Showing papers by "Medical University of South Carolina published in 2011"
Brigham and Women's Hospital1, Boston University2, University of California, Los Angeles3, Boston Children's Hospital4, University of Alabama at Birmingham5, Stanford University6, Northwestern University7, Aalborg University8, Cardiff University9, University of Pennsylvania10, Erasmus University Rotterdam11, Medical University of South Carolina12
TL;DR: The revised guidelines for the management of thyroid disease in pregnancy include recommendations regarding the interpretation of thyroid function tests in pregnancy, iodine nutrition, thyroid autoantibodies and pregnancy complications, thyroid considerations in infertile women, hypothyroidism in pregnancy and thyrotoxicosis in pregnancy.
Abstract: Background: Thyroid disease in pregnancy is a common clinical problem. Since the guidelines for the management of these disorders by the American Thyroid Association (ATA) were first published in 2...
2,409 citations
TL;DR: Treatment of women with acute uncomplicated cystitis and pyelonephritis is limited in these guidelines to premenopausal, non-pregnant women with no known urological abnormalities or co-morbidities.
Abstract: A Panel of International Experts was convened by the Infectious Diseases Society of America (IDSA) in collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) to update the 1999 Uncomplicated Urinary Tract Infection Guidelines by the IDSA. Co-sponsoring organizations include the American Congress of Obstetricians and Gynecologists, American Urological Association, Association of Medical Microbiology and Infectious Diseases-Canada, and the Society for Academic Emergency Medicine. The focus of this work is treatment of women with acute uncomplicated cystitis and pyelonephritis, diagnoses limited in these guidelines to premenopausal, non-pregnant women with no known urological abnormalities or co-morbidities. The issues of in vitro resistance prevalence and the ecological adverse effects of antimicrobial therapy (collateral damage) were considered as important factors in making optimal treatment choices and thus are reflected in the rankings of recommendations.
2,320 citations
TL;DR: In this article, the CAPACITY program was designed to confirm the results of a phase 2 study that suggested that pirfenidone, a novel antifibrotic and anti-inflammatory drug, reduces deterioration in lung function in patients with idiopathic pulmonary fibrosis.
1,685 citations
Medical University of South Carolina1, Emory University2, Washington University in St. Louis3, Stony Brook University4, National Institutes of Health5, Oregon Health & Science University6, University of Florida7, University at Buffalo8, University of Alabama at Birmingham9, Houston Methodist Hospital10, St. Joseph's Hospital and Medical Center11, University of Texas Southwestern Medical Center12, Medical College of Wisconsin13, Mayo Clinic14
TL;DR: In patients with intracranial arterial stenosis, aggressive medical management was superior to PTAS with the use of the Wingspan stent system, both because the risk of early stroke after PTAS was high and because therisk of stroke with aggressive medical therapy alone was lower than expected.
Abstract: Enrollment was stopped after 451 patients underwent randomization, because the 30-day rate of stroke or death was 14.7% in the PTAS group (nonfatal stroke, 12.5%; fatal stroke, 2.2%) and 5.8% in the medical-management group (nonfatal stroke, 5.3%; non–stroke-related death, 0.4%) (P = 0.002). Beyond 30 days, stroke in the same territory occurred in 13 patients in each group. Currently, the mean duration of followup, which is ongoing, is 11.9 months. The probability of the occurrence of a primary end-point event over time differed significantly between the two treatment groups (P = 0.009), with 1-year rates of the primary end point of 20.0% in the PTAS group and 12.2% in the medical-management group. Conclusions In patients with intracranial arterial stenosis, aggressive medical management was superior to PTAS with the use of the Wingspan stent system, both because the risk of early stroke after PTAS was high and because the risk of stroke with aggressive medical therapy alone was lower than expected. (Funded by the National Institute of Neurological Disorders and Stroke and others; SAMMPRIS ClinicalTrials.gov number, NCT00576693.)
1,377 citations
Constantine A. Gatsonis1, Denise R. Aberle2, Christine D. Berg, William C. Black3 +1333 more•Institutions (31)
TL;DR: The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer.
