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A Community-Integrated Home Based Depression Intervention For Older African Americans: Descripton Of The Beat The Blues Randomized Trial And Intervention Costs., Laura N Gitlin, Lynn Fields Harris, Megan Mccoy, Nancy L Chernett, Eric Jutkowitz, Laura T Pizzi

Center for Applied Research on Aging and Health Research Papers

ABSTRACT: BACKGROUND: Primary care is the principle setting for depression treatment; yet many older African Americans in the United States fail to report depressive symptoms or receive the recommended standard of care. Older African Americans are at high risk for depression due to elevated rates of chronic illness, disability and socioeconomic distress. There is an urgent need to develop and test new depression treatments that resonate with minority populations that are hard-to-reach and underserved and to evaluate their cost and cost-effectiveness. METHODS/DESIGN: Beat the Blues (BTB) is a single-blind parallel randomized trial to assess efficacy of a non-pharmacological intervention to …

Does Place Of Residence Affect Risk Of Suicide? A Spatial Epidemiologic Investigation In Kentucky From 1999 To 2008, Daniel M. Saman, Sabrina Walsh, Anna Borówko, Agricola Odoi

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: Approximately 32,000 people take their own lives every year in the United States. In Kentucky, suicide mortality rates have been steadily increasing since 1999. Few studies in the United States have assessed spatial clustering of suicides. The purpose of this study was to identify high-risk clusters of suicide at the county level in Kentucky and assess the characteristics of those suicide cases within the clusters.

METHODS: A spatial epidemiological study was undertaken using suicide data for the period January 1, 1999 to December 31, 2008, obtained from the Kentucky Office of Vital Statistics. Descriptive analyses using Pearson's chi-square test …

Identification Of Functionally Distinct Traf Proinflammatory And Pi3k/Mek Transforming Activities Emanating From The Ret/Ptc Fusion Oncoprotein, Josephine H.F. Wixted, Jay L. Rothstein, Laurence C. Eisenlohr

Kimmel Cancer Center Faculty Papers

Thyroid carcinomas that harbor RET/PTC oncogenes are well differentiated, relatively benign neoplasms compared with those expressing oncogenic RAS or BRAF mutations despite signaling through shared transforming pathways. A distinction, however, is that RET/PTCs induce immunostimulatory programs, suggesting that, in the case of this tumor type, the additional pro-inflammatory pathway reduces aggressiveness. Here, we demonstrate that pro-inflammatory programs are selectively activated by TRAF2 and TRAF6 association with RET/PTC oncoproteins. Eliminating this mechanism reduces pro-inflammatory cytokine production without decreasing transformation efficiency. Conversely, ablating MEK/ERK or PI3K/AKT signaling eliminates transformation but not pro-inflammatory cytokine secretion. Functional uncoupling of the two pathways demonstrates that …

Effects Of Preoperative Aspirin On Cardiocerebral And Renal Complications In Non-Emergent Cardiac Surgery Patients: A Sub-Group And Cohort Study., Longhui Cao, Scott Silvestry, Ning Zhao, James Diehl, Jianzhong Sun

Department of Anesthesiology Faculty Papers

BACKGROUND AND OBJECTIVE: Postoperative cardiocerebral and renal complications are a major threat for patients undergoing cardiac surgery. This study was aimed to examine the effect of preoperative aspirin use on patients undergoing cardiac surgery.

METHODS: An observational cohort study was performed on consecutive patients (n = 1879) receiving cardiac surgery at this institution. The patients excluded from the study were those with preoperative anticoagulants, unknown aspirin use, or underwent emergent cardiac surgery. Outcome events included were 30-day mortality, renal failure, readmission and a composite outcome - major adverse cardiocerebral events (MACE) that include permanent or transient stroke, coma, perioperative myocardial …

Efficacy And Safety Characteristics Of Mometasone Furoate/Formoterol Fumarate Fixed-Dose Combination In Subjects With Moderate To Very Severe Copd: Findings From Pooled Analysis Of Two Randomized, 52-Week Placebo-Controlled Trials, Donald P. Tashkin, Dennis E. Doherty, Edward Kerwin, Carlos E. Matiz-Bueno, Barbara Knorr, Tulin Shekar, Davis Gates, Heribert Staudinger

Internal Medicine Faculty Publications

Background:

The clinical efficacy and safety of a mometasone furoate/formoterol fumarate (MF/F) fixed-dose combination formulation administered via a metered-dose inhaler was investigated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).

