Pre-study feasibility and identifying sensitivity analyses for protocol pre-specification in comparative effectiveness research.

PubMed

Girman, Cynthia J; Faries, Douglas; Ryan, Patrick; Rotelli, Matt; Belger, Mark; Binkowitz, Bruce; O'Neill, Robert

2014-05-01

The use of healthcare databases for comparative effectiveness research (CER) is increasing exponentially despite its challenges. Researchers must understand their data source and whether outcomes, exposures and confounding factors are captured sufficiently to address the research question. They must also assess whether bias and confounding can be adequately minimized. Many study design characteristics may impact on the results; however, minimal if any sensitivity analyses are typically conducted, and those performed are post hoc. We propose pre-study steps for CER feasibility assessment and to identify sensitivity analyses that might be most important to pre-specify to help ensure that CER produces valid interpretable results.

Patient-provider communication and trust in relation to use of an online patient portal among diabetes patients: The Diabetes and Aging Study.

PubMed

Lyles, Courtney R; Sarkar, Urmimala; Ralston, James D; Adler, Nancy; Schillinger, Dean; Moffet, Howard H; Huang, Elbert S; Karter, Andrew J

2013-01-01

Patient-provider relationships influence diabetes care; less is known about their impact on online patient portal use. Diabetes patients rated provider communication and trust. In this study, we linked responses to electronic medical record data on being a registered portal user and using secure messaging (SM). We specified regression models to evaluate main effects on portal use, and subgroup analyses by race/ethnicity and age. 52% of subjects were registered users; among those, 36% used SM. Those reporting greater trust were more likely to be registered users (relative  risk (RR)=1.14) or SM users (RR=1.29). In subgroup analyses, increased trust was associated with being a registered user among white, Latino, and older patients, as well as SM use among white patients. Better communication ratings were also related to being a registered user among older patients. Since increased trust and communication were associated with portal use within subgroups, this suggests that patient-provider relationships encourage portal engagement.

Detecting treatment-subgroup interactions in clustered data with generalized linear mixed-effects model trees.

PubMed

Fokkema, M; Smits, N; Zeileis, A; Hothorn, T; Kelderman, H

2017-10-25

Identification of subgroups of patients for whom treatment A is more effective than treatment B, and vice versa, is of key importance to the development of personalized medicine. Tree-based algorithms are helpful tools for the detection of such interactions, but none of the available algorithms allow for taking into account clustered or nested dataset structures, which are particularly common in psychological research. Therefore, we propose the generalized linear mixed-effects model tree (GLMM tree) algorithm, which allows for the detection of treatment-subgroup interactions, while accounting for the clustered structure of a dataset. The algorithm uses model-based recursive partitioning to detect treatment-subgroup interactions, and a GLMM to estimate the random-effects parameters. In a simulation study, GLMM trees show higher accuracy in recovering treatment-subgroup interactions, higher predictive accuracy, and lower type II error rates than linear-model-based recursive partitioning and mixed-effects regression trees. Also, GLMM trees show somewhat higher predictive accuracy than linear mixed-effects models with pre-specified interaction effects, on average. We illustrate the application of GLMM trees on an individual patient-level data meta-analysis on treatments for depression. We conclude that GLMM trees are a promising exploratory tool for the detection of treatment-subgroup interactions in clustered datasets.

Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial

PubMed Central

Buchbinder, Susan P.; Mehrotra, Devan V.; Duerr, Ann; Fitzgerald, Daniel W.; Mogg, Robin; Li, David; Gilbert, Peter B.; Lama, Javier R.; Marmor, Michael; Rio, Carlos del; McElrath, M. Juliana; Casimiro, Danilo R.; Gottesdiener, Keith M.; Chodakewitz, Jeffrey A.; Corey, Lawrence; Robertson, Michael N.

2009-01-01

Background Observational data and non-human primate challenge studies suggest that cell-mediated immune (CMI) responses may provide control of HIV replication. The Step Study is the first direct assessment of the efficacy of a CMI vaccine to protect against HIV infection or alter early plasma HIV levels in humans. Method HIV-seronegative participants (3000) were randomized (1:1) to receive 3 injections of MRKAd5 HIV-1 gag/pol/nef vaccine or placebo. Randomization was pre-stratified by gender, baseline adenovirus type 5 (Ad5) titer, and study site. Participants were tested ~every 6 months for HIV acquisition; early plasma HIV RNA was measured ~3 months post-HIV diagnosis. Findings The vaccine elicited IFN-γ ELISPOT responses in 75% of vaccinees. In a pre-specified interim analysis among participants with baseline Ad5 ≤200, 24 of 741 vaccinees became HIV infected, versus 21 of 762 placebo recipients. All but one infection occurred in men. The early geometric mean plasma HIV RNA was comparable in infected vaccine and placebo recipients. In exploratory multivariate analyses, HIV incidence was higher in vaccinees versus placebo recipients among Ad5 seropositive men (5.1% versus 2.2% per year, respectively) and uncircumcised men (5.2% versus 1.4% per year, respectively). HIV incidence was similar in vaccinees versus placebo recipients among Ad5 seronegative men and circumcised men. Interpretation This CMI vaccine did not prevent HIV infection or lower early viral level. Mechanisms for failure of the vaccine to protect and for the increased HIV infection rates in subgroups of vaccinees are being explored. Additional follow-up will determine if elevated HIV incidence in vaccinee subgroups persists. PMID:19012954

Overview of reviews in child health: evidence synthesis and the knowledge base for a specific population.

PubMed

Thomson, Denise; Foisy, Michelle; Oleszczuk, Marta; Wingert, Aireen; Chisholm, Annabritt; Hartling, Lisa

2013-01-01

Overviews of reviews are an evolving form of evidence synthesis. The Cochrane Child Health Field has been producing overviews since 2006, during which time the methods that have been used have changed, both due to the development of guidance within The Cochrane Collaboration and to the decisions made by individual author teams. This paper studies the first 29 overviews published in EBCH. To describe some aspects of the approaches taken in EBCH overviews to producing evidence syntheses relevant to the healthcare needs of children; to highlight the contribution that overviews can make to the knowledge base for treatment for a particular population. Data was extracted on: whether the overview included systematic review (SR) data only, or also data from individual trials not present in the included SRs; name(s) of the Cochrane Review Group (CRG) that prepared the included SRs; topics of the overviews as compared to the topics of the included reviews; age-subgroup analyses presented in the overviews. In 23 overviews, all published in 2012, the authors included trial data as well as SR data; two overviews addressed conditions not explicitly addressed by the included reviews; three overviews included pre-specified age-subgroup analyses. The aim of clinical relevance has been achieved by means such as: drawing from reviews produced by multiple CRGs; using SR evidence to explore clinically relevant topics that may not match exactly with the topics covered by the SRs; ensuring that the evidence in overviews is as up to date as possible by redoing searches and including trials not incorporated in the included SRs; and, where permitted by the data, using age-subgroup analyses to present the data in a way which matches the stages of childhood development. Overview authors are dependent on the nature of the data and methods reported in the included SRs. This suggests a need for further study about how SRs could be conducted in order to facilitate the conduct of overviews. Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Validity and clinical utility of the DSM-5 severity specifier for bulimia nervosa: results from a multisite sample of patients who received evidence-based treatment.

PubMed

Dakanalis, Antonios; Bartoli, Francesco; Caslini, Manuela; Crocamo, Cristina; Zanetti, Maria Assunta; Riva, Giuseppe; Clerici, Massimo; Carrà, Giuseppe

2017-12-01

A new "severity specifier" for bulimia nervosa (BN), based on the frequency of inappropriate weight compensatory behaviours (IWCBs), was added to the DSM-5 as a means of documenting heterogeneity and variability in the severity of the disorder. Yet, evidence for its validity in clinical populations, including prognostic significance for treatment outcome, is currently lacking. Existing data from 281 treatment-seeking patients with DSM-5 BN, who received the best available treatment for their disorder (manual-based cognitive behavioural therapy; CBT) in an outpatient setting, were re-analysed to examine whether these patients subgrouped based on the DSM-5 severity levels would show meaningful and consistent differences on (a) a range of clinical variables assessed at pre-treatment and (b) post-treatment abstinence from IWCBs. Results highlight that the mild, moderate, severe, and extreme severity groups were statistically distinguishable on 22 variables assessed at pre-treatment regarding eating disorder pathological features, maintenance factors of BN, associated (current) and lifetime psychopathology, social maladjustment and illness-specific functional impairment, and abstinence outcome. Mood intolerance, a maintenance factor of BN but external to eating disorder pathological features (typically addressed within CBT), emerged as the primary clinical variable distinguishing the severity groups showing a differential treatment response. Overall, the findings speak to the concurrent and predictive validity of the new DSM-5 severity criterion for BN and are important because a common benchmark informing patients, clinicians, and researchers about severity of the disorder and allowing severity fluctuation and patient's progress to be tracked does not exist so far. Implications for future research are outlined.

Transfusion Indication Threshold Reduction (TITRe2) randomized controlled trial in cardiac surgery: statistical analysis plan.

PubMed

Pike, Katie; Nash, Rachel L; Murphy, Gavin J; Reeves, Barnaby C; Rogers, Chris A

2015-02-22

The Transfusion Indication Threshold Reduction (TITRe2) trial is the largest randomized controlled trial to date to compare red blood cell transfusion strategies following cardiac surgery. This update presents the statistical analysis plan, detailing how the study will be analyzed and presented. The statistical analysis plan has been written following recommendations from the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, prior to database lock and the final analysis of trial data. Outlined analyses are in line with the Consolidated Standards of Reporting Trials (CONSORT). The study aims to randomize 2000 patients from 17 UK centres. Patients are randomized to either a restrictive (transfuse if haemoglobin concentration <7.5 g/dl) or liberal (transfuse if haemoglobin concentration <9 g/dl) transfusion strategy. The primary outcome is a binary composite outcome of any serious infectious or ischaemic event in the first 3 months following randomization. The statistical analysis plan details how non-adherence with the intervention, withdrawals from the study, and the study population will be derived and dealt with in the analysis. The planned analyses of the trial primary and secondary outcome measures are described in detail, including approaches taken to deal with multiple testing, model assumptions not being met and missing data. Details of planned subgroup and sensitivity analyses and pre-specified ancillary analyses are given, along with potential issues that have been identified with such analyses and possible approaches to overcome such issues. ISRCTN70923932 .

Tensile bond strength of veneering resins to PEEK: impact of different adhesives.

PubMed

Stawarczyk, Bogna; Keul, Christine; Beuer, Florian; Roos, Malgorzata; Schmidlin, Patrick R

2013-01-01

This study tested tensile bond strength (TBS) between veneering resins and polyetheretherketone (PEEK) after pre-treatment with adhesive systems. Five-hundred-seventy-six PEEK disks were fabricated, air-abraded and divided into six pre-treatment groups (n=96/group): Z-Prime Plus, Ambarino P60, Monobond Plus, Visio.link, Signum PEEK Bond, and control group without pre-treatment. Each group was divided into three subgroups of different veneering resins (n=32): Sinfony, GC Gradia and VITA VM LC. After specimen preparation with a bond area of 6.6 mm(2), half of each subgroup (n=16) was tested initially, and the other half was thermo-cycled. TBS measurements were analysed by three-way and one-way ANOVA, t-test and Weibull statistics. Groups without pre-treatment and groups pre-treated by Z-Prime Plus and Ambarino P60 showed no TBS. Pre-treatment with Monobond Plus increased the TBS values. The highest TBS before and after thermo-cycling between PEEK and all tested veneering resins was observed for groups pre-treated with Visio.link and Signum PEEK Bond.

Summary Protocol for a Multi-Centre Randomised Controlled Trial of Enteral Lactoferrin Supplementation in Newborn Very Preterm Infants (ELFIN).

PubMed

2018-06-11

In a multi-centre randomised controlled trial (RCT), we are assessing whether giving very preterm (i.e., born at < 32 weeks' gestation) infants prophylactic enteral bovine lactoferrin supplementation (150 mg/kg/day) from shortly after birth until 34 weeks' post-menstrual age reduces the incidence of late-onset invasive infection (primary outcome), all-cause mortality, bronchopulmonary dysplasia, necrotising enterocolitis, retinopathy of prematurity, and the duration of antibiotic exposure, intensive care, and hospital admission. The trial is recruiting 2,200 participants from 37 neonatal care centres in the UK over 4 years. We will undertake an economic evaluation within the RCT to evaluate cost-effectiveness and provide an estimate of incremental costs for differences in the pre-specified outcomes in primary and subgroup analyses. If a statistically significant and clinically important effect on the primary outcome is detected, we will seek further funding and approval to assess the impact of enteral lactoferrin supplementation on rates of adverse neuro-developmental outcomes in the participating infants when they are 5 years old. © 2018 S. Karger AG, Basel.

Electroconvulsive Therapy Added to Non-Clozapine Antipsychotic Medication for Treatment Resistant Schizophrenia: Meta-Analysis of Randomized Controlled Trials.

PubMed

Zheng, Wei; Cao, Xiao-Lan; Ungvari, Gabor S; Xiang, Ying-Qiang; Guo, Tong; Liu, Zheng-Rong; Wang, Yuan-Yuan; Forester, Brent P; Seiner, Stephen J; Xiang, Yu-Tao

2016-01-01

This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of the combination of electroconvulsive therapy (ECT) and antipsychotic medication (except for clozapine) versus the same antipsychotic monotherapy for treatment-resistant schizophrenia (TRS). Two independent investigators extracted data for a random effects meta-analysis and pre-specified subgroup and meta-regression analyses. Weighted and standard mean difference (WMD/SMD), risk ratio (RR) ±95% confidence intervals (CIs), number needed to treat (NNT), and number needed to harm (NNH) were calculated. Eleven studies (n = 818, duration = 10.2±5.5 weeks) were identified for meta-analysis. Adjunctive ECT was superior to antipsychotic monotherapy regarding (1) symptomatic improvement at last-observation endpoint with an SMD of -0.67 (p<0.00001; I2 = 62%), separating the two groups as early as weeks 1–2 with an SMD of -0.58 (p<0.00001; I2 = 0%); (2) study-defined response (RR = 1.48, p<0.0001) with an NNT of 6 (CI = 4–9) and remission rate (RR = 2.18, p = 0.0002) with an NNT of 8 (CI = 6–16); (3) PANSS positive and general symptom sub-scores at endpoint with a WMD between -3.48 to -1.32 (P = 0.01 to 0.009). Subgroup analyses were conducted comparing double blind/rater-masked vs. open RCTs, those with and without randomization details, and high quality (Jadad≥adadup analyses were Jadad<3) studies. The ECT-antipsychotic combination caused more headache (p = 0.02) with an NNH of 6 (CI = 4–11) and memory impairment (p = 0.001) with an NNH of 3 (CI = 2–5). The use of ECT to augment antipsychotic treatment (clozapine excepted) can be an effective treatment option for TRS, with increased frequency of self-reported memory impairment and headache. CRD42014006689 (PROSPERO).

Insertion torque recordings for the diagnosis of contact between orthodontic mini-implants and dental roots: protocol for a systematic review.

PubMed

Meursinge Reynders, Reint; Ladu, Luisa; Ronchi, Laura; Di Girolamo, Nicola; de Lange, Jan; Roberts, Nia; Plüddemann, Annette

2015-04-02

Hitting a dental root during the insertion of orthodontic mini-implants (OMIs) is a common adverse effect of this intervention. This condition can permanently damage these structures and can cause implant instability. Increased torque levels (index test) recorded during the insertion of OMIs may provide a more accurate and immediate diagnosis of implant-root contact (target condition) than radiographic imaging (reference standard). An accurate index test could reduce or eliminate X-ray exposure. These issues, the common use of OMIs, the high prevalence of the target condition, and because most OMIs are placed between roots warrant a systematic review. We will assess 1) the diagnostic accuracy and the adverse effects of the index test, 2) whether OMIs with root contact have higher insertion torque values than those without, and 3) whether intermediate torque values have clinical diagnostic utility. The Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) 2015 statement was used as a the guideline for reporting this protocol. Inserting implants deliberately into dental roots of human participants would not be approved by ethical review boards and adverse effects of interventions are generally underreported. We will therefore apply broad spectrum eligibility criteria, which will include clinical, animal and cadaver models. Not including these models could slow down knowledge translation. Both randomized and non-randomized research studies will be included. Comparisons of interest and subgroups are pre-specified. We will conduct searches in MEDLINE and more than 40 other electronic databases. We will search the grey literature and reference lists and hand-search ten journals. All methodological procedures will be conducted by three reviewers. Study selection, data extraction and analyses, and protocols for contacting authors and resolving conflicts between reviewers are described. Designed specific risk of bias tools will be tailored to the research question. Different research models will be analysed separately. Parameters for exploring statistical heterogeneity and conducting meta-analyses are pre-specified. The quality of evidence for outcomes will be assessed through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The findings of this systematic review will be useful for patients, clinicians, researchers, guideline developers, policymakers, and surgical companies.

Using self-reported callous-unemotional traits to cross-nationally assess the DSM-5 'With Limited Prosocial Emotions' specifier.

PubMed

Kimonis, Eva R; Fanti, Kostas A; Frick, Paul J; Moffitt, Terrie E; Essau, Cecilia; Bijttebier, Patricia; Marsee, Monica A

2015-11-01

The presence of callous-unemotional (CU) traits designates an important subgroup of antisocial youth at risk for severe, persistent, and impairing conduct problems. As a result, the fifth revision of the Diagnostic and Statistical Manual includes a specifier for youth meeting diagnostic criteria for Conduct Disorder who show elevated CU traits. The current study evaluated the DSM-5 criteria using Item Response Theory (IRT) analyses and evaluated two methods for using a self-report measure of CU traits to make this diagnosis. The sample included 2257 adolescent (M age = 15.64, SD = 1.69 years) boys (53%) and girls (47%) from community and incarcerated settings in the United States and the European countries of Belgium, Germany, and Cyprus. IRT analyses suggested that four- or eight-item sets from the self-report measure (comparable to the symptoms used by the DSM-5 specifier) provided good model fit, suggesting that they assess a single underlying CU construct. Further, the most stringent method of scoring the self-report scale (i.e. taking only the most extreme responses) to approximate symptom presence provided the best discrimination in IRT analyses, showed reasonable prevalence rates of the specifier, and designated community adolescents who were highly antisocial, whereas the less stringent method best discriminated detained youth. Refined self-report scales developed on the basis of IRT findings provided good assessments of most of the symptoms used in the DSM-5 criteria. These scales may be used as one component of a multimethod assessment of the 'With Limited Prosocial Emotions' specifier for Conduct Disorder. © 2014 Association for Child and Adolescent Mental Health.

Statistical analysis plan for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). A randomized controlled trial

PubMed Central

Damiani, Lucas Petri; Berwanger, Otavio; Paisani, Denise; Laranjeira, Ligia Nasi; Suzumura, Erica Aranha; Amato, Marcelo Britto Passos; Carvalho, Carlos Roberto Ribeiro; Cavalcanti, Alexandre Biasi

2017-01-01

Background The Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) is an international multicenter randomized pragmatic controlled trial with allocation concealment involving 120 intensive care units in Brazil, Argentina, Colombia, Italy, Poland, Portugal, Malaysia, Spain, and Uruguay. The primary objective of ART is to determine whether maximum stepwise alveolar recruitment associated with PEEP titration, adjusted according to the static compliance of the respiratory system (ART strategy), is able to increase 28-day survival in patients with acute respiratory distress syndrome compared to conventional treatment (ARDSNet strategy). Objective To describe the data management process and statistical analysis plan. Methods The statistical analysis plan was designed by the trial executive committee and reviewed and approved by the trial steering committee. We provide an overview of the trial design with a special focus on describing the primary (28-day survival) and secondary outcomes. We describe our data management process, data monitoring committee, interim analyses, and sample size calculation. We describe our planned statistical analyses for primary and secondary outcomes as well as pre-specified subgroup analyses. We also provide details for presenting results, including mock tables for baseline characteristics, adherence to the protocol and effect on clinical outcomes. Conclusion According to best trial practice, we report our statistical analysis plan and data management plan prior to locking the database and beginning analyses. We anticipate that this document will prevent analysis bias and enhance the utility of the reported results. Trial registration ClinicalTrials.gov number, NCT01374022. PMID:28977255

The impact of body mass index and height on the risk for glioblastoma and other glioma subgroups: a large prospective cohort study.

PubMed

Wiedmann, Markus K H; Brunborg, Cathrine; Di Ieva, Antonio; Lindemann, Kristina; Johannesen, Tom B; Vatten, Lars; Helseth, Eirik; Zwart, John A

2017-07-01

Glioma comprises a heterogeneous group of mostly malignant brain tumors, whereof glioblastoma (GBM) represents the largest and most lethal subgroup. Body height and body mass index (BMI) are risk factors for other cancers, but no previous study has examined anthropometric data in relation to different glioma subgroups. This prospective cohort study includes 1.8 million Norwegian women and men between ages 14 and 80 years at baseline. Body weight and height were measured, and incident cases of glioma were identified by linkage to the National Cancer Registry. Cox regression analyses were performed to evaluate risk for different glioma subgroups in relation to anthropometric measures. During 54 million person-years of follow-up, 4,382 gliomas were identified. Overweight and obesity were not associated with risk for any glioma subgroup. Height was positively associated with risk for GBM and all other gliomas (hazard ratio [HR] per 10 cm increase: 1.24; 95% confidence interval [CI], 1.17-1.31 and 1.18; 95% CI, 1.09-1.29) but not with the proxy for isocitrate dehydrogenase (IDH)-mutant glioma (HR, 1.09; 95% CI, 0.98-1.21). In further subgroup analyses, the effect of height on glioma risk varied significantly with positive associations for oligoastrocytoma (HR, 1.74; 95% CI, 1.20-2.53) and malignant glioma not otherwise specified (NOS) (HR, 1.42; 95% CI, 1.16-1.76, but not with diffuse astrocytoma (WHO grades II and III) or oligodendroglioma. This epidemiologic study consolidates height as a risk factor for GBM and other gliomas. It further indicates that this association is not universal for gliomas but may differ between different glioma subgroups. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial.

PubMed

Maggioni, Aldo P; Greene, Stephen J; Fonarow, Gregg C; Böhm, Michael; Zannad, Faiez; Solomon, Scott D; Lewis, Eldrin F; Baschiera, Fabio; Hua, Tsushung A; Gimpelewicz, Claudio R; Lesogor, Anastasia; Gheorghiade, Mihai

2013-10-01

The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without DM.

Methodologic issues in terminating enrollment of a subgroup of patients in a multicenter randomized trial.

PubMed

Lee, Shing M; Wise, Robert; Sternberg, Alice L; Tonascia, James; Piantadosi, Steven

2004-01-01

The National Emphysema Treatment Trial (NETT) was a multicenter randomized controlled trial comparing medical treatment plus lung-volume-reduction surgery (LVRS) to medical treatment alone for the treatment of severe emphysema. The primary outcomes specified for the trial were mortality from all causes and change in functional status as indicated by the change in maximum exercise capacity measured two years after randomization. A secondary objective of the trial was to define criteria to identify subgroups of patients at risk of harm or benefit from LVRS. Stopping guidelines for safety and efficacy based on 30-day mortality and a combination of overall mortality and functional status at two years were specified at the inception of the trial. Although specific subgroups of patients likely to benefit were not identified in advance, several clinical factors were specified as likely to be important in defining subgroups with differential outcome. In May 2001, with 40% of expected deaths accrued, the Data and Safety Monitoring Board determined that a subgroup of patients was at significantly higher risk of 30-day mortality from LVRS without counterbalancing evidence of functional benefit, and recommended that the protocol be modified to exclude further randomization of such patients. The trial's sponsor, the National Heart, Lung and Blood Institute, accepted the recommendation, which was rapidly communicated to participating clinics. This paper describes the operational aspects of identification of the subgroup and implementation of the recommendation to continue the trial, but to terminate enrollment of new patients in the subgroup. These aspects include notification of the investigators, the institutional review boards, the Research Group, the patients and the medical community. We also describe the repercussions of the publication and the misinterpretations of the results based on media coverage.

Effect of physical activity on sex hormones in women: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Ennour-Idrissi, Kaoutar; Maunsell, Elizabeth; Diorio, Caroline

2015-11-05

Exposure to high levels of endogenous estrogens is a main risk factor for breast cancer in women, and in observational studies was found to be inversely associated with physical activity. The objective of the present study is to determine the effect of physical activity interventions on sex hormone levels in healthy women. Electronic databases (MEDLINE, EMBASE, CENTRAL), from inception to December 2014, and reference lists of relevant reviews and clinical trials were searched, with no language restrictions applied. Randomized controlled trials (RCTs) were included if they compared any type of exercise intervention to no intervention or other interventions, and assessed the effects on estrogens, androgens or the sex hormone binding globulin (SHBG) in cancer-free women. Following the method described in the Cochrane Handbook for Systematic Reviews of Interventions, data on populations, interventions, and outcomes were extracted, and combined using the inverse-variance method and a random-effects model. A pre-established protocol was drawn up, in which the primary outcome was the difference in circulating estradiol concentrations between the physical activity (experimental) and the control groups after intervention. Pre-specified subgroup analyses and sensitivity analysis according to the risk of bias were conducted. Data suitable for quantitative synthesis were available from 18 RCTs (1994 participants) for total estradiol and from 5 RCTs (1245 participants) for free estradiol. The overall effect of physical activity was a statistically significant decrease of both total estradiol (standardized mean difference [SMD] -0.12; 95 % confidence interval [CI] -0.20 to -0.03; P = 0.01; I (2) = 0 %) and free estradiol (SMD -0.20; 95 % CI -0.31 to -0.09; P = 0.0005; I (2) = 0 %). Subgroup analyses suggest that this effect is independent of menopausal status and is more noticeable for non-obese women and for high intensity exercise. Meta-analysis for secondary outcomes found that physical activity induces a statistically significant decline of free testosterone, androstenedione, dehydroepiandrosterone-sulfate and adiposity markers, while a significant increase of SHBG was observed. Although the effect is relatively modest, physical activity induces a decrease in circulating sex hormones and this effect is not entirely explained by weight loss. The findings emphasize the benefits of physical activity for women.

