Browsing by Subject "Time Factors"

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Open Access
10 Years with ICH E10: Choice of Control Groups.
(Pharm Stat, 2011-09) Rockhold, Frank W; Enas, Gregory G
Open Access
A beta-adrenergic receptor kinase-like enzyme is involved in olfactory signal termination.
(Proc Natl Acad Sci U S A, 1993-02-15) Schleicher, S; Boekhoff, I; Arriza, J; Lefkowitz, RJ; Breer, H
We have previously shown that second-messenger-dependent kinases (cAMP-dependent kinase, protein kinase C) in the olfactory system are essential in terminating second-messenger signaling in response to odorants. We now document that subtype 2 of the beta-adrenergic receptor kinase (beta ARK) is also involved in this process. By using subtype-specific antibodies to beta ARK-1 and beta ARK-2, we show that beta ARK-2 is preferentially expressed in the olfactory epithelium in contrast to findings in most other tissues. Heparin, an inhibitor of beta ARK, as well as anti-beta ARK-2 antibodies, (i) completely prevents the rapid decline of second-messenger signals (desensitization) that follows odorant stimulation and (ii) strongly inhibits odorant-induced phosphorylation of olfactory ciliary proteins. In contrast, beta ARK-1 antibodies are without effect. Inhibitors of protein kinase A and protein kinase C also block odorant-induced desensitization and phosphorylation. These data suggest that a sequential interplay of second-messenger-dependent and receptor-specific kinases is functionally involved in olfactory desensitization.
Open Access
A cohort study of 4,190 patients treated with low-intensity pulsed ultrasound (LIPUS): findings in the elderly versus all patients.
(BMC Musculoskelet Disord, 2015-03-01) Zura, Robert; Mehta, Samir; Rocca, Gregory J Della; Jones, John; Steen, R Grant
BACKGROUND: Patient age is one of many potential risk factors for fracture nonunion. Our hypothesis is that older patients (≥ 60) with fracture risk factors treated with low-intensity pulsed ultrasound (LIPUS) have similar heal rate (HR) to the population as a whole. We evaluate the impact of age in conjunction with other risk factors on HR in LIPUS-treated patients with fresh fracture (≤ 90 days old). METHODS: The Exogen Bone Healing System is a LIPUS device approved in 1994 to accelerate healing of fresh fracture. After approval, the FDA required a Post-Market Registry to assess performance. Patient data collected from October 1994 until October 1998 were individually reviewed and validated by a registered nurse. Four distinct data elements were required to report a patient: date fracture occurred; date treatment began; date treatment ended; and a dichotomous outcome of healed v. failed, by clinical and radiological criteria. Data were used to calculate two derived variables; days to treatment (DTT) and days on treatment (DOT). Every validated fresh fracture patient with DTT, DOT, and outcome is reported. RESULTS: The validated registry had 5,765 patients with fresh fracture; 73% (N = 4,190) are reported, while 13% of patients were lost to follow-up, 11% withdrew or were non-compliant, and 3% died or are missing outcome. Among treatment-compliant patients, HR was 96.2%. Logistic estimates of the odds ratio for healing are equivalent for patients age 30 to 79 years and all age cohorts had a HR > 94%. Open fracture, current smoking, diabetes, vascular insufficiency, osteoporosis, cancer, rheumatoid arthritis, and prescription NSAIDs all reduced HR, but older patients (≥ 60) had similar HRs to the population as a whole. DTT was significantly shorter for patients who healed (p < 0.0001). CONCLUSIONS: Comorbid conditions in conjunction with aging can reduce fracture HR. Patients with fracture who used LIPUS had a 96% HR, whereas the expected HR averages 93%. Time to treatment was significantly shorter among patients who healed (p < 0.0001), suggesting that it is beneficial to begin LIPUS treatment early. Older patients (≥ 60) with fracture risk factors treated with LIPUS exhibit similar heal rates to the population as a whole.
Open Access
A comparison of minimally invasive transforaminal lumbar interbody fusion and decompression alone for degenerative lumbar spondylolisthesis.