Methods:

Two 52-week, multicenter, double-blind, placebo-controlled trials with identical study designs were conducted in current or ex-smokers (aged =40 years), and pooled study results are presented herein. Subjects (n = 2251) were randomized to 26 weeks of twice-daily treatment with MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. After the 26-week treatment period, placebo subjects completed the trial and 75% …

Effects Of Mometasone Furoate/Formoterol Fumarate Fixed-Dose Combination Formulation On Chronic Obstructive Pulmonary Disease (Copd): Results From A 52-Week Phase Iii Trial In Subjects With Moderate-To-Very Severe Copd, Dennis E. Doherty, Donald P. Tashkin, Edward Kerwin, Barbara Knorr, Tulin Shekar, Sibabrata Banerjee, Heribert Staudinger

Internal Medicine Faculty Publications

RATIONALE: The purpose of this study was to investigate the clinical efficacy and safety of a fixed-dose combination of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate-to-very severe chronic obstructive pulmonary disease (COPD).

METHODS: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1196), at least 40 years old, were current or ex-smokers randomized to twice-daily inhaled MF/F 400/10 μg, MF/F 200/10 μg, MF 400 μg, F 10 μg, or placebo. The trial's co-primary endpoints were mean changes from baseline, as area under the curve (AUC), …

Efficacy And Safety Characteristics Of Mometasone Furoate/Formoterol Fumarate Fixed-Dose Combination In Subjects With Moderate To Very Severe Copd: Findings From Pooled Analysis Of Two Randomized, 52-Week Placebo-Controlled Trials, Donald P. Tashkin, Dennis E. Doherty, Edward Kerwin, Carlos E. Matiz-Bueno, Barbara Knorr, Tulin Shekar, Sibabrata Banerjee, Heribert Staudinger

Internal Medicine Faculty Publications

Background: A clinical trial of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate to very severe chronic obstructive pulmonary disease (COPD) investigated the efficacy and safety of a fixed-dose combination of MF/F.

Methods: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1055; ≥40 years) were current or ex-smokers randomized to twice-daily treatment with inhaled MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. The coprimary endpoints of the trial were mean changes from baseline in forced expiratory volume in 1 …

Using Health Information Technology To Engage Communities In Health, Education, And Research, Lisa K. Marriott, David A. Nelson, Shauntice Allen, Karen Calhoun, Christina Eldredge, Kim S. Kimminau, Robert J. Lucero, Fernando Pineda-Reyes, Bernice B. Rumala, Arti P. Varanasi, June S. Wasser, Jackilen Shannon

School of Information Faculty Publications

The August 2011 Clinical and Translational Science Awards conference "Using IT to Improve Community Health: How Health Care Reform Supports Innovation" convened four "Think Tank" sessions. Thirty individuals, representing various perspectives on community engagement, attended the "Health information technology (HIT) as a resource to improve community health and education" session, which focused on using HIT to improve patient health, education, and research involvement. Participants discussed a range of topics using a semistructured format. This article describes themes and lessons that emerged from that session, with a particular focus on using HIT to engage communities to improve health and reduce health …

Decorin-Mediated Inhibition Of Colorectal Cancer Growth And Migration Is Associated With E-Cadherin In Vitro And In Mice., Xiuli Bi, Nicole M Pohl, Zhibin Qian, George R Yang, Yuan Gou, Grace Guzman, Andre Kajdacsy-Balla, Renato V Iozzo, Wancai Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27(kip1) and E-cadherin and an upregulation of β-catenin signaling [Bi,X. et al. (2008) Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis, 29, 1435-1440]. However, the regulation of E-cadherin by decorin and its implication in cancer formation and metastasis is largely unknown. Using a decorin knockout mouse model (Dcn(-/-) mice) and manipulated expression of decorin …

Does International Normalized Ratio Level Predict Pulmonary Embolism?, Patricia Hansen, Benjamin Zmistowski, Camilo Restrepo, Javad Parvizi, Richard H Rothman

Rothman Institute Papers

BACKGROUND: Preventing pulmonary embolism is a priority after major musculoskeletal surgery. The literature contains discrepant data regarding the influence of anticoagulation on the incidence of pulmonary embolism after joint arthroplasty. The American College of Chest Physicians guidelines recommend administration of oral anticoagulants (warfarin), aiming for an international normalized ratio (INR) level between 2 and 3. However, recent studies show aggressive anticoagulation (INR > 2) can lead to hematoma formation and increased risk of subsequent infection.