Protocol for a prospective collaborative systematic review and meta-analysis of individual patient data from randomized controlled trials of vasoactive drugs in acute stroke: The Blood pressure in Acute Stroke Collaboration, stage-3.

PubMed

Sandset, Else Charlotte; Sanossian, Nerses; Woodhouse, Lisa J; Anderson, Craig; Berge, Eivind; Lees, Kennedy R; Potter, John F; Robinson, Thompson G; Sprigg, Nikola; Wardlaw, Joanna M; Bath, Philip M

2018-01-01

Rationale Despite several large clinical trials assessing blood pressure lowering in acute stroke, equipoise remains particularly for ischemic stroke. The "Blood pressure in Acute Stroke Collaboration" commenced in the mid-1990s focussing on systematic reviews and meta-analysis of blood pressure lowering in acute stroke. From the start, Blood pressure in Acute Stroke Collaboration planned to assess safety and efficacy of blood pressure lowering in acute stroke using individual patient data. Aims To determine the optimal management of blood pressure in patients with acute stroke, including both intracerebral hemorrhage and ischemic stroke. Secondary aims are to assess which clinical and therapeutic factors may alter the optimal management of high blood pressure in patients with acute stroke and to assess the effect of vasoactive treatments on hemodynamic variables. Methods and design Individual patient data from randomized controlled trials of blood pressure management in participants with ischemic stroke and/or intracerebral hemorrhage enrolled during the ultra-acute (pre-hospital), hyper-acute (<6 h), acute (<48 h), and sub-acute (<168 h) phases of stroke. Study outcomes The primary effect variable will be functional outcome defined by the ordinal distribution of the modified Rankin Scale; analyses will also be carried out in pre-specified subgroups to assess the modifying effects of stroke-related and pre-stroke patient characteristics. Key secondary variables will include clinical, hemodynamic and neuroradiological variables; safety variables will comprise death and serious adverse events. Discussion Study questions will be addressed in stages, according to the protocol, before integrating these into a final overreaching analysis. We invite eligible trials to join the collaboration.

Qualitative Treatment-Subgroup Interactions in a Randomized Clinical Trial of Treatments for Adolescents with ADHD: Exploring What Cognitive-Behavioral Treatment Works for Whom

PubMed Central

Geurts, Hilde M.; Prins, Pier J. M.; Van Mechelen, Iven; Van der Oord, Saskia

2016-01-01

Objective This study explored qualitative treatment-subgroup interactions within data of a RCT with two cognitive behavioral treatments (CBT) for adolescents with ADHD: a planning-focused (PML) and a solution-focused CBT (SFT). Qualitative interactions imply that which treatment is best differs across subgroups of patients, and are therefore most relevant for personalized medicine. Methods Adolescents with ADHD (N = 159) received either PML or SFT. Pre-, post- and three-month follow-up data were gathered on parent-rated ADHD symptoms and planning problems. Pretreatment characteristics were explored as potential qualitative moderators of pretest to follow-up treatment effects, using an innovative analyses technique (QUINT; Dusseldorp & Van Mechelen, 2014). In addition, qualitative treatment-subgroup interactions for the therapeutic changes from pre- to posttest and from post- to follow-up test were investigated. Results For the entire time span from pretest to follow-up only a quantitative interaction was found, while from posttest to follow-up qualitative interactions were found: Adolescents with less depressive symptoms but more anxiety symptoms showed more improvement when receiving PML than SFT, while for other adolescents the effects of PML and SFT were comparable. Discussion Whereas subgroups in both treatments followed different trajectories, no subgroup was found for which SFT outperformed PML in terms of the global change in symptoms from pretest to three months after treatment. This implies that, based on this exploratory study, there is no need for personalized treatment allocation with regard to the CBTs under study for adolescents with ADHD. However, for a subgroup with comorbid anxiety symptoms but low depression PML clearly appears the treatment of preference. Trial Registration Nederlands Trial Register NTR2142 PMID:26977602

Qualitative Treatment-Subgroup Interactions in a Randomized Clinical Trial of Treatments for Adolescents with ADHD: Exploring What Cognitive-Behavioral Treatment Works for Whom.

PubMed

Boyer, Bianca E; Doove, Lisa L; Geurts, Hilde M; Prins, Pier J M; Van Mechelen, Iven; Van der Oord, Saskia

2016-01-01

This study explored qualitative treatment-subgroup interactions within data of a RCT with two cognitive behavioral treatments (CBT) for adolescents with ADHD: a planning-focused (PML) and a solution-focused CBT (SFT). Qualitative interactions imply that which treatment is best differs across subgroups of patients, and are therefore most relevant for personalized medicine. Adolescents with ADHD (N = 159) received either PML or SFT. Pre-, post- and three-month follow-up data were gathered on parent-rated ADHD symptoms and planning problems. Pretreatment characteristics were explored as potential qualitative moderators of pretest to follow-up treatment effects, using an innovative analyses technique (QUINT; Dusseldorp & Van Mechelen, 2014). In addition, qualitative treatment-subgroup interactions for the therapeutic changes from pre- to posttest and from post- to follow-up test were investigated. For the entire time span from pretest to follow-up only a quantitative interaction was found, while from posttest to follow-up qualitative interactions were found: Adolescents with less depressive symptoms but more anxiety symptoms showed more improvement when receiving PML than SFT, while for other adolescents the effects of PML and SFT were comparable. Whereas subgroups in both treatments followed different trajectories, no subgroup was found for which SFT outperformed PML in terms of the global change in symptoms from pretest to three months after treatment. This implies that, based on this exploratory study, there is no need for personalized treatment allocation with regard to the CBTs under study for adolescents with ADHD. However, for a subgroup with comorbid anxiety symptoms but low depression PML clearly appears the treatment of preference. Nederlands Trial Register NTR2142.

Low-molecular-weight heparin venous thromboprophylaxis in critically ill patients with renal dysfunction: A subgroup analysis of the PROTECT trial

PubMed Central

Adhikari, Neill K. J.; Ostermann, Marlies; Heels-Ansdell, Diane; Douketis, James D.; Skrobik, Yoanna; Qushmaq, Ismael; Meade, Maureen; Guyatt, Gordon; Geerts, William; Walsh, Michael W.; Crowther, Mark A.; Friedrich, Jan O.; Burry, Lisa; Bellomo, Rinaldo; Brandão da Silva, Nilton; Costa Filho, Rubens; Cox, Michael J.; Alves Silva, Suzana; Cook, Deborah J.

2018-01-01

Introduction There is concern about excessive bleeding when low-molecular-weight heparins (LMWHs) are used for venous thromboembolism (VTE) prophylaxis in renal dysfunction. Our objective was to evaluate whether LMWH VTE prophylaxis was safe and effective in critically ill patients with renal dysfunction by conducting a subgroup analysis of PROTECT, a randomized blinded trial. Methods We studied intensive care unit (ICU) patients with pre-ICU dialysis-dependent end-stage renal disease (ESRD; pre-specified subgroup; n = 118), or severe renal dysfunction at ICU admission (defined as ESRD or non-dialysis dependent with creatinine clearance [CrCl] <30 ml/min; post hoc subgroup; n = 590). We compared dalteparin, 5000 IU daily, with unfractionated heparin (UFH), 5000 IU twice daily, and considered outcomes of proximal leg deep vein thrombosis (DVT); pulmonary embolism (PE); any VTE; and major bleeding. Adjusted hazard ratios [HR] were calculated using Cox regression. Results In patients with ESRD, there was no significant difference in DVT (8.3% vs. 5.2%, p = 0.76), any VTE (10.0% vs. 6.9%; p = 0.39) or major bleeding (5.0% vs. 8.6%; p = 0.32) between UFH and dalteparin. In patients with severe renal dysfunction, there was no significant difference in any VTE (10.0% vs. 6.4%; p = 0.07) or major bleeding (8.9% vs. 11.0%; p = 0.66) but an increase in DVT with dalteparin (7.6% vs. 3.7%; p = 0.04). Interaction p-values for comparisons of HRs (ESRD versus not) were non-significant. Conclusions In critically ill patients with ESRD, or severe renal dysfunction, there was no significant difference in any VTE or major bleeding between UFH and dalteparin. Patients with severe renal dysfunction who received dalteparin had more proximal DVTs than those on UFH; this finding did not hold in patients with ESRD alone. PMID:29856817

Biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents for primary percutaneous coronary revascularisation of acute myocardial infarction.

PubMed

Pilgrim, Thomas; Piccolo, Raffaele; Heg, Dik; Roffi, Marco; Tüller, David; Vuilliomenet, André; Muller, Olivier; Cook, Stéphane; Weilenmann, Daniel; Kaiser, Christoph; Jamshidi, Peiman; Khattab, Ahmed A; Taniwaki, Masanori; Rigamonti, Fabio; Nietlispach, Fabian; Blöchlinger, Stefan; Wenaweser, Peter; Jüni, Peter; Windecker, Stephan

2016-12-10

Our aim was to compare the safety and efficacy of a novel, ultrathin strut, biodegradable polymer sirolimus-eluting stent (BP-SES) with a thin strut, durable polymer everolimus-eluting stent (DP-EES) in a pre-specified subgroup of patients with acute ST-segment elevation myocardial infarction (STEMI) enrolled in the BIOSCIENCE trial. The BIOSCIENCE trial is an investigator-initiated, single-blind, multicentre, randomised non-inferiority trial (NCT01443104). Randomisation was stratified according to the presence or absence of STEMI. The primary endpoint, target lesion failure (TLF), is a composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularisation within 12 months. Between February 2012 and May 2013, 407 STEMI patients were randomly assigned to treatment with BP-SES or DP-EES. At one year, TLF occurred in seven (3.4%) patients treated with BP-SES and 17 (8.8%) patients treated with DP-EES (RR 0.38, 95% CI: 0.16-0.91, p=0.024). Rates of cardiac death were 1.5% in the BP-SES group and 4.7% in the DP-EES group (RR 0.31, 95% CI: 0.08-1.14, p=0.062); rates of target vessel myocardial infarction were 0.5% and 2.6% (RR 0.18, 95% CI: 0.02-1.57, p=0.082), respectively, and rates of clinically indicated target lesion revascularisation were 1.5% in the BP-SES group versus 2.1% in the DP-EES group (RR 0.69, 95% CI: 0.16-3.10, p=0.631). There was no difference in the risk of definite stent thrombosis. In this pre-specified subgroup analysis, BP-SES was associated with a lower rate of target lesion failure at one year compared to DP-EES in STEMI patients. These findings require confirmation in a dedicated STEMI trial.

The Effectiveness of a Peer Coaching Education on Control and Management of Type 2 Diabetes in Women: A Protocol for a Randomized Controlled Trial.

PubMed

Aalaa, Maryam; Sanjari, Mahnaz; Aghaei Meybodi, Hamid Reza; Amini, Mohammad Reza; Qorbani, Mostafa; Adibi, Hossien; Mehrdad, Neda

2017-04-01

Diabetes Education by Peer Coaching is a strategy which helps the patients with diabetes in the field of behavioral and emotional problems. However, the results of studies in this field in other countries could not be generalized in our context. So, the current study aimed to examine the effectiveness of Diabetes Education by Peer Coaching on Diabetes Management. Outcome variables for patients and peer coaches are measured at baseline and in3,6 and 12 months. The primary outcome consisted of Fasting Blood Sugar (FBS) and HbA1c. Secondary outcomes included Blood Pressure (BP), Body Mass Index (BMI,) Waist-Hip Ratio (WHR), Lipid Profile, diabetes self-care activities, diabetes-related quality of life, depression, and Social Capital levels.Initial analyses compared the frequency of baseline levels of outcome and other variables using a simple Chi-square test, t-test and the Mann-Whitney- U test. Sequential measurements in each group were evaluated by two-way analysis of variance. If significant differences in baseline characteristics were found, analyses were repeated adjusting for these differences using ANOVA and logistic regression for multivariate analyses. Additional analyses were conducted to look for the evidence of effect modification by pre-specified subgroups. The fact is that self-control and self-efficacy in diabetes management and treatment of diabetes could be important components. It seems that this research in this special setting with cultural differences would provide more evidence about peer-coaching model. It seems that if the peer-coaching model improves learning situations between patients with diabetes by offering one-on-one Diabetes Self Management Education, it could be an interactive approach to diabetic education. Trial Registration Number: IRCT201501128175N3.

Potential effectiveness of Chinese herbal medicine Yu ping feng san for adult allergic rhinitis: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Luo, Qiulan; Zhang, Claire Shuiqing; Yang, Lihong; Zhang, Anthony Lin; Guo, Xinfeng; Xue, Charlie Changli; Lu, Chuanjian

2017-11-06

Chinese herbal medicine formula Yu ping feng san (YPFS) is commonly used for allergic rhinitis (AR). Previous review had summarized the effectiveness and safety of YPFS, however without any subgroup analysis performed to provide detailed evidence for guiding clinical practice. YPFS was recommended for the management of AR by Chinese medicine clinical practice guideline, but the treatment duration of YPFS was also not specified. The aim of this study is to evaluate the effectiveness and safety of YPFS in treating adult AR with the most recent evidence, and attempt to specify the duration of utilisation through subgroup meta-analyses. Seven databases were searched from their inceptions to September 2017. Randomized controlled trials (RCTs) evaluating YPFS for adult AR were included. Methodological quality of studies was assessed using the Cochrane risk of bias tool. Meta-analysis and subgroup meta-analyses were conducted for evaluating the effectiveness of YPFS. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used for rating the quality of evidence. Twenty-two RCTs involving 23 comparisons were included in this review. YPFS was compared to placebo, pharmacotherapy, and used as an add-on treatment compared to pharmacotherapy. Meta-analyses were feasible for the outcomes of four individual nasal symptom scores and "effective rate". Four individual nasal symptom scores decreased after YPFS' combination treatment: itchy nose (MD-0.46, 95% CI[-0.50, -0.42]), sneezing (MD-0.41, 95% CI[-0.47, -0.35]), blocked nose (MD-0.46, 95% CI[-0.54, -0.39]) and runny nose (MD-0.42, 95% CI[-0.58, -0.26]). Based on "effective rate", meta-analysis showed that YPFS did not achieve better effect than pharmacotherapy (RR1.07, 95%CI [0.94, 1.22), but its combination with pharmacotherapy seemed more effective than pharmacotherapy alone (RR1.27, 95%CI [1.19, 1.34]) (low quality). Subgroup analysis suggested that YPFS was not superior to the second-generation antihistamine (RR1.04, 95%CI [0.90, 1.19]) (low quality). Further, YPFS' combination treatment seemed more beneficial when it was used for more than three weeks (RR1.15, 95%CI [1.01, 1.32]). In addition, YPFS was well-tolerated for treating adult AR. Chinese herbal medicine formula YPFS seems beneficial for adult AR. This potential benefit need to be further evaluated by more rigorous RCTs.

Factorial invariance of child self-report across age subgroups: a confirmatory factor analysis of ages 5 to 16 years utilizing the PedsQL 4.0 Generic Core Scales.

PubMed

Limbers, Christine A; Newman, Daniel A; Varni, James W

2008-01-01

The utilization of health-related quality of life (HRQOL) measurement in an effort to improve pediatric health and well-being and determine the value of health care services has grown dramatically over the past decade. The paradigm shift toward patient-reported outcomes (PROs) in clinical trials has provided the opportunity to emphasize the value and essential need for pediatric patient self-report. In order for HRQOL/PRO comparisons to be meaningful for subgroup analyses, it is essential to demonstrate factorial invariance. This study examined age subgroup factorial invariance of child self-report for ages 5 to 16 years on more than 8,500 children utilizing the PedsQL 4.0 Generic Core Scales. Multigroup Confirmatory Factor Analysis (MGCFA) was performed specifying a five-factor model. Two multigroup structural equation models, one with constrained parameters and the other with unconstrained parameters, were proposed to compare the factor loadings across the age subgroups. Metric invariance (i.e., equal factor loadings) across the age subgroups was demonstrated based on stability of the Comparative Fit Index between the two models, and several additional indices of practical fit including the Root Mean Squared Error of Approximation, the Non-Normed Fit Index, and the Parsimony Normed Fit Index. The findings support an equivalent five-factor structure across the age subgroups. Based on these data, it can be concluded that children across the age subgroups in this study interpreted items on the PedsQL 4.0 Generic Core Scales in a similar manner regardless of their age.

Meta-analysis of pre-operative magnetic resonance imaging (MRI) and surgical treatment for breast cancer.

PubMed

Houssami, Nehmat; Turner, Robin M; Morrow, Monica

2017-09-01

Although there is no consensus on whether pre-operative MRI in women with breast cancer (BC) benefits surgical treatment, MRI continues to be used pre-operatively in practice. This meta-analysis examines the association between pre-operative MRI and surgical outcomes in BC. A systematic review was performed to identify studies reporting quantitative data on pre-operative MRI and surgical outcomes (without restriction by type of surgery received or type of BC) and using a controlled design. Random-effects logistic regression calculated the pooled odds ratio (OR) for each surgical outcome (MRI vs. no-MRI groups), and estimated ORs stratified by study-level age. Subgroup analysis was performed for invasive lobular cancer (ILC). Nineteen studies met eligibility criteria: 3 RCTs and 16 comparative studies that included newly diagnosed BC of any type except for three studies restricted to ILC. Primary analysis (85,975 subjects) showed that pre-operative MRI was associated with increased odds of receiving mastectomy [OR 1.39 (1.23, 1.57); p < 0.001]; similar findings were shown in analyses stratified by study-level median age. Secondary analyses did not find statistical evidence of an effect of MRI on the rates of re-excision, re-operation, or positive margins; however, MRI was significantly associated with increased odds of receiving contralateral prophylactic mastectomy [OR 1.91 (1.25, 2.91); p = 0.003]. Subgroup analysis for ILC did not find any association between MRI and the odds of receiving mastectomy [OR 1.00 (0.75, 1.33); p = 0.988] or the odds of re-excision [OR 0.65 (0.35, 1.24); p = 0.192]. Pre-operative MRI is associated with increased odds of receiving ipsilateral mastectomy and contralateral prophylactic mastectomy as surgical treatment in newly diagnosed BC patients.

Intake of Fruit and Vegetables and the Incident Risk of Cognitive Disorders: A Systematic Review and Meta-Analysis of Cohort Studies.

PubMed

Wu, L; Sun, D; Tan, Y

2017-01-01

No quantitative assessment has been performed to specifically link the consumption of fruit and vegetables with the incident risk of cognitive disorders. We searched the PubMed and the Embase databases (both from the inception to June 13th, 2016) for records that report the intake of fruit and vegetables and the risk of developing cognitive disorders (Alzheimer's disease, dementia, and cognitive decline/impairment). A generic inverse-variance method (random-effects model) was used to combine the relative risks (RRs) and 95% confidence intervals (CIs). To explore the potential sources of heterogeneity, we performed the subgroup and meta-regression analyses by pre-specified characteristics. We identified 6 cohorts involving a total of 21,175 participants. The pooled analysis showed that consumption of fruit and vegetables was inversely associated with the incident risk of cognitive disorders, and the pooled RR (95% CI) was 0.74 (0.62, 0.88), with evidence of significant heterogeneity (I2 =68%). Furthermore, we found that the significant heterogeneity might be attributed to the ethnic difference. Further large prospective studies should be performed to quantify the potential dose-response patterns of fruit and/or vegetables intake and to explore the role of fruit or vegetables consumption separately on cognitive disorders in different populations.

Phase II trial of CoQ10 for ALS finds insufficient evidence to justify Phase III

PubMed Central

Kaufmann, Petra; Thompson, John L.P.; Levy, Gilberto; Buchsbaum, Richard; Shefner, Jeremy; Krivickas, Lisa S.; Katz, Jonathan; Rollins, Yvonne; Barohn, Richard J.; Jackson, Carlayne E.; Tiryaki, Ezgi; Lomen-Hoerth, Catherine; Armon, Carmel; Tandan, Rup; Rudnicki, Stacy A.; Rezania, Kourosh; Sufit, Robert; Pestronk, Alan; Novella, Steven P.; Heiman-Patterson, Terry; Kasarskis, Edward J.; Pioro, Erik P.; Montes, Jacqueline; Arbing, Rachel; Vecchio, Darleen; Barsdorf, Alexandra; Mitsumoto, Hiroshi; Levin, Bruce

2010-01-01

Objective Amyotrophic lateral sclerosis (ALS) is a devastating, and currently incurable, neuromuscular disease in which oxidative stress and mitochondrial impairment are contributing to neuronal loss. Coenzyme Q10 (CoQ10), an antioxidant and mitochondrial cofactor, has shown promise in ALS transgenic mice, and in clinical trials for neurodegenerative diseases other than ALS. Our aims were to choose between two high doses of CoQ10 for ALS, and to determine if it merits testing in a Phase III clinical trial. Methods We designed and implemented a multi-center trial with an adaptive, two-stage, bias-adjusted, randomized, placebo-controlled, double-blind, Phase II design (n=185). The primary outcome in both stages was decline in the ALS Functional Rating Scale-revised (ALSFRSr) score over 9 months. Stage 1 (dose selection, 35 participants per group) compared CoQ10 doses of 1,800 and 2,700 mg/day. Stage 2 (futility test, 75 patients per group) compared the dose selected in Stage 1 against placebo. Results Stage 1 selected the 2,700 mg dose. In Stage 2, the pre-specified primary null hypothesis that this dose is superior to placebo was not rejected. It was rejected, however, in an accompanying pre-specified sensitivity test, and further supplementary analyses. Pre-specified secondary analyses showed no significant differences between CoQ10 at 2,700 mg/day and placebo. There were no safety concerns. Interpretation CoQ10 at 2,700 mg daily for 9 months shows insufficient promise to warrant Phase III testing. Given this outcome, the adaptive Phase II design incorporating a dose selection and a futility test avoided the need for a much larger conventional Phase III trial. PMID:19743457

All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia: results of the randomized AMLSG 07-04 study.

PubMed

Schlenk, Richard F; Lübbert, Michael; Benner, Axel; Lamparter, Alexander; Krauter, Jürgen; Herr, Wolfgang; Martin, Hans; Salih, Helmut R; Kündgen, Andrea; Horst, Heinz-A; Brossart, Peter; Götze, Katharina; Nachbaur, David; Wattad, Mohammed; Köhne, Claus-Henning; Fiedler, Walter; Bentz, Martin; Wulf, Gerald; Held, Gerhard; Hertenstein, Bernd; Salwender, Hans; Gaidzik, Verena I; Schlegelberger, Brigitte; Weber, Daniela; Döhner, Konstanze; Ganser, Arnold; Döhner, Hartmut

2016-12-01

The aim of this clinical trial was to evaluate the impact of all-trans retinoic acid (ATRA) in combination with chemotherapy and to assess the NPM1 status as biomarker for ATRA therapy in younger adult patients (18-60 years) with acute myeloid leukemia (AML). Patients were randomized for intensive chemotherapy with or without open-label ATRA (45 mg/m 2 , days 6-8; 15 mg/m 2 , days 9-21). Two cycles of induction therapy were followed by risk-adapted consolidation with high-dose cytarabine or allogeneic hematopoietic cell transplantation. Due to the open label character of the study, analysis was performed on an intention-to-treat (ITT) and a per-protocol (PP) basis. One thousand one hundred patients were randomized (556, STANDARD; 544, ATRA) with 38 patients treated vice versa. Median follow-up for survival was 5.2 years. ITT analyses revealed no difference between ATRA and STANDARD for the total cohort and for the subset of NPM1-mutated AML with respect to event-free (EFS; p = 0.93, p = 0.17) and overall survival (OS; p = 0.24 and p = 0.32, respectively). Pre-specified PP analyses revealed better EFS in NPM1-mutated AML (p = 0.05) and better OS in the total cohort (p = 0.03). Explorative subgroup analyses on an ITT basis revealed better OS (p = 0.05) in ATRA for genetic low-risk patients according to ELN recommendations. The clinical trial is registered at clinicaltrialsregister.eu (EudraCT Number: 2004-004321-95).

Placebo in sports nutrition: a proof-of-principle study involving caffeine supplementation.

PubMed

Saunders, B; de Oliveira, L F; da Silva, R P; de Salles Painelli, V; Gonçalves, L S; Yamaguchi, G; Mutti, T; Maciel, E; Roschel, H; Artioli, G G; Gualano, B

2017-11-01

We investigated the effects of supplement identification on exercise performance with caffeine supplementation. Forty-two trained cyclists (age 37 ± 8 years, body mass [BM] 74.3 ± 8.4 kg, height 1.76 ± 0.06 m, maximum oxygen uptake 50.0 ± 6.8 mL/kg/min) performed a ~30 min cycling time-trial 1 h following either 6 mg/kgBM caffeine (CAF) or placebo (PLA) supplementation and one control (CON) session without supplementation. Participants identified which supplement they believed they had ingested ("caffeine", "placebo", "don't know") pre- and post-exercise. Subsequently, participants were allocated to subgroups for analysis according to their identifications. Overall and subgroup analyses were performed using mixed-model and magnitude-based inference analyses. Caffeine improved performance vs PLA and CON (P ≤ 0.001). Correct pre- and post-exercise identification of caffeine in CAF improved exercise performance (+4.8 and +6.5%) vs CON, with slightly greater relative increases than the overall effect of caffeine (+4.1%). Performance was not different between PLA and CON within subgroups (all P > 0.05), although there was a tendency toward improved performance when participants believed they had ingested caffeine post-exercise (P = 0.06; 87% likely beneficial). Participants who correctly identified placebo in PLA showed possible harmful effects on performance compared to CON. Supplement identification appeared to influence exercise outcome and may be a source of bias in sports nutrition. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dissecting psychiatric spectrum disorders by generative embedding☆☆☆

PubMed Central

Brodersen, Kay H.; Deserno, Lorenz; Schlagenhauf, Florian; Lin, Zhihao; Penny, Will D.; Buhmann, Joachim M.; Stephan, Klaas E.