(Neurosurgical focus, 2019-05) Chan, Andrew K; Bisson, Erica F; Bydon, Mohamad; Glassman, Steven D; Foley, Kevin T; Potts, Eric A; Shaffrey, Christopher I; Shaffrey, Mark E; Coric, Domagoj; Knightly, John J; Park, Paul; Wang, Michael Y; Fu, Kai-Ming; Slotkin, Jonathan R; Asher, Anthony L; Virk, Michael S; Kerezoudis, Panagiotis; Alvi, Mohammed Ali; Guan, Jian; Haid, Regis W; Mummaneni, Praveen V
OBJECTIVEThe optimal minimally invasive surgery (MIS) approach for grade 1 lumbar spondylolisthesis is not clearly elucidated. In this study, the authors compared the 24-month patient-reported outcomes (PROs) after MIS transforaminal lumbar interbody fusion (TLIF) and MIS decompression for degenerative lumbar spondylolisthesis.METHODSA total of 608 patients from 12 high-enrolling sites participating in the Quality Outcomes Database (QOD) lumbar spondylolisthesis module underwent single-level surgery for degenerative grade 1 lumbar spondylolisthesis, of whom 143 underwent MIS (72 MIS TLIF [50.3%] and 71 MIS decompression [49.7%]). Surgeries were classified as MIS if there was utilization of percutaneous screw fixation and placement of a Wiltse plane MIS intervertebral body graft (MIS TLIF) or if there was a tubular decompression (MIS decompression). Parameters obtained at baseline through at least 24 months of follow-up were collected. PROs included the Oswestry Disability Index (ODI), numeric rating scale (NRS) for back pain, NRS for leg pain, EuroQol-5D (EQ-5D) questionnaire, and North American Spine Society (NASS) satisfaction questionnaire. Multivariate models were constructed to adjust for patient characteristics, surgical variables, and baseline PRO values.RESULTSThe mean age of the MIS cohort was 67.1 ± 11.3 years (MIS TLIF 62.1 years vs MIS decompression 72.3 years) and consisted of 79 (55.2%) women (MIS TLIF 55.6% vs MIS decompression 54.9%). The proportion in each cohort reaching the 24-month follow-up did not differ significantly between the cohorts (MIS TLIF 83.3% and MIS decompression 84.5%, p = 0.85). MIS TLIF was associated with greater blood loss (mean 108.8 vs 33.0 ml, p < 0.001), longer operative time (mean 228.2 vs 101.8 minutes, p < 0.001), and longer length of hospitalization (mean 2.9 vs 0.7 days, p < 0.001). MIS TLIF was associated with a significantly lower reoperation rate (14.1% vs 1.4%, p = 0.004). Both cohorts demonstrated significant improvements in ODI, NRS back pain, NRS leg pain, and EQ-5D at 24 months (p < 0.001, all comparisons relative to baseline). In multivariate analyses, MIS TLIF-as opposed to MIS decompression alone-was associated with superior ODI change (β = -7.59, 95% CI -14.96 to -0.23; p = 0.04), NRS back pain change (β = -1.54, 95% CI -2.78 to -0.30; p = 0.02), and NASS satisfaction (OR 0.32, 95% CI 0.12-0.82; p = 0.02).CONCLUSIONSFor symptomatic, single-level degenerative spondylolisthesis, MIS TLIF was associated with a lower reoperation rate and superior outcomes for disability, back pain, and patient satisfaction compared with posterior MIS decompression alone. This finding may aid surgical decision-making when considering MIS for degenerative lumbar spondylolisthesis.
Open Access
A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.
(PLoS One, 2013) Woods, Christopher W; McClain, Micah T; Chen, Minhua; Zaas, Aimee K; Nicholson, Bradly P; Varkey, Jay; Veldman, Timothy; Kingsmore, Stephen F; Kingsmore, Stephen F; Huang, Yongsheng; Lambkin-Williams, Robert; Gilbert, Anthony G; Hero, Alfred O; Ramsburg, Elizabeth; Glickman, Seth; Lucas, Joseph E; Carin, Lawrence; Ginsburg, Geoffrey S
There is great potential for host-based gene expression analysis to impact the early diagnosis of infectious diseases. In particular, the influenza pandemic of 2009 highlighted the challenges and limitations of traditional pathogen-based testing for suspected upper respiratory viral infection. We inoculated human volunteers with either influenza A (A/Brisbane/59/2007 (H1N1) or A/Wisconsin/67/2005 (H3N2)), and assayed the peripheral blood transcriptome every 8 hours for 7 days. Of 41 inoculated volunteers, 18 (44%) developed symptomatic infection. Using unbiased sparse latent factor regression analysis, we generated a gene signature (or factor) for symptomatic influenza capable of detecting 94% of infected cases. This gene signature is detectable as early as 29 hours post-exposure and achieves maximal accuracy on average 43 hours (p = 0.003, H1N1) and 38 hours (p-value = 0.005, H3N2) before peak clinical symptoms. In order to test the relevance of these findings in naturally acquired disease, a composite influenza A signature built from these challenge studies was applied to Emergency Department patients where it discriminates between swine-origin influenza A/H1N1 (2009) infected and non-infected individuals with 92% accuracy. The host genomic response to Influenza infection is robust and may provide the means for detection before typical clinical symptoms are apparent.
