Large Clinical Population Research Articles

Binocular Rivalry Measured 2 Hours After Occlusion Therapy Predicts the Recovery Rate of the Amblyopic Eye in Anisometropic Children.

Recent studies on adults have shown that short-term monocular deprivation boosts the deprived eye signal in binocular rivalry, reflecting homeostatic plasticity. Here we investigate whether homeostatic plasticity is present also during occlusion therapy for moderate amblyopia. Binocular rivalry and visual acuity (using Snellen charts for children) were measured in 10 children (mean age 6.2 ± 1 years) with moderate anisometropic amblyopia before the beginning of treatment and at four intervals during occlusion therapy (2 hours, 1, 2, and 5 months). Visual stimuli were orthogonal gratings presented dichoptically through ferromagnetic goggles and children reported verbally visual rivalrous perception. Bangerter filters were applied on the spectacle lens over the best eye for occlusion therapy. Two hours of occlusion therapy increased the nonamblyopic eye predominance over the amblyopic eye compared with pretreatment measurements, consistent with the results in adults. The boost of the nonamblyopic eye was still present after 1 month of treatment, steadily decreasing afterward to reach pretreatment levels after 2 months of continuous occlusion. Across subjects, the increase in nonamblyopic eye predominance observed after 2 hours of occlusion correlated (rho = -0.65, P = 0.04) with the visual acuity improvement of the amblyopic eye measured after 2 months of treatment. Homeostatic plasticity operates during occlusion therapy for moderate amblyopia and the increase in nonamblyopic eye dominance observed at the beginning of treatment correlates with the amblyopic eye recovery rate. These results suggest that binocular rivalry might be used to monitor visual cortical plasticity during occlusion therapy, although further investigations on larger clinical populations are needed to validate the predictive power of the technique.

Predictors of Human Papillomavirus Vaccination in a Large Clinical Population of Males Aged 11 to 26 years in Maryland, 2012-2013.

Despite the recommendation for routine human papillomavirus (HPV) vaccination in males, coverage estimates remain low. We sought to identify predictors of receiving each HPV vaccine dose among a large clinical population of males. We conducted a cross-sectional analysis of electronic medical records for 14,688 males ages 11 to 26 years attending 26 outpatient clinics (January 2012-April 2013) in Maryland to identify predictors of each HPV vaccine dose using multivariate logistic regression models with generalized estimating equations. All analyses were stratified in accordance with vaccine age recommendations: 11 to 12 years, 13 to 21 years, and 22 to 26 years. Analyses of predictors of receipt of subsequent HPV doses were also stratified by the number of clinic visits (≤3 and >3). Approximately 15% of males initiated the HPV vaccine. Less than half of males eligible received the second and third doses, 49% and 47%, respectively. Non-Hispanic black males (vs. non-Hispanic white) ages 11 to 12 and 13 to 21 years and males with public insurance (vs. private) ages 13 to 21 years had significantly greater odds of vaccine initiation, but significantly decreased odds of receiving subsequent doses, respectively. Attendance to >3 clinic visits attenuated the inverse association between public insurance and receipt of subsequent doses. Overall, rates of HPV vaccine initiation and of subsequent doses were low. While non-Hispanic black and publicly insured males were more likely to initiate the HPV vaccine, they were less likely to receive subsequent doses. Tailoring different intervention strategies for increasing HPV vaccine initiation versus increasing rates of subsequent doses among males may be warranted.