2013-01-01

This proof-of-concept study examines the feasibility of defining subgroups in psychiatric spectrum disorders by generative embedding, using dynamical system models which infer neuronal circuit mechanisms from neuroimaging data. To this end, we re-analysed an fMRI dataset of 41 patients diagnosed with schizophrenia and 42 healthy controls performing a numerical n-back working-memory task. In our generative-embedding approach, we used parameter estimates from a dynamic causal model (DCM) of a visual–parietal–prefrontal network to define a model-based feature space for the subsequent application of supervised and unsupervised learning techniques. First, using a linear support vector machine for classification, we were able to predict individual diagnostic labels significantly more accurately (78%) from DCM-based effective connectivity estimates than from functional connectivity between (62%) or local activity within the same regions (55%). Second, an unsupervised approach based on variational Bayesian Gaussian mixture modelling provided evidence for two clusters which mapped onto patients and controls with nearly the same accuracy (71%) as the supervised approach. Finally, when restricting the analysis only to the patients, Gaussian mixture modelling suggested the existence of three patient subgroups, each of which was characterised by a different architecture of the visual–parietal–prefrontal working-memory network. Critically, even though this analysis did not have access to information about the patients' clinical symptoms, the three neurophysiologically defined subgroups mapped onto three clinically distinct subgroups, distinguished by significant differences in negative symptom severity, as assessed on the Positive and Negative Syndrome Scale (PANSS). In summary, this study provides a concrete example of how psychiatric spectrum diseases may be split into subgroups that are defined in terms of neurophysiological mechanisms specified by a generative model of network dynamics such as DCM. The results corroborate our previous findings in stroke patients that generative embedding, compared to analyses of more conventional measures such as functional connectivity or regional activity, can significantly enhance both the interpretability and performance of computational approaches to clinical classification. PMID:24363992

Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial.

PubMed

Tabernero, Josep; Van Cutsem, Eric; Lakomý, Radek; Prausová, Jana; Ruff, Paul; van Hazel, Guy A; Moiseyenko, Vladimir M; Ferry, David R; McKendrick, Joseph J; Soussan-Lazard, Karen; Chevalier, Soazig; Allegra, Carmen J

2014-01-01

The antiangiogenic agent aflibercept (ziv-aflibercept in the United States) in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) significantly improved survival in a phase III study of patients with metastatic colorectal cancer (mCRC) previously treated with an oxaliplatin-based regimen. In the present analysis, outcomes were evaluated in prespecified subgroups to assess the consistency of the treatment effect. Patients were randomised to receive FOLFIRI plus aflibercept or placebo every 2weeks until disease progression or unacceptable toxicity occurred. Efficacy and safety outcomes were analysed with respect to demographic and baseline characteristics, and stratification factors (prior bevacizumab treatment and Eastern Cooperative Oncology Group performance status). Median overall survival (OS, months [95.34% confidence interval (CI)]) for aflibercept versus placebo was 12.5 (10.8-15.5) versus 11.7 (9.8-13.8) in patients with prior bevacizumab treatment and 13.9 (12.7-15.6) versus 12.4 (11.2-13.5) in patients with no prior bevacizumab treatment. The p value for interaction was 0.5668, indicating there was no heterogeneity in these subgroups. For OS and progression-free survival (PFS), there was a significantly greater benefit (at the 2-sided 10% level) of treatment for patients with liver only metastases versus patients with no liver metastases/liver metastases with other organ involvement (p value for interaction: 0.0899 [OS]; 0.0076 [PFS]). There was no evidence of heterogeneity in treatment effect in any of the other subgroups examined. The benefits of aflibercept in combination with FOLFIRI in patients with mCRC previously treated with oxaliplatin were maintained across the specified patient subgroups, including in patients with or without prior bevacizumab treatment. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

A comparison of subgroup analyses in grant applications and publications.

PubMed

Boonacker, Chantal W B; Hoes, Arno W; van Liere-Visser, Karen; Schilder, Anne G M; Rovers, Maroeska M

2011-07-15

In this paper, the authors compare subgroup analyses as outlined in grant applications and their related publications. Grants awarded by the Netherlands Organization for Health Research and Development (ZonMw) from 2001 onward that were finalized before March 1, 2010, were studied. Of the 79 grant proposals, 50 (63%) were intervention studies, 18 (23%) were diagnostic studies, and 6 (8%) were prognostic studies. Subgroups were mentioned in 49 (62%) grant applications and in 53 (67%) publications. In 20 of the 79 projects (25%), the publications were completely in agreement with the grant proposal; that is, subgroups that were prespecified in the grant proposal were reported and no new subgroup analyses were introduced in the publications. Of the 149 prespecified subgroups, 46 (31%) were reported in the final report or scientific publications, and 143 of the 189 (76%) reported subgroups were based on post-hoc findings. For 77% of the subgroup analyses in the publications, there was no mention of whether these were prespecified or post hoc. Justification for subgroup analysis and methods to study subgroups were rarely reported. The authors conclude that there is a large discrepancy between grant applications and final publications regarding subgroup analyses. Both nonreporting prespecified subgroup analyses and reporting post-hoc subgroup analyses are common. More guidance is clearly needed.

Structured triglycerides versus physical mixtures of medium- and long-chain triglycerides for parenteral nutrition in surgical or critically ill adult patients: Systematic review and meta-analysis.

PubMed

Wu, Guo Hao; Zaniolo, Orietta; Schuster, Heidi; Schlotzer, Ewald; Pradelli, Lorenzo

2017-02-01

New generations of parenteral lipid emulsions combine Long Chain Triglycerides (LCTs) with Medium Chain Triglycerides (MCTs) either by physically mixing MCT- and LCT-containing oils or by using synthetically structured triglycerides (STGs). In order to clarify some open issues relating to their comparative effect, in particular in terms of clinical outcomes, pertinent evidence was systematically identified, reviewed and meta-analyzed. PubMed, Scopus, Wanfang Data, China Hospital Knowledge Database and Google Scholar were searched for published clinical trials comparing STGs vs. MCTs/LCTs PN regimens administered over 5-7 days in surgical and/or critically ill patients. Two independent investigators performed screening and data extraction using a predefined list of parameters. Data were pooled using RevMan ® 5.2. Quality of evidence was assessed according to Cochrane's risk of bias tool. Pre-specified high quality (HQ), incremental analyses and a post hoc subgroup analysis were performed. 21 studies were included. The meta-analysis revealed a significantly better cumulative nitrogen balance (Std. mean difference [95% CI]) (1.34 [0.98-1.7], p < 0.00001), as well as higher values for pre-albumin (24.99 mg/L [6.71-43.27], p < 0.000001), and albumin (1.22 g/L [0.66-1.77] p < 0.0001), while plasma triglycerides were significantly lower (-0.28 mmol/L [-0.41 to -0.15], p < 0.0001) in the STG vs. MCT/LCT group. ALT, AST, and GGT were significantly lower with STGs than with MCTs/LCTs, while for total bilirubin and ALP only a trend was observed. STGs were also associated with a trend to a shorter hospital length of stay (LOS) (-1.74 days [-3.49 to 0.01] p = 0.05). Quality of evidence was affected by an unclear risk of selection bias, mostly due to the lack of detailed reporting (random sequence generation, allocation concealment). For the other domains, most of the weighted information was judged at low risk of bias. HQ estimated effects, incremental and subgroup analyses were consistent with the main analysis. In postsurgical and/or critically ill patients, the administration of STGs vs. MCT/LCTs was significantly associated with improved protein economy, better liver tolerance and a more efficient triglyceride elimination. With regard to clinical outcomes a strong trend towards reduced LOS was observed for STG patients. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Influence of Measurement Methodology on the Accuracy of Electrical Waveform Distortion Analysis

NASA Astrophysics Data System (ADS)

Bartman, Jacek; Kwiatkowski, Bogdan

2018-04-01

The present paper covers a review of documents that specify measurement methods of voltage waveform distortion. It also presents measurement stages of waveform components that are uncommon in the classic fundamentals of electrotechnics and signal theory, including the creation process of groups and subgroups of harmonics and interharmonics. Moreover, the paper discusses selected distortion factors of periodic waveforms and presents analyses that compare the values of these distortion indices. The measurements were carried out in the cycle per cycle mode and the measurement methodology that was used complies with the IEC 61000-4-7 norm. The studies showed significant discrepancies between the values of analyzed parameters.

The impact of national cancer awareness campaigns for bowel and lung cancer symptoms on sociodemographic inequalities in immediate key symptom awareness and GP attendances.

PubMed

Moffat, J; Bentley, A; Ironmonger, L; Boughey, A; Radford, G; Duffy, S

2015-03-31

National campaigns focusing on key symptoms of bowel and lung cancer ran in England in 2012, targeting men and women over the age of 50 years, from lower socioeconomic groups. Data from awareness surveys undertaken with samples of the target audience (n=1245/1140 pre-/post-bowel campaign and n=1412/1246 pre-/post-lung campaign) and Read-code data extracted from a selection general practitioner (GP) practices (n=355 for bowel and n=486 for lung) were analysed by population subgroups. Unprompted symptom awareness: There were no significant differences in the magnitude of shift in ABC1 vs C2DE groups for either campaign. For the bowel campaign, there was a significantly greater increase in awareness of blood in stools in the age group 75+ years compared with the 55-74 age group, and of looser stools in men compared with women. Prompted symptom awareness: Endorsement of 'blood in poo' remained stable, overall and across different population subgroups. Men showed a significantly greater increase in endorsement of 'looser poo' as a definite warning sign of bowel cancer than women. There were no significant differences across subgroups in endorsement of a 3-week cough as a definite warning sign of lung cancer. GP attendances: Overall, there were significant increases in attendances for symptoms directly linked to the campaigns, with the largest percentage increase seen in the 50-59 age group. For the bowel campaign, the increase was significantly greater for men and for practices in the most-deprived quintile, whereas for lung the increase was significantly greater for practices in the least-deprived quintile. The national bowel and lung campaigns reached their target audience and have also influenced younger and more affluent groups. Differences in impact within the target audience were also seen. There would seem to be no unduly concerning widening in inequalities, but further analyses of the equality of impact across population subgroups is warranted.

Treatment Effects of Removable Functional Appliances in Pre-Pubertal and Pubertal Class II Patients: A Systematic Review and Meta-Analysis of Controlled Studies

PubMed Central

Perinetti, Giuseppe; Primožič, Jasmina; Franchi, Lorenzo; Contardo, Luca

2015-01-01

Background Treatment effects of removable functional appliances in Class II malocclusion patients according to the pre-pubertal or pubertal growth phase has yet to be clarified. Objectives To assess and compare skeletal and dentoalveolar effects of removable functional appliances in Class II malocclusion treatment between pre-pubertal and pubertal patients. Search methods Literature survey using the Medline, SCOPUS, LILACS and SciELO databases, the Cochrane Library from inception to May 31, 2015. A manual search was also performed. Selection criteria Randomised (RCTs) or controlled clinical trials with a matched untreated control group. No restrictions were set regarding the type of removable appliance whenever used alone. Data collection and analysis For the meta-analysis, cephalometric parameters on the supplementary mandibular growth were the main outcomes, with other cephalometric parameters considered as secondary outcomes. Risk of bias in individual and across studies were evaluated along with sensitivity analysis for low quality studies. Mean differences and 95% confidence intervals for annualised changes were computed according to a random model. Differences between pre-pubertal and pubertal patients were assessed by subgroup analyses. GRADE assessment was performed for the main outcomes. Results Twelve articles (but only 3 RCTs) were included accounting for 8 pre-pubertal and 7 pubertal groups. Overall supplementary total mandibular length and mandibular ramus height were 0.95 mm (0.38, 1.51) and 0.00 mm (-0.52, 0.53) for pre-pubertal patients and 2.91 mm (2.04, 3.79) and 2.18 mm (1.51, 2.86) for pubertal patients, respectively. The subgroup difference was significant for both parameters (p<0.001). No maxillary growth restrain or increase in facial divergence was seen in either subgroup. The GRADE assessment was low for the pre-pubertal patients, and generally moderate for the pubertal patients. Conclusions Taking into account the limited quality and heterogeneity of the included studies, functional treatment by removable appliances may be effective in treating Class II malocclusion with clinically relevant skeletal effects if performed during the pubertal growth phase. PMID:26510187

Chest CT scan findings in World Trade Center workers.

PubMed

de la Hoz, Rafael E; Weber, Jonathan; Xu, Dongming; Doucette, John T; Liu, Xiaoyu; Carson, Deborah A; Celedón, Juan C

2018-03-15

We examined the chest CT scans of 1,453 WTC responders using the International Classification of High-resolution CT for Occupational and Environmental Respiratory Diseases. Univariate and bivariate analyses of potential work-related pleural abnormalities were performed with pre-WTC and WTC-related occupational exposure data, spirometry, demographics and quantitative CT measurements. Logistic regression was used to evaluate occupational predictors of those abnormalities. Chest CT scans were performed first at a median of 6.8 years after 9/11/2001. Pleural abnormalities were the most frequent (21.1%) across all occupational groups In multivariable analyses, significant pre-WTC occupational asbestos exposure, and work as laborer/cleaner were predictive of pleural abnormalities, with prevalence being highest for the Polish subgroup (n = 237) of our population. Continued occupational lung disease surveillance is warranted in this cohort.

Performance of Stratified and Subgrouped Disproportionality Analyses in Spontaneous Databases.

PubMed

Seabroke, Suzie; Candore, Gianmario; Juhlin, Kristina; Quarcoo, Naashika; Wisniewski, Antoni; Arani, Ramin; Painter, Jeffery; Tregunno, Philip; Norén, G Niklas; Slattery, Jim

2016-04-01

Disproportionality analyses are used in many organisations to identify adverse drug reactions (ADRs) from spontaneous report data. Reporting patterns vary over time, with patient demographics, and between different geographical regions, and therefore subgroup analyses or adjustment by stratification may be beneficial. The objective of this study was to evaluate the performance of subgroup and stratified disproportionality analyses for a number of key covariates within spontaneous report databases of differing sizes and characteristics. Using a reference set of established ADRs, signal detection performance (sensitivity and precision) was compared for stratified, subgroup and crude (unadjusted) analyses within five spontaneous report databases (two company, one national and two international databases). Analyses were repeated for a range of covariates: age, sex, country/region of origin, calendar time period, event seriousness, vaccine/non-vaccine, reporter qualification and report source. Subgroup analyses consistently performed better than stratified analyses in all databases. Subgroup analyses also showed benefits in both sensitivity and precision over crude analyses for the larger international databases, whilst for the smaller databases a gain in precision tended to result in some loss of sensitivity. Additionally, stratified analyses did not increase sensitivity or precision beyond that associated with analytical artefacts of the analysis. The most promising subgroup covariates were age and region/country of origin, although this varied between databases. Subgroup analyses perform better than stratified analyses and should be considered over the latter in routine first-pass signal detection. Subgroup analyses are also clearly beneficial over crude analyses for larger databases, but further validation is required for smaller databases.

Official Japanese Version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale: validation against the original English version.

PubMed

Kashihara, Kenichi; Kondo, Tomoyoshi; Mizuno, Yoshikuni; Kikuchi, Seiji; Kuno, Sadako; Hasegawa, Kazuko; Hattori, Nobutaka; Mochizuki, Hideki; Mori, Hideo; Murata, Miho; Nomoto, Masahiro; Takahashi, Ryosuke; Takeda, Atsushi; Tsuboi, Yoshio; Ugawa, Yoshikazu; Yamanmoto, Mitsutoshi; Yokochi, Fusako; Yoshii, Fumihito; Stebbins, Glenn T; Tilley, Barbara C; Luo, Sheng; Wang, Lu; LaPelle, Nancy R; Goetz, Christopher G

2014-09-01

The Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease (PD) Rating Scale (UPDRS) (MDS-UPDRS) has been developed and is now available in English. Part of the overall program includes the establishment of official non-English translations of the MDS-UPDRS. We present the process for completing the official Japanese translation of the MDS-UPDRS with clinimetric testing results. In this trial, the MDS-UPDRS was translated into Japanese, underwent cognitive pre-testing, and the translation was modified after taking the results into account. The final translation was approved as Official Working Draft of the MDS-UPDRS Japanese version and tested in 365 native-Japanese-speaking patients with PD. Confirmatory analyses were used to determine whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Official Working Draft of the Japanese translation. As a secondary analysis, we used exploratory factor analyses to examine the underlying factor structure without the constraint of a pre-specified factor organization. Confirmatory factor analysis revealed that Comparative Fit Index for all Parts of the MDS-UPDRS exceeded the minimal standard of 0.90 relative to the English version and therefore Japanese translation met the pre-specified criterion to be designated called an OFFICIAL MDS TRANSLATION. Secondary analyses revealed some differences between the English-language MDS-UPDRS and the Japanese translation, however, these differences were considered to be within an acceptable range. The Japanese version of the MDS-UPDRS met the criterion as an Official MDS Translation and is now available for use (www.movementdisorders.org).

Valid randomization-based p-values for partially post hoc subgroup analyses.

PubMed

Lee, Joseph J; Rubin, Donald B

2015-10-30

By 'partially post-hoc' subgroup analyses, we mean analyses that compare existing data from a randomized experiment-from which a subgroup specification is derived-to new, subgroup-only experimental data. We describe a motivating example in which partially post hoc subgroup analyses instigated statistical debate about a medical device's efficacy. We clarify the source of such analyses' invalidity and then propose a randomization-based approach for generating valid posterior predictive p-values for such partially post hoc subgroups. Lastly, we investigate the approach's operating characteristics in a simple illustrative setting through a series of simulations, showing that it can have desirable properties under both null and alternative hypotheses. Copyright © 2015 John Wiley & Sons, Ltd.

Texting preferences in a Paediatric residency.

PubMed

Draper, Lauren; Kuklinski, Cadence; Ladley, Amy; Adamson, Greg; Broom, Matthew

2017-12-01

Text messaging is ubiquitous among residents, but remains an underused educational tool. Though feasibility has been demonstrated, evidence of its ability to improve standardised test scores and provide insight on resident texting preferences is lacking. The authors set out to evaluate: (1) satisfaction with a hybrid question-and-answer (Q&A) texting format; and (2) pre-/post-paediatric in-training exam (ITE) performance. A prospective study with paediatrics and internal medicine-paediatrics residents. Residents were divided into subgroups: adolescent medicine (AM) and developmental medicine (DM). Messages were derived from ITE questions and sent Monday-Friday with a 20 per cent variance in messages specific to the sub-group. Residents completed surveys gauging perceptions of the programme, and pre- and post-programme ITE scores were analysed. Forty-one residents enrolled and 32 (78%) completed a post-programme survey. Of those, 21 (66%) preferred a Q&A format with an immediate text response versus information-only texts. The percentage change in ITE scores between 2013 and 2014 was significant. Comparing subgroups, there was no significant difference between the percentage change in ITE scores. Neither group performed significantly better on either the adolescent or developmental sections of the ITE. Text messaging… remains an underused educational tool CONCLUSIONS: Overall, participants improved their ITE scores, but no improvement was seen in the targeted subgroups on the exam. Although Q&A texts are preferred by residents, further assessment is required to assess the effect on educational outcomes. © 2017 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

A randomized, placebo-controlled trial of patient education for acute low back pain (PREVENT Trial): statistical analysis plan.

PubMed

Traeger, Adrian C; Skinner, Ian W; Hübscher, Markus; Lee, Hopin; Moseley, G Lorimer; Nicholas, Michael K; Henschke, Nicholas; Refshauge, Kathryn M; Blyth, Fiona M; Main, Chris J; Hush, Julia M; Pearce, Garry; Lo, Serigne; McAuley, James H

Statistical analysis plans increase the transparency of decisions made in the analysis of clinical trial results. The purpose of this paper is to detail the planned analyses for the PREVENT trial, a randomized, placebo-controlled trial of patient education for acute low back pain. We report the pre-specified principles, methods, and procedures to be adhered to in the main analysis of the PREVENT trial data. The primary outcome analysis will be based on Mixed Models for Repeated Measures (MMRM), which can test treatment effects at specific time points, and the assumptions of this analysis are outlined. We also outline the treatment of secondary outcomes and planned sensitivity analyses. We provide decisions regarding the treatment of missing data, handling of descriptive and process measure data, and blinded review procedures. Making public the pre-specified statistical analysis plan for the PREVENT trial minimizes the potential for bias in the analysis of trial data, and in the interpretation and reporting of trial results. ACTRN12612001180808 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612001180808). Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

A Methodological Framework for Model Selection in Interrupted Time Series Studies.

PubMed

Lopez Bernal, J; Soumerai, S; Gasparrini, A

2018-06-06

Interrupted time series is a powerful and increasingly popular design for evaluating public health and health service interventions. The design involves analysing trends in the outcome of interest and estimating the change in trend following an intervention relative to the counterfactual (the expected ongoing trend if the intervention had not occurred). There are two key components to modelling this effect: first, defining the counterfactual; second, defining the type of effect that the intervention is expected to have on the outcome, known as the impact model. The counterfactual is defined by extrapolating the underlying trends observed before the intervention to the post-intervention period. In doing this, authors must consider the pre-intervention period that will be included, any time varying confounders, whether trends may vary within different subgroups of the population and whether trends are linear or non-linear. Defining the impact model involves specifying the parameters that model the intervention, including for instance whether to allow for an abrupt level change or a gradual slope change, whether to allow for a lag before any effect on the outcome, whether to allow a transition period during which the intervention is being implemented and whether a ceiling or floor effect might be expected. Inappropriate model specification can bias the results of an interrupted time series analysis and using a model that is not closely tailored to the intervention or testing multiple models increases the risk of false positives being detected. It is important that authors use substantive knowledge to customise their interrupted time series model a priori to the intervention and outcome under study. Where there is uncertainty in model specification, authors should consider using separate data sources to define the intervention, running limited sensitivity analyses or undertaking initial exploratory studies. Copyright © 2018. Published by Elsevier Inc.

Cardiac monitoring for detection of atrial fibrillation after TIA: A systematic review and meta-analysis.

PubMed

Korompoki, Eleni; Del Giudice, Angela; Hillmann, Steffi; Malzahn, Uwe; Gladstone, David J; Heuschmann, Peter; Veltkamp, Roland

2017-01-01

Background and purpose The detection rate of atrial fibrillation has not been studied specifically in transient ischemic attack (TIA) patients although extrapolation from ischemic stroke may be inadequate. We conducted a systematic review and meta-analysis to determine the rate of newly diagnosed atrial fibrillation using different methods of ECG monitoring in TIA. Methods A comprehensive literature search was performed following a pre-specified protocol the PRISMA statement. Prospective observational studies and randomized controlled trials were considered that included TIA patients who underwent cardiac monitoring for >12 h. Primary outcome was frequency of detection of atrial fibrillation ≥30 s. Analyses of subgroups and of duration and type of monitoring were performed. Results Seventeen studies enrolling 1163 patients were included. The pooled atrial fibrillation detection rate for all methods was 4% (95% CI: 2-7%). Yield of monitoring was higher in selected (higher age, more extensive testing for arrhythmias before enrolment, or presumed cardioembolic/cryptogenic cause) than in unselected cohorts (7% vs 3%). Pooled mean atrial fibrillation detection rates rose with duration of monitoring: 4% (24 h), 5% (24 h to 7 days) and 6% (>7 days), respectively. Yield of non-invasive was significantly lower than that of invasive monitoring (4% vs. 11%). Significant heterogeneity was observed among studies (I 2 =60.61%). Conclusion This first meta-analysis of atrial fibrillation detection in TIA patients finds a lower atrial fibrillation detection rate in TIA than reported for IS and TIA cohorts in previous meta-analyses. Prospective studies are needed to determine actual prevalence of atrial fibrillation and optimal diagnostic procedure for atrial fibrillation detection in TIA.

Identification of subgroups by risk of graft failure after paediatric renal transplantation: application of survival tree models on the ESPN/ERA-EDTA Registry.

PubMed

Lofaro, Danilo; Jager, Kitty J; Abu-Hanna, Ameen; Groothoff, Jaap W; Arikoski, Pekka; Hoecker, Britta; Roussey-Kesler, Gwenaelle; Spasojević, Brankica; Verrina, Enrico; Schaefer, Franz; van Stralen, Karlijn J

2016-02-01

Identification of patient groups by risk of renal graft loss might be helpful for accurate patient counselling and clinical decision-making. Survival tree models are an alternative statistical approach to identify subgroups, offering cut-off points for covariates and an easy-to-interpret representation. Within the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry data we identified paediatric patient groups with specific profiles for 5-year renal graft survival. Two analyses were performed, including (i) parameters known at time of transplantation and (ii) additional clinical measurements obtained early after transplantation. The identified subgroups were added as covariates in two survival models. The prognostic performance of the models was tested and compared with conventional Cox regression analyses. The first analysis included 5275 paediatric renal transplants. The best 5-year graft survival (90.4%) was found among patients who received a renal graft as a pre-emptive transplantation or after short-term dialysis (<45 days), whereas graft survival was poorest (51.7%) in adolescents transplanted after long-term dialysis (>2.2 years). The Cox model including both pre-transplant factors and tree subgroups had a significantly better predictive performance than conventional Cox regression (P < 0.001). In the analysis including clinical factors, graft survival ranged from 97.3% [younger patients with estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m(2) and dialysis <20 months] to 34.7% (adolescents with eGFR <60 mL/min/1.73 m(2) and dialysis >20 months). Also in this case combining tree findings and clinical factors improved the predictive performance as compared with conventional Cox model models (P < 0.0001). In conclusion, we demonstrated the tree model to be an accurate and attractive tool to predict graft failure for patients with specific characteristics. This may aid the evaluation of individual graft prognosis and thereby the design of measures to improve graft survival in the poor prognosis groups. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

The impact of national cancer awareness campaigns for bowel and lung cancer symptoms on sociodemographic inequalities in immediate key symptom awareness and GP attendances

PubMed Central

Moffat, J; Bentley, A; Ironmonger, L; Boughey, A; Radford, G; Duffy, S

2015-01-01

Background: National campaigns focusing on key symptoms of bowel and lung cancer ran in England in 2012, targeting men and women over the age of 50 years, from lower socioeconomic groups. Methods: Data from awareness surveys undertaken with samples of the target audience (n=1245/1140 pre-/post-bowel campaign and n=1412/1246 pre-/post-lung campaign) and Read-code data extracted from a selection general practitioner (GP) practices (n=355 for bowel and n=486 for lung) were analysed by population subgroups. Results: Unprompted symptom awareness: There were no significant differences in the magnitude of shift in ABC1 vs C2DE groups for either campaign. For the bowel campaign, there was a significantly greater increase in awareness of blood in stools in the age group 75+ years compared with the 55–74 age group, and of looser stools in men compared with women. Prompted symptom awareness: Endorsement of ‘blood in poo' remained stable, overall and across different population subgroups. Men showed a significantly greater increase in endorsement of ‘looser poo' as a definite warning sign of bowel cancer than women. There were no significant differences across subgroups in endorsement of a 3-week cough as a definite warning sign of lung cancer. GP attendances: Overall, there were significant increases in attendances for symptoms directly linked to the campaigns, with the largest percentage increase seen in the 50–59 age group. For the bowel campaign, the increase was significantly greater for men and for practices in the most-deprived quintile, whereas for lung the increase was significantly greater for practices in the least-deprived quintile. Conclusions: The national bowel and lung campaigns reached their target audience and have also influenced younger and more affluent groups. Differences in impact within the target audience were also seen. There would seem to be no unduly concerning widening in inequalities, but further analyses of the equality of impact across population subgroups is warranted. PMID:25734383

[Position paper on the results of Symplicity HTN-3 trial. Grupo de estudio de la hipertensión arterial resistente].