Open Access
A neurophysiological study into the foundations of tonal harmony.
(Neuroreport, 2009-02-18) Bergelson, Elika; Idsardi, William J
Our findings provide magnetoencephalographic evidence that the mismatch-negativity response to two-note chords (dyads) is modulated by a combination of abstract cognitive differences and lower-level differences in the auditory signal. Participants were presented with series of simple-ratio sinusoidal dyads (perfect fourths and perfect fifths) in which the difference between the standard and deviant dyad exhibited an interval change, a shift in pitch space, or both. In addition, the standard-deviant pair of dyads either shared one note or both notes were changed. Only the condition that featured both abstract changes (interval change and pitch-space shift) and two novel notes showed a significantly larger magnetoencephalographic mismatch-negativity response than the other conditions in the right hemisphere. Implications for music and language processing are discussed.
Open Access
A new algorithm for predicting time to disease endpoints in Alzheimer's disease patients.
(J Alzheimers Dis, 2014) Razlighi, Qolamreza R; Stallard, Eric; Brandt, Jason; Blacker, Deborah; Albert, Marilyn; Scarmeas, Nikolaos; Kinosian, Bruce; Yashin, Anatoliy I; Stern, Yaakov
BACKGROUND: The ability to predict the length of time to death and institutionalization has strong implications for Alzheimer's disease patients and caregivers, health policy, economics, and the design of intervention studies. OBJECTIVE: To develop and validate a prediction algorithm that uses data from a single visit to estimate time to important disease endpoints for individual Alzheimer's disease patients. METHOD: Two separate study cohorts (Predictors 1, N = 252; Predictors 2, N = 254), all initially with mild Alzheimer's disease, were followed for 10 years at three research centers with semiannual assessments that included cognition, functional capacity, and medical, psychiatric, and neurologic information. The prediction algorithm was based on a longitudinal Grade of Membership model developed using the complete series of semiannually-collected Predictors 1 data. The algorithm was validated on the Predictors 2 data using data only from the initial assessment to predict separate survival curves for three outcomes. RESULTS: For each of the three outcome measures, the predicted survival curves fell well within the 95% confidence intervals of the observed survival curves. Patients were also divided into quintiles for each endpoint to assess the calibration of the algorithm for extreme patient profiles. In all cases, the actual and predicted survival curves were statistically equivalent. Predictive accuracy was maintained even when key baseline variables were excluded, demonstrating the high resilience of the algorithm to missing data. CONCLUSION: The new prediction algorithm accurately predicts time to death, institutionalization, and need for full-time care in individual Alzheimer's disease patients; it can be readily adapted to predict other important disease endpoints. The algorithm will serve an unmet clinical, research, and public health need.
Open Access
A noisy linear map underlies oscillations in cell size and gene expression in bacteria.
(Nature, 2015-07-16) Tanouchi, Yu; Pai, Anand; Park, Heungwon; Huang, Shuqiang; Stamatov, Rumen; Buchler, Nicolas E; You, Lingchong
During bacterial growth, a cell approximately doubles in size before division, after which it splits into two daughter cells. This process is subjected to the inherent perturbations of cellular noise and thus requires regulation for cell-size homeostasis. The mechanisms underlying the control and dynamics of cell size remain poorly understood owing to the difficulty in sizing individual bacteria over long periods of time in a high-throughput manner. Here we measure and analyse long-term, single-cell growth and division across different Escherichia coli strains and growth conditions. We show that a subset of cells in a population exhibit transient oscillations in cell size with periods that stretch across several (more than ten) generations. Our analysis reveals that a simple law governing cell-size control-a noisy linear map-explains the origins of these cell-size oscillations across all strains. This noisy linear map implements a negative feedback on cell-size control: a cell with a larger initial size tends to divide earlier, whereas one with a smaller initial size tends to divide later. Combining simulations of cell growth and division with experimental data, we demonstrate that this noisy linear map generates transient oscillations, not just in cell size, but also in constitutive gene expression. Our work provides new insights into the dynamics of bacterial cell-size regulation with implications for the physiological processes involved.
Open Access
A predictive model and nomogram for predicting return to work at 3 months after cervical spine surgery: an analysis from the Quality Outcomes Database.