QUESTIONS/PURPOSES: We asked whether an INR greater than 2 protects against pulmonary embolism.

PATIENTS AND METHODS: We identified 9112 patients with 10,122 admissions for joint arthroplasty …

Mir-25 Targets Tnf-Related Apoptosis Inducing Ligand (Trail) Death Receptor-4 And Promotes Apoptosis Resistance In Cholangiocarcinoma., Nataliya Razumilava, Steve F. Bronk, Rory L. Smoot, Christian D. Fingas, Nathan W. Werneburg, Lewis R. Roberts, Justin L. Mott

Journal Articles: Biochemistry & Molecular Biology

It has been established that microRNA expression and function contribute to phenotypic features of malignant cells, including resistance to apoptosis. Although targets and functional roles for a number of microRNAs have been described in cholangiocarcinoma, many additional microRNAs dysregulated in this tumor have not been assigned functional roles. In this study, we identify elevated miR-25 expression in malignant cholangiocarcinoma cell lines as well as patient samples. In cultured cells, treatment with the Smoothened inhibitor, cyclopamine, reduced miR-25 expression, suggesting Hedgehog signaling stimulates miR-25 production. Functionally, miR-25 was shown to protect cells against TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Correspondingly, antagonism of …

The Formal And Informal Surgical Ethics Curriculum: Views Of Resident And Staff Surgeons In Toronto., Frazer Howard, Martin F. Mckneally, Ross E.G. Upshur, Alex V. Levin

Wills Eye Hospital Papers

BACKGROUND: Understanding what staff surgeons think surgical trainees should learn and the ethical issues that trainees need to manage can strengthen surgical ethics education.

METHODS: Participants were recruited from the 15 surgical specialty and subspecialty programs at the University of Toronto. Semistructured interviews and focus groups were conducted with 13 ethics coordinators from the surgical staff and 64 resident trainees. Data were analyzed qualitatively using modified thematic analysis.

RESULTS: All coordinators and trainees felt that ethics education was an important component of surgical training. Real cases, varying teaching methods, and teachers with applicable clinical experience were valued. Trainees identified intraprofessional …

Surgical Outcome In Pet-Positive, Mri-Negative Patients With Temporal Lobe Epilepsy, Carla Lopinto-Khoury, Michael R. Sperling, Christopher Skidmore, Maromi Nei, James Evans, Ashwini Sharan, Scott Mintzer

Department of Neurology Faculty Papers

PURPOSE:

Fluorodeoxyglucose positron emission computed tomography (FDG-PET) hypometabolism is important for surgical planning in patients with temporal lobe epilepsy (TLE), but its significance remains unclear in patients who do not have evidence of mesial temporal sclerosis (MTS) on magnetic resonance imaging (MRI). We examined surgical outcomes in a group of PET-positive, MRI-negative patients and compared them with those of patients with MTS.

METHODS:

We queried the Thomas Jefferson University Surgical Epilepsy Database for patients who underwent anterior temporal lobectomy (ATL) from 1991 to 2009 and who had unilateral temporal PET hypometabolism without an epileptogenic lesion on MRI (PET+/MRI-). We compared …

Predictors Of Survival In A Cohort Of Patients With Polymyositis And Dermatomyositis: Effect Of Corticosteroids, Methotrexate And Azathioprine, Elena Schiopu, Kristine Phillips, Paul M. Macdonald, Leslie J. Crofford, Emily C. Somers

Internal Medicine Faculty Publications

INTRODUCTION: The idiopathic inflammatory myopathies are rare diseases for which data regarding the natural history, response to therapies and factors affecting mortality are needed. We performed this study to examine the effects of treatment and clinical features on survival in polymyositis and dermatomyositis patients.

METHODS: A total of 160 consecutive patients (77 with polymyositis and 83 with dermatomyositis) seen at the University of Michigan from 1997 to 2003 were included. Medical records were abstracted for clinical, laboratory and therapeutic data, including initial steroid regimen and immunosuppressive use. State vital records were utilized to derive mortality and cause of death data. …

Influence Of Medical Journal Press Releases On The Quality Of Associated Newspaper Coverage: Retrospective Cohort Study, Lisa M. Schwartz, Steven Woloshin, Alice Andrews, Therese A. Stukel

Dartmouth Scholarship

Objective: To determine whether the quality of press releases issued by medical journals can influence the quality of associated newspaper stories.

