Showing papers by "Medical University of South Carolina published in 2013"
Radboud University Nijmegen Medical Centre1, University of Michigan2, Radboud University Nijmegen3, University of Toronto4, McGill University5, University of Basel6, University of Florence7, Auckland City Hospital8, University of Pittsburgh9, Charité10, University of California, Los Angeles11, University College London12, University of Zurich13, University of Paris14, Marche Polytechnic University15, University of Texas Health Science Center at Houston16, Newcastle University17, University of Pécs18, Georgetown University19, Istanbul University20, Medical University of Białystok21, University of Giessen22, Seconda Università degli Studi di Napoli23, University College Dublin24, Stanford University25, National Health Service26, University of Colorado Denver27, Medical College of Wisconsin28, University of Alabama at Birmingham29, University of Manchester30, Rutgers University31, Thomas Jefferson University32, Amgen33, University of Toledo34, Boston University35, Medical University of South Carolina36, University of Pennsylvania37, Northwestern University38
TL;DR: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria and should allow for more patients to be classified correctly as having the disease.
Abstract: OBJECTIVE: The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. METHODS: Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by 1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and 2) validating against the combined view of a group of experts on a set of cases with or without SSc. RESULTS: It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, 7 additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud's phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. CONCLUSION: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.
2,743 citations
Radboud University Nijmegen1, University of Michigan2, University of Toronto3, McGill University4, University of Basel5, University of Florence6, Auckland City Hospital7, University of Pittsburgh8, Complutense University of Madrid9, Charité10, University of California, Los Angeles11, University College London12, University of Zurich13, University of Paris14, Marche Polytechnic University15, University of Texas Health Science Center at Houston16, Newcastle University17, University of Pécs18, Georgetown University19, Istanbul University20, Medical University of Białystok21, University of Giessen22, Seconda Università degli Studi di Napoli23, University College Dublin24, Stanford University25, Amgen26, University of Colorado Denver27, Medical College of Wisconsin28, University of Alabama at Birmingham29, University of Manchester30, National Health Service31, Rutgers University32, Thomas Jefferson University33, University of Toledo34, Boston University35, University of Pennsylvania36, Medical University of South Carolina37, Northwestern University38, University of Western Ontario39
TL;DR: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria and should allow for more patients to be classified correctly as having the disease.
Abstract: Objective The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. Methods Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by (1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and (2) validating against the combined view of a group of experts on a set of cases with or without SSc. Results It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, seven additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud9s phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. Conclusions The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.
1,899 citations
University of Cincinnati1, Medical University of South Carolina2, Allen Institute for Brain Science3, University of Pittsburgh4, University of Melbourne5, University of Toronto6, Autonomous University of Barcelona7, Mayo Clinic8, Riverside Methodist Hospital9, Oregon Health & Science University10, Medical College of Wisconsin11, Utrecht University12, University of Paris13, University of Basel14, Royal Prince Alfred Hospital15, National Institutes of Health16
TL;DR: The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA, as compared with intravenoust-PA alone.
Abstract: BACKGROUND Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic stroke, but whether a combined approach is more effective than intravenous t-PA alone is uncertain. METHODS We randomly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified Rankin scale score of 2 or less (indicating functional independence) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). RESULTS The study was stopped early because of futility after 656 participants had undergone randomization (434 patients to endovascular therapy and 222 to intravenous t-PA alone). The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage points; 95% confidence interval [CI], −6.1 to 9.1, with adjustment for the National Institutes of Health Stroke Scale [NIHSS] score [8–19, indicating moderately severe stroke, or ≥20, indicating severe stroke]), nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8 percentage points; 95% CI, −4.4 to 18.1) and those with a score of 19 or lower (−1.0 percentage point; 95% CI, −10.8 to 8.8). Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively; P = 0.52) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P = 0.83). CONCLUSIONS The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA, as compared with intravenous t-PA alone. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00359424.)
1,702 citations
TL;DR: DSM-5 PTSD prevalence was higher among women than among men, and prevalence increased with greater traumatic event exposure, although only 2 of these differences were statistically significant.