(Neurosurgical focus, 2018-11) Devin, Clinton J; Bydon, Mohamad; Alvi, Mohammed Ali; Kerezoudis, Panagiotis; Khan, Inamullah; Sivaganesan, Ahilan; McGirt, Matthew J; Archer, Kristin R; Foley, Kevin T; Mummaneni, Praveen V; Bisson, Erica F; Knightly, John J; Shaffrey, Christopher I; Asher, Anthony L
OBJECTIVEBack pain and neck pain are two of the most common causes of work loss due to disability, which poses an economic burden on society. Due to recent changes in healthcare policies, patient-centered outcomes including return to work have been increasingly prioritized by physicians and hospitals to optimize healthcare delivery. In this study, the authors used a national spine registry to identify clinical factors associated with return to work at 3 months among patients undergoing a cervical spine surgery.METHODSThe authors queried the Quality Outcomes Database registry for information collected from April 2013 through March 2017 for preoperatively employed patients undergoing cervical spine surgery for degenerative spine disease. Covariates included demographic, clinical, and operative variables, and baseline patient-reported outcomes. Multiple imputations were used for missing values and multivariable logistic regression analysis was used to identify factors associated with higher odds of returning to work. Bootstrap resampling (200 iterations) was used to assess the validity of the model. A nomogram was constructed using the results of the multivariable model.RESULTSA total of 4689 patients were analyzed, of whom 82.2% (n = 3854) returned to work at 3 months postoperatively. Among previously employed and working patients, 89.3% (n = 3443) returned to work compared to 52.3% (n = 411) among those who were employed but not working (e.g., were on a leave) at the time of surgery (p < 0.001). On multivariable logistic regression the authors found that patients who were less likely to return to work were older (age > 56-65 years: OR 0.69, 95% CI 0.57-0.85, p < 0.001; age > 65 years: OR 0.65, 95% CI 0.43-0.97, p = 0.02); were employed but not working (OR 0.24, 95% CI 0.20-0.29, p < 0.001); were employed part time (OR 0.56, 95% CI 0.42-0.76, p < 0.001); had a heavy-intensity (OR 0.42, 95% CI 0.32-0.54, p < 0.001) or medium-intensity (OR 0.59, 95% CI 0.46-0.76, p < 0.001) occupation compared to a sedentary occupation type; had workers' compensation (OR 0.38, 95% CI 0.28-0.53, p < 0.001); had a higher Neck Disability Index score at baseline (OR 0.60, 95% CI 0.51-0.70, p = 0.017); were more likely to present with myelopathy (OR 0.52, 95% CI 0.42-0.63, p < 0.001); and had more levels fused (3-5 levels: OR 0.46, 95% CI 0.35-0.61, p < 0.001). Using the multivariable analysis, the authors then constructed a nomogram to predict return to work, which was found to have an area under the curve of 0.812 and good validity.CONCLUSIONSReturn to work is a crucial outcome that is being increasingly prioritized for employed patients undergoing spine surgery. The results from this study could help surgeons identify at-risk patients so that preoperative expectations could be discussed more comprehensively.
Open Access
A typology of time-scale mismatches and behavioral interventions to diagnose and solve conservation problems.
(Conserv Biol, 2016-02) Wilson, Robyn S; Hardisty, David J; Epanchin-Niell, Rebecca S; Runge, Michael C; Cottingham, Kathryn L; Urban, Dean L; Maguire, Lynn A; Hastings, Alan; Mumby, Peter J; Peters, Debra PC
Ecological systems often operate on time scales significantly longer or shorter than the time scales typical of human decision making, which causes substantial difficulty for conservation and management in socioecological systems. For example, invasive species may move faster than humans can diagnose problems and initiate solutions, and climate systems may exhibit long-term inertia and short-term fluctuations that obscure learning about the efficacy of management efforts in many ecological systems. We adopted a management-decision framework that distinguishes decision makers within public institutions from individual actors within the social system, calls attention to the ways socioecological systems respond to decision makers' actions, and notes institutional learning that accrues from observing these responses. We used this framework, along with insights from bedeviling conservation problems, to create a typology that identifies problematic time-scale mismatches occurring between individual decision makers in public institutions and between individual actors in the social or ecological system. We also considered solutions that involve modifying human perception and behavior at the individual level as a means of resolving these problematic mismatches. The potential solutions are derived from the behavioral economics and psychology literature on temporal challenges in decision making, such as the human tendency to discount future outcomes at irrationally high rates. These solutions range from framing environmental decisions to enhance the salience of long-term consequences, to using structured decision processes that make time scales of actions and consequences more explicit, to structural solutions aimed at altering the consequences of short-sighted behavior to make it less appealing. Additional application of these tools and long-term evaluation measures that assess not just behavioral changes but also associated changes in ecological systems are needed.