Systematic Review Of Peer Support For Breastfeeding Continuation: Metaregression Analysis Of The Effect Of Setting, Intensity, And Timing, Kate Jolly, Lucy Annang Ingram Phd, Khalid S. Khan, Jonathan J. Deeks, Nick Freemantle, Christine Macarthur

Faculty Publications

OBJECTIVE: To examine the effect of setting, intensity, and timing of peer support on breast feeding. DESIGN: Systematic review and metaregression analysis of randomised controlled trials. DATA SOURCES: Cochrane Library, Medline, CINAHL, the National Research Register, and British Nursing Index were searched from inception or from 1980 to 2011. Review methods Study selection, data abstraction, and quality assessment were carried out independently and in duplicate. Risk ratios and 95% confidence intervals were calculated for individual studies and pooled. Effects were estimated for studies grouped according to setting (high income countries, low or middle income countries, and the United Kingdom), intensity …

Protocol For A Randomized Controlled Trial Of A Specialized Health Coaching Intervention To Prevent Excessive Gestational Weight Gain And Postpartum Weight Retention In Women: The Hipp Study., Helen Skouteris, Marita Mccabe, Jeannette Milgrom, Bridie Kent, Lauren J. Bruce, Cathrine Mihalopoulos, Sharon J. Herring, Malcolm Barnett, Denise Patterson, Glyn Teale, Janette Gale

School of Nursing and Midwifery

BACKGROUND: Pregnancy is a time of significant physiological and physical change for women. In particular, it is a time at which many women are at risk of gaining excessive weight. We describe the rationale and methods of the Health in Pregnancy and Post-birth (HIPP) Study, a study which aims primarily to determine the effectiveness of a specialized health coaching (HC) intervention during pregnancy, compared to education alone, in preventing excessive gestational weight gain and postpartum weight retention 12 months post birth. A secondary aim of this study is to evaluate the mechanisms by which our HC intervention impacts on weight …

A Spatial Cluster Analysis Of Tractor Overturns In Kentucky From 1960 To 2002, Daniel M. Saman, Henry P. Cole, Agricola Odoi, Melvin L. Myers, Daniel I. Carey, Susan C. Westneat

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: Agricultural tractor overturns without rollover protective structures are the leading cause of farm fatalities in the United States. To our knowledge, no studies have incorporated the spatial scan statistic in identifying high-risk areas for tractor overturns. The aim of this study was to determine whether tractor overturns cluster in certain parts of Kentucky and identify factors associated with tractor overturns.

METHODS: A spatial statistical analysis using Kulldorff's spatial scan statistic was performed to identify county clusters at greatest risk for tractor overturns. A regression analysis was then performed to identify factors associated with tractor overturns.

RESULTS: The spatial analysis …

Primary Care Providers’ Perspectives On Online Weight-Loss Programs: A Big Wish List, Kevin O Hwang, Heather L Stuckey, Monica C Chen, Jennifer L Kraschnewski, Samuel N Forjuoh, Jennifer M Poger, Kathleen M Mctigue, Christopher N Sciamanna

Faculty, Staff and Student Publications

BACKGROUND: Integrating online weight-loss programs into the primary care setting could yield substantial public health benefit. Little is known about primary care providers' perspectives on online weight-loss programs.

OBJECTIVE: To assess primary care providers' perspectives on online weight-loss programs.

METHODS: We conducted focus group discussions with providers in family medicine, internal medicine, and combined internal medicine/pediatrics in Texas and Pennsylvania, USA. Open-ended questions addressed their experience with and attitudes toward online weight-loss programs; useful characteristics of existing online weight-loss programs; barriers to referring patients to online weight-loss programs; and preferred characteristics of an ideal online weight-loss program. Transcripts were analyzed …

Structural Basis For Activation Of Calcineurin By Calmodulin, Julie Rumi-Masante, Farai I. Rusinga, Terrence E. Lester, Tori B. Dunlap, Todd D. Williams, A. Keith Dunker, David D. Weis, Trevor P. Creamer