PubMed

Azpiri-López, José Ramón; Assad-Morell, José Luis; Ponce de León-Martínez, Enrique; Monreal-Puente, Rogelio; Dávila-Bortoni, Adrián; Vázquez-Díaz, Luis Alberto; Treviño-Frutos, Ramón Javier; Barrera-Oranday, Félix; Del Angel-Soto, Juan Gustavo; Martínez, José Guadalupe; Arellano-Torres, Marcelo

2015-01-01

Renal artery denervation has shown to be an effective treatment for resistant hypertension. Symplicity HTN 1 and 2 trials showed in small and uncontrolled groups, significant systolic blood pressure reductions down to 30 mm Hg. Symplicity HTN-3, a double blind, randomized, placebo controlled clinical trial shaded this initial enthusiasm. Surprisingly, their results showed that renal denervation has a similar effect to placebo. Pre-specified subgroup analysis showed that non-black race individuals, younger than 65 years and with normal renal function, had a statistically significant systolic blood pressure decrease. This manuscript critically appraises the Symplicity HTN-3 trial, proposing possible explanations for the results. Also declares our group position and future actions regarding renal denervation. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Travel-associated infection presenting in Europe (2008-12): an analysis of EuroTravNet longitudinal, surveillance data, and evaluation of the effect of the pre-travel consultation.

PubMed

Schlagenhauf, Patricia; Weld, Leisa; Goorhuis, Abraham; Gautret, Philippe; Weber, Rainer; von Sonnenburg, Frank; Lopez-Vélez, Rogelio; Jensenius, Mogens; Cramer, Jakob P; Field, Vanessa K; Odolini, Silvia; Gkrania-Klotsas, Effrossyni; Chappuis, Francois; Malvy, Denis; van Genderen, Perry J J; Mockenhaupt, Frank; Jauréguiberry, Stéphane; Smith, Catherine; Beeching, Nicholas J; Ursing, Johan; Rapp, Christophe; Parola, Philippe; Grobusch, Martin P

2015-01-01

Travel is important in the acquisition and dissemination of infection. We aimed to assess European surveillance data for travel-related illness to profile imported infections, track trends, identify risk groups, and assess the usefulness of pre-travel advice. We analysed travel-associated morbidity in ill travellers presenting at EuroTravNet sites during the 5-year period of 2008-12. We calculated proportionate morbidity per 1000 ill travellers and made comparisons over time and between subgroups. We did 5-year trend analyses (2008-12) by testing differences in proportions between subgroups using Pearson's χ(2) test. We assessed the effect of the pre-travel consultation on infection acquisition and outcome by use of proportionate morbidity ratios. The top diagnoses in 32 136 patients, ranked by proportionate morbidity, were malaria and acute diarrhoea, both with high proportionate morbidity (>60). Dengue, giardiasis, and insect bites had high proportionate morbidity (>30) as well. 5-year analyses showed increases in vector borne infections with significant peaks in 2010; examples were increased Plasmodium falciparum malaria (χ(2)=37·57, p<0·001); increased dengue fever (χ(2)=135·9, p<0·001); and a widening geographic range of acquisition of chikungunya fever. The proportionate morbidity of dengue increased from 22 in 2008 to 36 in 2012. Five dengue cases acquired in Europe contributed to this increase. Dermatological diagnoses increased from 851 in 2008 to 1102 in 2012, especially insect bites and animal-related injuries. Respiratory infection trends were dominated by the influenza H1N1 pandemic in 2009. Illness acquired in Europe accounted for 1794 (6%) of all 32 136 cases-mainly, gastrointestinal (634) and respiratory (357) infections. Migration within Europe was associated with more serious infection such as hepatitis C, tuberculosis, hepatitis B, and HIV/AIDS. Pre-travel consultation was associated with significantly lower proportionate morbidity ratios for P falciparum malaria and also for acute hepatitis and HIV/AIDS. The pattern of travel-related infections presenting in Europe is complex. Trend analyses can inform on emerging infection threats. Pre-travel consultation is associated with reduced malaria proportionate morbidity ratios and less severe illness. These findings support the importance and effectiveness of pre-travel advice on malaria prevention, but cast doubt on the effectiveness of current strategies to prevent travel-related diarrhoea. European Centre for Disease Prevention and Control, University Hospital Institute Méditerranée Infection, US Centers for Disease Control and Prevention, and the International Society of Travel Medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

No improvement in the reporting of clinical trial subgroup effects in high-impact general medical journals.

PubMed

Gabler, Nicole B; Duan, Naihua; Raneses, Eli; Suttner, Leah; Ciarametaro, Michael; Cooney, Elizabeth; Dubois, Robert W; Halpern, Scott D; Kravitz, Richard L

2016-07-16

When subgroup analyses are not correctly analyzed and reported, incorrect conclusions may be drawn, and inappropriate treatments provided. Despite the increased recognition of the importance of subgroup analysis, little information exists regarding the prevalence, appropriateness, and study characteristics that influence subgroup analysis. The objective of this study is to determine (1) if the use of subgroup analyses and multivariable risk indices has increased, (2) whether statistical methodology has improved over time, and (3) which study characteristics predict subgroup analysis. We randomly selected randomized controlled trials (RCTs) from five high-impact general medical journals during three time periods. Data from these articles were abstracted in duplicate using standard forms and a standard protocol. Subgroup analysis was defined as reporting any subgroup effect. Appropriate methods for subgroup analysis included a formal test for heterogeneity or interaction across treatment-by-covariate groups. We used logistic regression to determine the variables significantly associated with any subgroup analysis or, among RCTs reporting subgroup analyses, using appropriate methodology. The final sample of 416 articles reported 437 RCTs, of which 270 (62 %) reported subgroup analysis. Among these, 185 (69 %) used appropriate methods to conduct such analyses. Subgroup analysis was reported in 62, 55, and 67 % of the articles from 2007, 2010, and 2013, respectively. The percentage using appropriate methods decreased over the three time points from 77 % in 2007 to 63 % in 2013 (p < 0.05). Significant predictors of reporting subgroup analysis included industry funding (OR 1.94 (95 % CI 1.17, 3.21)), sample size (OR 1.98 per quintile (1.64, 2.40), and a significant primary outcome (OR 0.55 (0.33, 0.92)). The use of appropriate methods to conduct subgroup analysis decreased by year (OR 0.88 (0.76, 1.00)) and was less common with industry funding (OR 0.35 (0.18, 0.70)). Only 33 (18 %) of the RCTs examined subgroup effects using a multivariable risk index. While we found no significant increase in the reporting of subgroup analysis over time, our results show a significant decrease in the reporting of subgroup analyses using appropriate methods during recent years. Industry-sponsored trials may more commonly report subgroup analyses, but without utilizing appropriate methods. Suboptimal reporting of subgroup effects may impact optimal physician-patient decision-making.

Design of a multi-center immunophenotyping analysis of peripheral blood, sputum and bronchoalveolar lavage fluid in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS).

PubMed

Freeman, Christine M; Crudgington, Sean; Stolberg, Valerie R; Brown, Jeanette P; Sonstein, Joanne; Alexis, Neil E; Doerschuk, Claire M; Basta, Patricia V; Carretta, Elizabeth E; Couper, David J; Hastie, Annette T; Kaner, Robert J; O'Neal, Wanda K; Paine, Robert; Rennard, Stephen I; Shimbo, Daichi; Woodruff, Prescott G; Zeidler, Michelle; Curtis, Jeffrey L

2015-01-27

Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) is a multi-center longitudinal, observational study to identify novel phenotypes and biomarkers of chronic obstructive pulmonary disease (COPD). In a subset of 300 subjects enrolled at six clinical centers, we are performing flow cytometric analyses of leukocytes from induced sputum, bronchoalveolar lavage (BAL) and peripheral blood. To minimize several sources of variability, we use a "just-in-time" design that permits immediate staining without pre-fixation of samples, followed by centralized analysis on a single instrument. The Immunophenotyping Core prepares 12-color antibody panels, which are shipped to the six Clinical Centers shortly before study visits. Sputum induction occurs at least two weeks before a bronchoscopy visit, at which time peripheral blood and bronchoalveolar lavage are collected. Immunostaining is performed at each clinical site on the day that the samples are collected. Samples are fixed and express shipped to the Immunophenotyping Core for data acquisition on a single modified LSR II flow cytometer. Results are analyzed using FACS Diva and FloJo software and cross-checked by Core scientists who are blinded to subject data. Thus far, a total of 152 sputum samples and 117 samples of blood and BAL have been returned to the Immunophenotyping Core. Initial quality checks indicate useable data from 126 sputum samples (83%), 106 blood samples (91%) and 91 BAL samples (78%). In all three sample types, we are able to identify and characterize the activation state or subset of multiple leukocyte cell populations (including CD4+ and CD8+ T cells, B cells, monocytes, macrophages, neutrophils and eosinophils), thereby demonstrating the validity of the antibody panel. Our study design, which relies on bi-directional communication between clinical centers and the Core according to a pre-specified protocol, appears to reduce several sources of variability often seen in flow cytometric studies involving multiple clinical sites. Because leukocytes contribute to lung pathology in COPD, these analyses will help achieve SPIROMICS aims of identifying subgroups of patients with specific COPD phenotypes. Future analyses will correlate cell-surface markers on a given cell type with smoking history, spirometry, airway measurements, and other parameters. This study was registered with ClinicalTrials.gov as NCT01969344 .

High proportion of subgroup A' (genotype A) among Brazilian isolates of Hepatitis B virus.

PubMed

Araujo, N M; Mello, F C A; Yoshida, C F T; Niel, C; Gomes, S A

2004-07-01

Hepatitis B virus (HBV) genotype A has been divided recently into two subgroups, designated A-A' (genotype A excluding A') and A'. Isolates belonging to subgroup A' have been identified in Africa. A new genotyping method, based on PCR amplification of the pre-S/S genome region and subsequent restriction fragment length polymorphism (RFLP) analysis, was developed, that established a correlation between RFLP subtypes and subgroups within genotype A. To investigate the occurrence of subgroup A' in South America, 119 Brazilian HBV isolates were analyzed. Ninety-three (78%) of them belonged to genotype A, with three predominating RFLP subtypes: 44 (37%) isolates were classified as AI, 30 (25%) were AII, and 18 (15%) were AIII. Pre-S/S nucleotide sequences of 15 genotype A isolates were determined. Phylogenetic analysis performed with these 15 and an additional 41 sequences revealed that isolates AI and AII clustered in subgroup A', whereas isolates AIII were classified into subgroup A-A'. The correlation RFLP subtypes-subgroups was confirmed by the presence of amino acid residues specific for subgroup A' in the surface antigens and polymerase of isolates AI and AII. The high proportion (63%) of isolates from subgroup A' suggested an African origin for a large number of Brazilian HBVs.

Detection of lymphoid leukosis tumors in white leghorn chickens of line ALV6 that is resistant to subgroups A and E avian leukosis virus and maintained under specific pathogen-free conditions

USDA-ARS?s Scientific Manuscript database

Chickens from Avian Disease and Oncology Laboratory (ADOL) line alv6 that is known to be resistant to infection with subgroups A and E avian leukosis virus (ALV) were vaccinated at hatch with a Marek’s disease (MD) vaccine containing serotypes 1, 2 and 3 MD viruses, and were maintained under specifi...

[Correlation analysis of the pre-pregnant body mass index, the gestational weight gain and umbilical cord blood C peptide].

PubMed

Chen, X L; Han, Y; Zhao, X M; Liu, Y; Lü, J J

2017-01-03

Objective: To explore the correlation among the pre-pregnant body mass index (BMI), gestational weight gain (GWG) and umbilical cord blood C peptide, and to investigate the influence of maternal weight management on the incidence of baby long-term metabolic syndrome. Methods: During May to Aug.2015, 485 pregnant women in Zhejiang Taizhou first people's hospital and Taizhou Huangyan maternal &child care service centre were selected in random and divided into four groups according to pre-pregnant BMI: low body mass, normal body mass, over body mass and obese group, and also divided into two groups for getting gestational diabetes mellitus (GDM) or not. According to the gestational weight gain (GWG), all the cases were divided into two groups: above the Institute Of Medicine (IMO) 2009 recommendations or not. According to the outcome, the GDM group which had received weight control treatment, was divided into successful treat group or not. At last, we tested the umbilical cord blood C peptide and birth weight of each newborn and compared the difference in all subgroups. The correlation between the umbilical cord blood C peptide and birth weight were analysed. Results: (1) In the pre-pregnant BMI groups, there were significant differences of incidence of GDM ( P <0.05). But, there were no significant differences of incidence of GWG in four groups ( P >0.05). (2) Newborn birth weight and the umbilical cord blood C peptide were positively correlated ( r =0.673, P <0.05). (3) Umbilical cord blood C peptide showed the correlation in all subgroups for different pre-pregnant BMI, GDM or not, overweight or not ( P <0.05), but only the GDM or not group had relation to newborn birth weight in all subgroups. (4) All groups showed correlations with neonatal umbilical cord blood C peptide, the GDM mostly (β=0.58), pre-pregnant BMI secondly (β: 0.36, 0.38) , and GWG weakly (β=0.17). (5) By stratification analysis, in GDM group, low body mass was negatively correlated with umbilical cord blood C peptide ( P <0.05, β=-1.41); in non-GDM group, over body mass group and obsess group were positively correlated with umbilical cord blood C peptide ( P <0.05, β=0.37, 0.46). Conclusion: There was direct correlation between the pre-pregnant body mass index, the gestational weight gain and umbilical cord blood C peptide. Suitable maternal weight control especially pre-pregnant body mass index control will lower the baby long-term metabolic syndrome incidence.

Subgroup analyses in confirmatory clinical trials: time to be specific about their purposes.

PubMed

Tanniou, Julien; van der Tweel, Ingeborg; Teerenstra, Steven; Roes, Kit C B

2016-02-18

It is well recognized that treatment effects may not be homogeneous across the study population. Subgroup analyses constitute a fundamental step in the assessment of evidence from confirmatory (Phase III) clinical trials, where conclusions for the overall study population might not hold. Subgroup analyses can have different and distinct purposes, requiring specific design and analysis solutions. It is relevant to evaluate methodological developments in subgroup analyses against these purposes to guide health care professionals and regulators as well as to identify gaps in current methodology. We defined four purposes for subgroup analyses: (1) Investigate the consistency of treatment effects across subgroups of clinical importance, (2) Explore the treatment effect across different subgroups within an overall non-significant trial, (3) Evaluate safety profiles limited to one or a few subgroup(s), (4) Establish efficacy in the targeted subgroup when included in a confirmatory testing strategy of a single trial. We reviewed the methodology in line with this "purpose-based" framework. The review covered papers published between January 2005 and April 2015 and aimed to classify them in none, one or more of the aforementioned purposes. In total 1857 potentially eligible papers were identified. Forty-eight papers were selected and 20 additional relevant papers were identified from their references, leading to 68 papers in total. Nineteen were dedicated to purpose 1, 16 to purpose 4, one to purpose 2 and none to purpose 3. Seven papers were dedicated to more than one purpose, the 25 remaining could not be classified unambiguously. Purposes of the methods were often not specifically indicated, methods for subgroup analysis for safety purposes were almost absent and a multitude of diverse methods were developed for purpose (1). It is important that researchers developing methodology for subgroup analysis explicitly clarify the objectives of their methods in terms that can be understood from a patient's, health care provider's and/or regulator's perspective. A clear operational definition for consistency of treatment effects across subgroups is lacking, but is needed to improve the usability of subgroup analyses in this setting. Finally, methods to particularly explore benefit-risk systematically across subgroups need more research.

Evaluation of the DSM-5 Severity Specifier for Bulimia Nervosa in Treatment-Seeking Youth.

PubMed

Dakanalis, Antonios; Colmegna, Fabrizia; Zanetti, Maria Assunta; Di Giacomo, Ester; Riva, Giuseppe; Clerici, Massimo

2018-02-01

A new severity specifier for bulimia nervosa (BN), based on the frequency of inappropriate weight compensatory behaviours (e.g., laxative misuse, self-induced vomiting, fasting, diuretic misuse, and excessive exercise), has been added to the most recent (fifth) edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a means of addressing variability and heterogeneity in the severity of the disorder. While existing research provides support for the DSM-5 severity specifier for BN in adult patients, evidence for its validity and clinical utility in youth is currently lacking. To address this gap, data from 272 treatment-seeking adolescents with DSM-5 BN (94.2% female, M age  = 15.3 years, SD 1.7) were analysed to examine whether these patients, sub-grouped based on the DSM-5 severity definitions, would show meaningful differences in a broad range of clinical variables and demographic and physical characteristics. Analyses revealed that participants categorized with mild, moderate, severe, and extreme severity of BN significantly differed from each other in 15 variables regarding eating disorder pathological features and putative maintenance factors (i.e., core low self-esteem, perfectionism, social appearance anxiety, body surveillance, and mood intolerance), health-related quality of life and comorbid psychiatric (i.e., affective and anxiety) disorders (large effect sizes). Between-group differences in demographics, body mass index, or age-of-BN onset were not observed. Collectively, our findings provide support for the utility of the frequency of inappropriate weight compensatory behaviours as a severity indicator for BN and suggest that age-at-onset of BN is probably more disorder- than severity-dependent. Implications for future research are outlined.

Covariate Imbalance and Adjustment for Logistic Regression Analysis of Clinical Trial Data

PubMed Central

Ciolino, Jody D.; Martin, Reneé H.; Zhao, Wenle; Jauch, Edward C.; Hill, Michael D.; Palesch, Yuko Y.

2014-01-01

In logistic regression analysis for binary clinical trial data, adjusted treatment effect estimates are often not equivalent to unadjusted estimates in the presence of influential covariates. This paper uses simulation to quantify the benefit of covariate adjustment in logistic regression. However, International Conference on Harmonization guidelines suggest that covariate adjustment be pre-specified. Unplanned adjusted analyses should be considered secondary. Results suggest that that if adjustment is not possible or unplanned in a logistic setting, balance in continuous covariates can alleviate some (but never all) of the shortcomings of unadjusted analyses. The case of log binomial regression is also explored. PMID:24138438

Chest physical therapy: comparative efficacy of preoperative and postoperative in the elderly.

PubMed

Castillo, R; Haas, A

1985-06-01

Although chest physical therapy (PT) immediately after surgery lowers the risk of postoperative pulmonary complications, several reports indicate preoperative chest PT results in further improvement. This study compares the effects of initiating chest PT either before and/or after chest surgery in patients over age 65. We studied two groups: 130 patients (the PRE group) undergoing both pre- and postoperative therapy and 150 patients (the POST group) undergoing only postoperative therapy, dividing them into four surgical subgroups: lung, cardiac and other thoracic surgery, upper abdominal, and lower abdominal (considered low risk compared with the other three). Overall complication rates and atelectasis rates were significantly lower in the PRE high-risk subgroups. PRE and POST pneumonia rates, however, were statistically equivalent in all surgical subgroups. Since the low rate of pulmonary complications for PRE-group patients undergoing thoracic or upper abdominal procedures is comparable to that for PRE-group therapy in much younger populations, advanced age alone does not appear to be a significant risk factor. The lack of effect on incidence of pneumonia indicates that preoperative chest PT only counters the altered pulmonary mechanics responsible for atelectasis, but has no effect on pulmonary complications due to infection.

Activation and connectivity patterns of the presupplementary and dorsal premotor areas during free improvisation of melodies and rhythms.

PubMed

de Manzano, Örjan; Ullén, Fredrik

2012-10-15

Free, i.e. non-externally cued generation of movement sequences is fundamental to human behavior. We have earlier hypothesized that the dorsal premotor cortex (PMD), which has been consistently implicated in cognitive aspects of planning and selection of spatial motor sequences may be particularly important for the free generation of spatial movement sequences, whereas the pre-supplementary motor area (pre-SMA), which shows increased activation during perception, learning and reproduction of temporal sequences, may contribute more to the generation of temporal structures. Here we test this hypothesis using fMRI and musical improvisation in professional pianists as a model behavior. We employed a 2 × 2 factorial design with the factors Melody (Specified/Improvised) and Rhythm (Specified/Improvised). The main effect analyses partly confirmed our hypothesis: there was a main effect of Melody in the PMD; the pre-SMA was present in the main effect of Rhythm, as predicted, as well as in the main effect of Melody. A psychophysiological interaction analysis of functional connectivity demonstrated that the correlation in activity between the pre-SMA and cerebellum was higher during rhythmic improvisation than during the other conditions. In summary, there were only subtle differences in activity level between the pre-SMA and PMD during improvisation, regardless of condition. Consequently, the free generation of rhythmic and melodic structures, appears to be largely integrated processes but the functional connectivity between premotor areas and other regions may change during free generation in response to sequence-specific spatiotemporal demands. Copyright © 2012 Elsevier Inc. All rights reserved.

Gambling Disorder: Exploring Pre-treatment and In-treatment Dropout Predictors. A UK Study.

PubMed

Ronzitti, Silvia; Soldini, Emiliano; Smith, Neil; Clerici, Massimo; Bowden-Jones, Henrietta

2017-12-01

The aim of this study was to identify predictors of treatment dropout in a sample of gamblers attending a specialist clinic for gambling disorder. We analysed data on 846 treatment-seeking pathological gamblers. Firstly, we investigated differences in socio-demographic and clinical variables between treatment completers and pre-treatment dropouts, as well as between treatment completers and during-treatment dropouts. Subsequently, variables were entered into a multinomial logistic regression model to identify significant predictors of pre-treatment and in-treatment dropout. Overall, 44.8% of clients did not complete the treatment: 27.4% dropped out before starting it, while 17.4% dropped out during the treatment. Younger age and use of drugs were associated with pre-treatment dropout, while family history of gambling disorder, a lower PGSI score, and being a smoker were related with in-treatment dropout. Our findings suggest that pre-treatment dropouts differ from in-treatment dropouts, and, thus, further research will benefit from considering these groups separately. In addition, this newly gained knowledge will also be helpful in increasing treatment retention in specific subgroups of problem gamblers.

Dairy product consumption is associated with pre-diabetes and newly diagnosed type 2 diabetes in the Lifelines Cohort Study.

PubMed

Brouwer-Brolsma, Elske M; Sluik, Diewertje; Singh-Povel, Cecile M; Feskens, Edith J M

2018-02-01

Previous studies show associations between dairy product consumption and type 2 diabetes, but only a few studies conducted detailed analyses for a variety of dairy subgroups. Therefore, we examined cross-sectional associations of a broad variety of dairy subgroups with pre-diabetes and newly diagnosed type 2 diabetes (ND-T2DM) among Dutch adults. In total, 112 086 adults without diabetes completed a semi-quantitative FFQ and donated blood. Pre-diabetes was defined as fasting plasma glucose (FPG) between 5·6 and 6·9 mmol/l or HbA1c% of 5·7-6·4 %. ND-T2DM was defined as FPG ≥7·0 mmol/l or HbA1c ≥6·5 %. Logistic regression analyses were conducted by 100 g or serving increase and dairy tertiles (T1ref), while adjusting for demographic, lifestyle and dietary covariates. Median dairy product intake was 324 (interquartile range 227) g/d; 25 549 (23 %) participants had pre-diabetes; and 1305 (1 %) had ND-T2DM. After full adjustment, inverse associations were observed of skimmed dairy (OR100 g 0·98; 95 % CI 0·97, 1·00), fermented dairy (OR100 g 0·98; 95 % CI 0·97, 0·99) and buttermilk (OR150 g 0·97; 95 % CI 0·94, 1·00) with pre-diabetes. Positive associations were observed for full-fat dairy (OR100 g 1·003; 95 % CI 1·01, 1·06), non-fermented dairy products (OR100 g 1·01; 95 % CI 1·00, 1·02) and custard (ORserving/150 g 1·13; 95 % CI 1·03, 1·24) with pre-diabetes. Moreover, full-fat dairy products (ORT3 1·16; 95 % CI 0·99, 1·35), non-fermented dairy products (OR100 g 1·05; 95 % CI 1·01, 1·09) and milk (ORserving/150 g 1·08; 95 % CI 1·02, 1·15) were positively associated with ND-T2DM. In conclusion, our data showed inverse associations of skimmed and fermented dairy products with pre-diabetes. Positive associations were observed for full-fat and non-fermented dairy products with pre-diabetes and ND-T2DM.

Should applicants to Nottingham University Medical School study a non-science A-level? A cohort study.