Q-space trajectory imaging for clinical schizophrenia studies

Event Abstract Back to Event Q-space trajectory imaging for clinical schizophrenia studies Ofer Pasternak1* 1 Harvard Medical School, Department of Radiology, Bringham and Women's Hospital, United States As q-space trajectory imaging (QTI), and other advanced diffusion encoding schemes, become available, an important question is the feasibility and utility of these schemes for clinical studies. Schizophrenia is one of the main clinical fields in which diffusion imaging provided new ways to identify and understand the disorder. For example, paradigms involving demyelination, neuroinflammation and disconnectivity became substantial following evidence from diffusion imaging studies. In my talk I will review some of the key findings of diffusion imaging in schizophrenia, and will outline the need for more advanced imaging modalities, such as QTI. QTI provides sensitivity to new features, such as eccentricity, however, and perhaps more important for schizophrenia studies, QTI can disentangle several contributions that affect current diffusion measures. These more specific measures provide a stronger link between the identification of group-wise imaging abnormalities, and the understanding of the underlying pathologies, bringing us closer to understanding the etiology and pathophysiology of the disorder. We have implemented QTI on clinical scanners and collected a small pilot dataset from subjects diagnosed with schizophrenia, along with controls. I will present findings from this pilot study, where QTI measures are able to explain changes that are identified in conventional diffusion MRI. I will also present our current sequences that are being used to collect QTI on larger clinical populations. The sequences require less than 15 minutes, similar to advanced DTI measures, demonstrating that QTI sequences can be acquired in clinical feasible times. Keywords: Diffusion, MRI, dMRI, multidimensional, diffusion encoding Conference: New dimensions in diffusion encoding, Fjälkinge, Sweden, 11 Jan - 14 Jan, 2016. Presentation Type: Oral presentation Topic: New Dimensions in Diffusion Encoding Citation: Pasternak O (2016). Q-space trajectory imaging for clinical schizophrenia studies. Front. Phys. Conference Abstract: New dimensions in diffusion encoding. doi: 10.3389/conf.FPHY.2016.01.00002 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 07 Jul 2016; Published Online: 07 Jul 2016. * Correspondence: Prof. Ofer Pasternak, Harvard Medical School, Department of Radiology, Bringham and Women's Hospital, Boston, Massachusetts, MA 02215, United States, ofer@bwh.harvard.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Ofer Pasternak Google Ofer Pasternak Google Scholar Ofer Pasternak PubMed Ofer Pasternak Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

A meta-analysis of four randomized clinical trials to confirm the reliability and responsiveness of the Shortness of Breath with Daily Activities (SOBDA) questionnaire in chronic obstructive pulmonary disease.

BackgroundChronic obstructive pulmonary disease (COPD) is characterized by non-reversible airflow limitation. A common symptom of COPD is dyspnea or shortness of breath. Dyspnea may vary daily, with a large impact on patients’ lives. Previous clinical trials used patient-reported outcome (PRO) measures that quantified dyspnea at discrete intervals and hence did not reflect this variability. Recently the Shortness of Breath with Daily Activities (SOBDA) questionnaire was developed as a PRO measure of dyspnea utilizing a daily diary. This confirmatory post hoc meta-analysis of SOBDA data from a large clinical study program further supports the questionnaire and clarifies the minimum threshold of SOBDA response.MethodsData from four clinical trials (DB2113361, NCT01313637; DB2113373, NCT01313650; DB2113360, NCT01316900; DB2113374, NCT01316913) were analyzed. These 24-week trials were randomized, blinded studies investigating the efficacy and safety of several COPD treatments. These post hoc analyses focused on the SOBDA questionnaire properties. This electronic-diary consists of 13 items completed daily, in which patients rate their breathlessness level during common daily activities. Resultant SOBDA scores were compared with related, commonly used assessments: modified Medical Research Council Research Dyspnea Scale (mMRC), Baseline Dyspnea Index (BDI), Transition Dyspnea Index (TDI), St George’s Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), and trough forced expiratory volume in 1 s (FEV1). The consistency, reliability, validity (convergent, known groups), and responsiveness of the SOBDA questionnaire was assessed.ResultsIn total, 4967 patients with COPD provided data for these analyses. The SOBDA questionnaire had high internal consistency (Cronbach’s alpha = 0.936), high test-retest reliability (Pearson’s correlation coefficient = 0.86) and convergent validity with related measures (SGRQ total score, Pearson’s correlation coefficient = 0.59; CAT, Spearman rank-order correlation coefficient = 0.50). SOBDA scores were statistically significantly lower in responders (as defined by TDI, SGRQ, CAT, and trough FEV1 levels) versus non-responders (p < 0.001 for all assessments and all time points). Using an anchor-based method, the threshold of a minimum response was calculated as a SOBDA score change of −0.2 (SOBDA score range = 1–4).ConclusionsThe reliability, validity, and responsiveness of the SOBDA questionnaire as a PRO measure to quantify dyspnea was supported in a large clinical trial population of patients with moderate–very severe COPD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12955-015-0369-3) contains supplementary material, which is available to authorized users.