Center for Structural Biology Faculty Publications

The highly conserved phosphatase calcineurin (CaN) plays vital roles in numerous processes including T-cell activation, development and function of the central nervous system, and cardiac growth. It is activated by the calcium sensor calmodulin (CaM). CaM binds to a regulatory domain (RD) within CaN, causing a conformational change that displaces an autoinhibitory domain (AID) from the active site, resulting in activation of the phosphatase. This is the same general mechanism by which CaM activates CaM-dependent protein kinases. Previously published data have hinted that the RD of CaN is intrinsically disordered. In this work, we demonstrate that the RD is unstructured …

Inflammatory Signaling Compromises Cell Responses To Interferon Alpha., W-C Huangfu, J Qian, C Liu, J Liu, A E Lokshin, D P Baker, H Rui, S Y Fuchs

Department of Cancer Biology Faculty Papers

Interferon alpha (IFNα) is widely used for treatment of melanoma and certain other malignancies. This cytokine as well as the related IFNβ exerts potent anti-tumorigenic effects; however, their efficacy in patients is often suboptimal. Here, we report that inflammatory signaling impedes the effects of IFNα/β. Melanoma cells can secrete pro-inflammatory cytokines that inhibit cellular responses to IFNα/β via activating the ligand-independent pathway for the phosphorylation and subsequent ubiquitination and accelerated degradation of the IFNAR1 chain of type I IFN receptor. Catalytic activity of the p38 protein kinase was required for IFNAR1 downregulation and inhibition of IFNα/β signaling induced by proinflammatory …

The Social Production Of Substance Abuse And Hiv/Hcv Risk: An Exploratory Study Of Opioid-Using Immigrants From The Former Soviet Union Living In New York City, Honoria Guarino, Sarah K. Moore, Lisa A. Marsch, Sal Florio

Dartmouth Scholarship

Several former Soviet countries have witnessed the rapid emergence of major epidemics of injection drug use (IDU) and associated HIV/HCV, suggesting that immigrants from the former Soviet Union (FSU) may be at heightened risk for similar problems. This exploratory study examines substance use patterns among the understudied population of opioid-using FSU immigrants in the U.S., as well as social contextual factors that may increase these immigrants' susceptibility to opioid abuse and HIV/HCV infection. In-depth interviews were conducted with 10 FSU immigrants living in New York City who initiated opioid use in adolescence or young adulthood, and with 6 drug treatment …

Electrophysiological Examination Of Embodiment In Vision And Action., Jeremy Goslin, Thomas Dixon, Martin H. Fischer, Angelo Cangelosi, Rob Ellis

School of Psychology

A wealth of behavioral data has shown that the visual properties of objects automatically potentiate motor actions linked with them, but how deeply are these affordances embedded in visual processing? In the study reported here, we used electrophysiological measures to examine the time course of affordance resulting from the leftward or rightward orientation of the handles of common objects. Participants were asked to categorize those objects using a left- or right-handed motor response. Lateralized readiness potentials showed rapid motor preparation in the hand congruent with the affordance provided by the object only 100 to 200 ms after stimulus presentation and …

Phylogenetic Search Through Partial Tree Mixing., Kenneth Sundberg, Mark Clement, Quinn Snell, Dan Ventura, Michael Whiting, Keith Crandall

Computational Biology Institute

BACKGROUND: Recent advances in sequencing technology have created large data sets upon which phylogenetic inference can be performed. Current research is limited by the prohibitive time necessary to perform tree search on a reasonable number of individuals. This research develops new phylogenetic algorithms that can operate on tens of thousands of species in a reasonable amount of time through several innovative search techniques.

RESULTS: When compared to popular phylogenetic search algorithms, better trees are found much more quickly for large data sets. These algorithms are incorporated in the PSODA application available at http://dna.cs.byu.edu/psoda

CONCLUSIONS: The use of Partial Tree Mixing …

Posttraumatic Stress Disorder Prevalence And Risk Of Recurrence In Acute Coronary Syndrome Patients: A Meta-Analytic Review., D. Edmondson, S. Richardson, L. Falzon, K. W. Davidson, M. A. Mills, Y. Neria

Journal Articles

BACKGROUND: Acute coronary syndromes (ACS; myocardial infarction or unstable angina) can induce posttraumatic stress disorder (PTSD), and ACS-induced PTSD may increase patients' risk for subsequent cardiac events and mortality.

OBJECTIVE: To determine the prevalence of PTSD induced by ACS and to quantify the association between ACS-induced PTSD and adverse clinical outcomes using systematic review and meta-analysis.