Abstract: Prevalence of posttraumatic stress disorder (PTSD) defined according to the American Psychiatric Association's Diagnostic and Statistical Manual fifth edition (DSM-5; 2013) and fourth edition (DSM-IV; 1994) was compared in a national sample of U.S. adults (N = 2,953) recruited from an online panel. Exposure to traumatic events, PTSD symptoms, and functional impairment were assessed online using a highly structured, self-administered survey. Traumatic event exposure using DSM-5 criteria was high (89.7%), and exposure to multiple traumatic event types was the norm. PTSD caseness was determined using Same Event (i.e., all symptom criteria met to the same event type) and Composite Event (i.e., symptom criteria met to a combination of event types) definitions. Lifetime, past-12-month, and past 6-month PTSD prevalence using the Same Event definition for DSM-5 was 8.3%, 4.7%, and 3.8% respectively. All 6 DSM-5 prevalence estimates were slightly lower than their DSM-IV counterparts, although only 2 of these differences were statistically significant. DSM-5 PTSD prevalence was higher among women than among men, and prevalence increased with greater traumatic event exposure. Major reasons individuals met DSM-IV criteria, but not DSM-5 criteria were the exclusion of nonaccidental, nonviolent deaths from Criterion A, and the new requirement of at least 1 active avoidance symptom.
1,365 citations
TL;DR: It is demonstrated that PET scanning is more accurate than CT scanning, but tissue biopsy is still required to confirm PET scan findings, and evidence suggests that more complete staging improves patient outcomes.
1,167 citations
TL;DR: Adequate vitamin D supplementation and sensible sunlight exposure to reach optimal vitamin D status are among the front line factors of prophylaxis for the spectrum of disorders.
704 citations
TL;DR: The use of the PLCO(M2012) model was more sensitive than the NLST criteria for lung-cancer detection and compared the accuracy of PLCo(M 2012) criteria withNLST criteria to detect lung cancer.
Abstract: Background The National Lung Screening Trial (NLST) used risk factors for lung cancer (e.g., ≥30 pack-years of smoking and <15 years since quitting) as selection criteria for lung-cancer screening. Use of an accurate model that incorporates additional risk factors to select persons for screening may identify more persons who have lung cancer or in whom lung cancer will develop. Methods We modified the 2011 lung-cancer risk-prediction model from our Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to ensure applicability to NLST data; risk was the probability of a diagnosis of lung cancer during the 6-year study period. We developed and validated the model (PLCOM2012) with data from the 80,375 persons in the PLCO control and intervention groups who had ever smoked. Discrimination (area under the receiver-operating-characteristic curve [AUC]) and calibration were assessed. In the validation data set, 14,144 of 37,332 persons (37.9%) met NLST criteria. For comparison, 14,144 highest-risk...
699 citations
TL;DR: By phylogenetic analysis, it is shown that system x(c)(-) is a rather evolutionarily new amino acid transport system and its diverse roles in the regulation of the immune response, in various aspects of cancer and in the eye and the CNS are highlighted.
Abstract: The antiporter system xc− imports the amino acid cystine, the oxidized form of cysteine, into cells with a 1:1 counter-transport of glutamate. It is composed of a light chain, xCT, and a heavy chain, 4F2 heavy chain (4F2hc), and, thus, belongs to the family of heterodimeric amino acid transporters. Cysteine is the rate-limiting substrate for the important antioxidant glutathione (GSH) and, along with cystine, it also forms a key redox couple on its own. Glutamate is a major neurotransmitter in the central nervous system (CNS). By phylogenetic analysis, we show that system xc− is a rather evolutionarily new amino acid transport system. In addition, we summarize the current knowledge regarding the molecular mechanisms that regulate system xc−, including the transcriptional regulation of the xCT light chain, posttranscriptional mechanisms, and pharmacological inhibitors of system xc−. Moreover, the roles of system xc− in regulating GSH levels, the redox state of the extracellular cystine/cysteine re...
631 citations
TL;DR: For example, this article found that 46.6% were aware of ENDS (U.S., UK: 73%, UK: 54%, Canada: 40%, Australia: 20%) and 2.9% were current users (39% of triers).
623 citations
TL;DR: Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world.
551 citations
Fred Hutchinson Cancer Research Center1, City of Hope National Medical Center2, University of New Mexico3, Vancouver General Hospital4, University of Toronto5, University of Chicago6, University of Michigan7, Loyola University Medical Center8, Medical University of South Carolina9, Memorial Sloan Kettering Cancer Center10, Karolinska University Hospital11
TL;DR: In this study, the addition of GO to induction or postconsolidation therapy failed to show improvement in CR rate, disease-free survival, or overall survival.
TL;DR: Screening with low-dose CT prevented the greatest number of deaths from lung cancer among participants who were at highest risk and prevented very few deaths among those at lowest risk.