Prevalence and determinants of white coat effect in a large UK hypertension clinic population.

White coat hypertension (WCH) is common and termed white coat effect (WCE) in those on treatment for hypertension. The UK guideline suggests that all patients in stage 1 and 2 hypertension, but not stage 3 hypertension, should have ambulatory blood pressure monitoring (ABPM) performed before commencing treatment. The relationship between office blood pressure (BP) and ABPM and the factors that influence the WCE were examined in a large British cohort (n=2056) from 2 hypertension clinics (1998-2011). Data were collected prospectively: the median age was 56 years: 53% were female, 76% Caucasian, 9% African Caribbean, 15% South Asian and 86% taking antihypertensives. Fifty-one percent had WCE and differences between clinic BP and ABPM measurements increased with the stage of hypertension varying from 2/4 (normotensive), 13/10 (stage 1 hypertension), 24/14 (stage 2) and 40/20 mm Hg (stage 3). The degree of difference is greater in this study than described in other populations. A positive correlation was found between clinic systolic and diastolic BP and the WCE (r=0.74 and r=0.56, respectively, P<0.0001). Significant (P<0.05) independent associations of systolic WCE were clinic systolic BP (β=0.707), Caucasian ethnicity (South Asian β=-0.06; African Caribbean β=-0.043), female gender (male β=-0.047), nonsmoking status (smoker β=-0.100) and reduced renal function (estimated glomerular filtration rate β=-0.036). Significant independent associations of diastolic WCH were clinic diastolic BP (β=0.624), age (β=0.207), female gender (male β=-0.104), Caucasian ethnicity (South Asian β=-0.052, African Caribbean β=-0.079) and being a nonsmoker (β=-0.082) or ex-smoker (β=0.046). The results support current UK guidelines but suggest those with stage 3 hypertension would also benefit from ABPM.

Abstract 5591: Factors associated with HPV vaccine initiation among males aged 11-26 years attending outpatient clinics in the Baltimore Metro Area during 2012 - 2013