Open Access
Absence of July Phenomenon in Acute Ischemic Stroke Care Quality and Outcomes.
(Journal of the American Heart Association, 2018-01-31) Gonzalez-Castellon, Marco; Ju, Christine; Xian, Ying; Hernandez, Adrian; Fonarow, Gregg C; Schwamm, Lee; Smith, Eric E; Bhatt, Deepak L; Reeves, Matthew; Willey, Joshua Z
BACKGROUND:Lower care quality and an increase in adverse outcomes as a result of new medical trainees is a concept well rooted in popular belief, termed the "July phenomenon." Whether this phenomenon occurs in acute ischemic stroke has not been well studied. METHODS AND RESULTS:We analyzed data from patients admitted with ischemic stroke in 1625 hospitals participating in the Get With The Guidelines-Stroke program for the 5-year period between January 2009 and December 2013. We compared acute stroke treatment processes and in-hospitals outcomes among the 4 quarters (first quarter: July-September, last quarter: April-June) of the academic year. Multivariable logistic regression models were used to evaluate the relationship between academic year transition and processes measures. A total of 967 891 patients were included in the study. There was a statistically significant, but modest (<4 minutes or 5 percentage points) difference in distribution of or quality and clinical metrics including door-to-computerized tomography time, door-to-needle time, the proportion of patients with symptomatic intracranial hemorrhage within 36 hours of admission, and the proportion of patients who received defect-free care in stroke performance measures among academic year quarters (P<0.0001). In multivariable analyses, there was no evidence that quarter 1 of the academic year was associated with lower quality of care or worse in-hospital outcomes in teaching and nonteaching hospitals. CONCLUSIONS:We found no evidence of the "July phenomenon" in patients with acute ischemic stroke among hospitals participating in the Get With The Guidelines-Stroke program.
Open Access
Adjunctive albuterol enhances the response to enzyme replacement therapy in late-onset Pompe disease.
(FASEB J, 2014-05) Koeberl, Dwight D; Austin, Stephanie; Case, Laura E; Smith, Edward C; Buckley, Anne F; Young, Sarah P; Bali, Deeksha; Kishnani, Priya S
Effective dosages for enzyme replacement therapy (ERT) in Pompe disease are much higher than for other lysosomal storage disorders, which has been attributed to low cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle. We have previously demonstrated the benefit of increased CI-MPR-mediated uptake of recombinant human acid-α-glucosidase during ERT in mice with Pompe disease following addition of albuterol therapy. Currently we have completed a pilot study of albuterol in patients with late-onset Pompe disease already on ERT for >2 yr, who were not improving further. The 6-min walk test (6MWT) distance increased in all 7 subjects at wk 6 (30±13 m; P=0.002), wk 12 (34±14 m; P=0.004), and wk 24 (42±37 m; P=0.02), in comparison with baseline. Grip strength was improved significantly for both hands at wk 12. Furthermore, individual subjects reported benefits; e.g., a female patient could stand up from sitting on the floor much more easily (time for supine to standing position decreased from 30 to 11 s), and a male patient could readily swing his legs out of his van seat (hip abduction increased from 1 to 2+ on manual muscle testing). Finally, analysis of the quadriceps biopsies suggested increased CI-MPR at wk 12 (P=0.08), compared with baseline. With the exception of 1 patient who succumbed to respiratory complications of Pompe disease in the first week, only mild adverse events have been reported, including tremor, transient difficulty falling asleep, and mild urinary retention (requiring early morning voiding). Therefore, this pilot study revealed initial safety and efficacy in an open label study of adjunctive albuterol therapy in patients with late-onset Pompe disease who had been stable on ERT with no improvements noted over the previous several years.
Open Access
Adoption of direct-acting antiviral medications for hepatitis C: a retrospective observational study.
(BMC health services research, 2019-07-25) Zullig, Leah L; Bhatia, Haresh L; Gellad, Ziad F; Eatherly, Mark; Henderson, Rochelle; Bosworth, Hayden B
Background
Approximately 3.5 million Americans are infected with the hepatitis C virus (HCV). Although many patients with HCV are asymptomatic, HCV is the leading cause of infection-related death in the U.S. With advances in curative medication therapy for HCV, many of these deaths are preventable. Access to innovative therapies may be unevenly distributed. Our objective was to describe medication prescribers' adoption of innovative HCV pharmacotherapy across prescriber, geographical location, and time.