Abstract: Background In the National Lung Screening Trial (NLST), screening with low-dose computed tomography (CT) resulted in a 20% reduction in lung-cancer mortality among participants between the ages of 55 and 74 years with a minimum of 30 pack-years of smoking and no more than 15 years since quitting. It is not known whether the benefits and potential harms of such screening vary according to lung-cancer risk. Methods We assessed the variation in efficacy, the number of false positive results, and the number of lung-cancer deaths prevented among 26,604 participants in the NLST who underwent low-dose CT screening, as compared with the 26,554 participants who underwent chest radiography, according to the quintile of 5-year risk of lung-cancer death (ranging from 0.15 to 0.55% in the lowest-risk group [quintile 1] to more than 2.00% in the highest-risk group [quintile 5]). Results The number of lung-cancer deaths per 10,000 person-years that were prevented in the CT-screening group, as compared with the radiograp...
TL;DR: The findings support the efficacy and safety of the S-ICD System for the treatment of life-threatening ventricular arrhythmias and detection and conversion of spontaneous episodes.
Abstract: Background—The most frequent complications associated with implantable cardioverter-defibrillators (ICDs) involve the transvenous leads. A subcutaneous implantable cardioverter-defibrillator (S-ICD) has been developed as an alternative system. This study evaluated the safety and effectiveness of the S-ICD System (Cameron Health/Boston Scientific) for the treatment of life-threatening ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation). Methods and Results—This prospective, nonrandomized, multicenter trial included adult patients with a standard indication for an ICD, who neither required pacing nor had documented pace-terminable ventricular tachycardia. The primary safety end point was the 180-day S-ICD System complication-free rate compared with a prespecified performance goal of 79%. The primary effectiveness end point was the induced ventricular fibrillation conversion rate compared with a prespecified performance goal of 88%, with success defined as 2 consecutive ventricular fib...
TL;DR: In this article, two case studies were presented to demonstrate that children who experience trauma-related nightmares may benefit from cognitive-behavioral therapy for this sleep problem, adapted from the empirically supported adult treatment for chronic trauma related night-mares: exposure, relaxation, and rescripting therapy (ERRT).
Abstract: Two case studies are presented to demonstrate that children who experience trauma-related nightmares may benefit from cognitive-behavioral therapy for this sleep problem. The treatment was adapted from the empirically supported adult treatment for chronic trauma-related night- mares: exposure, relaxation, and rescripting therapy (ERRT). Pretreatment and posttreatment nightmare frequency and severity were measured in addition to subjective nightmare-related distress, behavioral problems, sleep quality and quantity, and symptoms of posttraumatic stress disorder (PTSD), anxiety, and depression. Improvement in nightmare and sleep disturbance fre- quencies were found as well as reductions in parents' reports of child behavior problems. This study provides preliminary support for the use of ERRT with children.
TL;DR: A list of caveats is developed to inform would-be users of such data as well as provide an informatics roadmap that aims to insure this opportunity to augment comparative effectiveness research can be best leveraged.
Abstract: The growing amount of data in operational electronic health record systems provides unprecedented opportunity for its reuse for many tasks, including comparative effectiveness research. However, there are many caveats to the use of such data. Electronic health record data from clinical settings may be inaccurate, incomplete, transformed in ways that undermine their meaning, unrecoverable for research, of unknown provenance, of insufficient granularity, and incompatible with research protocols. However, the quantity and real-world nature of these data provide impetus for their use, and we develop a list of caveats to inform would-be users of such data as well as provide an informatics roadmap that aims to insure this opportunity to augment comparative effectiveness research can be best leveraged.
TL;DR: A functional metabolic portrait of 46 independently derived breast cell lines is constructed, revealing a therapeutic target in breast tumors of poorest prognosis and a lead compound for rapid, effective drug development.
TL;DR: In this article, the authors used activation likelihood estimation, a quantitative, coordinate-based meta-analytic method, to analyze the brain areas activated by alcohol-related cues across studies, and examined whether these areas were differentially activated between cases and controls.