Abstract Introduction: Few studies have examined factors associated with HPV vaccine initiation among males, particularly after the Advisory Committee on Immunization Practices upgraded their recommendation in late 2011. The aim of our study was to identify demographic characteristics and care-seeking behaviors associated with HPV vaccine initiation among a large clinical population of age-eligible males. Methods: This is a cross-sectional analysis of electronic health record data from 15,970 males aged 11-26 years attending 24 Johns Hopkins Community Physicians clinics from January 2012 - April 2013 in Baltimore, MD. Our outcome was receipt of first dose of the HPV vaccine series (“initiation”). We calculated mutually adjusted odds ratios (aOR) of initiation and 95% Confidence Intervals (95% CI) using multivariate logistic regression models with generalized estimating equations to account for clustering within clinics for age (continuous), race (black, Asian, other vs. white), insurance type (public, military, vs. private), number of clinic visits (1 vs. 2+), attendance to a preventive care visit during the study period (vs. not), and practice specialty (Internal Medicine, Pediatrics, Med-Peds vs. Family Practice). Results were stratified by the following age groups: 11-12 years (target age for vaccination, “target”), 13-21 years (catch-up age for vaccination, “catch-up”), and 22-26 years (permissive age for vaccination, “permissive”). Results: A total of 2,193 (14%) males initiated the HPV vaccine. Initiation varied by age; 23.2%, 16.5%, and 1.9% in the target, catch-up, and permissive age groups respectively. Among the target age group, black race (aOR 1.3; 95% CI 1.0-1.7), 1 clinic visit (aOR 0.7; 95% CI 0.5-0.9), and attendance to a preventive care visit (aOR 8.1; 95% CI 4.9-13.4) were significantly associated with odds of initiation. Among the catch-up age group, age (aOR 0.9; 95% CI 0.9-0.95), black race (aOR 1.2; 95% CI 1.0 - 1.4), 1 clinic visit (aOR 0.6; 95% CI 0.5-0.7), attendance to a preventive care visit (aOR 4.6; 95% CI 3.6-5.8) and Internal Medicine practice (aOR 0.4; 95% CI 0.3-0.5) were significantly associated with odds of initiation. Among the permissive age group, age (aOR 0.8; 95% CI 0.7 - 1.0), 1 clinic visit (aOR 0.4, 95% CI 0.3-0.5) attendance to a preventive care visit (aOR 5.1; 95% CI 3.0-8.9), military insurance (aOR 3.0; 95% CI 1.4 - 6.4) and Internal Medicine practice (aOR 0.5; 95% CI 0.3-0.8) were significantly associated with odds of initiation. Discussion: Overall, HPV vaccine initiation rates fell below state and national averages. In line with other studies, initiation was highest among black males. Among all ages, preventive care visits were associated with initiation. More education on the value of catch-up vaccination among adult-focused specialties (e.g. Internal Medicine) may increase HPV vaccination initiation among males aged 13 - 26 years. Citation Format: Megan Clarke, Darcy F. Phelan-Emrick, Francesca Coutinho, Betty Chou, Corinne E. Joshu. Factors associated with HPV vaccine initiation among males aged 11-26 years attending outpatient clinics in the Baltimore Metro Area during 2012 - 2013. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5591. doi:10.1158/1538-7445.AM2015-5591

Study Design Implications of Death and Hospitalization as End Points in Idiopathic Pulmonary Fibrosis

The feasibility of an interventional clinical trial in idiopathic pulmonary fibrosis (IPF) using death and hospitalization as primary end points is an area of uncertainty. Using data from a large well-characterized clinical trial population, this article aims to illustrate the impact of cohort enrichment and study duration on sample size requirements for IPF clinical trials in which death alone or death plus hospitalization serve as the primary end point. Event rate estimates for death and hospitalization were determined from patients enrolled in National Institutes of Health-sponsored IPF Clinical Research Network clinical trials. Standard equations were applied to estimate the total sample size required for varying gender, age, and pulmonary function (GAP) stage-based cohorts. Risk estimates for death and hospitalization in the clinical trial cohort were substantially lower than those published. An IPF trial with death as its primary end point enrolling subjects designated as GAP stage 1 and 2 over 1 year with a minimum follow-up of 1 year would require an estimated 7,986 subjects to achieve 90% power for a hazard ratio of 0.70. Alternatively, an IPF trial with death plus hospitalization as its primary end point enrolling subjects with GAP stage 2 and 3 over 2 years with a minimum follow-up of 1 year would require an estimated 794 subjects for the same power and hazard ratio. Study design decisions, in particular cohort enrichment strategies, have a substantial impact on sample size requirements for IPF clinical trials using time-to-event primary end points such as death and death plus hospitalization.

Attempted suicide in patients with eating disorders.