PubMed

Yates, Janet; Smith, Jennifer; James, David; Ferguson, Eamonn

2009-01-21

It has been suggested that studying non-science subjects at A-level should be compulsory for medical students. Our admissions criteria specify only Biology, Chemistry and one or more additional subjects. This study aimed to determine whether studying a non-science subject for A-level is an independent predictor of achievement on the undergraduate medical course. The subjects of this retrospective cohort study were 164 students from one entry-year group (October 2000), who progressed normally on the 5-year undergraduate medical course at Nottingham. Pre-admission academic and socio-demographic data and undergraduate course marks were obtained. T-test and hierarchical multiple linear regression analyses were undertaken to identify independent predictors of five course outcomes at different stages throughout the course. There was no evidence that the choice of science or non-science as the third or fourth A-level subject had any influence on course performance. Demographic variables (age group, sex, and fee status) had some predictive value but ethnicity did not. Pre-clinical course performance was the strongest predictor in the clinical phases (pre-clinical Themes A&B (knowledge) predicted Clinical Knowledge, p < 0.001, and pre-clinical Themes C&D (skills) predicted Clinical Skills, p = or< 0.01). This study of one year group at Nottingham Medical School provided no evidence that the admissions policy on A-level requirements should specify the choice of third or fourth subject.

Should applicants to Nottingham University Medical School study a non-science A-level? A cohort study

PubMed Central

Yates, Janet; Smith, Jennifer; James, David; Ferguson, Eamonn

2009-01-01

Background It has been suggested that studying non-science subjects at A-level should be compulsory for medical students. Our admissions criteria specify only Biology, Chemistry and one or more additional subjects. This study aimed to determine whether studying a non-science subject for A-level is an independent predictor of achievement on the undergraduate medical course. Methods The subjects of this retrospective cohort study were 164 students from one entry-year group (October 2000), who progressed normally on the 5-year undergraduate medical course at Nottingham. Pre-admission academic and socio-demographic data and undergraduate course marks were obtained. T-test and hierarchical multiple linear regression analyses were undertaken to identify independent predictors of five course outcomes at different stages throughout the course. Results There was no evidence that the choice of science or non-science as the third or fourth A-level subject had any influence on course performance. Demographic variables (age group, sex, and fee status) had some predictive value but ethnicity did not. Pre-clinical course performance was the strongest predictor in the clinical phases (pre-clinical Themes A&B (knowledge) predicted Clinical Knowledge, p < 0.001, and pre-clinical Themes C&D (skills) predicted Clinical Skills, p = < 0.01). Conclusion This study of one year group at Nottingham Medical School provided no evidence that the admissions policy on A-level requirements should specify the choice of third or fourth subject. PMID:19159444

Monitoring the safety of quadrivalent human papillomavirus vaccine: findings from the Vaccine Safety Datalink.

PubMed

Gee, Julianne; Naleway, Allison; Shui, Irene; Baggs, James; Yin, Ruihua; Li, Rong; Kulldorff, Martin; Lewis, Edwin; Fireman, Bruce; Daley, Matthew F; Klein, Nicola P; Weintraub, Eric S

2011-10-26

In 7 large managed care organizations (MCOs), we performed a post-licensure safety assessment of quadrivalent human papillomavirus vaccine (HPV4) among 9-26 year-old female vaccine recipients between August 2006 and October 2009. Sequential analyses were conducted weekly to detect associations between HPV4 exposure and pre-specified outcomes. The pre-specified outcomes identified by ICD-9 codes using computerized data at the participating MCOs included: Guillan-Barré Syndrome (GBS), stroke, venous thromboembolism (VTE), appendicitis, seizures, syncope, allergic reactions, and anaphylaxis. For rare outcomes, historical background rates were used as the comparison group. For more common outcomes, a concurrent unexposed comparison group was utilized. A standardized review of medical records was conducted for all cases of GBS, VTE, and anaphylaxis. A total of 600,558 HPV4 doses were administered during the study period. We found no statistically significant increased risk for the outcomes studied. However, a non-statistically significant relative risk (RR) for VTE ICD-9 codes following HPV4 vaccination of 1.98 was detected among females age 9-17 years. Medical record review of all 8 vaccinated potential VTE cases in this age group revealed that 5 met the standard case definition for VTE. All 5 confirmed cases had known risk factors for VTE (oral contraceptive use, coagulation disorders, smoking, obesity or prolonged hospitalization). In a study of over 600,000 HPV4 vaccine doses administered, no statistically significant increased risk for any of the pre-specified adverse events after vaccination was detected. Further study of a possible association with VTE following HPV4 vaccination is warranted. Published by Elsevier Ltd.

Is glans penis width a risk factor for complications after hypospadias repair?

PubMed

Faasse, M A; Johnson, E K; Bowen, D K; Lindgren, B W; Maizels, M; Marcus, C R; Jovanovic, B D; Yerkes, E B

2016-08-01

Recent studies have suggested that a smaller glans penis size may be associated with a higher likelihood of complications after hypospadias repair. Accurate identification of risk factors other than the well-understood variable of meatal location would allow development of better prognostic models and individualized risk stratification. To test the hypothesis that a smaller width of the glans penis predicts adverse outcomes after hypospadias surgery. Prospectively recorded clinical data were reviewed from a single-institution registry of primary hypospadias repairs performed between 2011 and 2014. Follow-up records were examined for occurrence of complications. Urethroplasty complications were defined to include meatal stenosis, dehiscence, urethrocutaneous fistula, urethral stricture, and/or urethral diverticulum. The subset of meatal stenosis and dehiscence were regarded as glanular complications. Regression analyses were performed to determine association between glans width and occurrence of complications. Because pre-operative androgen stimulation is known to increase glans penis size, separate subgroup analyses were included of patients with and without pre-operative use of testosterone cream. A total of 159 patients met criteria for inclusion in the study cohort: 140 patients underwent a single-stage repair, while 19 patients had a two-stage repair. The median glans penis width was 15 mm (range 10-22). Eighty-four patients (53%) received testosterone cream pre-operatively and had a significantly wider glans penis than the 75 patients who did not (median 15.5 vs 14 mm; P < 0.001). Median clinical follow-up was 7 months (IQR 1-12), with a minimum time elapsed since surgery of 10 months at the time of chart review. Twenty-four patients (15%) had one or more urethroplasty complications, including 11 (7%) with glanular complications. Overall, there was no statistically significant association between glans width and urethroplasty complications (P = 0.26) or glanular complications (P = 0.90) (Summary Table). Subgroup analyses of patients with and without pre-operative testosterone also revealed no significant associations between glans width and complications. Glans penis width was not a risk factor for complications after hypospadias repair. This finding differs from the results of other recent studies and encourages further research into the value of measuring penile parameters in patients undergoing hypospadias repair. Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Treatment effect heterogeneity for univariate subgroups in clinical trials: Shrinkage, standardization, or else

PubMed Central

Varadhan, Ravi; Wang, Sue-Jane

2016-01-01

Treatment effect heterogeneity is a well-recognized phenomenon in randomized controlled clinical trials. In this paper, we discuss subgroup analyses with prespecified subgroups of clinical or biological importance. We explore various alternatives to the naive (the traditional univariate) subgroup analyses to address the issues of multiplicity and confounding. Specifically, we consider a model-based Bayesian shrinkage (Bayes-DS) and a nonparametric, empirical Bayes shrinkage approach (Emp-Bayes) to temper the optimism of traditional univariate subgroup analyses; a standardization approach (standardization) that accounts for correlation between baseline covariates; and a model-based maximum likelihood estimation (MLE) approach. The Bayes-DS and Emp-Bayes methods model the variation in subgroup-specific treatment effect rather than testing the null hypothesis of no difference between subgroups. The standardization approach addresses the issue of confounding in subgroup analyses. The MLE approach is considered only for comparison in simulation studies as the “truth” since the data were generated from the same model. Using the characteristics of a hypothetical large outcome trial, we perform simulation studies and articulate the utilities and potential limitations of these estimators. Simulation results indicate that Bayes-DS and Emp-Bayes can protect against optimism present in the naïve approach. Due to its simplicity, the naïve approach should be the reference for reporting univariate subgroup-specific treatment effect estimates from exploratory subgroup analyses. Standardization, although it tends to have a larger variance, is suggested when it is important to address the confounding of univariate subgroup effects due to correlation between baseline covariates. The Bayes-DS approach is available as an R package (DSBayes). PMID:26485117

The Effect of an EDTA-based Chelation Regimen on Patients with Diabetes and Prior Myocardial Infarction in TACT

PubMed Central

Escolar, Esteban; Lamas, Gervasio A.; Mark, Daniel B.; Boineau, Robin; Goertz, Christine; Rosenberg, Yves; Nahin, Richard L.; Ouyang, Pamela; Rozema, Theodore; Magaziner, Allan; Nahas, Richard; Lewis, Eldrin F.; Lindblad, Lauren; Lee, Kerry L.

2014-01-01

Background The Trial to Assess Chelation Therapy (TACT) showed clinical benefit of an ethylene diamine tetraacetic acid (EDTA-based) infusion regimen in patients 50 years or older with prior myocardial infarction (MI). Diabetes prior to enrollment was a pre-specified subgroup. Methods and Results Patients received 40 infusions of EDTA chelation or placebo. 633 (37%) had diabetes (322 EDTA, 311 placebo). EDTA reduced the primary endpoint (death, reinfarction, stroke, coronary revascularization, or hospitalization for angina) [25% vs 38%, hazard ratio (HR) 0.59, 95% confidence interval (CI) (0.44, 0.79), p<0.001] over 5 years. The result remained significant after Bonferroni adjustment for multiple subgroups (99.4% CI (0.39, 0.88), adjusted p=0.002). All-cause mortality was reduced by EDTA chelation [10% vs 16%, HR 0.57, 95% CI (0.36, 0.88) p=0.011], as was the secondary endpoint (cardiovascular death, reinfarction, or stroke) [11% vs 17% HR 0.60, 95% CI (0.39, 0.91), p=0.017]. After adjusting for multiple subgroups, however, those results were no longer significant. The number needed to treat to reduce one primary endpoint was 6.5 over 5 years (95% CI (4.4, 12.7). There was no reduction in events in non-diabetics (n=1075, p=0.877), resulting in a treatment by diabetes interaction (p=0.004). Conclusions Post-MI diabetic patients age 50 or older demonstrated a marked reduction in cardiovascular events with EDTA chelation. These findings support efforts to replicate these findings and define the mechanisms of benefit. They do not, however, constitute sufficient evidence to indicate the routine use of chelation therapy for all post-MI diabetic patients. PMID:24254885

The sociocommunicative deficit subgroup in anorexia nervosa: autism spectrum disorders and neurocognition in a community-based, longitudinal study

PubMed Central

Anckarsäter, H.; Hofvander, B.; Billstedt, E.; Gillberg, I. C.; Gillberg, C.; Wentz, E.; Råstam, M.

2012-01-01

Background A subgroup of persons with anorexia nervosa (AN) have been proposed to have sociocommunicative problems corresponding to autism spectrum disorders [ASDs, i.e. DSM-IV pervasive developmental disorders (PDDs): autistic disorder, Asperger's disorder, PDD not otherwise specified (NOS)]. Here, clinical problems, personality traits, cognitive test results and outcome are compared across 16 subjects (32%) with teenage-onset AN who meet or have met ASD criteria (AN+ASD), 34 ASD-negative AN subjects and matched controls from a longitudinal Swedish study including four waves of independent assessments from the teens to the early thirties. Method The fourth wave included the Structured Clinical Interview for DSM-IV (SCID)-I and the SCID-II (cluster C, i.e. ‘anxious’ PDs) interviews, the Asperger Syndrome Diagnostic Interview, self-assessments by the Autism Spectrum Quotient and the Temperament and Character Inventory, neurocognitive tests by subscales from the Wechsler scales, continuous performance tests, Tower of London, and Happé's cartoons. Results The ASD assessments had substantial inter-rater reliability over time (Cohen's κ between 0.70 and 0.80 with previous assessments), even if only six subjects had been assigned a diagnosis of an ASD in all four waves of the study, including retrospective assessments of pre-AN neurodevelopmental problems. The AN+ASD group had the highest prevalence of personality disorders and the lowest Morgan–Russell scores. The non-ASD AN group also differed significantly from controls on personality traits related to poor interpersonal functioning and on neurocognitive tests. Conclusions A subgroup of subjects with AN meet criteria for ASDs. They may represent the extreme of neurocognitive and personality problems to be found more generally in AN. PMID:22186945

A retrospective analysis of biochemical and haematological parameters in patients with eating disorders.

PubMed

Barron, Leanne J; Barron, Robert F; Johnson, Jeremy C S; Wagner, Ingrid; Ward, Cameron J B; Ward, Shannon R B; Barron, Faye M; Ward, Warren K

2017-01-01

The objective of the study was to determine whether levels of biochemical and haematological parameters in patients with eating disorders (EDs) varied from the general population. Whilst dietary restrictions can lead to nutritional deficiencies, specific abnormalities may be relevant to the diagnosis, pathogenesis and treatment of EDs. With ethics approval and informed consent, a retrospective chart audit was conducted of 113 patients with EDs at a general practice in Brisbane, Australia. This was analysed first as a total group (TG) and then in 4 ED subgroups: Anorexia nervosa (AN), Bulimia nervosa (BN), ED Not Otherwise Specified (EDNOS), and AN/BN. Eighteen parameters were assessed at or near first presentation: cholesterol, folate, vitamin B12, magnesium, manganese, zinc, calcium, potassium, urate, sodium, albumin, phosphate, ferritin, vitamin D, white cell count, neutrophils, red cell count and platelets. Results were analysed using IBM SPSS 21 and Microsoft Excel 2013 by two-tailed, one-sample t-tests (TG and 4 subgroups) and chi-square tests (TG only) and compared to the population mean standards. Results for the TG and each subgroup individually were then compared with the known reference interval (RI). For the total sample, t-tests showed significant differences for all parameters ( p  < 0.05) except cholesterol. Most parameters gave results below population levels, but folate, phosphate, albumin, calcium and vitamin B12 were above. More patients than expected were below the RI for most parameters in the TG and subgroups. At diagnosis, in patients with EDs, there are often significant differences in multiple haematological and biochemical parameters. Early identification of these abnormalities may provide additional avenues of ED treatment through supplementation and dietary guidance, and may be used to reinforce negative impacts on health caused by the ED to the patient, their family and their treatment team (general practitioner, dietitian and mental health professionals). Study data would support routine measurement of a full blood count and electrolytes, phosphate, magnesium, liver function tests, ferritin, vitamin B12, red cell folate, vitamin D, manganese and zinc for all patients at first presentation with an ED.

40 CFR 89.407 - Engine dynamometer test run.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Perform the pre-test procedure as specified in § 89.406. (3) Read and record the general test data as... (c)(5)(i) through (iii) of this section. (6) Read and record all pre-test data specified in § 89.405... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Engine dynamometer test run. 89.407...

40 CFR 89.407 - Engine dynamometer test run.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Perform the pre-test procedure as specified in § 89.406. (3) Read and record the general test data as... (c)(5)(i) through (iii) of this section. (6) Read and record all pre-test data specified in § 89.405... 40 Protection of Environment 21 2013-07-01 2013-07-01 false Engine dynamometer test run. 89.407...

40 CFR 89.407 - Engine dynamometer test run.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Perform the pre-test procedure as specified in § 89.406. (3) Read and record the general test data as... (c)(5)(i) through (iii) of this section. (6) Read and record all pre-test data specified in § 89.405... 40 Protection of Environment 21 2012-07-01 2012-07-01 false Engine dynamometer test run. 89.407...

40 CFR 89.407 - Engine dynamometer test run.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Perform the pre-test procedure as specified in § 89.406. (3) Read and record the general test data as... (c)(5)(i) through (iii) of this section. (6) Read and record all pre-test data specified in § 89.405... 40 Protection of Environment 20 2014-07-01 2013-07-01 true Engine dynamometer test run. 89.407...

40 CFR 89.407 - Engine dynamometer test run.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Perform the pre-test procedure as specified in § 89.406. (3) Read and record the general test data as... (c)(5)(i) through (iii) of this section. (6) Read and record all pre-test data specified in § 89.405... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Engine dynamometer test run. 89.407...

Data Shared Lasso: A Novel Tool to Discover Uplift.

PubMed

Gross, Samuel M; Tibshirani, Robert

2016-09-01

A model is presented for the supervised learning problem where the observations come from a fixed number of pre-specified groups, and the regression coefficients may vary sparsely between groups. The model spans the continuum between individual models for each group and one model for all groups. The resulting algorithm is designed with a high dimensional framework in mind. The approach is applied to a sentiment analysis dataset to show its efficacy and interpretability. One particularly useful application is for finding sub-populations in a randomized trial for which an intervention (treatment) is beneficial, often called the uplift problem. Some new concepts are introduced that are useful for uplift analysis. The value is demonstrated in an application to a real world credit card promotion dataset. In this example, although sending the promotion has a very small average effect, by targeting a particular subgroup with the promotion one can obtain a 15% increase in the proportion of people who purchase the new credit card.

Data Shared Lasso: A Novel Tool to Discover Uplift

PubMed Central

Gross, Samuel M.; Tibshirani, Robert

2017-01-01

A model is presented for the supervised learning problem where the observations come from a fixed number of pre-specified groups, and the regression coefficients may vary sparsely between groups. The model spans the continuum between individual models for each group and one model for all groups. The resulting algorithm is designed with a high dimensional framework in mind. The approach is applied to a sentiment analysis dataset to show its efficacy and interpretability. One particularly useful application is for finding sub-populations in a randomized trial for which an intervention (treatment) is beneficial, often called the uplift problem. Some new concepts are introduced that are useful for uplift analysis. The value is demonstrated in an application to a real world credit card promotion dataset. In this example, although sending the promotion has a very small average effect, by targeting a particular subgroup with the promotion one can obtain a 15% increase in the proportion of people who purchase the new credit card. PMID:29056802

Data-Driven Subclassification of Speech Sound Disorders in Preschool Children

PubMed Central

Vick, Jennell C.; Campbell, Thomas F.; Shriberg, Lawrence D.; Green, Jordan R.; Truemper, Klaus; Rusiewicz, Heather Leavy; Moore, Christopher A.

2015-01-01

Purpose The purpose of the study was to determine whether distinct subgroups of preschool children with speech sound disorders (SSD) could be identified using a subgroup discovery algorithm (SUBgroup discovery via Alternate Random Processes, or SUBARP). Of specific interest was finding evidence of a subgroup of SSD exhibiting performance consistent with atypical speech motor control. Method Ninety-seven preschool children with SSD completed speech and nonspeech tasks. Fifty-three kinematic, acoustic, and behavioral measures from these tasks were input to SUBARP. Results Two distinct subgroups were identified from the larger sample. The 1st subgroup (76%; population prevalence estimate = 67.8%–84.8%) did not have characteristics that would suggest atypical speech motor control. The 2nd subgroup (10.3%; population prevalence estimate = 4.3%– 16.5%) exhibited significantly higher variability in measures of articulatory kinematics and poor ability to imitate iambic lexical stress, suggesting atypical speech motor control. Both subgroups were consistent with classes of SSD in the Speech Disorders Classification System (SDCS; Shriberg et al., 2010a). Conclusion Characteristics of children in the larger subgroup were consistent with the proportionally large SDCS class termed speech delay; characteristics of children in the smaller subgroup were consistent with the SDCS subtype termed motor speech disorder—not otherwise specified. The authors identified candidate measures to identify children in each of these groups. PMID:25076005

Atezolizumab as first-line therapy in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial

PubMed Central

Balar, Arjun V; Galsky, Matthew D; Rosenberg, Jonathan E; Powles, Thomas; Petrylak, Daniel P; Bellmunt, Joaquim; Loriot, Yohann; Necchi, Andrea; Hoffman-Censits, Jean; Perez-Gracia, Jose Luis; Dawson, Nancy A; van der Heijden, Michiel S; Dreicer, Robert; Srinivas, Sandy; Retz, Margitta M; Joseph, Richard W; Drakaki, Alexandra; Vaishampayan, Ulka N; Sridhar, Srikala S; Quinn, David I; Durán, Ignacio; Shaffer, David R; Eigl, Bernhard J; Grivas, Petros D; Yu, Evan Y; Li, Shi; Kadel, Edward E; Boyd, Zachary; Bourgon, Richard; Hegde, Priti S; Mariathasan, Sanjeev; Thåström, AnnChristine; Abidoye, Oyewale O; Fine, Gregg D; Bajorin, Dean F

2017-01-01

Summary Background First-line chemotherapy for patients with cisplatin-ineligible locally-advanced or metastatic urothelial carcinoma (mUC) is associated with short response duration, poor survival, and high toxicity. This multicenter, 2-cohort phase 2 study evaluated atezolizumab (anti–programmed death-ligand 1 [PD-L1]) as treatment for mUC in this setting, as well as in later lines. Methods In a cohort of previously untreated patients who were cisplatin ineligible, atezolizumab was given 1200 mg every 3 weeks until progression. The primary endpoint was independently confirmed objective response rate per Response Evaluation Criteria In Solid Tumors v1.1 (central review), evaluated in pre-specified subgroups based on PD-L1 expression and in all patients. Secondary endpoints included response duration, progression-free survival, overall survival, and safety. Exploratory analyses included biomarker correlates of response and survival. This study is registered with ClinicalTrials.gov, number NCT02108652. Findings Of 119 patients who received atezolizumab in the first-line setting, 83 (70%) had baseline renal impairment, and 24 (20%) had Eastern Cooperative Oncology Group performance status 2. At 17·2 months’ median follow-up, the objective response rate was 23% (95% CI 16–31), the complete response rate was 9%, and 19 of 27 responses were ongoing. Median response duration was not reached. Responses occurred across all PD-L1 and poor prognostic factor subgroups. Median progression-free survival was 2·7 months. Median overall survival was 15·9 months. Tumour mutation load was associated with response. Treatment-related adverse events ≥10% were fatigue, diarrhoea, and pruritus. One treatment-related death (sepsis) occurred. Nine patients (8%) had an adverse event leading to treatment discontinuation. Immune-mediated events occurred in 14 (12%) patients. Interpretation Atezolizumab demonstrated encouraging durable response rates, survival, and tolerability, supporting its therapeutic use in untreated mUC. Funding F. Hoffmann-La Roche Ltd./Genentech, Inc., a member of the Roche Group. PMID:27939400

Telehealth methods to deliver multifactorial dietary interventions in adults with chronic disease: a systematic review protocol.

PubMed

Kelly, Jaimon T; Reidlinger, Dianne P; Hoffmann, Tammy C; Campbell, Katrina L

2015-12-22

The long-term management of chronic diseases requires adoption of complex dietary recommendations, which can be facilitated by regular coaching to support sustained behaviour change. Telehealth interventions can overcome patient-centred barriers to accessing face-to-face programs and provide feasible delivery methods, ubiquitous and accessible regardless of geographic location. The protocol for this systematic review explains the methods that will be utilised to answer the review question of whether telehealth interventions are effective at promoting change in dietary intake and improving diet quality in people with chronic disease. A structured search of Medline, EMBASE, CINAHL, and PsychINFO, from their inception, will be conducted. We will consider randomised controlled trials which evaluate complex dietary interventions in adults with chronic disease. Studies must provide diet education in an intervention longer than 4 weeks in duration, and at least half of the intervention contact must be delivered via telehealth. Comparisons will be made against usual care or a non-telehealth intervention. The primary outcome of interest is dietary change with secondary outcomes relating to clinical markers pre-specified in the methodology. The process for selecting studies, extracting data, and resolving conflicts will follow a set protocol. Two authors will independently appraise the studies and extract the data, using specified methods. Meta-analyses will be conducted where appropriate, with parameters for determining statistical heterogeneity pre-specified. The GRADE tool will be used for determining the quality of evidence for analysed outcomes. To date, there has been a considerable variability in the strategies used to deliver dietary education, and the overall effectiveness of telehealth dietary interventions for facilitating dietary change has not been reviewed systematically in adults with chronic disease. A systematic synthesis of telehealth strategies will inform the development of evidence-based telehealth programs that can be tailored to deliver dietary interventions specific to chronic disease conditions. PROSPERO CRD42015026398.

Insights into plant cell wall structure, architecture, and integrity using glycome profiling of native and AFEXTM-pre-treated biomass

PubMed Central

Pattathil, Sivakumar; Hahn, Michael G.; Dale, Bruce E.; Chundawat, Shishir P. S.

2015-01-01

Cell walls, which constitute the bulk of plant biomass, vary considerably in their structure, composition, and architecture. Studies on plant cell walls can be conducted on both native and pre-treated plant biomass samples, allowing an enhanced understanding of these structural and compositional variations. Here glycome profiling was employed to determine the relative abundance of matrix polysaccharides in several phylogenetically distinct native and pre-treated plant biomasses. Eight distinct biomass types belonging to four different subgroups (i.e. monocot grasses, woody dicots, herbaceous dicots, and softwoods) were subjected to various regimes of AFEX™ (ammonia fiber expansion) pre-treatment [AFEX is a trademark of MBI, Lansing (http://www.mbi.org]. This approach allowed detailed analysis of close to 200 cell wall glycan epitopes and their relative extractability using a high-throughput platform. In general, irrespective of the phylogenetic origin, AFEX™ pre-treatment appeared to cause loosening and improved accessibility of various xylan epitope subclasses in most plant biomass materials studied. For most biomass types analysed, such loosening was also evident for other major non-cellulosic components including subclasses of pectin and xyloglucan epitopes. The studies also demonstrate that AFEX™ pre-treatment significantly reduced cell wall recalcitrance among diverse phylogenies (except softwoods) by inducing structural modifications to polysaccharides that were not detectable by conventional gross composition analyses. It was found that monitoring changes in cell wall glycan compositions and their relative extractability for untreated and pre-treated plant biomass can provide an improved understanding of variations in structure and composition of plant cell walls and delineate the role(s) of matrix polysaccharides in cell wall recalcitrance. PMID:25911738

Insights into plant cell wall structure, architecture, and integrity using glycome profiling of native and AFEX TM -pre-treated biomass

DOE PAGES

Pattathil, Sivakumar; Hahn, Michael G.; Dale, Bruce E.; ...