Methods
This is a retrospective, secondary data analysis among a national cohort of patients prescribed direct-acting antiviral HCV medications with curative intent. We assessed prescriptions by time, geographic location, and provider type.
Results
The peak of the adoption rate occurred within 45 days; nearly one-sixth of all prescribers had already prescribed one of the new drugs. Geographical regions (Midwest, South, and West all p ≥ 0.05) nor gender (p = 0.455) of a prescriber impacted adoption. Similarly, patient income did not influence the likelihood of a prescriber to adopt the new drugs earlier (p = 0.175). Gastroenterologists or hepatologists were more likely earlier adopters compared to primary care physicians (p = 0.01).
Conclusions
Because of the relative advantage of newer therapies, we anticipated that there would be an initial surge as early adopters prescribed the new medications and use would dwindle over time as the initial HCV cohort was cured. The data demonstrate that our hypothesis is essentially supported. There is a reduction in prescriptions at approximately 5 months post-approval and treatment is typically required for 3 months. There has been a surge in clinicians' adoption of innovative HCV treatments. As patients are cured of their infection, we anticipate a decreased need for chronic management of HCV.
Trial registration
Not applicable.
Open Access
Adult age differences in frontostriatal representation of prediction error but not reward outcome.
(Cogn Affect Behav Neurosci, 2014-06) Samanez-Larkin, Gregory R; Worthy, Darrell A; Mata, Rui; McClure, Samuel M; Knutson, Brian
Emerging evidence from decision neuroscience suggests that although younger and older adults show similar frontostriatal representations of reward magnitude, older adults often show deficits in feedback-driven reinforcement learning. In the present study, healthy adults completed reward-based tasks that did or did not depend on probabilistic learning, while undergoing functional neuroimaging. We observed reductions in the frontostriatal representation of prediction errors during probabilistic learning in older adults. In contrast, we found evidence for stability across adulthood in the representation of reward outcome in a task that did not require learning. Together, the results identify changes across adulthood in the dynamic coding of relational representations of feedback, in spite of preserved reward sensitivity in old age. Overall, the results suggest that the neural representation of prediction error, but not reward outcome, is reduced in old age. These findings reveal a potential dissociation between cognition and motivation with age and identify a potential mechanism for explaining changes in learning-dependent decision making in old adulthood.
Open Access
Alcohol and drug dependence symptom items as brief screeners for substance use disorders: results from the Clinical Trials Network.
(Journal of psychiatric research, 2012-03) Wu, Li-Tzy; Blazer, Dan G; Woody, George E; Burchett, Bruce; Yang, Chongming; Pan, Jeng-Jong; Ling, Walter
AIM:To address an urgent need for screening of substance use problems in medical settings, we examined substance-specific dependence criteria as potential brief screeners for the detection of patients with a substance use disorder (SUD). METHODS:The sample included 920 opioid-dependent adults who were recruited from outpatient treatment settings at 11 programs in 10 U.S. cities and who completed intake assessments of SUDs for a multisite study of the National Drug Abuse Treatment Clinical Trials Network (CTN003). Data were analyzed by factor analysis, item response theory (IRT), sensitivity, and specificity procedures. RESULTS:Across all substances (alcohol, amphetamines, cannabis, cocaine, sedatives), withdrawal was among the least prevalent symptoms, while taking large amounts and inability to cut down were among the most prevalent symptoms. Items closely related to the latent trait of a SUD showed good-to-high values of area under the receiver operating characteristic curve in identifying cases of a SUD; IRT-defined severe and less discriminative items exhibited low sensitivity in identifying cases of a SUD (withdrawal for all substances; time using for alcohol and sedatives; giving up activities for sedatives). CONCLUSIONS:Study results suggest that withdrawal and time using are much less reliable indicators for a SUD than taking larger amounts than intended and inability to cut down and that the latter two items should be studied further for consideration in developing a simplified tool for screening patients for SUDs in medical settings. These findings have implications for the use of common health indicators in electronic health records systems to improve patient care.
Open Access
Algorithm for the early diagnosis and treatment of patients with cross reactive immunologic material-negative classic infantile pompe disease: a step towards improving the efficacy of ERT.
