.^ Four separated copies of the original images were made each having a different change in the MTF using a defocusing technique whereby copies of the original were obtained by light exposure through different thicknesses (spacing) of transparent film base.^ The mammograms were randomized, and evaluated by three experienced mammographers for the degree of visibility of various anatomical breast structures and pathological lesions (masses and calicifications), subjective image quality, and mammographic interpretation.^ 3,000 separate evaluations were anayzed by several statistical techniques including Receiver Operating Characteristic curve analysis, McNemar test for differences between proportions and the Landis et al. method of agreement weighted kappa for ordinal categorical data.^ Results from the statistical analysis show: (1) There were no statistical significant differences in the diagnostic accuracy of the observers when diagnosing from mammograms with the same MTF. (2) There were no statistically significant differences in diagnostic accuracy for each observer when diagnosing from mammograms with the different MTF's used in the study. (3) There statistical significant differences in detail visibility between the copies and the originals. Detail visibility was better in the originals. (4) Feature interpretations were not significantly different between the originals and the copies. (5) Perception of image quality did not affect image interpretation.^ Continuation and improvement of this research ca be accomplished by: using a case population more sensitive to MTF changes, i.e., asymptomatic women with minimum breast cancer, more observers (including less experienced radiologists and experienced technologists) must collaborate in the study, and using a minimum of 200 benign and 200 malignant cases.^

An analysis of the effects of a peer mentor program and other factors on HIV patients' retention in care and clinical outcomes at Thomas Street Health Clinic, Houston Texas

Research examining programs designed to retain patients in health care focus on repeated interactions between outreach workers and patients (Bradford et al. 2007; Cheever 2007). The purpose of this study was to determine if patients who are peer-mentored at their intake exam remain in care longer and attend more physicians' visits than those who were not mentored. Using patients' medical records and a previously created mentor database, the study determined how many patients attended their intake visit but subsequently failed to establish regular care. The cohort study examined risk factors for establishing care, determined if patients lacking a peer mentor failed to establish care more than peer mentor assisted patients, and subsequently if peer mentored patients had better health outcomes. The sample consists of 1639 patients who were entered into the Thomas Street Patient Mentor Database between May 2005 and June 2007. The assignment to the mentored group was haphazardly conducted based on mentor availability. The data from the Mentor Database was then analyzed using descriptive statistical software (SPSS version 15; SPSS Inc., Chicago, Illinois, USA). Results indicated that patients who had a mentor at intake were more likely to return for primary care HIV visits at 90 and 180 days. Mentored patients also were more likely to be prescribed ART within 180 days from intake. Other risk factors that impacted remaining in care included gender, previous care status, time from diagnosis to intake visit, and intravenous drug use. Clinical health outcomes did not differ significantly between groups. This supports that mentoring did improve outcomes. Continuing to use peer-mentoring programs for HIV care may help in increasing retention of patients in care and improving patients' health in a cost effective manner. Future research on the effects of peer mentoring on mentors, and effects of concordance of mentor and patient demographics may help to further improve peer-mentoring programs. ^

A simulation study of the effects of small center enrollment in multi -center clinical trials

Multi-center clinical trials are very common in the development of new drugs and devices. One concern in such trials, is the effect of individual investigational sites enrolling small numbers of patients on the overall result. Can the presence of small centers cause an ineffective treatment to appear effective when treatment-by-center interaction is not statistically significant?^ In this research, simulations are used to study the effect that centers enrolling few patients may have on the analysis of clinical trial data. A multi-center clinical trial with 20 sites is simulated to investigate the effect of a new treatment in comparison to a placebo treatment. Twelve of these 20 investigational sites are considered small, each enrolling less than four patients per treatment group. Three clinical trials are simulated with sample sizes of 100, 170 and 300. The simulated data is generated with various characteristics, one in which treatment should be considered effective and another where treatment is not effective. Qualitative interactions are also produced within the small sites to further investigate the effect of small centers under various conditions.^ Standard analysis of variance methods and the "sometimes-pool" testing procedure are applied to the simulated data. One model investigates treatment and center effect and treatment-by-center interaction. Another model investigates treatment effect alone. These analyses are used to determine the power to detect treatment-by-center interactions, and the probability of type I error.^ We find it is difficult to detect treatment-by-center interactions when only a few investigational sites enrolling a limited number of patients participate in the interaction. However, we find no increased risk of type I error in these situations. In a pooled analysis, when the treatment is not effective, the probability of finding a significant treatment effect in the absence of significant treatment-by-center interaction is well within standard limits of type I error. ^

In vitro staining effects of stannous fluoride and sodium fluoride on ceramic material.