2015-04-23

We report that cell walls, which constitute the bulk of plant biomass, vary considerably in their structure, composition, and architecture. Studies on plant cell walls can be conducted on both native and pre-treated plant biomass samples, allowing an enhanced understanding of these structural and compositional variations. Here glycome profiling was employed to determine the relative abundance of matrix polysaccharides in several phylogenetically distinct native and pre-treated plant biomasses. Eight distinct biomass types belonging to four different subgroups (i.e. monocot grasses, woody dicots, herbaceous dicots, and softwoods) were subjected to various regimes of AFEX™ (ammonia fiber expansion) pre-treatment [AFEX is amore » trademark of MBI, Lansing (http://www.mbi.org]. This approach allowed detailed analysis of close to 200 cell wall glycan epitopes and their relative extractability using a high-throughput platform. In general, irrespective of the phylogenetic origin, AFEX™ pre-treatment appeared to cause loosening and improved accessibility of various xylan epitope subclasses in most plant biomass materials studied. For most biomass types analysed, such loosening was also evident for other major non-cellulosic components including subclasses of pectin and xyloglucan epitopes. The studies also demonstrate that AFEX™ pre-treatment significantly reduced cell wall recalcitrance among diverse phylogenies (except softwoods) by inducing structural modifications to polysaccharides that were not detectable by conventional gross composition analyses. Lastly, we found that monitoring changes in cell wall glycan compositions and their relative extractability for untreated and pre-treated plant biomass can provide an improved understanding of variations in structure and composition of plant cell walls and delineate the role(s) of matrix polysaccharides in cell wall recalcitrance.« less

Pre-migration Trauma Exposure and Psychological Distress for Asian American Immigrants: Linking the Pre- and Post-migration Contexts.

PubMed

Li, Miao; Anderson, James G

2016-08-01

Drawing on the life course perspective and the assumptive world theory, this paper examines whether pre-migration trauma exposure is associated with psychological distress through post-migration perceived discrimination for Asian American immigrants. The study is based on cross-sectional data from the National Latino and Asian American Study (N = 1639). Structural equation model is used to estimate the relationship between pre-migration trauma, post-migration perceived discrimination, and psychological distress. Additional models are estimated to explore possible variations across ethnic groups as well as across different types of pre-migration trauma experience. Pre-migration trauma exposure is associated with higher levels of psychological distress, both directly and indirectly through higher level of perceived discrimination, even after controlling for demographic/acculturative factors and post-migration trauma exposure. This pattern holds for the following sub-types of pre-migration trauma: political trauma, crime victimization, physical violence, accidental trauma, and relational trauma. Multi-group analyses show that this pattern holds for all Asian immigrant subgroups except the Vietnamese. Studies of immigrant mental health primarily focus on post-migration stressors. Few studies have considered the link between pre- and post-migration contexts in assessing mental health outcomes. The study illustrates the usefulness of bridging the pre- and post-migration context in identifying the mental health risks along the immigrant life course.

Is it all worth it? The experiences of new PhDs on the job market, 2007-10.

PubMed

McFall, Brooke Helppie; Murray-Close, Marta; Willis, Robert J; Chen, Uniko

This paper describes the job market experiences of new PhD economists, 2007-10. Using information from PhD programs' job candidate websites and original surveys, the authors present information about job candidates' characteristics, preferences and expectations; how job candidates fared at each stage of the market; and predictors of outcomes at each stage. Some information presented in this paper updates findings of prior studies. However, design features of the data used in this paper may result in more generalizable findings. This paper is unique in comparing pre-market expectations and preferences with post-market outcomes on the new PhD job market. It shows that outcomes tend to align with pre-market preferences, and candidates' expectations are somewhat predictive of their outcomes. Several analyses also shed light on sub-group differences.

Ambient Temperature and Stroke Occurrence: A Systematic Review and Meta-Analysis.

PubMed

Wang, Xia; Cao, Yongjun; Hong, Daqing; Zheng, Danni; Richtering, Sarah; Sandset, Else Charlotte; Leong, Tzen Hugh; Arima, Hisatomi; Islam, Shariful; Salam, Abdul; Anderson, Craig; Robinson, Thompson; Hackett, Maree L

2016-07-12

Biologically plausible associations exist between climatic conditions and stroke risk, but study results are inconsistent. We aimed to summarize current evidence on ambient temperature and overall stroke occurrence, and by age, sex, and variation of temperature. We performed a systematic literature search across MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and GEOBASE, from inception to 16 October 2015 to identify all population-based observational studies. Where possible, data were pooled for meta-analysis with Odds ratios (OR) and corresponding 95% confidence intervals (CI) by means of the random effects meta-analysis. We included 21 studies with a total of 476,511 patients. The data were varied as indicated by significant heterogeneity across studies for both ischemic stroke (IS) and intracerebral hemorrhage (ICH). Pooled OR (95% CI) in every 1 degree Celsius increase in ambient temperature was significant for ICH 0.97 (0.94-1.00), but not for IS 1.00 (0.99-1.01) and subarachnoid hemorrhage (SAH) 1.00 (0.98-1.01). Meta-analysis was not possible for the pre-specified subgroup analyses by age, sex, and variation of temperature. Change in temperature over the previous 24 h appeared to be more important than absolute temperature in relation to the risk of stroke, especially in relation to the risk of ICH. Older age appeared to increase vulnerability to low temperature for both IS and ICH. To conclude, this review shows that lower mean ambient temperature is significantly associated with the risk of ICH, but not with IS and SAH. Larger temperature changes were associated with higher stroke rates in the elderly.

Evaluation of Evidence of Statistical Support and Corroboration of Subgroup Claims in Randomized Clinical Trials.

PubMed

Wallach, Joshua D; Sullivan, Patrick G; Trepanowski, John F; Sainani, Kristin L; Steyerberg, Ewout W; Ioannidis, John P A

2017-04-01

Many published randomized clinical trials (RCTs) make claims for subgroup differences. To evaluate how often subgroup claims reported in the abstracts of RCTs are actually supported by statistical evidence (P < .05 from an interaction test) and corroborated by subsequent RCTs and meta-analyses. This meta-epidemiological survey examines data sets of trials with at least 1 subgroup claim, including Subgroup Analysis of Trials Is Rarely Easy (SATIRE) articles and Discontinuation of Randomized Trials (DISCO) articles. We used Scopus (updated July 2016) to search for English-language articles citing each of the eligible index articles with at least 1 subgroup finding in the abstract. Articles with a subgroup claim in the abstract with or without evidence of statistical heterogeneity (P < .05 from an interaction test) in the text and articles attempting to corroborate the subgroup findings. Study characteristics of trials with at least 1 subgroup claim in the abstract were recorded. Two reviewers extracted the data necessary to calculate subgroup-level effect sizes, standard errors, and the P values for interaction. For individual RCTs and meta-analyses that attempted to corroborate the subgroup findings from the index articles, trial characteristics were extracted. Cochran Q test was used to reevaluate heterogeneity with the data from all available trials. The number of subgroup claims in the abstracts of RCTs, the number of subgroup claims in the abstracts of RCTs with statistical support (subgroup findings), and the number of subgroup findings corroborated by subsequent RCTs and meta-analyses. Sixty-four eligible RCTs made a total of 117 subgroup claims in their abstracts. Of these 117 claims, only 46 (39.3%) in 33 articles had evidence of statistically significant heterogeneity from a test for interaction. In addition, out of these 46 subgroup findings, only 16 (34.8%) ensured balance between randomization groups within the subgroups (eg, through stratified randomization), 13 (28.3%) entailed a prespecified subgroup analysis, and 1 (2.2%) was adjusted for multiple testing. Only 5 (10.9%) of the 46 subgroup findings had at least 1 subsequent pure corroboration attempt by a meta-analysis or an RCT. In all 5 cases, the corroboration attempts found no evidence of a statistically significant subgroup effect. In addition, all effect sizes from meta-analyses were attenuated toward the null. A minority of subgroup claims made in the abstracts of RCTs are supported by their own data (ie, a significant interaction effect). For those that have statistical support (P < .05 from an interaction test), most fail to meet other best practices for subgroup tests, including prespecification, stratified randomization, and adjustment for multiple testing. Attempts to corroborate statistically significant subgroup differences are rare; when done, the initially observed subgroup differences are not reproduced.

Effects of whole body vibration on bone mineral density in postmenopausal women: a systematic review and meta-analysis.

PubMed

Oliveira, L C; Oliveira, R G; Pires-Oliveira, D A A

2016-10-01

This systematic review and meta-analysis of randomized controlled trials (RCTs) identified significant effects of whole body vibration (WBV) on bone mineral density (BMD) of the lumbar spine (in the sensitivity analysis and seven subgroup analyses), femoral neck (in one subgroup analysis), and trochanter (four subgroup analyses) in postmenopausal women, but not other measurements of BMD. Interventions using WBV training have been conducted in postmenopausal women, aimed at increasing BMD; however, the results are contradictory. Our objective is to conduct a systematic review and meta-analysis of RCTs examining WBV effect on BMD. RCTs were considered eligible, with follow-up ≥6 months, which verified the effects of WBV on the BMD of postmenopausal women. The calculations of the meta-analysis were performed through the weighted mean difference between the WBV and control groups, or the WBV and combined training, through the absolute change between pre- and post-intervention in the areal bone mineral density (aBMD) or trabecular volumetric bone mineral density (vBMDt). Fifteen RCTs were included in the meta-analysis. No differences were observed in the primary analysis. WBV was found to improve aBMD compared with the control group, after exclusion of studies with low quality methodological (lumbar spine), when excluding the studies which combined WBV with medication or combined training (lumbar spine), with the use of low frequency and high magnitude (lumbar spine and trochanter), high frequency and low magnitude (lumbar spine), high cumulative dose and low magnitude (lumbar spine), low cumulative dose and high magnitude (lumbar spine and trochanter), with semi-flexed knee (lumbar spine, femoral neck, and trochanter), and side-alternating type of vibration (lumbar spine and trochanter). Despite WBV presenting potential to act as a coadjuvant in the prevention or treatment of osteoporosis, especially for aBMD of the lumbar spine, the ideal intervention is not yet clear. Our subgroup analyses helped to demonstrate the various factors which appear to influence the effects of WBV on BMD, contributing to clinical practice and the definition of protocols for future interventions.

Sodium content and labelling of processed and ultra-processed food products marketed in Brazil.

PubMed

Martins, Carla Adriano; de Sousa, Anete Araújo; Veiros, Marcela Boro; González-Chica, David Alejandro; Proença, Rossana Pacheco da Costa

2015-05-01

To analyse the Na content and labelling of processed and ultra-processed food products marketed in Brazil. Cross-sectional study. A large supermarket in Florianopolis, southern Brazil. Ingredient lists and Na information on nutrition labels of all processed and ultra-processed pre-prepared meals and prepared ingredients, used in lunch or dinner, available for sale in the supermarket. The study analysed 1416 products, distributed into seven groups and forty-one subgroups. Five products did not have Na information. Most products (58.8 %; 95 % CI 55.4, 62.2 %) had high Na content (>600 mg/100 g). In 78.0 % of the subgroups, variation in Na content was at least twofold between similar products with high and low Na levels, reaching 634-fold difference in the 'garnishes and others' subgroup. More than half of the products (52.0 %; 95 % CI 48.2, 55.6 %) had at least one Na-containing food additive. There was no relationship between the appearance of salt on the ingredients list (first to third position on the list) and a product's Na content (high, medium or low; P=0.08). Most food products had high Na content, with great variation between similar products, which presents new evidence for reformulation opportunities. There were inconsistencies in Na labelling, such as lack of nutritional information and incomplete ingredient descriptions. The position of salt on the ingredients list did not facilitate the identification of high-Na foods. We therefore recommend a reduction in Na in these products and a review of Brazilian legislation.

Robust pre-specified time synchronization of chaotic systems by employing time-varying switching surfaces in the sliding mode control scheme

NASA Astrophysics Data System (ADS)

Khanzadeh, Alireza; Pourgholi, Mahdi

2016-08-01

In the conventional chaos synchronization methods, the time at which two chaotic systems are synchronized, is usually unknown and depends on initial conditions. In this work based on Lyapunov stability theory a sliding mode controller with time-varying switching surfaces is proposed to achieve chaos synchronization at a pre-specified time for the first time. The proposed controller is able to synchronize chaotic systems precisely at any time when we want. Moreover, by choosing the time-varying switching surfaces in a way that the reaching phase is eliminated, the synchronization becomes robust to uncertainties and exogenous disturbances. Simulation results are presented to show the effectiveness of the proposed method of stabilizing and synchronizing chaotic systems with complete robustness to uncertainty and disturbances exactly at a pre-specified time.

Debate: Subgroup analyses in clinical trials: fun to look at - but don't believe them!

PubMed Central

Sleight, Peter

2000-01-01

Analysis of subgroup results in a clinical trial is surprisingly unreliable, even in a large trial. This is the result of a combination of reduced statistical power, increased variance and the play of chance. Reliance on such analyses is likely to be more erroneous, and hence harmful, than application of the overall proportional (or relative) result in the whole trial to the estimate of absolute risk in that subgroup. Plausible explanations can usually be found for effects that are, in reality, simply due to the play of chance. When clinicians believe such subgroup analyses, there is a real danger of harm to the individual patient. PMID:11714402

Can the Children's Communication Checklist Differentiate Autism Spectrum Subtypes?

ERIC Educational Resources Information Center

Verte, Sylvie; Geurts, Hilde M.; Roeyers, Herbert; Rosseel, Yves; Oosterlaan, Jaap; Sergeant, Joseph A.

2006-01-01

The study explored whether children with high functioning autism (HFA), Asperger syndrome (AS), and pervasive developmental disorder not otherwise specified (PDD-NOS) can be differentiated on the Children's Communication Checklist (CCC). The study also investigated whether empirically derived autistic subgroups can be identified with a cluster…

40 CFR 1065.520 - Pre-test verification procedures and pre-test data collection.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Pre-test verification procedures and pre-test data collection. 1065.520 Section 1065.520 Protection of Environment ENVIRONMENTAL PROTECTION... Specified Duty Cycles § 1065.520 Pre-test verification procedures and pre-test data collection. (a) If your...

40 CFR 1065.520 - Pre-test verification procedures and pre-test data collection.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 34 2012-07-01 2012-07-01 false Pre-test verification procedures and pre-test data collection. 1065.520 Section 1065.520 Protection of Environment ENVIRONMENTAL PROTECTION... Specified Duty Cycles § 1065.520 Pre-test verification procedures and pre-test data collection. (a) If your...

40 CFR 1065.520 - Pre-test verification procedures and pre-test data collection.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Pre-test verification procedures and pre-test data collection. 1065.520 Section 1065.520 Protection of Environment ENVIRONMENTAL PROTECTION... Specified Duty Cycles § 1065.520 Pre-test verification procedures and pre-test data collection. (a) For...

40 CFR 1065.520 - Pre-test verification procedures and pre-test data collection.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Pre-test verification procedures and pre-test data collection. 1065.520 Section 1065.520 Protection of Environment ENVIRONMENTAL PROTECTION... Specified Duty Cycles § 1065.520 Pre-test verification procedures and pre-test data collection. (a) If your...

40 CFR 1065.520 - Pre-test verification procedures and pre-test data collection.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 33 2011-07-01 2011-07-01 false Pre-test verification procedures and pre-test data collection. 1065.520 Section 1065.520 Protection of Environment ENVIRONMENTAL PROTECTION... Specified Duty Cycles § 1065.520 Pre-test verification procedures and pre-test data collection. (a) If your...

Young adult outcomes in the follow-up of the multimodal treatment study of attention-deficit/hyperactivity disorder: symptom persistence, source discrepancy, and height suppression.

PubMed

Swanson, James M; Arnold, L Eugene; Molina, Brooke S G; Sibley, Margaret H; Hechtman, Lily T; Hinshaw, Stephen P; Abikoff, Howard B; Stehli, Annamarie; Owens, Elizabeth B; Mitchell, John T; Nichols, Quyen; Howard, Andrea; Greenhill, Laurence L; Hoza, Betsy; Newcorn, Jeffrey H; Jensen, Peter S; Vitiello, Benedetto; Wigal, Timothy; Epstein, Jeffery N; Tamm, Leanne; Lakes, Kimberly D; Waxmonsky, James; Lerner, Marc; Etcovitch, Joy; Murray, Desiree W; Muenke, Maximilian; Acosta, Maria T; Arcos-Burgos, Mauricio; Pelham, William E; Kraemer, Helena C

2017-06-01

The Multimodal Treatment Study (MTA) began as a 14-month randomized clinical trial of behavioral and pharmacological treatments of 579 children (7-10 years of age) diagnosed with attention-deficit/hyperactivity disorder (ADHD)-combined type. It transitioned into an observational long-term follow-up of 515 cases consented for continuation and 289 classmates (258 without ADHD) added as a local normative comparison group (LNCG), with assessments 2-16 years after baseline. Primary (symptom severity) and secondary (adult height) outcomes in adulthood were specified. Treatment was monitored to age 18, and naturalistic subgroups were formed based on three patterns of long-term use of stimulant medication (Consistent, Inconsistent, and Negligible). For the follow-up, hypothesis-generating analyses were performed on outcomes in early adulthood (at 25 years of age). Planned comparisons were used to estimate ADHD-LNCG differences reflecting persistence of symptoms and naturalistic subgroup differences reflecting benefit (symptom reduction) and cost (height suppression) associated with extended use of medication. For ratings of symptom severity, the ADHD-LNCG comparison was statistically significant for the parent/self-report average (0.51 ± 0.04, p < .0001, d = 1.11), documenting symptom persistence, and for the parent/self-report difference (0.21 ± 0.04, p < .0001, d = .60), documenting source discrepancy, but the comparisons of naturalistic subgroups reflecting medication effects were not significant. For adult height, the ADHD group was 1.29 ± 0.55 cm shorter than the LNCG (p < .01, d = .21), and the comparisons of the naturalistic subgroups were significant: the treated group with the Consistent or Inconsistent pattern was 2.55 ± 0.73 cm shorter than the subgroup with the Negligible pattern (p < .0005, d = .42), and within the treated group, the subgroup with the Consistent pattern was 2.36 ± 1.13 cm shorter than the subgroup with the Inconsistent pattern (p < .04, d = .38). In the MTA follow-up into adulthood, the ADHD group showed symptom persistence compared to local norms from the LNCG. Within naturalistic subgroups of ADHD cases, extended use of medication was associated with suppression of adult height but not with reduction of symptom severity. © 2017 Association for Child and Adolescent Mental Health.

Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein

PubMed Central

Ardoin, Stacy P; Schanberg, Laura Eve; Sandborg, Christy I; Barnhart, Huiman X; Evans, Greg W; Yow, Eric; Mieszkalski, Kelly L; Ilowite, Norman T; Eberhard, Anne; Imundo, Lisa F; Kimura, Yuki; Levy, Deborah; von Scheven, Emily; Silverman, Earl; Bowyer, Suzanne L; Punaro, L; Singer, Nora G; Sherry, David D; McCurdy, Deborah K; Klein-Gitelman, Marissa; Wallace, Carol; Silver, Richard M; Wagner-Weiner, Linda; Higgins, Gloria C; Brunner, Hermine I; Jung, Lawrence; Soep, Jennifer B; Reed, Ann M; Thompson, Susan D

2014-01-01

Objective Participants in the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) trial were randomised to placebo or atorvastatin for 36 months. The primary endpoint, reduced carotid intima medial thickness (CIMT) progression, was not met but atorvastatin-treated participants showed a trend of slower CIMT progression. Post-hoc analyses were performed to assess subgroup benefit from atorvastatin therapy. Methods Subgroups were prespecified and defined by age (> or ≤15.5 years), systemic lupus erythematosus (SLE) duration (> or ≤24 months), pubertal status (Tanner score ≥4 as post-pubertal or <4 as pre-pubertal), low density lipoprotein cholesterol (LDL) (≥ or <110 mg/dl) and high-sensitivity C reactive protein (hsCRP) (≥ or <1.5 mg/l). A combined subgroup (post-pubertal and hsCRP≥1.5 mg/l) was compared to all others. Longitudinal linear mixed-effects models were developed using 12 CIMT and other secondary APPLE outcomes (lipids, hsCRP, disease activity and damage, and quality of life). Three way interaction effects were assessed for models. Results Significant interaction effects with trends of less CIMT progression in atorvastatin-treated participants were observed in pubertal (3 CIMT segments), high hsCRP (2 CIMT segments), and the combined high hsCRP and pubertal group (5 CIMT segments). No significant treatment effect trends were observed across subgroups defined by age, SLE duration, LDL for CIMT or other outcome measures. Conclusions Pubertal status and higher hsCRP were linked to lower CIMT progression in atorvastatin-treated subjects, with most consistent decreases in CIMT progression in the combined pubertal and high hsCRP group. While secondary analyses must be interpreted cautiously, results suggest further research is needed to determine whether pubertal lupus patients with high CRP benefit from statin therapy. ClinicalTrials.gov identifier NCT00065806. PMID:23436914

Is it all worth it? The experiences of new PhDs on the job market, 2007–10

PubMed Central

McFall, Brooke Helppie; Murray-Close, Marta; Willis, Robert J; Chen, Uniko

2016-01-01

This paper describes the job market experiences of new PhD economists, 2007-10. Using information from PhD programs' job candidate websites and original surveys, the authors present information about job candidates' characteristics, preferences and expectations; how job candidates fared at each stage of the market; and predictors of outcomes at each stage. Some information presented in this paper updates findings of prior studies. However, design features of the data used in this paper may result in more generalizable findings. This paper is unique in comparing pre-market expectations and preferences with post-market outcomes on the new PhD job market. It shows that outcomes tend to align with pre-market preferences, and candidates' expectations are somewhat predictive of their outcomes. Several analyses also shed light on sub-group differences. PMID:27616783

Comparative evaluation of effect of preoperative alprazolam and diclofenac potassium on the success of inferior alveolar, Vazirani-Akinosi, and Gow-Gates techniques for teeth with irreversible pulpitis: Randomized controlled trial

PubMed Central

Shetkar, Pratibha; Jadhav, Ganesh Ranganath; Mittal, Priya; Surapaneni, Saikalyan; Kalra, Dheeraj; Sakri, Mohan; Basavaprabhu, A

2016-01-01

Introduction: In teeth with irreversible pulpitis, successful local anesthesia is hard to achieve irrespective of the amount of local anesthesia and technique used. Such cases can be managed by concoction of pre-medications like anxiolytics, analgesics and effective local anesthesia. This double-blind, placebo-controlled study was planned to evaluate the effect of oral administration of alprazolam and diclofenac potassium on the success rate of inferior alveolar nerve block (IANB), Gow-Gates (GG) and Vazirani-Akinosi (VA) techniques for the root canal treatment of mandibular molars with irreversible pulpitis. Method: 198 emergency patients with symptomatic irreversible pulpitis were randomly divided into three groups as – A, B and C receiving IANB, GG or V-A respectively using 2% lidocaine with 1: 100,000 epinephrine. These groups were sub-divided into sub-groups I and II as control and pre-medication groups. Patients who did not react to the stimulus made by an explorer between the canine and first premolar and showing subjective lip and tongue numbness were included in the study. Result: All sub-groups showed statistically significant reduction in VAS score. However sub-groups V and VI (that is GG with and without pre-medication respectively) showed best improvement in initial severe pain in mandibular molars with irreversible pulpitis. Moreover, all pre-medication sub-groups showed better pain control compared to respective control groups. Conclusion: It was concluded that use of pre-medications in the form of combination of anxiolytics and analgesics improves the success rate of local anesthesia in teeth with irreversible pulpitis. Use of anxiolytics eases the patient in endodontic emergencies. Also use of GG along with pre-medication is the best method for effective pain management of acute pain in irreversible pulpitis. PMID:27656053

7 CFR 42.133 - Portion of production acceptance criteria.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CONTAINER REGULATIONS STANDARDS FOR CONDITION OF FOOD CONTAINERS On-Line Sampling and Inspection Procedures... determined by comparing the calculated CuSum value with the acceptance limit (“L”) for the specified AQL. (b) A portion of production is acceptable if the CuSum value, calculated from the subgroup representing...

Pre-training evaluation and feedback improved skills retention of basic life support in medical students.

PubMed

Li, Qi; Zhou, Rong-hua; Liu, Jin; Lin, Jing; Ma, Er-Li; Liang, Peng; Shi, Ting-wei; Fang, Li-qun; Xiao, Hong

2013-09-01

Pre-training evaluation and feedback have been shown to improve medical students' skills acquisition of basic life support (BLS) immediately following training. The impact of such training on BLS skills retention is unknown. This study was conducted to investigate effects of pre-training evaluation and feedback on BLS skills retention in medical students. Three hundred and thirty 3rd year medical students were randomized to two groups, the control group (C group) and pre-training evaluation and feedback group (EF group). Each group was subdivided into four subgroups according to the time of retention-test (at 1-, 3-, 6-, 12-month following the initial training). After a 45-min BLS lecture, BLS skills were assessed (pre-training evaluation) in both groups before training. Following this, the C group received 45 min training. 15 min of group feedback corresponding to students' performance in pre-training evaluation was given only in the EF group that was followed by 30 min of BLS training. BLS skills were assessed immediately after training (post-test) and at follow up (retention-test). No skills difference was observed between the two groups in pre-training evaluation. Better skills acquisition was observed in the EF group (85.3 ± 7.3 vs. 68.1 ± 12.2 in C group) at post-test (p<0.001). In all retention-test, better skills retention was observed in each EF subgroup, compared with its paired C subgroup. Pre-training evaluation and feedback improved skills retention in the EF group for 12 months after the initial training, compared with the control group. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Dropouts In Two-Year Colleges: Better Prediction With The Use Of Moderator Subgroups

ERIC Educational Resources Information Center

Capoor, Madan; Eagle, Norman

1977-01-01

This article demonstrates, through a case study, the use of pre-existing subgroups as moderator variables to increase the predictive effectiveness of educational research. Use of moderator variables in this study increased the amount of explained variance by 460 percent. (JDS)

Long-Term Prognostic Effects of Plasma Epstein-Barr Virus DNA by Minor Groove Binder-Probe Real-Time Quantitative PCR on Nasopharyngeal Carcinoma Patients Receiving Concurrent Chemoradiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, J.-C.; Wang, W.-Y.; Liang, W.-M.