Abstract: The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5% It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase For these reasons, there is intense interest and intuitive appeal in lung cancer screening with low-dose CT The use of survival as the determinant of screening effectiveness is, however, confounded by the well-described biases of lead time, length, and overdiagnosis Despite previous attempts, no test has been shown to reduce lung cancer mortality, an endpoint that circumvents screening biases and provides a definitive measure of benefit when assessed in a randomized controlled trial that enables comparison of mortality rates between screened individuals and a control group that does not undergo the screening intervention of interest The NLST is such a trial The rationale for and design of the NLST are presented
1,036 citations
University of California, Irvine1, Massachusetts Institute of Technology2, University of California, Los Angeles3, University of Pennsylvania4, University of Southern California5, National Institutes of Health6, Oregon Health & Science University7, University of Rochester8, Georgetown University9, University of Washington10, Medical University of South Carolina11, University of Lethbridge12, University of Illinois at Urbana–Champaign13, Emory University14, University of California, San Francisco15, Harvard University16, University of Michigan17, Cornell University18, University of Colorado Boulder19, Stanford University20
TL;DR: Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.
Abstract: Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections. Major advances in the understanding of neuroplasticity have to date yielded few established interventions. To advance the translation of neuroplasticity research towards clinical applications, the National Institutes of Health Blueprint for Neuroscience Research sponsored a workshop in 2009. Basic and clinical researchers in disciplines from central nervous system injury/stroke, mental/addictive disorders, paediatric/developmental disorders and neurodegeneration/ageing identified cardinal examples of neuroplasticity, underlying mechanisms, therapeutic implications and common denominators. Promising therapies that may enhance training-induced cognitive and motor learning, such as brain stimulation and neuropharmacological interventions, were identified, along with questions of how best to use this body of information to reduce human disability. Improved understanding of adaptive mechanisms at every level, from molecules to synapses, to networks, to behaviour, can be gained from iterative collaborations between basic and clinical researchers. Lessons can be gleaned from studying fields related to plasticity, such as development, critical periods, learning and response to disease. Improved means of assessing neuroplasticity in humans, including biomarkers for predicting and monitoring treatment response, are needed. Neuroplasticity occurs with many variations, in many forms, and in many contexts. However, common themes in plasticity that emerge across diverse central nervous system conditions include experience dependence, time sensitivity and the importance of motivation and attention. Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.
907 citations
TL;DR: It is shown that P. gingivalis, at very low colonization levels, triggers changes to the amount and composition of the oral commensal microbiota leading to inflammatory periodontal bone loss, demonstrating that a single, low-abundance species can disrupt host-microbial homeostasis to cause inflammatory disease.
890 citations
University of Cincinnati1, National Institutes of Health2, University of Toronto3, Medical University of South Carolina4, Niigata University5, Oregon Health & Science University6, Cleveland Clinic7, University of Florida8, University of Texas Health Science Center at Tyler9, University of Colorado Denver10, University of California, Los Angeles11, Harvard University12, Cincinnati Children's Hospital Medical Center13, Mayo Clinic14, University of South Florida15
TL;DR: In patients with LAM, sirolimus stabilized lung function, reduced serum VEGF-D levels, and was associated with a reduction in symptoms and improvement in quality of life.
Abstract: Background Lymphangioleiomyomatosis (LAM) is a progressive, cystic lung disease in women; it is associated with inappropriate activation of mammalian target of rapamycin (mTOR) signaling, which regulates cellular growth and lymphangiogenesis. Sirolimus (also called rapamycin) inhibits mTOR and has shown promise in phase 1–2 trials involving patients with LAM. Methods We conducted a two-stage trial of sirolimus involving 89 patients with LAM who had moderate lung impairment — a 12-month randomized, double-blind comparison of sirolimus with placebo, followed by a 12-month observation period. The primary end point was the difference between the groups in the rate of change (slope) in forced expiratory volume in 1 second (FEV1). Results During the treatment period, the FEV1 slope was −12±2 ml per month in the placebo group (43 patients) and 1±2 ml per month in the sirolimus group (46 patients) (P<0.001). The absolute between-group difference in the mean change in FEV1 during the treatment period was 153 ml, o...
851 citations
Centers for Disease Control and Prevention1, Mario Negri Institute for Pharmacological Research2, University of Texas Health Science Center at Houston3, Northern Illinois University4, Children's Memorial Hospital5, Mayo Clinic6, Fudan University7, Columbia University8, Boston University9, RTI International10, University of Arizona11, University of Hawaii at Manoa12, University of Bari13, Wellcome Trust14, University College London15, University of California, San Francisco16, Mississippi University for Women17, University of Limoges18, UCL Institute of Neurology19, Medical University of South Carolina20, National Institutes of Health21, Karolinska Institutet22, University of Calgary23
TL;DR: The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population‐based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health.
Abstract: Worldwide, about 65 million people are estimated to have epilepsy. Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy. However, different definitions and epidemiologic methods complicate the tasks of these studies and their interpretations and comparisons. The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population-based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health. We discuss: (1) conceptual and operational definitions of epilepsy, (2) data resources and recommended data elements, and (3) methods and analyses appropriate for epidemiologic studies or the surveillance of epilepsy. Variations in these are considered, taking into account differing resource availability and needs among countries and differing purposes among studies.