Abstract: A comprehensive understanding of the neurobiology of alcohol cue reactivity is critical in identifying the neuropathology of alcohol use disorders (AUD) and developing treatments that may attenuate alcohol craving and reduce relapse risk. Functional neuroimaging studies have identified many brain areas in which alcohol cues elicit activation. However, extant studies have included relatively small numbers of cases, with AUD of varying severity, and have employed many different cue paradigms. We used activation likelihood estimation, a quantitative, coordinate-based meta-analytic method, to analyze the brain areas activated by alcohol-related cues across studies, and to examine whether these areas were differentially activated between cases and controls. Secondarily, we reviewed correlations between behavioral measures and cue-elicited activation, as well as treatment effects on such activation. Data analyzed were from 28 studies of 679 cases and 174 controls. Among cases, alcohol cues elicited robust activation of limbic and prefrontal regions, including ventral striatum, anterior cingulate and ventromedial prefrontal cortex. As compared to controls, cases demonstrated greater activation of parietal and temporal regions, including posterior cingulate, precuneus and superior temporal gyrus. Cue-elicited activation of ventral striatum was most frequently correlated with behavioral measures and most frequently reduced by treatment, but these results were often derived from region-of-interest analyses that interrogated only limbic regions. These findings support long-standing theories of mesolimbic involvement in alcohol cue processing, but suggest that cue-elicited activation of other brain areas may more clearly differentiate cases from controls. Prevention and treatment for AUD should consider interventions that may reduce cue-elicited activation of these areas.
TL;DR: QRS duration is a powerful predictor of the effects of CRT on morbidity and mortality in patients with symptomatic HF and left ventricular systolic dysfunction who are in sinus rhythm.
Abstract: Aims Cardiac resynchronization therapy (CRT) with or without a defibrillator reduces morbidity and mortality in selected patients with heart failure (HF) but response can be variable. We sought to identify pre-implantation variables that predict the response to CRT in a meta-analysis using individual patient-data.
Methods and results An individual patient meta-analysis of five randomized trials, funded by Medtronic, comparing CRT either with no active device or with a defibrillator was conducted, including the following baseline variables: age, sex, New York Heart Association class, aetiology, QRS morphology, QRS duration, left ventricular ejection fraction (LVEF), and systolic blood pressure. Outcomes were all-cause mortality and first hospitalization for HF or death. Of 3782 patients in sinus rhythm, median (inter-quartile range) age was 66 (58–73) years, QRS duration was 160 (146–176) ms, LVEF was 24 (20–28)%, and 78% had left bundle branch block. A multivariable model suggested that only QRS duration predicted the magnitude of the effect of CRT on outcomes. Further analysis produced estimated hazard ratios for the effect of CRT on all-cause mortality and on the composite of first hospitalization for HF or death that suggested increasing benefit with increasing QRS duration, the 95% confidence bounds excluding 1.0 at ∼140 ms for each endpoint, suggesting a high probability of substantial benefit from CRT when QRS duration exceeds this value.
Conclusion QRS duration is a powerful predictor of the effects of CRT on morbidity and mortality in patients with symptomatic HF and left ventricular systolic dysfunction who are in sinus rhythm. QRS morphology did not provide additional information about clinical response.
ClinicalTrials.gov numbers NCT00170300, [NCT00271154][1], [NCT00251251][2].
[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00271154&atom=%2Fehj%2F34%2F46%2F3547.atom
[2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00251251&atom=%2Fehj%2F34%2F46%2F3547.atom
TL;DR: In this paper, the authors evaluated the safety and efficacy of 24 weeks of treatment with omalizumab in patients with persistent chronic idiopathic urticaria/chronic spontaneous urticria (CIU/CSU) despite treatment with H 1 -antihistamines at up to 4 times the approved dose plus H 2 -antiHistamines, leukotriene receptor antagonists, or both.
Abstract: Background Patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) often continue to experience symptoms despite receiving standard-of-care therapy with H 1 -antihistamines along with 1 or more add-on therapies. Objectives We sought to evaluate the safety and efficacy of 24 weeks of treatment with omalizumab in patients with persistent CIU/CSU despite treatment with H 1 -antihistamines at up to 4 times the approved dose plus H 2 -antihistamines, leukotriene receptor antagonists, or both. Methods In this phase III study patients were randomized to receive 6 subcutaneous injections at 4-week intervals of either 300 mg of omalizumab or placebo, followed by a 16-week observation period. The primary objective of the study was to evaluate the overall safety of omalizumab compared with placebo. Efficacy (itch severity, hive, and urticaria activity scores) was evaluated at weeks 12 and 24. Results The overall incidence and severity of adverse events and serious adverse events were similar between omalizumab and placebo recipients; the safety profile was consistent with omalizumab in patients with allergic asthma. At week 12, the mean change from baseline in weekly itch severity score was −8.6 (95% CI, −9.3 to −7.8) in the omalizumab group compared with −4.0 (95% CI, −5.3 to −2.7) in the placebo group ( P Conclusion Omalizumab was well tolerated and reduced the signs and symptoms of CIU/CSU in patients who remained symptomatic despite the use of H 1 -antihistamines (up to 4 times the approved dose) plus H 2 -antihistamines, leukotriene receptor antagonists, or both.