(PLoS One, 2013) Banugaria, Suhrad G; Prater, Sean N; Patel, Trusha T; Dearmey, Stephanie M; Milleson, Christie; Sheets, Kathryn B; Bali, Deeksha S; Rehder, Catherine W; Raiman, Julian AJ; Wang, Raymond A; Labarthe, Francois; Charrow, Joel; Harmatz, Paul; Chakraborty, Pranesh; Rosenberg, Amy S; Kishnani, Priya S
OBJECTIVE: Although enzyme replacement therapy (ERT) is a highly effective therapy, CRIM-negative (CN) infantile Pompe disease (IPD) patients typically mount a strong immune response which abrogates the efficacy of ERT, resulting in clinical decline and death. This study was designed to demonstrate that immune tolerance induction (ITI) prevents or diminishes the development of antibody titers, resulting in a better clinical outcome compared to CN IPD patients treated with ERT monotherapy. METHODS: We evaluated the safety, efficacy and feasibility of a clinical algorithm designed to accurately identify CN IPD patients and minimize delays between CRIM status determination and initiation of an ITI regimen (combination of rituximab, methotrexate and IVIG) concurrent with ERT. Clinical and laboratory data including measures of efficacy analysis for response to ERT were analyzed and compared to CN IPD patients treated with ERT monotherapy. RESULTS: Seven CN IPD patients were identified and started on the ITI regimen concurrent with ERT. Median time from diagnosis of CN status to commencement of ERT and ITI was 0.5 months (range: 0.1-1.6 months). At baseline, all patients had significant cardiomyopathy and all but one required respiratory support. The ITI regimen was safely tolerated in all seven cases. Four patients never seroconverted and remained antibody-free. One patient died from respiratory failure. Two patients required another course of the ITI regimen. In addition to their clinical improvement, the antibody titers observed in these patients were much lower than those seen in ERT monotherapy treated CN patients. CONCLUSIONS: The ITI regimen appears safe and efficacious and holds promise in altering the natural history of CN IPD by increasing ERT efficacy. An algorithm such as this substantiates the benefits of accelerated diagnosis and management of CN IPD patients, thus, further supporting the importance of early identification and treatment initiation with newborn screening for IPD.
Open Access
An active learning approach for rapid characterization of endothelial cells in human tumors.
(PLoS One, 2014) Padmanabhan, Raghav K; Somasundar, Vinay H; Griffith, Sandra D; Zhu, Jianliang; Samoyedny, Drew; Tan, Kay See; Hu, Jiahao; Liao, Xuejun; Carin, Lawrence; Yoon, Sam S; Flaherty, Keith T; Dipaola, Robert S; Heitjan, Daniel F; Lal, Priti; Feldman, Michael D; Roysam, Badrinath; Lee, William MF
Currently, no available pathological or molecular measures of tumor angiogenesis predict response to antiangiogenic therapies used in clinical practice. Recognizing that tumor endothelial cells (EC) and EC activation and survival signaling are the direct targets of these therapies, we sought to develop an automated platform for quantifying activity of critical signaling pathways and other biological events in EC of patient tumors by histopathology. Computer image analysis of EC in highly heterogeneous human tumors by a statistical classifier trained using examples selected by human experts performed poorly due to subjectivity and selection bias. We hypothesized that the analysis can be optimized by a more active process to aid experts in identifying informative training examples. To test this hypothesis, we incorporated a novel active learning (AL) algorithm into FARSIGHT image analysis software that aids the expert by seeking out informative examples for the operator to label. The resulting FARSIGHT-AL system identified EC with specificity and sensitivity consistently greater than 0.9 and outperformed traditional supervised classification algorithms. The system modeled individual operator preferences and generated reproducible results. Using the results of EC classification, we also quantified proliferation (Ki67) and activity in important signal transduction pathways (MAP kinase, STAT3) in immunostained human clear cell renal cell carcinoma and other tumors. FARSIGHT-AL enables characterization of EC in conventionally preserved human tumors in a more automated process suitable for testing and validating in clinical trials. The results of our study support a unique opportunity for quantifying angiogenesis in a manner that can now be tested for its ability to identify novel predictive and response biomarkers.
Open Access
An Initial Evaluation of the Impact of Pokémon GO on Physical Activity.