844 citations
TL;DR: It is shown that either knockout or catalytic inactivation of the DNA repair enzyme thymine DNA glycosylase (TDG) leads to embryonic lethality in mice, and a dual role for TDG in promoting proper epigenetic states during development is highlighted, suggesting a two-step mechanism for DNA demethylation in mammals.
750 citations
TL;DR: No clinical benefit was observed in patients with a non-LBBB QRS pattern (right bundle-branch block or intraventricular conduction disturbances), and heart failure patients with New York Heart Association class I or II and LBBB derive substantial clinical benefit from CRT-D: a Reduction in heart failure progression and a reduction in the risk of ventricular tachyarrhythmias.
Abstract: Background—This study aimed to determine whether QRS morphology identifies patients who benefit from cardiac resynchronization therapy with a defibrillator (CRT-D) and whether it influences the risk of primary and secondary end points in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT) trial. Methods and Results—Baseline 12-lead ECGs were evaluated with regard to QRS morphology. Heart failure event or death was the primary end point of the trial. Death, heart failure event, ventricular tachycardia, and ventricular fibrillation were secondary end points. Among 1817 patients with available sinus rhythm ECGs at baseline, there were 1281 (70%) with left bundle-branch block (LBBB), 228 (13%) with right bundle-branch block, and 308 (17%) with nonspecific intraventricular conduction disturbances. The latter 2 groups were defined as non-LBBB groups. Hazard ratios for the primary end point for comparisons of CRT-D patients versus patients...
TL;DR: Deconjugation enzymes such as β‐glucuronidase and sulfatase, as well as specific tissue accumulation of resveratrol, may enhance resver atrol efficacy at target sites, and methylated derivatives with improved bioavailability may be important in future research.
Abstract: This paper reviews our current understanding of the absorption, bioavailability, and metabolism of resveratrol, with an emphasis on humans. The oral absorption of resveratrol in humans is about 75% and is thought to occur mainly by transepithelial diffusion. Extensive metabolism in the intestine and liver results in an oral bioavailability considerably less than 1%. Dose escalation and repeated dose administration of resveratrol does not appear to alter this significantly. Metabolic studies, both in plasma and in urine, have revealed major metabolites to be glucuronides and sulfates of resveratrol. However, reduced dihydroresveratrol conjugates, in addition to highly polar unknown products, may account for as much as 50% of an oral resveratrol dose. Although major sites of metabolism include the intestine and liver (as expected), colonic bacterial metabolism may be more important than previously thought. Deconjugation enzymes such as β-glucuronidase and sulfatase, as well as specific tissue accumulation of resveratrol, may enhance resveratrol efficacy at target sites. Resveratrol analogs, such as methylated derivatives with improved bioavailability, may be important in future research.
TL;DR: It is concluded that vitamin D supplementation of 4000 IU/d for pregnant women is safe and most effective in achieving sufficiency in all women and their neonates regardless of race, whereas the current estimated average requirement is comparatively ineffective at achieving adequate circulating 25(OH)D concentrations, especially in African Americans.
Abstract: The need, safety, and effectiveness of vitamin D supplementation during pregnancy remain controversial. In this randomized, controlled trial, women with a singleton pregnancy at 12 to 16 weeks' gestation received 400, 2000, or 4000 IU of vitamin D3 per day until delivery. The primary outcome was maternal/neonatal circulating 25-hydroxyvitamin D [25(OH)D] concentration at delivery, with secondary outcomes of a 25(OH)D concentration of 80 nmol/L or greater achieved and the 25(OH)D concentration required to achieve maximal 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] production. Of the 494 women enrolled, 350 women continued until delivery: Mean 25(OH)D concentrations by group at delivery and 1 month before delivery were significantly different (p < 0.0001), and the percent who achieved sufficiency was significantly different by group, greatest in 4000-IU group (p < 0.0001). The relative risk (RR) for achieving a concentration of 80 nmol/L or greater within 1 month of delivery was significantly different between the 2000- and the 400-IU groups (RR = 1.52, 95% CI 1.24–1.86), the 4000- and the 400-IU groups (RR = 1.60, 95% CI 1.32–1.95) but not between the 4000- and. 2000-IU groups (RR = 1.06, 95% CI 0.93–1.19). Circulating 25(OH)D had a direct influence on circulating 1,25(OH)2D3 concentrations throughout pregnancy (p < 0.0001), with maximal production of 1,25(OH)2D3 in all strata in the 4000-IU group. There were no differences between groups on any safety measure. Not a single adverse event was attributed to vitamin D supplementation or circulating 25(OH)D levels. It is concluded that vitamin D supplementation of 4000 IU/d for pregnant women is safe and most effective in achieving sufficiency in all women and their neonates regardless of race, whereas the current estimated average requirement is comparatively ineffective at achieving adequate circulating 25(OH)D concentrations, especially in African Americans. © 2011 American Society for Bone and Mineral Research
Charité1, Odense University Hospital2, Autonomous University of Barcelona3, University of Montpellier4, University of Southampton5, Norfolk and Norwich University Hospital6, St Thomas' Hospital7, Hiroshima University8, Medical University of South Carolina9, Johns Hopkins University School of Medicine10, Peking University11
TL;DR: A GA2LEN task force report concluded that chronic spontaneous urticaria is a “hidden epidemic” that needs to be addressed to address the unmet clinical needs of patients.