Suicide is a major cause of mortality for patients with eating disorders (ED), especially for patients with anorexia nervosa. Attempted suicide is also relatively common in patients with anorexia or bulimia nervosa. This study aimed at examining associations between attempted suicide and trait- and state-dependent characteristics in a large clinical population of ED patients. The sample consisted of 1,436 in- and outpatients of the Centre for Eating Disorders of the Ghent University Hospital. Measures of ED symptoms, psychopathology, and personality traits were compared between ED patients with and ED patients without a history of attempted suicide. A history of attempted suicide was found in 11.8% of the ED patients and lifetime suicidal ideation was reported by 43.3%. Multivariate analyses showed that a history of attempted suicide was associated with higher scores on depression, purging symptomatology, early-developed cognitive schemes (impaired autonomy and increased inhibition), and social insecurity. These findings support the increased risk of suicidal behavior in ED. The presence of particular personality traits, of cognitive schemes, and of purging and depressive symptoms should increase vigilance for suicidal behavior.

Contact sensitization in patients with suspected cosmetic intolerance: results of the IVDK 2006-2011.

Ingredients of leave-on cosmetics and body care products may sensitize. However, not every case of cosmetic intolerance is due to contact sensitization. To describe the frequency of contact sensitization due to cosmetics in a large clinic population, and a possible particular allergen pattern. Retrospective analysis of data from the Information Network of Departments of Dermatology, 2006-2011. Of 69 487 patients tested, 'cosmetics, creams, sunscreens' was the only suspected allergen source category in 10 124 patients (14.6%). A final diagnosis 'allergic contact dermatitis' was stated in 2658 of these patients (26.3%).Compared to a control group, there were significantly more reactions to fragrance mixes I and II, balsam of Peru, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and lanolin alcohols. No special pattern of fragrance sensitization could be identified. Among the preservatives, MI was by far the leading allergen, while sensitization to other widely used compounds like parabens or phenoxyethanol was rare. True allergic reactions to cosmetic ingredients are rarer than generally assumed. Limitation of exposure to MI in leave-on cosmetics and body care products is urgently needed.

Toxgnostics: predicting and preventing chemotherapy-induced side effects.

Toxgnostics: predicting and preventing chemotherapy-induced side effects.

Rates of Glaucomatous Visual Field Change in a Large Clinical Population

To determine the rate of glaucomatous visual field change in routine clinical care. Mean deviation (MD) rate was computed in one randomly selected eye of all glaucoma patients and suspects with ≥5 examinations in a tertiary eye-care center. Proportions of "fast" (MD rate, <-1 to -2 dB/y) and "catastrophic" (<-2 dB/y) progressors were determined. The MD rates were computed in tertile groups by the number of examinations, baseline age, and MD. The MD rates were compared to the Canadian Glaucoma Study (CGS), a prospective study with IOP interventions mandated by visual field progression, by pairwise matching of patients by baseline MD. There were 2324 patients with median (interquartile range) baseline age and MD of 65 (56, 74) years and -2.44 (-5.44, -0.86) dB, and follow-up of 7.1 (4.8, 10.2) years with 8 (6, 11) examinations. The median MD rate was -0.05 (0.13, -0.30) dB/y, while the mean follow-up IOP was 17.1 (15.0, 19.7) mm Hg. The MD rate was progressively worse, with a doubling of fast and catastrophic progressors, with each tertile of increasing age. Worse MD rate was associated with lower follow-up IOP. Neither MD rate nor the number of fast and catastrophic progressors was significantly different in clinical care patients matched to CGS patients. Most patients under routine glaucoma care demonstrate slow rates of visual field progression. The MD rate in the current study was similar to an interventional prospective study, but considerably less negative compared to published studies with similar design.

Characteristics of HIV+ lung cancer cases in a large clinical population: Implications for lung cancer screening.

1569 Background: Lung cancer (LCa) accounts for ~30% of cancer deaths and 10% of non-HIV-related deaths among HIV(+)s. Compared to those in the general population, even after accounting for smoking...