Yeshiva University1, University of Kansas2, United States Department of Veterans Affairs3, Icahn School of Medicine at Mount Sinai4, University of Florida5, Institute of Medical Science6, Medical University of South Carolina7, University of Michigan8, University of Southern California9, University of Pittsburgh10, University of Chicago11, Saint Louis University12, Indiana University – Purdue University Indianapolis13
TL;DR: This review summarizes recent advances in understanding the roles that autophagy plays in normal hepatic physiology and pathophysiology with the intent of furthering the development of autophileagy-based therapies for human liver diseases.
Abstract: Autophagy has emerged as a critical lysosomal pathway that maintains cell function and survival through the degradation of cellular components such as organelles and proteins. Investigations specifically employing the liver or hepatocytes as experimental models have contributed significantly to our current knowledge of autophagic regulation and function. The diverse cellular functions of autophagy, along with unique features of the liver and its principal cell type the hepatocyte, suggest that the liver is highly dependent on autophagy for both normal function and to prevent the development of disease states. However, instances have also been identified in which autophagy promotes pathological changes such as the development of hepatic fibrosis. Considerable evidence has accumulated that alterations in autophagy are an underlying mechanism of a number of common hepatic diseases including toxin-, drug- and ischemia/reperfusion-induced liver injury, fatty liver, viral hepatitis and hepatocellular carcinoma. This review summarizes recent advances in understanding the roles that autophagy plays in normal hepatic physiology and pathophysiology with the intent of furthering the development of autophagy-based therapies for human liver diseases.
TL;DR: Among internal medicine and nurse practitioner trainees, simulation-based communication training compared with usual education did not improve quality of communication about end-of-life care or quality of end- of- life care but was associated with a small increase in patients' depressive symptoms.
Abstract: Importance Communication about end-of-life care is a core clinical skill. Simulation-based training improves skill acquisition, but effects on patient-reported outcomes are unknown. Objective To assess the effects of a communication skills intervention for internal medicine and nurse practitioner trainees on patient- and family-reported outcomes. Design, Setting, and Participants Randomized trial conducted with 391 internal medicine and 81 nurse practitioner trainees between 2007 and 2013 at the University of Washington and Medical University of South Carolina. Intervention Participants were randomized to an 8-session, simulation-based, communication skills intervention (N = 232) or usual education (N = 240). Main Outcomes and Measures Primary outcome was patient-reported quality of communication (QOC; mean rating of 17 items rated from 0-10, with 0 = poor and 10 = perfect). Secondary outcomes were patient-reported quality of end-of-life care (QEOLC; mean rating of 26 items rated from 0-10) and depressive symptoms (assessed using the 8-item Personal Health Questionnaire [PHQ-8]; range, 0-24, higher scores worse) and family-reported QOC and QEOLC. Analyses were clustered by trainee. Results There were 1866 patient ratings (44% response) and 936 family ratings (68% response). The intervention was not associated with significant changes in QOC or QEOLC. Mean values for postintervention patient QOC and QEOLC were 6.5 (95% CI, 6.2 to 6.8) and 8.3 (95% CI, 8.1 to 8.5) respectively, compared with 6.3 (95% CI, 6.2 to 6.5) and 8.3 (95% CI, 8.1 to 8.4) for control conditions. After adjustment, comparing intervention with control, there was no significant difference in the QOC score for patients (difference, 0.4 points [95% CI, −0.1 to 0.9];P = .15) or families (difference, 0.1 [95% CI, −0.8 to 1.0];P = .81). There was no significant difference in QEOLC score for patients (difference, 0.3 points [95% CI, −0.3 to 0.8];P = .34) or families (difference, 0.1 [95% CI, −0.7 to 0.8];P = .88). The intervention was associated with significantly increased depression scores among patients of postintervention trainees (mean score, 10.0 [95% CI, 9.1 to 10.8], compared with 8.8 [95% CI, 8.4 to 9.2]) for control conditions; adjusted model showed an intervention effect of 2.2 (95% CI, 0.6 to 3.8;P = .006). Conclusions and Relevance Among internal medicine and nurse practitioner trainees, simulation-based communication training compared with usual education did not improve quality of communication about end-of-life care or quality of end-of-life care but was associated with a small increase in patients’ depressive symptoms. These findings raise questions about skills transfer from simulation training to actual patient care and the adequacy of communication skills assessment. Trial Registration clinicaltrials.gov Identifier:NCT00687349
TL;DR: The PARADIGM-HF trial as discussed by the authors evaluated the effect of angiotensin receptor neprilysin inhibitors (ARNIs) on the risk of heart failure in patients with chronic heart failure.