Purpose: To evaluate the long-term prognostic impact of plasma Epstein-Barr virus (EBV) DNA concentration measured by real-time quantitative polymerase chain reaction (RTQ-PCR) in nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT). Methods and Materials: Epstein-Barr virus DNA was retrospectively measured from stock plasma of 152 biopsy-proven NPC patients with Stage II-IV (M0) disease with a RTQ-PCR using the minor groove binder-probe. All patients received CCRT with a median follow-up of 78 months. We divided patients into three subgroups: (1) low pretreatment EBV DNA (<1,500 copies/mL) and undetectable posttreatment EBV DNA (pre-L/post-U) (2) high pretreatment EBV DNA ({>=}1,500 copies/mL) and undetectablemore » posttreatment EBV DNA (pre-H/post-U), and (3) low or high pretreatment EBV DNA and detectable posttreatment EBV DNA (pre-L or H/post-D) for prognostic analyses. Results: Epstein-Barr virus DNA (median concentration, 573 copies/mL; interquartile range, 197-3,074) was detected in the pretreatment plasma of 94.1% (143/152) of patients. After treatment, plasma EBV DNA decreased or remained 0 for all patients and was detectable in 31 patients (20.4%) with a median concentration 0 copy/mL (interquartile range, 0-0). The 5-year overall survival rates of the pre-L/post-U, pre-H/post-U, and pre-L or H/post-D subgroups were 87.2%, 71.0%, and 38.7%, respectively (p < 0.0001). The relapse-free survival showed similar results with corresponding rates of 85.6%, 75.9%, and 26.9%, respectively (p < 0.0001). Multivariate Cox analysis confirmed the superior effects of plasma EBV DNA compared to other clinical parameters in prognosis prediction. Conclusion: Plasma EBV DNA is the most valuable prognostic factor for NPC. More chemotherapy should be considered for patients with persistently detectable EBV DNA after CCRT.« less

Loss of LOFSEP Transcription Factor Function Converts Spikelet to Leaf-Like Structures in Rice1[OPEN

PubMed Central

Zhu, Wanwan

2018-01-01

SEPALLATA (SEP)-like genes, which encode a subfamily of MADS-box transcription factors, are essential for specifying floral organ and meristem identity in angiosperms. Rice (Oryza sativa) has five SEP-like genes with partial redundancy and overlapping expression domains, yet their functions and evolutionary conservation are only partially known. Here, we describe the biological role of one of the SEP genes of rice, OsMADS5, in redundantly controlling spikelet morphogenesis. OsMADS5 belongs to the conserved LOFSEP subgroup along with OsMADS1 and OsMADS34. OsMADS5 was expressed strongly across a broad range of reproductive stages and tissues. No obvious phenotype was observed in the osmads5 single mutants when compared with the wild type, which was largely due to the functional redundancy among the three LOFSEP genes. Genetic and molecular analyses demonstrated that OsMADS1, OsMADS5, and OsMADS34 together regulate floral meristem determinacy and specify the identities of spikelet organs by positively regulating the other MADS-box floral homeotic genes. Experiments conducted in yeast also suggested that OsMADS1, OsMADS5, and OsMADS34 form protein-protein interactions with other MADS-box floral homeotic members, which seems to be a typical, conserved feature of plant SEP proteins. PMID:29217592

42 CFR 37.95 - Specifications for performing spirometry examinations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... examinations must include the following: (1) Pre-test checklist. A short Spirometry Pre-Test Checklist (Form... spirometry examinations electronically with content as specified in § 37.96(b), pre-test screening checklists... spirometry examinations, pre-test checklists, and standardized respiratory assessment results in electronic...

Time-Based and Event-Based Prospective Memory in Autism Spectrum Disorder: The Roles of Executive Function and Theory of Mind, and Time-Estimation

ERIC Educational Resources Information Center

Williams, David; Boucher, Jill; Lind, Sophie; Jarrold, Christopher

2013-01-01

Prospective memory (remembering to carry out an action in the future) has been studied relatively little in ASD. We explored time-based (carry out an action at a pre-specified time) and event-based (carry out an action upon the occurrence of a pre-specified event) prospective memory, as well as possible cognitive correlates, among 21…

Quality, Quantity, And Surprise! Trade-Offs In X-Raser ASAT Attrition

NASA Astrophysics Data System (ADS)

Callaham, Michael B.; Scibilia, Frank M.

1984-08-01

In order to characterize the effects of technological superiority, numerical superiority, and pre-emption on space battle outcomes, we have constructed a battle simulation in which "Red" and "Blue" ASATs, each armed with a specified number of x-ray lasers of specified range, move along specified orbits and fire on one another according to a pair of battle management algorithms. The simulated battle proceeds until apparent steady-state force levels are reached. Battle outcomes are characterized by terminal force ratio and by terminal force-exchange ratio as effective weapon range, multiplicity (x-rasers per ASAT), and pre-emptive role are varied parametrically. A major conclusion is that pre-emptive advantage increases with increasing x-raser range and multiplicity (x-rasers per ASAT) and with increasing force size. That is, the "use 'em or lose 'em" dilemma will become more stark as such weapons are refined and proliferated.

An Out-of-Pocket Cost Removal Intervention on Fecal Occult Blood Test Attendance.

PubMed

Tabuchi, Takahiro; Murayama, Hiroshi; Hoshino, Takahiro; Nakayama, Tomio

2017-08-01

To date, no comparative study has assessed the impact of a cost-removal intervention on fecal occult blood testing (FOBT). In 2012, the Japanese government introduced a nationwide project to remove out-of-pocket costs for FOBT. The study objective was to evaluate the differential impact of the intervention on FOBT attendance in the total population and various subgroups. This study analyzed 309,103 people in national, repeated cross-sectional studies, observed pre- and post-intervention (2010 and 2013), using covariate-adjusted difference-in-differences estimates to compare intervention and no-intervention groups. The outcome measure was uptake of FOBT attendance resulting from the intervention. Stratified analyses were conducted according to sociodemographic and health-related characteristics. The intervention was associated with significantly positive uptake of FOBT in both genders, but the impact was greater in women than men: 6.7% (95% CI=5.2, 8.1) for women and 2.7% (95% CI=1.1, 4.3) for men in the covariate-adjusted models. Post-intervention, attendance increased in almost all subgroups in women. However, among men, some socially advantaged subgroups, such as high expenditure, high education, and public officers, showed no effect. Some subgroups such as current smokers and less than high school education were identified as hard-to-reach populations that may be less sensitive to the intervention, irrespective of gender. This is the first comparative study of cost-removal intervention for uptake of FOBT. The intervention may increase FOBT attendance. However, the size of the effect is not great, especially in men, and differential effects occurred across subgroups including gender and socioeconomic differences. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Equity effects of children's physical activity interventions: a systematic scoping review.

PubMed

Love, Rebecca E; Adams, Jean; van Sluijs, Esther M F

2017-10-02

Differential effects of physical activity (PA) interventions across population sub-groups may contribute to inequalities in health. This systematic scoping review explored the state of the evidence on equity effects in response to interventions targeting children's PA promotion. The aims were to assess and summarise the availability of evidence on differential intervention effects of children's PA interventions across gender, body mass index, socioeconomic status, ethnicity, place of residence and religion. Using a pre-piloted search strategy, six electronic databases were searched for controlled intervention trials, aiming to increase PA in children (6-18 years of age), that used objective forms of measurement. Screening and data extraction were conducted in duplicate. Reporting of analyses of differential effects were summarized for each equity characteristic and logistic regression analyses run to investigate intervention characteristics associated with the reporting of equity analyses. The literature search identified 13,052 publications and 7963 unique records. Following a duplicate screening process 125 publications representing 113 unique intervention trials were included. Although the majority of trials collected equity characteristics at baseline, few reported differential effects analyses across the equity factors of interest. All 113 included interventions reported gender at baseline with 46% of non-gender targeted interventions reporting differential effect analyses by gender. Respective figures were considerably smaller for body mass index, socioeconomic status, ethnicity, place of residence and religion. There was an increased likelihood of studying differential effects in school based interventions (OR: 2.9 [1.2-7.2]) in comparison to interventions in other settings, larger studies (per increase in 100 participants; 1.2 [1.0 - 1.4]); and where a main intervention effect on objectively measured PA was reported (3.0 [1.3-6.8]). Despite regularly collecting relevant information at baseline, most controlled trials of PA interventions in children do not report analyses of differences in intervention effect across outlined equity characteristics. Consequently, there is a scarcity of evidence concerning the equity effects of these interventions, particularly beyond gender, and a lack of understanding of subgroups that may benefit from, or be disadvantaged by, current intervention efforts. Further evidence synthesis and primary research is needed to effectively understand the impact of PA interventions on existing behavioural inequalities within population subgroups of children. PROSPERO (PROSPERO 2016: CRD42016034020 ).

A retrospective study on changes in residents' physical activities, social interactions, and neighborhood cohesion after moving to a walkable community.

PubMed

Zhu, Xuemei; Yu, Chia-Yuan; Lee, Chanam; Lu, Zhipeng; Mann, George

2014-12-01

This study is to examine changes in residents' physical activities, social interactions, and neighborhood cohesion after they moved to a walkable community in Austin, Texas. Retrospective surveys (N=449) were administered in 2013-2014 to collect pre- and post-move data about the outcome variables and relevant personal, social, and physical environmental factors. Walkability of each resident's pre-move community was measured using the Walk Score. T tests were used to examine the pre-post move differences in the outcomes in the whole sample and across sub-groups with different physical activity levels, neighborhood conditions, and neighborhood preferences before the move. After the move, total physical activity increased significantly in the whole sample and all sub-groups except those who were previously sufficiently active; lived in communities with high walkability, social interactions, or neighborhood cohesion; or had moderate preference for walkable neighborhoods. Walking in the community increased in the whole sample and all subgroups except those who were previously sufficiently active, moved from high-walkability communities, or had little to no preference for walkable neighborhoods. Social interactions and neighborhood cohesion increased significantly after the move in the whole sample and all sub-groups. This study explored potential health benefits of a walkable community in promoting physically and socially active lifestyles, especially for populations at higher risk of obesity. The initial result is promising, suggesting the need for more work to further examine the relationships between health and community design using pre-post assessments. Copyright © 2014 Elsevier Inc. All rights reserved.

Menstrual cycle characteristics as determinants of plasma concentrations of perfluoroalkyl substances (PFASs) in the Norwegian Mother and Child Cohort (MoBa study).

PubMed

Singer, Alison B; Whitworth, Kristina W; Haug, Line S; Sabaredzovic, Azemira; Impinen, Antti; Papadopoulou, Eleni; Longnecker, Matthew P

2018-06-04

Perfluoroalkyl substances (PFASs) are fluorinated organic compounds that have been used in a variety of industrial and consumer applications. Menstruation is implicated as a possible route of elimination for PFASs in women. The overall purpose of this study was to examine menstrual cycle characteristics as determinants of plasma PFAS concentrations in women. Our study sample consisted of 1977 pregnant women from the Norwegian Mother and Child Cohort (MoBa) study. The women were asked about menstrual cycle regularity in the year before the pregnancy and typical menstrual cycle length as well as other demographic and reproductive characteristics in a questionnaire completed during the pregnancy. Blood samples were collected around 17-18 weeks gestation and PFAS concentrations were measured in plasma. We examined the association between menstrual cycle characteristics and seven PFASs (perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), and perfluorooctane sulfonate (PFOS)) using multiple linear regression, adjusted for age, pre-pregnancy body mass index, smoking, education, income, parity, oral contraceptive use, inter-pregnancy interval, and breastfeeding duration. Irregular cycles were not associated with PFAS concentrations. Overall, we found no evidence of associations between menstrual cycle length and PFAS concentrations. In subgroup analyses we found some evidence, among parous women, of decreased PFHpS and PFOS with short menstrual cycles; we also found, among recent OC users (in the 12 months before the questionnaire) increased PFNA and PFUnDA with long cycle length. Limitations of our study include misclassification of menstrual cycle characteristics, small sample sizes in the sub-group analyses, and a lack of information on duration and volume of menses. In the entire study sample, we found little evidence of menstrual cycle characteristics as determinants of PFAS concentrations. However, we observed some associations between cycle length and PFAS concentrations with some select PFAS compounds in subgroup analyses. Copyright © 2018 Elsevier Inc. All rights reserved.

Testing GSTP1 genotypes and haplotypes interactions in Slovenian post-/pre-menopausal women: novel involvement of glutathione S-transferases in bone remodeling process.

PubMed

Mlakar, Simona Jurkovic; Prezelj, Janez; Marc, Janja

2012-02-01

Osteoporosis (OP) is an age-related disease associated with increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense system, such as low activity of glutathione S-transferase (GST) family. The enzyme activity of the member of GSTs, GSTP1, depends on gene polymorphisms such as: Ala114Val and Ile105Val. The aim of this study was to evaluate the association between genetic polymorphisms of the GSTP1 gene and BMD variation and biochemical bone remodeling markers in 523 Slovenian pre- and post-menopausal women. Observational pilot study in a representative cohort of Slovenian patients with adjustment for potential confounders (age, height, weight, years since menopause, smoking status and glucocorticoid use) using univariate one-way and two-way analyses. Ala114Val and Ile105Val polymorphisms genotypes of GSTP1 gene, bone mineral density (BMD) values of total hip (_th), femoral neck (_fn) and lumbar spine (_ls), plasma osteocalcin (OC), serum bone alkaline phosphatase (BALP), free soluble RANKL and serum osteoprotegerin (sOPG) concentrations were determined. Our results show that the Ala114Val heterozygotes are (borderline) significantly associated with higher concentrations of pOC (p=0.052) and decreased BMD_fn values (p=0.053) and the same trend is shown for BMD_th and BMD_ls values in osteopenic postmenopausal women. Furthermore, significantly higher concentrations of pOC were determined among Val allele carriers of Ile105Val gene polymorphism (p=0.037) and in carriers with the absent 114Ala-105Ile haplotype combination, again in osteopenic post-menopausal women. In addition, in pre-menopausal women the significant associations between sOPG and Ala114Val genotypes subgroups and between sBALP and Ile105Val genotypes subgroups, alone or in combination with Ala114Val, were determined (0.032, 0.026 and 0.008, respectively). Since significant associations existed in Ala114Val genotype and 114Ala-105Ile haplotype subgroups, these variations can be useful for determining low BMD and high pOC risk in postmenopausal women. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Wide brick tunnel randomization - an unequal allocation procedure that limits the imbalance in treatment totals.

PubMed

Kuznetsova, Olga M; Tymofyeyev, Yevgen

2014-04-30

In open-label studies, partial predictability of permuted block randomization provides potential for selection bias. To lessen the selection bias in two-arm studies with equal allocation, a number of allocation procedures that limit the imbalance in treatment totals at a pre-specified level but do not require the exact balance at the ends of the blocks were developed. In studies with unequal allocation, however, the task of designing a randomization procedure that sets a pre-specified limit on imbalance in group totals is not resolved. Existing allocation procedures either do not preserve the allocation ratio at every allocation or do not include all allocation sequences that comply with the pre-specified imbalance threshold. Kuznetsova and Tymofyeyev described the brick tunnel randomization for studies with unequal allocation that preserves the allocation ratio at every step and, in the two-arm case, includes all sequences that satisfy the smallest possible imbalance threshold. This article introduces wide brick tunnel randomization for studies with unequal allocation that allows all allocation sequences with imbalance not exceeding any pre-specified threshold while preserving the allocation ratio at every step. In open-label studies, allowing a larger imbalance in treatment totals lowers selection bias because of the predictability of treatment assignments. The applications of the technique in two-arm and multi-arm open-label studies with unequal allocation are described. Copyright © 2013 John Wiley & Sons, Ltd.

Large-scale brain network abnormalities in Huntington's disease revealed by structural covariance.

PubMed

Minkova, Lora; Eickhoff, Simon B; Abdulkadir, Ahmed; Kaller, Christoph P; Peter, Jessica; Scheller, Elisa; Lahr, Jacob; Roos, Raymund A; Durr, Alexandra; Leavitt, Blair R; Tabrizi, Sarah J; Klöppel, Stefan

2016-01-01

Huntington's disease (HD) is a progressive neurodegenerative disorder that can be diagnosed with certainty decades before symptom onset. Studies using structural MRI have identified grey matter (GM) loss predominantly in the striatum, but also involving various cortical areas. So far, voxel-based morphometric studies have examined each brain region in isolation and are thus unable to assess the changes in the interrelation of brain regions. Here, we examined the structural covariance in GM volumes in pre-specified motor, working memory, cognitive flexibility, and social-affective networks in 99 patients with manifest HD (mHD), 106 presymptomatic gene mutation carriers (pre-HD), and 108 healthy controls (HC). After correction for global differences in brain volume, we found that increased GM volume in one region was associated with increased GM volume in another. When statistically comparing the groups, no differences between HC and pre-HD were observed, but increased positive correlations were evident for mHD, relative to pre-HD and HC. These findings could be explained by a HD-related neuronal loss heterogeneously affecting the examined network at the pre-HD stage, which starts to dominate structural covariance globally at the manifest stage. Follow-up analyses identified structural connections between frontoparietal motor regions to be linearly modified by disease burden score (DBS). Moderator effects of disease load burden became significant at a DBS level typically associated with the onset of unequivocal HD motor signs. Together with existing findings from functional connectivity analyses, our data indicates a critical role of these frontoparietal regions for the onset of HD motor signs. © 2015 Wiley Periodicals, Inc.

Identifying Changes in Youth's Subgroup Membership over Time Based on Their Targeted Communication about Substance Use with Parents and Friends

ERIC Educational Resources Information Center

Kam, Jennifer A.

2011-01-01

Using latent class/transition analyses, this study: (a) identified subgroups of youth based on their targeted communication about substance use with parents and friends, (b) examined subgroup differences in substance use, and (c) considered changes in subgroup membership over four years. Among 5,874 youth, five subgroups emerged, with parents-only…

Increased Airway Wall Thickness is Associated with Adverse Longitudinal First-Second Forced Expiratory Volume Trajectories of Former World Trade Center workers.

PubMed

de la Hoz, Rafael E; Liu, Xiaoyu; Doucette, John T; Reeves, Anthony P; Bienenfeld, Laura A; Wisnivesky, Juan P; Celedón, Juan C; Lynch, David A; San José Estépar, Raúl

2018-05-24

Occupational exposures at the WTC site after September 11, 2001 have been associated with several presumably inflammatory lower airway diseases. In this study, we describe the trajectories of expiratory air flow decline, identify subgroups with adverse progression, and investigate the association of a quantitative computed tomography (QCT) imaging measurement of airway wall thickness, and other risk factors for adverse progression. We examined the trajectories of expiratory air flow decline in a group of 799 former WTC workers and volunteers with QCT-measured (with two independent systems) wall area percent (WAP) and at least 3 periodic spirometries. We calculated individual regression lines for first-second forced expiratory volume (FEV 1 ), identified subjects with rapidly declining and increasing ("gainers"), and compared them to subjects with normal and "stable" FEV 1 decline. We used multivariate logistic regression to model decliner vs. stable trajectories. The mean longitudinal FEV 1 slopes for the entire study population, and its stable, decliner, and gainer subgroups were, respectively, - 35.8, - 8, - 157.6, and + 173.62 ml/year. WAP was associated with "decliner" status (OR adj 1.08, 95% CI 1.02, 1.14, per 5% increment) compared to stable. Age, weight gain, baseline FEV 1 percent predicted, bronchodilator response, and pre-WTC occupational exposures were also significantly associated with accelerated FEV 1 decline. Analyses of gainers vs. stable subgroup showed WAP as a significant predictor in unadjusted but not consistently in adjusted analyses. The apparent normal age-related rate of FEV 1 decline results from averaging widely divergent trajectories. WAP is significantly associated with accelerated air flow decline in WTC workers.

[Combined use of wide-detector and adaptive statistical iterative reconstruction-V technique in abdominal CT with low radiation dose].

PubMed

Wang, H X; Lü, P J; Yue, S W; Chang, L Y; Li, Y; Zhao, H P; Li, W R; Gao, J B

2017-12-05

Objective: To investigate the image quality and radiation dose with wide-detector(80 mm) and adaptive statistical iterative reconstruction-V (ASIR-V) technique at abdominal contrast enhanced CT scan. Methods: In the first phantom experiment part, the percentage of ASIR-V for half dose of combined wide detector with ASIR-V technique as compared with standard-detector (40 mm) technique was determined. The human experiment was performed based on the phantom study, 160 patients underwent contrast-enhanced abdominal CT scan were prospectively collected and divided into the control group ( n =40) with image reconstruction using 40% ASIR (group A) and the study group ( n =120) with random number table. According to pre-ASIR-V percentage, the study group was assigned into three groups[40 cases in each group, group B: 0 pre-ASIR-V scan with image reconstruction of 0-100% post-ASIR-V (interval 10%, subgroups B0-B10); group C: 20% pre-ASIR-V with 20%, 40% and 60% post-ASIR-V (subgroups C1-C3); group D: 40%pre-ASIR-V with 40% and 60% post-ASIR-V (subgroups D1-D2)]. Image noise, CT attenuation values and CNR of the liver, pancreas, aorta and portal vein were compared by using two sample t test and One-way ANOVA. Qualitative visual parameters (overall image quality as graded on a 5-point scale) was compared by Mann-Whitney U test and Kruskal-Wallis H test. Results: The phantom experiment showed that the percentage of pre-ASIR-V for half dose was 40%. With the 40% pre-ASIR-V, radiation dose in the study group was reduced by 35.5% as compared with the control group. Image noise in the subgroups of B2-B10, C2-C3 and D1-D2 were lower ( t =-14.681--3.046, all P <0.05) while CNR in the subgroups of B4-B10, C2-3 and D1-D2 were higher( t =2.048-9.248, all P <0.05)than those in group A, except the CNR of liver in the arterial phase (AP) in C2, D1 and D2 and the CNR of pancreas in AP in D1 ( t =0.574-1.327, all P >0.05). The subjective image quality scores increased gradually in the range of 0-60% post-ASIR-V and decreased with post-ASIR-V larger than 70%. The overall image quality of subgroup B3-B8, C2-C3 and D1-D2 were higher than that in group A ( Z =-2.229--6.533, all P <0.05). Conclusion: Compared with stand-detector together with ASIR technique, wide-detector combined with 40% pre-ASIR-V technique with 60% post-ASIR-V image reconstruction can reduce radiation dose while maintain good overall image quality.

No Effects of D-Cycloserine Enhancement in Exposure With Response Prevention Therapy in Panic Disorder With Agoraphobia: A Double-Blind, Randomized Controlled Trial.

PubMed

Hofmeijer-Sevink, Mieke Klein; Duits, Puck; Rijkeboer, Marleen M; Hoogendoorn, Adriaan W; van Megen, Harold J; Vulink, Nienke C; Denys, Damiaan A; van den Hout, Marcel A; van Balkom, Anton J; Cath, Danielle C

2017-10-01

D-cycloserine (DCS) is a partial N-methyl-D-aspartate receptor agonist that potentially augments response to exposure therapy in anxiety disorders by enhancing extinction learning. This randomized, double-blinded, placebo-controlled augmentation trial examined (1) the effectiveness of adding 125 mg of DCS to exposure therapy (before or directly after the first 6 treatment sessions) in patients with panic disorder with agoraphobia and (2) the effectiveness of DCS augmentation preceding exposure relative to DCS augmentation directly postexposure. Fifty-seven patients were allocated to 1 of 3 medication conditions (placebo and pre-exposure and postexposure DCS) as an addition to 6 exposure sessions within a 12-session exposure and response prevention protocol. The primary outcome measure was the mean score on the "alone" subscale of the Mobility Inventory (MI). No differences were found in treatment outcome between DCS and placebo, administered either pre-exposure or postexposure therapy, although at 3-month follow-up, the DCS postexposure group compared with DCS pre-exposure, exhibited greater symptom reduction on the MI-alone subscale. Ancillary analyses in specific subgroups (responders vs nonresponders, early vs late responders, severely vs mildly affected patients) did not reveal any between-group DCS versus placebo differences. Finally, the study did not find an effect of DCS relative to placebo to be specific for successful exposure sessions. This study does not find an effect of augmentation with DCS in patients with severe panic disorder and agoraphobia administered either pretreatment or directly posttreatment sessions. Moreover, no preferential effects are revealed in specific subgroups nor in successful exposure sessions. Yet, a small effect of DCS administration postexposure therapy cannot be ruled out, given the relatively small sample size of this study.

DASH for asthma: A pilot study of the DASH diet in not-well-controlled adult asthma⋆

PubMed Central

Ma, Jun; Strub, Peg; Lavori, Phillip W.; Buist, A. Sonia; Camargo, Carlos A.; Nadeau, Kari C.; Wilson, Sandra R.; Xiao, Lan

2014-01-01

This pilot study aims to provide effect size confidence intervals, clinical trial and intervention feasibility data, and procedural materials for a full-scale randomized controlled trial that will determine the efficacy of Dietary Approaches to Stop Hypertension (DASH) as adjunct therapy to standard care for adults with uncontrolled asthma. The DASH diet encompasses foods (e.g., fresh fruit, vegetables, and nuts) and antioxidant nutrients (e.g., vitamins A, C, E, and zinc) with potential benefits for persons with asthma, but it is unknown whether the whole diet is beneficial. Participants (n = 90) will be randomized to receive usual care alone or combined with a DASH intervention consisting of 8 group and 3 individual sessions during the first 3 months, followed by at least monthly phone consultations for another 3 months. Follow-up assessments will occur at 3 and 6 months. The primary outcome measure is the 7-item Juniper Asthma Control Questionnaire, a validated composite measure of daytime and nocturnal symptoms, activity limitations, rescue medication use, and percentage predicted forced expiratory volume in 1 second. We will explore changes in inflammatory markers important to asthma pathophysiology (e.g., fractional exhaled nitric oxide) and their potential to mediate the intervention effect on disease control. We will also conduct pre-specified subgroup analyses by genotype (e.g., polymorphisms on the glutathione S transferase gene) and phenotype (e.g., atopy, obesity). By evaluating a dietary pattern approach to improving asthma control, this study could advance the evidence base for refining clinical guidelines and public health recommendations regarding the role of dietary modifications in asthma management. PMID:23648395

Mining Health App Data to Find More and Less Successful Weight Loss Subgroups

PubMed Central

2016-01-01

Background More than half of all smartphone app downloads involve weight, diet, and exercise. If successful, these lifestyle apps may have far-reaching effects for disease prevention and health cost-savings, but few researchers have analyzed data from these apps. Objective The purposes of this study were to analyze data from a commercial health app (Lose It!) in order to identify successful weight loss subgroups via exploratory analyses and to verify the stability of the results. Methods Cross-sectional, de-identified data from Lose It! were analyzed. This dataset (n=12,427,196) was randomly split into 24 subsamples, and this study used 3 subsamples (combined n=972,687). Classification and regression tree methods were used to explore groupings of weight loss with one subsample, with descriptive analyses to examine other group characteristics. Data mining validation methods were conducted with 2 additional subsamples. Results In subsample 1, 14.96% of users lost 5% or more of their starting body weight. Classification and regression tree analysis identified 3 distinct subgroups: “the occasional users” had the lowest proportion (4.87%) of individuals who successfully lost weight; “the basic users” had 37.61% weight loss success; and “the power users” achieved the highest percentage of weight loss success at 72.70%. Behavioral factors delineated the subgroups, though app-related behavioral characteristics further distinguished them. Results were replicated in further analyses with separate subsamples. Conclusions This study demonstrates that distinct subgroups can be identified in “messy” commercial app data and the identified subgroups can be replicated in independent samples. Behavioral factors and use of custom app features characterized the subgroups. Targeting and tailoring information to particular subgroups could enhance weight loss success. Future studies should replicate data mining analyses to increase methodology rigor. PMID:27301853

Elevated Fasting Blood Glucose Is Predictive of Poor Outcome in Non-Diabetic Stroke Patients: A Sub-Group Analysis of SMART.