Validation of the Italian version Inventory of Complicated Grief (ICG): A study comparing CG patients versus bipolar disorder, PTSD and healthy controls

BackgroundA minority (9%–20%) of bereaved individuals experience symptoms of persistent intense grief associated with significant distress and impairment. This recently identified distinct post-loss syndrome has been variously named complicated grief, prolonged grief disorder, traumatic grief and persistent complex bereavement disorder. The Inventory of Complicated Grief (ICG) is a self-report instrument used to reliably identify this syndrome. We undertook a study to: 1) validate the Italian version of the ICG; 2) examine its performance in a clinical of bereaved individuals with complicated grief, post-traumatic stress disorder, bipolar disorder and healthy controls. MethodsStudy participants included 171 bereaved individuals clinically diagnosed with complicated grief (n=64); post-traumatic stress disorder (n=72); bipolar disorder (n=35) and 58 bereaved healthy controls. Assessments included the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I/P) and the Italian version of the ICG. ResultsThe mean total ICG score was significantly different among the study groups [F(3.228)=94.19, p<.001]. Post-hoc Games–Howell comparisons indicated significantly higher scores in complicated grief patients with respect to the other three groups and significantly lower scores in healthy controls compared to all other participants. The scale demonstrated a high level of internal consistency: Cronbach’s alpha value for the whole sample was 0.947. Factor analyses demonstrated a single-factor solution. ConclusionsThis study provides evidence of the validation of the Italian version of the ICG, tested in a large and well-characterized clinical help-seeking population. These data further support the existence of a unique grief-related syndrome different from bipolar and post-traumatic stress disorders.

Suicide attempts and mortality in eating disorders: a follow-up study of eating disorder patients

ObjectiveThe aim of this study is to explore the prevalence of hospital-treated suicide attempts in a large clinical population of eating disorder patients. MethodFollow-up study of adults (N=2462, 95% women, age 18–62 years) admitted to the Eating Disorder Clinic of Helsinki University Central Hospital in the period 1995–2010. For each patient, four controls were selected and matched for age, sex and place of residence. The end point events were modeled using Cox’s proportional hazard model, taking matching into account. ResultsWe identified 156 patients with eating disorder (6.3%) and 139 controls (1.4%) who had required hospital treatment for attempted suicide. Of them, 66 (42.3%) and 37 (26.6%) had more than one attempt. The rate ratio (RR) for suicide attempt in patients with eating disorder was 4.70 [95% confidence interval (CI) 1.41–15.74]. In anorexia nervosa, RR was 8.01 (95% CI 5.40–11.87), and in bulimia nervosa, it was 5.08 (95% CI 3.46–7.42). In eating disorder patients with a history of suicide attempt, the risk of death from any cause was 12.8%, suicide being the main cause in 45% of the deaths. ConclusionSuicide attempts and repeated attempts are common among patients with eating disorders. Suicidal ideation should be routinely assessed from patients with eating disorders.

EPA-1337 – Validation of the italian version inventory of complicated grief (ICG): a study on complicated grief symptom profile

Background A minority (9–20%) of subjects facing bereavement may develop symptoms of unresolved grief associated with significant distress and impairment that have been recently identified as a distinct post-loss syndrome named complicated grief. The Inventory of Complicated Grief is a self-report instrument to assess complicated grief. Aim of this study was to: 1) validate the Italian version of the Inventory of Complicated Grief; 2) provide additional evidence of complicated grief diagnosis through analysis of complicated grief symptoms in a clinical data set consisting of bereaved individuals with complicated grief, Post-Traumatic Stress Disorder, bipolar disorder and healthy controls. Methods 229 bereaved subjects were consecutively enrolled: 64 with complicated grief; 72 with post-traumatic stress disorder; 35 with bipolar disorder; 58 healthy controls. Assessments included: the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I/P) and the Italian version of the Inventory of Complicated Grief. Results The mean total ICG score was significantly different among the study groups [F(3.228)=94.19, p Conclusions This study provides evidence of the validation of the Italian version of the ICG, tested in a large and well-characterized clinical help-seeking population. It also supports the proposition that complicated grief is an independent diagnosis.