(Journal of the American Heart Association, 2017-05-16) Xian, Ying; Xu, Hanzhang; Xu, Haolin; Liang, Li; Hernandez, Adrian F; Wang, Tracy Y; Peterson, Eric D
Pokémon GO is a location-based augmented reality game. Using GPS and the camera on a smartphone, the game requires players to travel in real world to capture animated creatures, called Pokémon. We examined the impact of Pokémon GO on physical activity (PA).A pre-post observational study of 167 Pokémon GO players who were self-enrolled through recruitment flyers or online social media was performed. Participants were instructed to provide screenshots of their step counts recorded by the iPhone Health app between June 15 and July 31, 2016, which was 3 weeks before and 3 weeks after the Pokémon GO release date. Of 167 participants, the median age was 25 years (interquartile range, 21-29 years). The daily average steps of participants at baseline was 5678 (SD, 2833; median, 5718 [interquartile range, 3675-7279]). After initiation of Pokémon GO, daily activity rose to 7654 steps (SD, 3616; median, 7232 [interquartile range, 5041-9744], pre-post change: 1976; 95% CI, 1494-2458, or a 34.8% relative increase [P<0.001]). On average, 10 000 "XP" points (a measure of game progression) was associated with 2134 additional steps per day (95% CI, 1673-2595), suggesting a potential dose-response relationship. The number of participants achieving a goal of 10 000+ steps per day increased from 15.3% before to 27.5% after (odds ratio, 2.06; 95% CI, 1.70-2.50). Increased PA was also observed in subgroups, with the largest increases seen in participants who spent more time playing Pokémon GO, those who were overweight/obese, or those with a lower baseline PA level.Pokémon GO participation was associated with a significant increase in PA among young adults. Incorporating PA into gameplay may provide an alternative way to promote PA in persons who are attracted to the game.URL: http://www.clinicaltrials.gov. Unique identifier: NCT02888314.
Open Access
Analysis of educational materials and destruction/opt-out initiatives for storage and use of residual newborn screening samples.
(Genet Test Mol Biomarkers, 2010-10) Haga, Susanne B
In recent years, the storage and use of residual newborn screening (NBS) samples has gained attention. To inform ongoing policy discussions, this article provides an update of previous work on new policies, educational materials, and parental options regarding the storage and use of residual NBS samples. A review of state NBS Web sites was conducted for information related to the storage and use of residual NBS samples in January 2010. In addition, a review of current statutes and bills introduced between 2005 and 2009 regarding storage and/or use of residual NBS samples was conducted. Fourteen states currently provide information about the storage and/or use of residual NBS samples. Nine states provide parents the option to request destruction of the residual NBS sample after the required storage period or the option to exclude the sample for research uses. In the coming years, it is anticipated that more states will consider policies to address parental concerns about the storage and use of residual NBS samples. Development of new policies regarding storage and use of residual NBS samples will require careful consideration of impact on NBS programs, parent and provider educational materials, and respect for parents among other issues.
Open Access
Are quit attempts among U.S. female nurses who smoke different from female smokers in the general population? An analysis of the 2006/2007 tobacco use supplement to the current population survey.
(BMC Womens Health, 2012-03-19) Sarna, Linda; Bialous, Stella Aguinaga; Nandy, Karabi; Yang, Qing
BACKGROUND: Smoking is a significant women's health issue. Examining smoking behaviors among occupational groups with a high prevalence of women may reveal the culture of smoking behavior and quit efforts of female smokers. The purpose of this study was to examine how smoking and quitting characteristics (i.e., ever and recent quit attempts) among females in the occupation of nursing are similar or different to those of women in the general population. METHODS: Cross-sectional data from the Tobacco Use Supplement of the Current Population Survey 2006/2007 were used to compare smoking behaviors of nurses (n = 2, 566) to those of non-healthcare professional women (n = 93, 717). Smoking characteristics included years of smoking, number of cigarettes, and time to first cigarette with smoking within the first 30 minutes as an indicator of nicotine dependence. Logistic regression models using replicate weights were used to determine correlates of ever and previous 12 months quit attempts. RESULTS: Nurses had a lower smoking prevalence than other women (12.1% vs 16.6%, p < 0.0001); were more likely to have ever made a quit attempt (77% vs 68%, p = 0.0002); but not in the previous 12 months (42% vs 43%, p = 0.77). Among those who ever made a quit attempt, nurses who smoked within 30 minutes of waking, were more likely to have made a quit attempt compared to other women (OR = 3.1, 95% CI: 1.9, 5.1). When considering quit attempts within the last 12 months, nurses whose first cigarette was after 30 minutes of waking were less likely to have made a quit attempt compared to other females (OR = 0.69, 95% CI: 0.49, 0.98). There were no other significant differences in ever/recent quitting. CONCLUSIONS: Smoking prevalence among female nurses was lower than among women who were not in healthcare occupations, as expected. The lack of difference in recent quit efforts among female nurses as compared to other female smokers has not been previously reported. The link between lower level of nicotine dependence, as reflected by the longer time to first cigarette, and lower quit attempts among nurses needs further exploration.

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