Abstract: Aims
Although the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin–angiotensin–aldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNIs), which both block the RAAS and augment natriuretic peptides.
Methods
Patients with chronic HF, NYHA class II–IV symptoms, an elevated plasma BNP or NT-proBNP level, and an LVEF of ≤40% were enrolled in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortailty and morbidity in Heart Failure trial (PARADIGM-HF). Patients entered a single-blind enalapril run-in period (titrated to 10 mg b.i.d.), followed by an LCZ696 run-in period (100 mg titrated to 200 mg b.i.d.). A total of 8436 patients tolerating both periods were randomized 1:1 to either enalapril 10 mg b.i.d. or LCZ696 200 mg b.i.d. The primary outcome is the composite of cardiovascular death or HF hospitalization, although the trial is powered to detect a 15% relative risk reduction in cardiovascular death.
Perspectives
PARADIGM-HF will determine the place of the ARNI LCZ696 as an alternative to enalapril in patients with systolic HF. PARADIGM-HF may change our approach to neurohormonal modulation in HF.
Trial registration
NCT01035255
TL;DR: Non-invasive vascular imaging methods that could be used to identify high-risk patients include fractional flow on magnetic resonance angiography (MRA), quantitative MRA, and high-resolution MRI of the atherosclerotic plaque.
Abstract: Intracranial atherosclerosis is one of the most common causes of stroke worldwide and is associated with a high risk of recurrent stroke. New therapeutic approaches to treat this high-risk disease include dual antiplatelet treatment, intensive management of risk factors, and endovascular therapy. Early data from randomised trials indicate that aggressive medical therapy is better than stenting for prevention of recurrent stroke in high-risk patients with atherosclerotic stenosis of a major intracranial artery. Nevertheless, there are subgroups of patients who remain at high risk of stroke despite aggressive medical therapy. Further research is needed to identify these high-risk subgroups and to develop more effective treatments. Non-invasive vascular imaging methods that could be used to identify high-risk patients include fractional flow on magnetic resonance angiography (MRA), quantitative MRA, and high-resolution MRI of the atherosclerotic plaque. Alternative therapies to consider for future clinical trials include angioplasty alone, indirect surgical bypass procedures, ischaemic preconditioning, and new anticoagulants (direct thrombin or Xa inhibitors).
TL;DR: This review covers several important natural proteins and polysaccharides widely used as hydrogels for articular cartilage tissue engineering and the mechanical properties, structures, modification, and structure–performance relationship of theseHydrogels are discussed since the chemical structures and physical properties dictate the in vivo performance and applications of polymer hydrogeled regeneration and repair.
Abstract: Articular cartilage has poor ability to heal once damaged. Tissue engineering with scaffolds of polymer hydrogels is promising for cartilage regeneration and repair. Polymer hydrogels composed of highly hydrated crosslinked networks mimic the collagen networks of the cartilage extracellular matrix and thus are employed as inserts at cartilage defects not only to temporarily relieve the pain but also to support chondrocyte proliferation and neocartilage regeneration. The biocompatibility, biofunctionality, mechanical properties, and degradation of the polymer hydrogels are the most important parameters for hydrogel-based cartilage tissue engineering. Degradable biopolymers with natural origin have been widely used as biomaterials for tissue engineering because of their outstanding biocompatibility, low immunological response, low cytotoxicity, and excellent capability to promote cell adhesion, proliferation, and regeneration of new tissues. This review covers several important natural proteins (collagen, gelatin, fibroin, and fibrin) and polysaccharides (chitosan, hyaluronan, alginate and agarose) widely used as hydrogels for articular cartilage tissue engineering. The mechanical properties, structures, modification, and structure–performance relationship of these hydrogels are discussed since the chemical structures and physical properties dictate the in vivo performance and applications of polymer hydrogels for articular cartilage regeneration and repair. © 2012 Society of Chemical Industry
University of Toledo1, University of Michigan2, Johns Hopkins University3, Virginia Mason Medical Center4, University of Iowa5, Mayo Clinic6, Medical University of South Carolina7, University of Utah8, Overlook Medical Center9, Harvard University10, Emerson Hospital11, University of Texas Health Science Center at San Antonio12, Northwestern University13, Louisiana State University14, Memorial Hospital of South Bend15
TL;DR: This guideline addresses needs by encouraging accurate and efficient diagnosis and treatment and, when applicable, facilitating patient follow-up to address the management of long-term sequelae or evaluation of new or worsening symptoms not indicative of Bell’s palsy.