STATEMENT OF PROBLEM: Long-term fluoride application on the teeth of patients receiving radiation therapy for head and neck tumors results in excessive staining and roughening of ceramic restorations. PURPOSE: The purpose of this in vitro study was to compare the staining effects of 2 fluoride treatments on ceramic disks by simulating 1 year of clinical exposure at 10 minutes per day. In addition, 2 different surface preparations were tested. MATERIAL AND METHODS: Eighty ceramic disks (IPS Empress), 20 x 2 mm, were fabricated. Half of the disks were glazed, and the remaining disks were polished. All disks were brushed for 3 minutes with a soft-bristle power toothbrush and mild dentifrice (baseline) and were immersed in 1 of the 2 fluoride products (0.4% SnF(2), Gel-Kam Gel, or 1.1% NaF, Prevident 5000) for 10 days (n=20). Means and standard deviations of color change (Delta E), surface roughness (Ra, um), and surface gloss (GU) of the ceramic material were measured with a reflection spectrophotometer, a profilometer, and a gloss meter, respectively, at baseline and after fluoride treatment. Two- and 3-way ANOVA (alpha=.05), with surface preparation (polished vs. glazed) and fluoride treatment (0.4% SnF(2) or 1.1% NaF) as independent variables and condition (baseline vs. after fluoride treatment) as a repeated measure, was used to analyze the data. Fisher's PLSD intervals (alpha=.05) were calculated for comparisons among the means. RESULTS: The polished specimens had significantly higher Delta E values, significantly higher surface gloss values, and significantly lower surface roughness values than the glazed specimens before fluoride treatment (P<.001). After both fluoride treatments, ceramic disks exhibited significantly higher surface roughness values when polished and significantly lower surface gloss values when glazed or polished (P<.001). The glazed specimens presented significantly higher surface roughness (P<.001) and lower surface gloss values (P<.001) when treated with 0.4% SnF(2) as compared to NaF. For the polished specimens, there was no significant difference in surface roughness and surface gloss values between the 2 fluoride treatments. CONCLUSIONS: Use of 0.4% SnF(2) and 1.1% NaF gels, in vitro, caused significant color change in the polished IPS Empress ceramic disks. Polishing of the ceramic surface before immersion in either fluoride agent caused the ceramic tested to be more resistant to etching by the 2 solutions tested. The NaF caused less deterioration of the porcelain surface and was less stain inducing than SnF(2).

Computerized provider order entry adoption: implications for clinical workflow.

OBJECTIVE: To identify and describe unintended adverse consequences related to clinical workflow when implementing or using computerized provider order entry (CPOE) systems. METHODS: We analyzed qualitative data from field observations and formal interviews gathered over a three-year period at five hospitals in three organizations. Five multidisciplinary researchers worked together to identify themes related to the impacts of CPOE systems on clinical workflow. RESULTS: CPOE systems can affect clinical work by 1) introducing or exposing human/computer interaction problems, 2) altering the pace, sequencing, and dynamics of clinical activities, 3) providing only partial support for the work activities of all types of clinical personnel, 4) reducing clinical situation awareness, and 5) poorly reflecting organizational policy and procedure. CONCLUSIONS: As CPOE systems evolve, those involved must take care to mitigate the many unintended adverse effects these systems have on clinical workflow. Workflow issues resulting from CPOE can be mitigated by iteratively altering both clinical workflow and the CPOE system until a satisfactory fit is achieved.

Determination of an inoculum effect with various cephalosporins among clinical isolates of methicillin-susceptible Staphylococcus aureus.

Using 98 clinical methicillin-susceptible Staphylococcus aureus isolates of known beta-lactamase (Bla) type, we found a pronounced inoculum effect for cephalexin (mostly Bla type A and C strains), a mild inoculum effect for cephalothin (especially types B and C), and no inoculum effects for ceftriaxone and cefuroxime. Ceftobiprole showed the lowest MICs at a high inoculum but with a slight increase for Bla-positive versus Bla-negative strains. Since a potential therapeutic effect associated with a cephalosporin inoculum effect has been described, further studies are warranted.

Genes to blood pressure: The effects of variation in genes of the renin-angiotensin system on the hormonal and renal control of blood pressure

Objective. Essential hypertension affects 25% of the US adult population and is a leading contributor to morbidity and mortality. Because BP is a multifactorial phenotype that resists simple genetic analysis, intermediate phenotypes within the complex network of BP regulatory systems may be more accessible to genetic dissection. The Renin-Angiotensin System (RAS) is known to influence intermediate and long-term blood pressure regulation through alterations in vascular tone and renal sodium and fluid resorption. This dissertation examines associations between renin (REN), angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1) gene variation and interindividual differences in plasma hormone levels, renal hemodynamics, and BP homeostasis.^ Methods. A total of 150 unrelated men and 150 unrelated women, between 20.0 and 49.9 years of age and free of acute or chronic illness except for a history of hypertension (11 men and 7 women, all off medications), were studied after one week on a controlled sodium diet. RAS plasma hormone levels, renal hemodynamics and BP were determined prior to and during angiotensin II (Ang II) infusion. Individuals were genotyped by PCR for a variable number tandem repeat (VNTR) polymorphism in REN, and for the following restriction fragment length polymorphisms (RFLP): AGT M235T, ACE I/D, and AT1 A1166C. Associations between clinical measurements and allelic variation were examined using multiple linear regression statistical models.^ Results. Women homozygous for the AT1 1166C allele demonstrated higher intracellular levels of sodium (p = 0.044). Men homozygous for the AGT T235 allele demonstrated a blunted decrement in renal plasma flow in response to Ang II infusion (p = 0.0002). There were no significant associations between RAS gene variation and interindividual variation in RAS plasma hormone levels or BP.^ Conclusions. Rather than identifying new BP controlling genes or alleles, the study paradigm employed in this thesis (i.e., measured genes, controlled environments and interventions) may provide mechanistic insight into how candidate genes affect BP homeostasis. ^