GW24-e3041 The prevalence of myocardial delayed enhancement of cardiac magnetic resonance imaging in different kinds of structural heart disease and influence on left ventricular remodelling

ObjectivesRecent studies have demonstrated LGE characteristics had a great role in diagnosis and evaluation of heart disease and provide risk stratification for cardiovascular disease. In the present study, we were...

Protective Effect of Angiotensin-Converting Enzyme Inhibitor Therapy Among Persons With HIV and Proteinuria

To the Editors: Proteinuria has been shown to be predictive of death in populations with and without HIV disease.1,2 In addition to diagnosing HIV infection early to prompt timely initiation of antiretroviral therapy, early consideration of angiotensin-converting enzyme (ACE) inhibitor therapy among persons with HIV and proteinuria to improve survival should be considered. To determine the potential protective effect of ACE inhibitor therapy for selected adverse outcomes among patients with HIV and proteinuria, a retrospective review of a large ambulatory clinic population with HIV based in New Orleans was performed. Patients were eligible for the study if they were ≥18 years and had at least 2 valid urinalyses between 7/06 and 6/08. Urinalyses showing gross blood (defined as ≥10 red blood cells per high-power field) and/or pyuria (defined as ≥10 white blood cells per high-power field) were considered invalid. Patients meeting the study criteria were followed up through 6/11 for hospitalization and all-cause mortality. Of the 140 patients having at least 2 valid urinalyses, 41 (29%) had ≥2 tests, 43 (31%) had only 1 test, and 56 (40%) had no urinalyses demonstrating proteinuria at levels of ≥25 mg/dL. Characteristics of the cohort showed 38 (27%) were women and 109 (78%) were African American. Median baseline age, CD4 cell count, and HIV RNA copies were 45 years, 154 cells per cubic millimeter, and 63,900 copies per milliliter, respectively. Of the 140 patients, 39 (28%) were on an ACE inhibitor. Bivariate analysis showed that ever proteinuria was not associated with sex, race, age, substance use, antiretroviral therapy, body mass index, systolic or diastolic blood pressure, ACE therapy, or selected medical conditions (including diabetes, hypertension, renal disease, and hepatitis). Proteinuria (levels ≥25 mg/dL on ≥1 urinalysis) was associated with ever having a CD4 cell count <200 cells per cubic millimeter (P = 0.03), a detectable HIV RNA level >400 copies per milliliter (P = 0.03), or a baseline albumin level of <3.5 mg/dL. On bivariate analyses, proteinuria was also significantly associated with hospitalization or death, but only in patients not on an ACE inhibitor. As shown in Table 1, on multivariate analyses including the entire cohort, the association between proteinuria and hospitalization or death remained significant after controlling for confounding factors (including sex, race, CD4 count, HIV RNA level, creatinine, and baseline albumin). In analyses stratified by ACE inhibitor therapy, the association between the adverse outcomes and proteinuria was only significant among patients not on an ACE inhibitor. Patients off an ACE inhibitor compared with those on an ACE inhibitor had 2 and 4 times the risk of hospitalization and death, respectively.TABLE 1: Proteinuria* as a Risk of Hospitalization and Death Stratified by ACE Inhibitor TherapyOur results demonstrate that both recurrent and ever low-level proteinuria were relatively common among persons with advanced HIV disease. Hospitalization and death outcomes were more frequent among all persons with ever compared with never proteinuria. However, proteinuria was a significant predictor for these adverse outcomes only among persons not on an ACE inhibitor. Our data suggest that patients with HIV and any proteinuria, even episodic low levels, may benefit from ACE inhibitor therapy. Larger prospective studies need to confirm these results.