DATA SOURCES: Articles were identified by searching Ovid MEDLINE, PsycINFO, and Scopus, and through manual search of reference lists.

METHODOLOGY/PRINCIPAL FINDINGS: Observational cohort studies that assessed PTSD with specific reference to an ACS event at least 1 month prior. We extracted estimates of the …

Cooperative Cluster Formation, Dna Bending And Base-Flipping By O6-Alkylguanine-Dna Alkyltransferase, Ingrid Tessmer, Manana Melikishvili, Michael G. Fried

Center for Structural Biology Faculty Publications

O⁶-Alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O⁶-alkylguanine and O⁴-alkylthymine adducts in DNA, protecting the genome and also contributing to the resistance of tumors to chemotherapeutic alkylating agents. AGT binds DNA cooperatively, and cooperative interactions are likely to be important in lesion search and repair. We examined morphologies of complexes on long, unmodified DNAs, using analytical ultracentrifugation and atomic force microscopy. AGT formed clusters of ≤11 proteins. Longer clusters, predicted by the McGhee–von Hippel model, were not seen even at high [protein]. Interestingly, torsional stress due to DNA unwinding has the potential to limit cluster size …

Follicle-Stimulating Hormone Is Independently Associated With Lean Mass But Not Bmd In Younger Postmenopausal Women, Margaret L Gourlay, Bonny Specker, Chenxi Li, Catherine A. Hammett-Stabler, Jordan B. Renner, Janet E Rubin

Ethel Austin Martin Program Publications

PURPOSE: Increased follicle-stimulating hormone (FSH) has been associated with lower bone mineral density (BMD) in animal models and longitudinal studies of women, but a direct effect has not been demonstrated.
METHODS: We tested associations between FSH, non-bone body composition measures and BMD in 94 younger (aged 50 to 64 years) postmenopausal women without current use of hormone therapy, adjusting for sex hormone concentrations and clinical risk factors for osteoporosis. Lean mass, fat mass and areal BMD (aBMD) at the spine, femoral neck and total hip were measured using dual energy X-ray absorptiometry (DXA). Volumetric BMD (vBMD) was measured at the …

Antibiotics For Leptospirosis, David Brett-Major, Rodney Coldren

Journal Articles: Epidemiology

BACKGROUND: Leptospirosis has a wide-ranging clinical and public health impact. Leptospira are globally distributed. Case attack rates are as high as 1:4 to 2:5 persons in exposed populations. In some settings mortality has exceeded 10% of infected people. The benefit of antibiotic therapy in the disease has been unclear.

OBJECTIVES: We sought to characterise the risks and benefits associated with use of antibiotic therapy in the management of leptospirosis.

SEARCH METHODS: We searched the The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded …

Effects Of Inhaled Corticosteroids On Airway Inflammation In Chronic Obstructive Pulmonary Disease: A Systematic Review And Meta-Analysis, Rachel Jen, Stephen I. Rennard, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the small airways. The effect of inhaled corticosteroids (ICS) on lung inflammation in COPD remains uncertain. We sought to determine the effects of ICS on inflammatory indices in bronchial biopsies and bronchoalveolar lavage fluid of patients with COPD.

METHODS: We searched Medline, Embase, Cinahl, and the Cochrane database for randomized, controlled clinical trials that used bronchial biopsies and bronchoalveolar lavage to evaluate the effects of ICS in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of inflammatory cells before and after treatment …

A Randomized Placebo-Controlled Trial Of Varenicline For Smoking Cessation Allowing Flexible Quit Dates, Stephen I. Rennard, John Hughes, Paul M. Cinciripini, Eva Kralikova, Tobias Raupach, Carmen Arteaga, Lisa B. St Aubin, Cristina Russ, The Flexible Quit Date Study Group

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy. However, providing flexibility in the date of quitting may be more acceptable to some smokers. The objective of this study was to compare varenicline 1 mg twice daily (b.i.d.) with placebo in subjects using a flexible quit date paradigm after starting medication.

METHODS: In this double-blind, randomized, placebo-controlled international study, smokers of ≥10 cigarettes/day, aged 18-75 years, and who were motivated to quit were randomized (3:1) to receive varenicline 1 mg b.i.d. or placebo for 12 weeks. Subjects were followed up through Week 24. Subjects were …