Abstract: ObjectiveBell’s palsy, named after the Scottish anatomist, Sir Charles Bell, is the most common acute mono-neuropathy, or disorder affecting a single nerve, and is the most common diagnosis associa...
TL;DR: The ADAPT technique is a simple and effective approach to acute ischemic stroke thrombectomy and Utilizing the latest generation of large bore aspiration catheters in this fashion has allowed us to achieve excellent clinical and angiographic outcomes.
Abstract: Background The development of new revascularization devices has improved recanalization rates and time but not clinical outcomes. We report our initial results with a new technique utilizing a direct aspiration first pass technique with a large bore aspiration catheter as the primary method for vessel recanalization. Methods A retrospective evaluation of a prospectively captured database of 37 patients at six institutions was performed on patients where the ADAPT technique was utilized. The data represent the initial experience with this technique. Results The ADAPT technique alone was successful in 28 of 37 (75%) cases although six cases had large downstream emboli that required additional aspiration. Nine cases required the additional use of a stent retriever and one case required the addition of a Penumbra aspiration separator to achieve recanalization. The average time from groin puncture to at least Thrombolysis in Cerebral Ischemia (TICI) 2b recanalization was 28.1 min, and all cases were successfully revascularized. TICI 3 recanalization was achieved 65% of the time. On average, patients presented with an admitting National Institutes of Health Stroke Scale (NIHSS) score of 16.3 and improved to an NIHSS score of 4.2 by the time of hospital discharge. There was one procedural complication. Discussion This initial experience highlights the fact that the importance of the technique with which new stroke thrombectomy devices are used may be as crucial as the device itself. The ADAPT technique is a simple and effective approach to acute ischemic stroke thrombectomy. Utilizing the latest generation of large bore aspiration catheters in this fashion has allowed us to achieve excellent clinical and angiographic outcomes.
TL;DR: Patients cared for in ICU rooms with copper alloy surfaces had a significantly lower rate of incident HAI and/or colonization with MRSA or VRE than did patients treated in standard rooms.
Abstract: objective. Healthcare-acquired infections (HAIs) cause substantial patient morbidity and mortality. Items in the environment harbor microorganisms that may contribute to HAIs. Reduction in surface bioburden may be an effective strategy to reduce HAIs. The inherent biocidal properties of copper surfaces offer a theoretical advantage to conventional cleaning, as the effect is continuous rather than episodic. We sought to determine whether placement of copper alloy–surfaced objects in an intensive care unit (ICU) reduced the risk of HAI. design. Intention-to-treat randomized control trial between July 12, 2010, and June 14, 2011. setting. The ICUs of 3 hospitals. patients. Patients presenting for admission to the ICU. methods. Patients were randomly placed in available rooms with or without copper alloy surfaces, and the rates of incident HAI and/ or colonization with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) in each type of room were compared. results. The rate of HAI and/or MRSA or VRE colonization in ICU rooms with copper alloy surfaces was significantly lower than that in standard ICU rooms (0.071 vs 0.123; ). For HAI only, the rate was reduced from 0.081 to 0.034 ( ). P p .020 P p .013 conclusions. Patients cared for in ICU rooms with copper alloy surfaces had a significantly lower rate of incident HAI and/or colonization with MRSA or VRE than did patients treated in standard rooms. Additional studies are needed to determine the clinical effect of copper alloy surfaces in additional patient populations and settings.
University of California, Los Angeles1, Washington University in St. Louis2, Saint Louis University3, Medical University of South Carolina4, College of Charleston5, University of Hawaii at Manoa6, Iowa State University7, University of British Columbia8, Benaroya Research Institute9, Carleton University10, Illinois State University11, University of South Alabama12, Harvard University13, University of Florida14, University of California, San Francisco15, University of Toronto16, Duke University17, University of Texas at Arlington18, University of Colorado Denver19, University of California, Berkeley20, University of Oxford21, Rajiv Gandhi Centre for Biotechnology22, University of California, Santa Cruz23, Comenius University in Bratislava24
TL;DR: Common vertebrate regulatory networks, some of which have analogs in human diseases, are often involved in the western painted turtle's extraordinary physiological capacities, and may offer important insights into the management of a number of human health disorders.