BioBanking as the central tool for translational medicine CTM issue 2013

The impact of mapping the human proteomeGlobally, the health care organizations are under resource and cost constrains due to the increasing number of patients that are due to a fast increase of the 65+ age group requiring extensive medical hospitalization and treatments. Hospitals worldwide strive to seek the best cure for patients, suffering from various diseases. A consequence of these global changes, of healthy populations in relation to patients forms the basis for the build of large and centralized biobank facilities, with strategies where the search for an understanding of diseases at a molecular level is at heart. The efforts made lies within large governmental resource allocations where patient centers are collecting samples from clinical study participants in order to try to discover universal expression patterns and molecular signatures of disease and disease stages. Most developments in this area are aimed towards the discovery, and understanding diagnosis implementations. By providing the right treatment alternatives for patients care, at the right time point i.e., at a given disease stage development becomes a major goal where pharmaceutical industry, academia and the health care sector joins forces in large clinical epidemiological, population-, and disease based studies. This becomes a clear strategic link to the enhancement and prospects for personalized medicines and target directed diagnosis developments (Companion Diagnostics), which require coordinated efforts across a wide range of disciplines. Currently, companion diagnostics is at the core of the personalized medicine paradigm shift. It will identify patients who are most likely to benefit from a particular therapeutic product, as well as identify patients likely to be at increased risk for serious adverse reactions as a result of treatment with a particular therapeutic agent. It is predicted that more than half of all new drugs will require a companion diagnostic, which opens up for an endeavor for Proteomics research implementations.

Microstructural analysis of pineal volume using trueFISP imaging

To determine the spectrum of pineal microstructures (solid/cystic parts) in a large clinical population using a high-resolution 3D-T2-weighted sequence. A total of 347 patients enrolled for cranial magnetic resonance imaging were randomly included in this study. Written informed consent was obtained from all patients. The exclusion criteria were artifacts or mass lesions prohibiting evaluation of the pineal gland in any of the sequences. True-FISP-3D-imaging (1.5-T, isotropic voxel 0.9 mm) was performed in 347 adults (55.4 ± 18.1 years). Pineal gland volume (PGV), cystic volume, and parenchyma volume (cysts excluded) were measured manually. Overall, 40.3% of pineal glands were cystic. The median PGV was 54.6 mm(3) (78.33 ± 89.0 mm(3)), the median cystic volume was 5.4 mm(3) (15.8 ± 37.2 mm(3)), and the median parenchyma volume was 53.6 mm(3) (71.9 ± 66.7 mm(3)). In cystic glands, the standard deviation of the PGV was substantially higher than in solid glands (98% vs 58% of the mean). PGV declined with age (r = -0.130, P = 0.016). The high interindividual volume variation is mainly related to cysts. Pineal parenchyma volume decreased slightly with age, whereas gender-related effects appear to be negligible.

Analysis of Higher-Order Aberrations in a Large Clinical Population

To use a large wave-front database of a clinical population to investigate relationships between refractions and higher-order aberrations and between aberrations of right and left eyes. Third- and fourth-order aberration coefficients and higher-order root-mean-squared aberrations (HO RMS), scaled to a pupil size of 4.5-mm diameter, were analyzed in a population of approximately 24,000 patients from Carl Zeiss Vision's European wave-front database. Correlations were determined between the aberrations and the variables of refraction, near addition, and cylinder. Most aberration coefficients were significantly dependent upon these variables, but the proportion of aberrations that could be explained by these factors was less than 2% except for spherical aberration (12%), horizontal coma (9%), and HO RMS (7%). Near addition was the major contributor for horizontal coma (8.5% out of 9.5%) and spherical equivalent was the major contributor for spherical aberration (7.7% out of 11.6%). Interocular correlations were highly significant for all aberration coefficients, varying between 0.16 and 0.81. Anisometropia was a variable of significance for three aberrations (vertical coma, secondary astigmatism, and tetrafoil), but little importance can be placed on this finding because of the small proportion of aberrations that can be explained by refraction (all <1.0%). Most third- and fourth-order aberration coefficients were significantly dependent upon spherical equivalent, near addition, and cylinder, but only horizontal coma (9%) and spherical aberration (12%) showed dependencies greater than 2%. Interocular correlations were highly significant for all aberration coefficients, but anisometropia had little influence on aberration coefficients.