Abstract: Chronic spontaneous urticaria, formerly also known as chronic idiopathic urticaria and chronic urticaria (CU), is more common than previously thought. At any time, 0.5-1% of the population suffers from the disease (point prevalence). Although all age groups can be affected, the peak incidence is seen between 20 and 40 years of age. The duration of the disease is generally 1-5 years but is likely to be longer in more severe cases, cases with concurrent angioedema, in combination with physical urticaria or with a positive autologous serum skin test (autoreactivity). Chronic spontaneous urticaria has major detrimental effects on quality of life, with sleep deprivation and psychiatric comorbidity being frequent. It also has a large impact on society in terms of direct and indirect health care costs as well as reduced performance at work and in private life. In the majority of patients, an underlying cause cannot be identified making a causal and/or curative treatment difficult. Nonsedating H₁-antihistamines are the mainstay of symptomatic therapy, but treatment with licensed doses relieves symptoms effectively in < 50% of patients. Although guideline-recommended updosing up to fourfold increases symptom control in many patients, a substantial number of patients have only little benefit from H₁ -antihistamines. Consequently, there is a great need for new therapeutic strategies.
SUNY Downstate Medical Center1, University of Mississippi2, Johns Hopkins University3, Children's National Medical Center4, Howard University5, Duke University6, University of Texas at Dallas7, Medical University of South Carolina8, University of Miami9, Emory University10, Boston Children's Hospital11, University of Alabama at Birmingham12, Georgia Regents University13, National Institutes of Health14
TL;DR: Hydroxycarbamide can now be considered for all very young children with sickle-cell anaemia, with some evidence for decreased acute chest syndrome, hospitalisation rates, and transfusion.
TL;DR: It is argued that sensitization remains a useful model for determining the neural basis of addiction, and an example is provided in which data from sensitization studies led to potential pharmacotherapies that have been tested in animal models of relapse and in human addicts.
Abstract: Repeated exposure to drugs of abuse enhances the motor-stimulant response to these drugs, a phenomenon termed behavioral sensitization. Animals that are extinguished from self-administration training readily relapse to drug, conditioned cue, or stress priming. The involvement of sensitization in reinstated drug-seeking behavior remains controversial. This review describes sensitization and reinstated drug seeking as behavioral events, and the neural circuitry, neurochemistry, and neuropharmacology underlying both behavioral models will be described, compared, and contrasted. It seems that although sensitization and reinstatement involve overlapping circuitry and neurotransmitter and receptor systems, the role of sensitization in reinstatement remains ill-defined. Nevertheless, it is argued that sensitization remains a useful model for determining the neural basis of addiction, and an example is provided in which data from sensitization studies led to potential pharmacotherapies that have been tested in animal models of relapse and in human addicts.
TL;DR: Exercise compares favorably to antidepressant medications as a first-line treatment for mild to moderate depression and has also been shown to improve depressive symptoms when used as an adjunct to medications.
Abstract: Depression and anxiety are the most common psychiatric conditions seen in the general medical setting, affecting millions of individuals in the United States. The treatments for depression and anxiety are multiple and have varying degrees of effectiveness. Physical activity has been shown to be associated with decreased symptoms of depression and anxiety. Physical activity has been consistently shown to be associated with improved physical health, life satisfaction, cognitive functioning, and psychological well-being. Conversely, physical inactivity appears to be associated with the development of psychological disorders. Specific studies support the use of exercise as a treatment for depression. Exercise compares favorably to antidepressant medications as a first-line treatment for mild to moderate depression and has also been shown to improve depressive symptoms when used as an adjunct to medications. While not as extensively studied, exercise has been shown to be an effective and cost-efficient treatment alternative for a variety of anxiety disorders. While effective, exercise has not been shown to reduce anxiety to the level achieved by psychopharmaceuticals.