Abstract: Background: We describe the genome of the western painted turtle, Chrysemys picta bellii, one of the most widespread, abundant, and well-studied turtles. We place the genome into a comparative evolutionary context, and focus on genomic features associated with tooth loss, immune function, longevity, sex differentiation and determination, and the species’ physiological capacities to withstand extreme anoxia and tissue freezing. Results: Our phylogenetic analyses confirm that turtles are the sister group to living archosaurs, and demonstrate an extraordinarily slow rate of sequence evolution in the painted turtle. The ability of the painted turtle to withstand complete anoxia and partial freezing appears to be associated with common vertebrate gene networks, and we identify candidate genes for future functional analyses. Tooth loss shares a common pattern of pseudogenization and degradation of tooth-specific genes with birds, although the rate of accumulation of mutations is much slower in the painted turtle. Genes associated with sex differentiation generally reflect phylogeny rather than convergence in sex determination functionality. Among gene families that demonstrate exceptional expansions or show signatures of strong natural selection, immune function and musculoskeletal patterning genes are consistently over-represented. Conclusions: Our comparative genomic analyses indicate that common vertebrate regulatory networks, some of which have analogs in human diseases, are often involved in the western painted turtle’s extraordinary physiological capacities. As these regulatory pathways are analyzed at the functional level, the painted turtle may offer important insights into the management of a number of human health disorders.
TL;DR: Regular appearing NBI surface patterns did not harbour high-grade dysplasia/cancer, suggesting that biopsies could be avoided in these areas, and high-definition white light examinations with NBI can have the same IM detection rate as an HD-WLE examination with the Seattle protocol while requiring fewerBiopsies.
Abstract: Background White light endoscopy with random biopsies is the standard for detection of intestinal metaplasia (IM) and neoplasia in patients with Barrett9s oesophagus (BO). Narrow band imaging (NBI) highlights surface patterns that correlate with IM and neoplasia in BO. Objective To compare high-definition white light (HD-WLE) and NBI for detection of IM and neoplasia in BO. Design International, randomised, crossover trial comparing HD-WLE and NBI. Patients referred for BO screening/surveillance at three tertiary referral centres were prospectively enrolled and randomised to HD-WLE or NBI followed by other procedures in 3–8 weeks. During HD-WLE, four quadrant biopsies every 2 cm, together with targeted biopsies of visible lesions (Seattle protocol), were obtained. During NBI examination, mucosal and vascular patterns were noted and targeted biopsies were obtained. All biopsies were read by a single expert gastrointestinal pathologist in a blinded fashion. Results 123 patients with BO (mean age 61; 93% male; 97% Caucasian) with mean circumferential and maximal extents of 1.8 and 3.6 cm, respectively, were enrolled. Both HD-WLE and NBI detected 104/113 (92%) patients with IM, but NBI required fewer biopsies per patient (3.6 vs 7.6, p Conclusions NBI targeted biopsies can have the same IM detection rate as an HD-WLE examination with the Seattle protocol while requiring fewer biopsies. In addition, NBI targeted biopsies can detect more areas with dysplasia. Regular appearing NBI surface patterns did not harbour high-grade dysplasia/cancer, suggesting that biopsies could be avoided in these areas.
TL;DR: Adolescents with higher BMI had a strong association with neurostructural deficits evident in the OFC and future research should be longitudinal and use a uniform method of EF measurement to better establish causality between EF and obesity and consequently direct future intervention strategies.
Abstract: The objective of this paper is to examine the relationship between the development of executive function (EF) and obesity in children and adolescents. We reviewed 1,065 unique abstracts: 31 from PubMed, 87 from Google Scholar, 16 from Science Direct, and 931 from PsycINFO. Of those abstracts, 28 met inclusion criteria and were reviewed. From the articles reviewed, an additional 3 articles were added from article references (N = 31). Twenty-three studies pertained to EF (2 also studied the prefrontal and orbitofrontal cortices (OFCs); 6 also studied cognitive function), five studied the relationship between obesity and prefrontal and orbitofrontal cortices, and three evaluated cognitive function and obesity. Inhibitory control was most often studied in both childhood (76.9%) and adolescent (72.7%) studies, and obese children performed significantly worse (P < 0.05) than healthy weight controls on various tasks measuring this EF domain. Although 27.3% of adolescent studies measured mental flexibility, no childhood studies examined this EF domain. Adolescents with higher BMI had a strong association with neurostructural deficits evident in the OFC. Future research should be longitudinal and use a uniform method of EF measurement to better establish causality between EF and obesity and consequently direct future intervention strategies.