TL;DR: In this article, the authors defined uncontrolled hypertension as blood pressure ≥140/≥90 mm Hg and apparent treatment-resistant hypertension (aTRH) when subjects reported taking ≥3 antihypertensive medications.
Abstract: Background—Despite progress, many hypertensive patients remain uncontrolled. Defining characteristics of uncontrolled hypertensives may facilitate efforts to improve blood pressure control. Methods and Results—Subjects included 13 375 hypertensive adults from National Health and Nutrition Examination Surveys (NHANESs) subdivided into 1988 to 1994, 1999 to 2004, and 2005 to 2008. Uncontrolled hypertension was defined as blood pressure ≥140/≥90 mm Hg and apparent treatment-resistant hypertension (aTRH) when subjects reported taking ≥3 antihypertensive medications. Framingham 10-year coronary risk was calculated. Multivariable logistic regression was used to identify clinical characteristics associated with untreated, treated uncontrolled on 1 to 2 blood pressure medications, and aTRH across all 3 survey periods. More than half of uncontrolled hypertensives were untreated across surveys, including 52.2% in 2005 to 2008. Clinical factors linked with untreated hypertension included male sex, infrequent healthc...
University of Minnesota1, Johns Hopkins University2, City of Hope National Medical Center3, Medical University of South Carolina4, Ohio State University5, University of Florida6, University of Kansas7, Harvard University8, Vanderbilt University9, Medical College of Wisconsin10, University of Washington11
TL;DR: These multicenter studies confirm the utility of dUCB and Haplo-marrow as alternative donor sources and set the stage for a multicenter randomized clinical trial to assess the relative efficacy of these 2 strategies.
TL;DR: The authors found that cells from the adaptive immune system—T cells—governed bacterial control by releasing the cytokine interferon-γ (IFN-γ), which then activated infected macrophages, inciting the cells to attack the invading M. tuberculosis.
Abstract: Control of tuberculosis worldwide depends on our understanding of human immune mechanisms, which combat the infection. Acquired T cell responses are critical for host defense against microbial pathogens, yet the mechanisms by which they act in humans remain unclear. We report that T cells, by the release of interferon-γ (IFN-γ), induce autophagy, phagosomal maturation, the production of antimicrobial peptides such as cathelicidin, and antimicrobial activity against Mycobacterium tuberculosis in human macrophages via a vitamin D–dependent pathway. IFN-γ induced the antimicrobial pathway in human macrophages cultured in vitamin D–sufficient sera, but not in sera from African-Americans that have lower amounts of vitamin D and who are more susceptible to tuberculosis. In vitro supplementation of vitamin D–deficient serum with 25-hydroxyvitamin D3 restored IFN-γ–induced antimicrobial peptide expression, autophagy, phagosome-lysosome fusion, and antimicrobial activity. These results suggest a mechanism in which vitamin D is required for acquired immunity to overcome the ability of intracellular pathogens to evade macrophage-mediated antimicrobial responses. The present findings underscore the importance of adequate amounts of vitamin D in all human populations for sustaining both innate and acquired immunity against infection.
McLean Hospital1, Yale University2, National Institute on Drug Abuse3, West Virginia University4, Harvard University5, Oregon Health & Science University6, New York University7, Columbia University8, University of California, Los Angeles9, Duke University10, National Institutes of Health11, University of California, San Francisco12, Yeshiva University13, University of Cincinnati14, Medical University of South Carolina15
TL;DR: Prescription opioid-dependent patients are most likely to reduce opioid use during buprenorphine-naloxone treatment; if tapered off bupreliminary treatment, even after 12 weeks of treatment, the likelihood of an unsuccessful outcome is high, even in patients receiving counseling in addition to SMM.
Abstract: Context No randomized trials have examined treatments for prescription opioid dependence, despite its increasing prevalence. Objective To evaluate the efficacy of brief and extended buprenorphine hydrochloride-naloxone hydrochloride treatment, with different counseling intensities, for patients dependent on prescription opioids. Design Multisite, randomized clinical trial using a 2-phase adaptive treatment research design. Brief treatment (phase 1) included 2-week buprenorphine-naloxone stabilization, 2-week taper, and 8-week postmedication follow-up. Patients with successful opioid use outcomes exited the study; unsuccessful patients entered phase 2: extended (12-week) buprenorphine-naloxone treatment, 4-week taper, and 8-week postmedication follow-up. Setting Ten US sites. Patients A total of 653 treatment-seeking outpatients dependent on prescription opioids. Interventions In both phases, patients were randomized to standard medical management (SMM) or SMM plus opioid dependence counseling; all received buprenorphine-naloxone. Main outcome measures Predefined "successful outcome" in each phase: composite measures indicating minimal or no opioid use based on urine test-confirmed self-reports. Results During phase 1, only 6.6% (43 of 653) of patients had successful outcomes, with no difference between SMM and SMM plus opioid dependence counseling. In contrast, 49.2% (177 of 360) attained successful outcomes in phase 2 during extended buprenorphine-naloxone treatment (week 12), with no difference between counseling conditions. Success rates 8 weeks after completing the buprenorphine-naloxone taper (phase 2, week 24) dropped to 8.6% (31 of 360), again with no counseling difference. In secondary analyses, successful phase 2 outcomes were more common while taking buprenorphine-naloxone than 8 weeks after taper (49.2% [177 of 360] vs 8.6% [31 of 360], P Conclusions Prescription opioid-dependent patients are most likely to reduce opioid use during buprenorphine-naloxone treatment; if tapered off buprenorphine-naloxone, even after 12 weeks of treatment, the likelihood of an unsuccessful outcome is high, even in patients receiving counseling in addition to SMM.
TL;DR: MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments.
Abstract: Case reports indicate that psychiatrists administered ±3,4-methylenedioxymethamphetamine (MDMA) as a catalyst to psychotherapy before recreational use of MDMA as ‘Ecstasy’ resulted in its criminalization in 1985. Over two decades later, this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct. Twenty patients with chronic posttraumatic stress disorder, refractory to both psychotherapy and psychopharmacology, were randomly assigned to psychotherapy with concomitant active drug (n = 12) or inactive placebo (n = 8) administered during two 8-h experimental psychotherapy sessions. Both groups received preparatory and follow-up non-drug psychotherapy. The primary outcome measure was the Clinician-Administered PTSD Scale, administered at baseline, 4 days after each experimental session, and 2 months after the second session. Neurocognitive testing, blood pressure, and temperature monitoring were performed. After 2-month follow-up, placebo subjects were offered the option to re-en...
Erasmus University Medical Center1, University of Zurich2, Humboldt University of Berlin3, Queen Mary University of London4, Katholieke Universiteit Leuven5, Medical University of South Carolina6, Leiden University Medical Center7, Turku University Hospital8, Utrecht University9, Papworth Hospital10, Innsbruck Medical University11, Harvard University12
TL;DR: The results suggest that the Diamond-Forrester model overestimates the probability of obstructive coronary artery disease especially in women.
Abstract: Prospectively collected data from 14 hospitals on patients with chest pain without a history of CAD and referred for conventional coronary angiography (CCA) were used. Primary outcome was obstructive CAD, defined as ≥50% ste- nosis in one or more vessels on CCA. The validity of the Diamond-Forrester model was assessed using calibration plots, calibration-in-the-large, and recalibration in logistic regression. The model was subsequently updated and extended by revising the predictive value of age, sex, and type of chest pain. Diagnostic performance was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) and reclassification was deter- mined. We included 2260 patients, of whom 1319 had obstructive CAD on CCA. Validation demonstrated an over- estimation of the CAD probability, especially in women. The updated and extended models demonstrated a c-statistic of 0.79 (95% CI 0.77-0.81) and 0.82 (95% CI 0.80-0.84), respectively. Sixteen per cent of men and 64% of women were correctly reclassified. The predicted probability of obstructive CAD ranged from 10% for 50-year-old females with non-specific chest pain to 91% for 80-year-old males with typical chest pain. Predictions varied across hospitals due to differences in disease prevalence.
TL;DR: Left ventricular hypertrophy or concentric remodeling, LA enlargement, and diastolic dysfunction were present in the majority of patients with HFPEF, and left ventricular mass and LA size were independently associated with an increased risk of morbidity and mortality.
Abstract: Background—The purpose of this study was to examine the prevalence of abnormalities in cardiac structure and function present in patients with heart failure and a preserved ejection fraction (HFPEF) and to determine whether these alterations in structure and function were associated with cardiovascular morbidity and mortality. Methods and Results—The Irbesartan in HFPEF trial (I-PRESERVE) enrolled 4128 patients; echocardiographic determination of left ventricular (LV) volume, mass, left atrial (LA) size, systolic function, and diastolic function were made at baseline in 745 patients. The primary end point was death or protocol-specific cardiovascular hospitalization. A secondary end point was the composite of heart failure death or heart failure hospitalization. Associations between baseline structure and function and patient outcomes were examined using univariate and multivariable Cox proportional hazard analyses. In this substudy, LV hypertrophy or concentric remodeling was present in 59%, LA enlargeme...
TL;DR: There is increasing evidence to support that one or more infectious agents may cause sarcoidosis, although this organism may no longer be viable in the patient, and new and more potent antiinflammatory agents have been developed.
Abstract: This is an update on sarcoidosis, focusing on etiology, diagnosis, and treatment. In the area of etiopathogenesis, we now have a better understanding of the immune response that leads to the disease as well as genetic factors that modify both the risk for the disease and its clinical outcome. Several groups have also identified possible agents as a cause for sarcoidosis. Although none of these potential causes has been definitely confirmed, there is increasing evidence to support that one or more infectious agents may cause sarcoidosis, although this organism may no longer be viable in the patient. The diagnosis of sarcoidosis has been significantly aided by new technology. This includes the endobronchial ultrasound, which has been shown to increase the yield of needle aspiration of mediastinal and hilar lymph nodes. The positive emission tomography scan has proven useful for selecting possible biopsy sites by identifying organ involvement not appreciated by routine methodology. It has also helped in assessing cardiac involvement. The biologic agents, such as the anti–tumor necrosis factor antibodies, have changed the approach to refractory sarcoidosis. There is increasing evidence that the clinician can identify which patient is most likely to benefit from such therapy. As new and more potent antiinflammatory agents have been developed, it is clear that there are other factors that burden the patient with sarcoidosis, including fatigue and sarcoidosis-associated pulmonary hypertension. There have been several recent studies demonstrating treatment options for these problems.
TL;DR: The present findings support the efficacy of combined naltrexone/bupropion therapy as an adjunct to intensive BMOD for obesity, and the former had significantly greater improvements in markers of cardiometabolic disease risk.
Abstract: This 56-week, randomized, placebo-controlled trial examined the efficacy and safety of naltrexone plus bupropion as an adjunct to intensive behavior modification (BMOD). A total of 793 participants (BMI = 36.5 ± 4.2 kg/m2) was randomly assigned in a 1:3 ratio to: (i) placebo + BMOD (N = 202); or (ii) naltrexone sustained-release (SR, 32 mg/day), combined with bupropion SR (360 mg/day) plus BMOD (i.e., NB32 + BMOD; N = 591). Both groups were prescribed an energy-reduced diet and 28 group BMOD sessions. Co-primary end points were percentage change in weight and the proportion of participants who lost ≥5% weight at week 56. Efficacy analyses were performed on a modified intent-to-treat population (ITT; i.e., participants with ≥1 postbaseline weight while taking study drug (placebo + BMOD, N = 193; NB32 + BMOD, N = 482)). Missing data were replaced with the last observation obtained on study drug. At week 56, weight loss was 5.1 ± 0.6% with placebo + BMOD vs. 9.3 ± 0.4% with NB32 + BMOD (P < 0.001). A completers analysis revealed weight losses of 7.3 ± 0.9% (N = 106) vs. 11.5 ± 0.6% (N = 301), respectively (P < 0.001). A third analysis, which included all randomized participants, yielded losses of 4.9 ± 0.6 vs. 7.8 ± 0.4%, respectively (P < 0.001). Significantly more NB32 + BMOD- vs. placebo + BMOD-treated participants lost ≥5 and ≥10% of initial weight, and the former had significantly greater improvements in markers of cardiometabolic disease risk. NB32 + BMOD was generally well tolerated, although associated with more reports of nausea than placebo + BMOD. The present findings support the efficacy of combined naltrexone/bupropion therapy as an adjunct to intensive BMOD for obesity.
TL;DR: The current manuscript is a revised manual (BATD-R), reflecting key modifications that simplify and clarify key treatment elements, procedures, and treatment forms, including greater emphasis on treatment rationale and therapeutic alliance.
Abstract: Following from the seminal work of Ferster, Lewinsohn, and Jacobson, as well as theory and research on the Matching Law, Lejuez, Hopko, LePage, Hopko, and McNeil developed a reinforcement-based depression treatment that was brief, uncomplicated, and tied closely to behavioral theory. They called this treatment the brief behavioral activation treatment for depression (BATD), and the original manual was published in this journal. The current manuscript is a revised manual (BATD-R), reflecting key modifications that simplify and clarify key treatment elements, procedures, and treatment forms. Specific modifications include (a) greater emphasis on treatment rationale, including therapeutic alliance; (b) greater clarity regarding life areas, values, and activities; (c) simplified (and fewer) treatment forms; (d) enhanced procedural details, including troubleshooting and concept reviews; and (e) availability of a modified Daily Monitoring Form to accommodate low literacy patients. Following the presentation of the manual, the authors conclude with a discussion of the key barriers in greater depth, including strategies for addressing these barriers.
Roskilde University1, University of Wisconsin-Madison2, University of Georgia3, University of Pennsylvania4, University of Leicester5, University of Oklahoma Health Sciences Center6, University of Connecticut7, University of Burgundy8, Universidade Federal do Rio Grande do Sul9, Xi'an Jiaotong University10, National Institutes of Health11, Annamalai University12, University of Hawaii at Hilo13, University of Bordeaux14, Indian Institute of Toxicology Research15, Seoul National University16, Medical University of Vienna17, University of Agriculture, Faisalabad18, Medical University of South Carolina19, New York Medical College20
TL;DR: The published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources, and animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials.
Abstract: Background: Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingor, Denmark. Methodology: Literature search in databases as PubMed and ISI Web of Science in combination with manual search was used to answer the following five questions: 1 Can resveratrol be recommended in the prevention or treatment of human diseases?; 2 Are there observed ‘‘side effects’’ caused by the intake of resveratrol in humans?; 3 What is the relevant dose of resveratrol?; 4 What valid data are available regarding an effect in various species of experimental animals?; 5 Which relevant (overall) mechanisms of action of resveratrol have been documented? Conclusions/Significance: The overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources. On the other hand, animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials. Finally, we suggest directions for future research in resveratrol regarding its mechanism of action and its safety and toxicology in human subjects.
TL;DR: A rigorous definition of a pilot study is presented, recommendations for the design, analysis and sample size justification of pilot studies in clinical and translational research are offered, and the important role that well‐designed pilot studies play in the advancement of science and scientific careers are emphasized.
Abstract: Advances in clinical and translation science are facilitated by building on prior knowledge gained through experimentation and observation. In the context of drug development, preclinical studies are followed by a progression of phase I through phase IV clinical trials. At each step, the study design and statistical strategies are framed around research questions that are prerequisites for the next phase. In other types of biomedical research, pilot studies are used for gathering preliminary support for the next research step. However, the phrase "pilot study" is liberally applied to projects with little or no funding, characteristic of studies with poorly developed research proposals, and usually conducted with no detailed thought of the subsequent study. In this article, we present a rigorous definition of a pilot study, offer recommendations for the design, analysis and sample size justification of pilot studies in clinical and translational research, and emphasize the important role that well-designed pilot studies play in the advancement of science and scientific careers.
TL;DR: In this paper, the authors compared the efficacy and safety of oral dabigatran, a direct thrombin inhibitor, versus subcutaneous enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty.
Abstract: This trial compared the efficacy and safety of oral dabigatran, a direct thrombin inhibitor, versus subcutaneous enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty. A total of 2,055 patients were randomised to 28–35 days treatment with oral dabigatran, 220 mg once-daily, starting with a half-dose 1–4 hours after surgery, or subcutaneous enoxaparin 40mg once-daily, starting the evening before surgery. The primary efficacy outcome was a composite of total venous thromboembolism [VTE] (venographic or symptomatic) and death from all-causes. The main secondary composite outcome was major VTE (proximal deep-vein thrombosis or non-fatal pulmonary embolism) plus VTE-related death. The main safety outcome was major bleeding. In total, 2,013 were treated, of whom 1,577 operated patients were included in the primary efficacy analysis. The primary efficacy outcome occurred in 7.7% of the dabigatran group versus 8.8% of the enoxaparin group, risk difference (RD) –1.1% (95%CI –3.8 to 1.6%); p<0.0001 for the pre-specified non-inferiority margin. Major VTE plus VTE-related death occurred in 2.2% of the dabigatran group versus 4.2% of the enoxaparin group, RD –1.9% (-3.6% to –0.2%); p=0.03. Major bleeding occurred in 1.4% of the dabigatran group and 0.9% of the enoxaparin group (p=0.40). The incidence of adverse events, including liver enzyme elevations and cardiac events, during treatment was similar between the groups. Extended prophylaxis with oral dabigatran 220 mg once-daily was as effective as subcutaneous enoxaparin 40 mg once-daily in reducing the risk of VTE after total hip arthroplasty, and superior to enoxaparin for reducing the risk of major VTE. The risk of bleeding and safety profiles were similar.