PubMed

Yao, Ming; Ni, Jun; Zhou, Lixin; Peng, Bin; Zhu, Yicheng; Cui, Liying

2016-01-01

Although increasing evidence suggests that hyperglycemia following acute stroke adversely affects clinical outcome, whether the association between glycaemia and functional outcome varies between stroke patients with\\without pre-diagnosed diabetes remains controversial. We aimed to investigate the relationship between the fasting blood glucose (FBG) and the 6-month functional outcome in a subgroup of SMART cohort and further to assess whether this association varied based on the status of pre-diagnosed diabetes. Data of 2862 patients with acute ischemic stroke (629 with pre-diagnosed diabetics) enrolled from SMART cohort were analyzed. Functional outcome at 6-month post-stroke was measured by modified Rankin Scale (mRS) and categorized as favorable (mRS:0-2) or poor (mRS:3-5). Binary logistic regression model, adjusting for age, gender, educational level, history of hypertension and stroke, baseline NIHSS and treatment group, was used in the whole cohort to evaluate the association between admission FBG and functional outcome. Stratified logistic regression analyses were further performed based on the presence/absence of pre-diabetes history. In the whole cohort, multivariable logistical regression showed that poor functional outcome was associated with elevated FBG (OR1.21 (95%CI 1.07-1.37), p = 0.002), older age (OR1.64 (95% CI1.38-1.94), p<0.001), higher NIHSS (OR2.90 (95%CI 2.52-3.33), p<0.001) and hypertension (OR1.42 (95%CI 1.13-1.98), p = 0.04). Stratified logistical regression analysis showed that the association between FBG and functional outcome remained significant only in patients without pre-diagnosed diabetes (OR1.26 (95%CI 1.03-1.55), p = 0.023), but not in those with premorbid diagnosis of diabetes (p = 0.885). The present results demonstrate a significant association between elevated FBG after stroke and poor functional outcome in patients without pre-diagnosed diabetes, but not in diabetics. This finding confirms the importance of glycemic control during acute phase of ischemic stroke especially in patients without pre-diagnosed diabetes. Further investigation for developing optimal strategies to control blood glucose level in hyperglycemic setting is therefore of great importance. ClinicalTrials.gov NCT00664846.

Role of assessment tests in the stability of intelligence scoring of pre-school children with uneven/delayed cognitive profile.

PubMed

Yang, P; Jong, Y-J; Hsu, H-Y; Lung, F-W

2011-05-01

As part of an ongoing clinical service programme for pre-school children with developmental delay in an Asian developing country, we analysed the effect of three assessment tests, that is, Bayley Scale of Infant Development-II, Leiter International Performance Scale - Revised and Wechsler Preschool and Primary Scale of Intelligence - Revised - Chinese, on the stability of intelligence quotient (IQ) of children from pre-school through early childhood. The participants were 313 Taiwanese pre-school children with uneven or delayed cognitive profile and they were followed through early childhood. IQ stability was explored by different tests and among children of different clinical diagnosis: 168 children with non-autistic intellectual disability, 73 children with autism spectrum disorder, 58 children with mixed receptive-expressive language disorder and 14 children of other heterogeneous diagnoses. Stability of scores was evaluated using the r-squared for Pearson's coefficients to see the correlation between initial IQ (IQ1) and follow-up IQ (IQ2). Multiple linear regressions were also applied to see whether IQ1 had predictive ability for IQ2 and test-test difference in the total 313 children and each diagnostic subgroup. Results revealed that mean IQ1 was 65.8 ± 15.4 while mean IQ2 was 73.2 ± 17.9 for the total 313 children. The IQs were stable across an average follow-up duration of 38.6 ± 22.1 month from pre-school into early childhood. Patterns of positive correlations between IQ1 and IQ2 were noted by all the tests (r-squared = 0.43-0.5, all P < 0.001) and in the majority of diagnostic subgroups. Multiple regressions analysis also revealed that IQ1 could predict IQ2 significantly in all the tests (all P < 0.001). After careful choice of appropriate initial test, stability of IQ in children with developmental delay was noted from pre-school through early childhood. In addition, the translated version of cognitive assessment was valid for the required context of an Asian developing country. With the current emphasis on early identification and intervention for pre-school children with developmental delay, this information bears merit in clinical practice. © 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.

30 CFR 5.30 - Fee calculation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... authorizes the fee estimate. (1) The applicant may pre-authorize an expenditure for services under this subchapter, and may further choose to pre-authorize either a maximum dollar amount or an expenditure without a specified maximum amount. All applications containing a pre-authorization statement will...

30 CFR 5.30 - Fee calculation.

Code of Federal Regulations, 2013 CFR

2013-07-01

... authorizes the fee estimate. (1) The applicant may pre-authorize an expenditure for services under this subchapter, and may further choose to pre-authorize either a maximum dollar amount or an expenditure without a specified maximum amount. All applications containing a pre-authorization statement will...

30 CFR 5.30 - Fee calculation.

Code of Federal Regulations, 2011 CFR

2011-07-01

... authorizes the fee estimate. (1) The applicant may pre-authorize an expenditure for services under this subchapter, and may further choose to pre-authorize either a maximum dollar amount or an expenditure without a specified maximum amount. All applications containing a pre-authorization statement will...

Sensitivity, Specificity, and Posttest Probability of Parotid Fine-Needle Aspiration: A Systematic Review and Meta-analysis.

PubMed

Liu, C Carrie; Jethwa, Ashok R; Khariwala, Samir S; Johnson, Jonas; Shin, Jennifer J

2016-01-01

(1) To analyze the sensitivity and specificity of fine-needle aspiration (FNA) in distinguishing benign from malignant parotid disease. (2) To determine the anticipated posttest probability of malignancy and probability of nondiagnostic and indeterminate cytology with parotid FNA. Independently corroborated computerized searches of PubMed, Embase, and Cochrane Central Register were performed. These were supplemented with manual searches and input from content experts. Inclusion/exclusion criteria specified diagnosis of parotid mass, intervention with both FNA and surgical excision, and enumeration of both cytologic and surgical histopathologic results. The primary outcomes were sensitivity, specificity, and posttest probability of malignancy. Heterogeneity was evaluated with the I(2) statistic. Meta-analysis was performed via a 2-level mixed logistic regression model. Bayesian nomograms were plotted via pooled likelihood ratios. The systematic review yielded 70 criterion-meeting studies, 63 of which contained data that allowed for computation of numerical outcomes (n = 5647 patients; level 2a) and consideration of meta-analysis. Subgroup analyses were performed in studies that were prospective, involved consecutive patients, described the FNA technique utilized, and used ultrasound guidance. The I(2) point estimate was >70% for all analyses, except within prospectively obtained and ultrasound-guided results. Among the prospective subgroup, the pooled analysis demonstrated a sensitivity of 0.882 (95% confidence interval [95% CI], 0.509-0.982) and a specificity of 0.995 (95% CI, 0.960-0.999). The probabilities of nondiagnostic and indeterminate cytology were 0.053 (95% CI, 0.030-0.075) and 0.147 (95% CI, 0.106-0.188), respectively. FNA has moderate sensitivity and high specificity in differentiating malignant from benign parotid lesions. Considerable heterogeneity is present among studies. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.

Sensitivity, Specificity, and Posttest Probability of Parotid Fine-Needle Aspiration: A Systematic Review and Meta-analysis

PubMed Central

Liu, C. Carrie; Jethwa, Ashok R.; Khariwala, Samir S.; Johnson, Jonas; Shin, Jennifer J.

2016-01-01

Objectives (1) To analyze the sensitivity and specificity of fine-needle aspiration (FNA) in distinguishing benign from malignant parotid disease. (2) To determine the anticipated posttest probability of malignancy and probability of non-diagnostic and indeterminate cytology with parotid FNA. Data Sources Independently corroborated computerized searches of PubMed, Embase, and Cochrane Central Register were performed. These were supplemented with manual searches and input from content experts. Review Methods Inclusion/exclusion criteria specified diagnosis of parotid mass, intervention with both FNA and surgical excision, and enumeration of both cytologic and surgical histopathologic results. The primary outcomes were sensitivity, specificity, and posttest probability of malignancy. Heterogeneity was evaluated with the I2 statistic. Meta-analysis was performed via a 2-level mixed logistic regression model. Bayesian nomograms were plotted via pooled likelihood ratios. Results The systematic review yielded 70 criterion-meeting studies, 63 of which contained data that allowed for computation of numerical outcomes (n = 5647 patients; level 2a) and consideration of meta-analysis. Subgroup analyses were performed in studies that were prospective, involved consecutive patients, described the FNA technique utilized, and used ultrasound guidance. The I2 point estimate was >70% for all analyses, except within prospectively obtained and ultrasound-guided results. Among the prospective subgroup, the pooled analysis demonstrated a sensitivity of 0.882 (95% confidence interval [95% CI], 0.509–0.982) and a specificity of 0.995 (95% CI, 0.960–0.999). The probabilities of nondiagnostic and indeterminate cytology were 0.053 (95% CI, 0.030–0.075) and 0.147 (95% CI, 0.106–0.188), respectively. Conclusion FNA has moderate sensitivity and high specificity in differentiating malignant from benign parotid lesions. Considerable heterogeneity is present among studies. PMID:26428476

Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation.

PubMed

Lo, Wai-Kit; Goldberg, Hilary J; Boukedes, Steve; Burakoff, Robert; Chan, Walter W

2018-02-01

Acid reflux has been associated with poor outcomes following lung transplantation. Unlike surgical fundoplication, the role of noninvasive, pharmacologic acid suppression remains uncertain. To assess the relationship between post-transplant acid suppression with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) and onset of early allograft injury or chronic rejection following lung transplantation. This was a retrospective cohort study of lung transplant recipients at a tertiary center in 2007-2014. Patients with pre-transplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess acid suppression therapy and onset of acute or chronic rejection, defined histologically and clinically. Subgroup analyses were performed to assess PPI versus H2RA use. A total of 188 subjects (60% men, mean age 54, follow-up 554 person-years) met inclusion criteria. During follow-up, 115 subjects (61.5%) developed rejection, with all-cause mortality of 27.6%. On univariate analyses, acid suppression and BMI, but not other patient demographics, were associated with rejection. The Kaplan-Meier curve demonstrated decreased rejection with use of acid suppression therapy (log-rank p = 0.03). On multivariate analyses, acid suppression (HR 0.39, p = 0.04) and lower BMI (HR 0.67, p = 0.04) were independently predicted against rejection. Subgroup analyses demonstrated that persistent PPI use was more protective than H2RA or no antireflux medications. Post-lung transplant exposure to persistent PPI therapy results in the greatest protection against rejection in lung transplant recipients, independent of other clinical predictors including BMI, suggesting that PPI may have antireflux or anti-inflammatory effects in enhancing allograft protection.

The use of selective serotonin receptor inhibitors (SSRIs) is not associated with increased risk of endoscopy-refractory bleeding, rebleeding or mortality in peptic ulcer bleeding.

PubMed

Laursen, S B; Leontiadis, G I; Stanley, A J; Hallas, J; Schaffalitzky de Muckadell, O B

2017-08-01

Observational studies have consistently shown an increased risk of upper gastrointestinal bleeding in users of selective serotonin receptor inhibitors (SSRIs), probably explained by their inhibition of platelet aggregation. Therefore, treatment with SSRIs is often temporarily withheld in patients with peptic ulcer bleeding. However, abrupt discontinuation of SSRIs is associated with development of withdrawal symptoms in one-third of patients. Further data are needed to clarify whether treatment with SSRIs is associated with poor outcomes, which would support temporary discontinuation of treatment. To identify if treatment with SSRIs is associated with increased risk of: (1) endoscopy-refractory bleeding, (2) rebleeding or (3) 30-day mortality due to peptic ulcer bleeding. A nationwide cohort study. Analyses were performed on prospectively collected data on consecutive patients admitted to hospital with peptic ulcer bleeding in Denmark in the period 2006-2014. Logistic regression analyses were used to investigate the association between treatment with SSRIs and outcome following adjustment for pre-defined confounders. Sensitivity and subgroup analyses were performed to evaluate the validity of the findings. A total of 14 343 patients were included. Following adjustment, treatment with SSRIs was not associated with increased risk of endoscopy-refractory bleeding (odds ratio [OR] [95% Confidence Interval (CI)]: 1.03 [0.79-1.33]), rebleeding (OR [95% CI]: 0.96 [0.83-1.11]) or 30-day mortality (OR [95% CI]: 1.01 [0.85-1.19]. These findings were supported by sensitivity and subgroup analyses. According to our data, treatment with SSRIs does not influence the risk of endoscopy-refractory bleeding, rebleeding or 30-day mortality in peptic ulcer bleeding. © 2017 John Wiley & Sons Ltd.

Salivary cortisol, alpha-amylase and immunoglobulin a responses to a morning session of basketball or volleyball training in boys aged 14-18 years.

PubMed

Bruzda-Zwiech, A; Konieczka, M; Hilt, A; Daszkowska, M; Grzegorczyk, J; Szczepańska, J

2017-01-01

This study investigates whether a single session of routine morning basketball or volleyball training affects saliva levels of cortisol, alpha-amylase (sAA) and secretory immunoglobulin A (sIgA) in boys aged 14–18 years. Twenty-nine boys who participate in basketball or volleyball training, recruited from the Marcin Gortat’s Athletic Championship School in Lodz, were enrolled in the study. The 90-minute routine exercise program included 15 minutes of warm-up followed by basketball or volleyball practice. Unstimulated saliva samples were collected prior to and immediately after the exercise, and were analysed using ELISA. One training session resulted in a significant increase of sAA concentration in all participants, as well as in the volleyball and basketball subgroups (p=0.00022; p=0.0029; p=0.0011; respectively). Post-exercise cortisol levels were significantly lower than pre-exercise levels (p=0.00002) throughout the group, as well as in the volleyball and basketball subgroups (p=0.0048; p=0.0019; p=0.0048; respectively). The exercise protocol did not significantly affect sIgA level, either in the whole examined group or the volleyball subgroup, however a weak significant increase of sIgA was observed in the basketball subgroup (p=0.046). The routine morning training session comprising a warm-up followed by basketball or volleyball practice seems to activate the sympatho-adrenal-medullary system, with a subsequent increase of alpha-amylase, but does not affect oral immunity in 14-18-year-old boys.

Biopsychosocial influence on shoulder pain: rationale and protocol for a pre-clinical trial

PubMed Central

George, Steven Z.; Staud, Roland; Borsa, Paul A.; Wu, Samuel S.; Wallace, Margaret R.; Greenfield, Warren. H.; Mackie, Lauren N.; Fillingim, Roger B.

2017-01-01

Background Chronic musculoskeletal pain conditions are a prevalent and disabling problem. Preventing chronic musculoskeletal pain requires multifactorial treatment approaches that address its complex etiology. Prior cohort studies identified a high risk subgroup comprised of variation in COMT genotype and pain catastrophizing. This subgroup had increased chance of heightened pain responses (in a pre-clinical model) and higher 12 month post-operatives pain intensity ratings (in a clinical model). This pre-clinical trial will test mechanisms and efficacy of personalized pain interventions matched to the genetic and psychological characteristics of the high-risk subgroup. Methods Potential participants will be screened for high risk subgroup membership, appropriateness for exercise-induced muscle injury protocol, and appropriateness for propranolol administration. Eligible participants that consent to the study will then be randomized into one of four treatment groups; 1) personalized pharmaceutical and psychological education; 2) personalized pharmaceutical and general education; 3) placebo pharmaceutical and psychological education; 4) placebo pharmaceutical and psychological education. Over the 5-day study period participants will complete an exercise-induced muscle injury protocol and receive study interventions. Pain and disability assessments will be completed daily, with primary outcomes being duration of shoulder pain (number of days until recovery), peak shoulder pain intensity, and peak shoulder disability. Secondary outcomes include inflammatory markers, psychological mediators, and measures of pain sensitivity regulation. Conclusion This pre-clinical trial builds on prior cohort studies and its completion will provide foundational data supporting efficacy and mechanisms of personalized interventions for individuals that may be at increased risk for developing chronic shoulder pain. Trial Registration ClinicalTrials.gov registry, NCT02620579 (Registered on November 13, 2015) PMID:28315479

Biopsychosocial influence on shoulder pain: Rationale and protocol for a pre-clinical trial.

PubMed

George, Steven Z; Staud, Roland; Borsa, Paul A; Wu, Samuel S; Wallace, Margaret R; Greenfield, Warren H; Mackie, Lauren N; Fillingim, Roger B

2017-05-01

Chronic musculoskeletal pain conditions are a prevalent and disabling problem. Preventing chronic musculoskeletal pain requires multifactorial treatment approaches that address its complex etiology. Prior cohort studies identified a high risk subgroup comprised of variation in COMT genotype and pain catastrophizing. This subgroup had increased chance of heightened pain responses (in a pre-clinical model) and higher 12month post-operatives pain intensity ratings (in a clinical model). This pre-clinical trial will test mechanisms and efficacy of personalized pain interventions matched to the genetic and psychological characteristics of the high-risk subgroup. Potential participants will be screened for high risk subgroup membership, appropriateness for exercise-induced muscle injury protocol, and appropriateness for propranolol administration. Eligible participants that consent to the study will then be randomized into one of four treatment groups; 1) personalized pharmaceutical and psychological education; 2) personalized pharmaceutical and general education; 3) placebo pharmaceutical and psychological education; 4) placebo pharmaceutical and psychological education. Over the 5-day study period participants will complete an exercise-induced muscle injury protocol and receive study interventions. Pain and disability assessments will be completed daily, with primary outcomes being duration of shoulder pain (number of days until recovery), peak shoulder pain intensity, and peak shoulder disability. Secondary outcomes include inflammatory markers, psychological mediators, and measures of pain sensitivity regulation. This pre-clinical trial builds on prior cohort studies and its completion will provide foundational data supporting efficacy and mechanisms of personalized interventions for individuals that may be at increased risk for developing chronic shoulder pain. ClinicalTrials.gov registry, NCT02620579 (Registered on November 13, 2015). Copyright © 2017 Elsevier Inc. All rights reserved.

3-D surface reconstruction of patient specific anatomic data using a pre-specified number of polygons.

PubMed

Aharon, S; Robb, R A

1997-01-01

Virtual reality environments provide highly interactive, natural control of the visualization process, significantly enhancing the scientific value of the data produced by medical imaging systems. Due to the computational and real time display update requirements of virtual reality interfaces, however, the complexity of organ and tissue surfaces which can be displayed is limited. In this paper, we present a new algorithm for the production of a polygonal surface containing a pre-specified number of polygons from patient or subject specific volumetric image data. The advantage of this new algorithm is that it effectively tiles complex structures with a specified number of polygons selected to optimize the trade-off between surface detail and real-time display rates.

Dropouts in Two-Year Colleges: Better Prediction with the Use of Moderator Subgroups.

ERIC Educational Resources Information Center

Capoor, Madan; Eagle, Norman

Failure to identify and account for the effect of moderator variables is an important reason for the low explanatory power of much educational research. Pre-existing subgroups such as sex, ethnicity, and curriculum offer an easily identifiable and theoretically meaningful source of moderator variables. Tests for intercept and slope differences in…

Non-inferiority tests for anti-infective drugs using control group quantiles.

PubMed

Fay, Michael P; Follmann, Dean A

2016-12-01

In testing for non-inferiority of anti-infective drugs, the primary endpoint is often the difference in the proportion of failures between the test and control group at a landmark time. The landmark time is chosen to approximately correspond to the qth historic quantile of the control group, and the non-inferiority margin is selected to be reasonable for the target level q. For designing these studies, a troubling issue is that the landmark time must be pre-specified, but there is no guarantee that the proportion of control failures at the landmark time will be close to the target level q. If the landmark time is far from the target control quantile, then the pre-specified non-inferiority margin may not longer be reasonable. Exact variable margin tests have been developed by Röhmel and Kieser to address this problem, but these tests can have poor power if the observed control failure rate at the landmark time is far from its historic value. We develop a new variable margin non-inferiority test where we continue sampling until a pre-specified proportion of failures, q, have occurred in the control group, where q is the target quantile level. The test does not require any assumptions on the failure time distributions, and hence, no knowledge of the true [Formula: see text] control quantile for the study is needed. Our new test is exact and has power comparable to (or greater than) its competitors when the true control quantile from the study equals (or differs moderately from) its historic value. Our nivm R package performs the test and gives confidence intervals on the difference in failure rates at the true target control quantile. The tests can be applied to time to cure or other numeric variables as well. A substantial proportion of new anti-infective drugs being developed use non-inferiority tests in their development, and typically, a pre-specified landmark time and its associated difference margin are set at the design stage to match a specific target control quantile. If through changing standard of care or selection of a different population the target quantile for the control group changes from its historic value, then the appropriateness of the pre-specified margin at the landmark time may be questionable. Our proposed test avoids this problem by sampling until a pre-specified proportion of the controls have failed. © The Author(s) 2016.

Evaluation of the DSM-5 severity indicator for binge eating disorder in a clinical sample

PubMed Central

Grilo, Carlos M.; Ivezaj, Valentina; White, Marney A.

2015-01-01

Objective This study tested the new DSM-5 severity criterion for binge eating disorder (BED) based on frequency of binge-eating in a clinical sample. This study also tested overvaluation of shape/weight as an alternative severity specifier. Method Participants were 834 treatment-seeking adults diagnosed with DSM-5 BED using semistructured diagnostic and eating-disorder interviews. Participants sub-grouped based on DSM-5 severity levels and on overvaluation of shape/weight were compared on demographic and clinical variables. Results Based on DSM-5 severity definitions, 331 (39.7%) participants were categorized as mild, 395 (47.5%) as moderate, 83 (10.0%) as severe, and 25 (3.0%) as extreme. Analyses comparing three (mild, moderate, and severe/extreme) severity groups revealed no significant differences in demographic variables or body mass index (BMI). Analyses revealed significantly higher eating-disorder psychopathology in the severe/extreme than moderate and mild groups and higher depression in moderate and severe/extreme groups than the mild group; effect sizes were small. Participants characterized with overvaluation (N = 449; 54%) versus without overvaluation (N = 384; 46%) did not differ significantly in age, sex, BMI, or binge-eating frequency, but had significantly greater eating-disorder psychopathology and depression. The robustly greater eating-disorder psychopathology and depression levels (medium-to-large effect sizes) in the overvaluation group was observed without attenuation of effect sizes after adjusting for ethnicity/race and binge-eating severity/frequency. Conclusions Our findings provide support for overvaluation of shape/weight as a severity specifier for BED as it provides stronger information about the severity of homogeneous groupings of patients than the DSM-5 rating based on binge-eating. PMID:26114779

40 CFR 85.1403 - Particulate standard for pre-1994 model year urban buses effective at time of engine rebuild or...

Code of Federal Regulations, 2010 CFR

2010-07-01

... section. (iii)(A) Pre-rebuild particulate emission levels and projected post-rebuild particulate emission... specified in the following table. The appropriate particulate level, pre-rebuild or post-rebuild, shall be... of engine Pre-rebuild particulate level (g/bhp-hr) Projected post-rebuild particulate level (g/bhp-hr...

40 CFR 85.1403 - Particulate standard for pre-1994 model year urban buses effective at time of engine rebuild or...

Code of Federal Regulations, 2014 CFR

2014-07-01

... section. (iii)(A) Pre-rebuild particulate emission levels and projected post-rebuild particulate emission... specified in the following table. The appropriate particulate level, pre-rebuild or post-rebuild, shall be... of engine Pre-rebuild particulate level (g/bhp-hr) Projected post-rebuild particulate level (g/bhp-hr...

40 CFR 85.1403 - Particulate standard for pre-1994 model year urban buses effective at time of engine rebuild or...

Code of Federal Regulations, 2012 CFR

2012-07-01

... section. (iii)(A) Pre-rebuild particulate emission levels and projected post-rebuild particulate emission... specified in the following table. The appropriate particulate level, pre-rebuild or post-rebuild, shall be... of engine Pre-rebuild particulate level (g/bhp-hr) Projected post-rebuild particulate level (g/bhp-hr...

40 CFR 85.1403 - Particulate standard for pre-1994 model year urban buses effective at time of engine rebuild or...

Code of Federal Regulations, 2013 CFR

2013-07-01

... section. (iii)(A) Pre-rebuild particulate emission levels and projected post-rebuild particulate emission... specified in the following table. The appropriate particulate level, pre-rebuild or post-rebuild, shall be... of engine Pre-rebuild particulate level (g/bhp-hr) Projected post-rebuild particulate level (g/bhp-hr...

40 CFR 85.1403 - Particulate standard for pre-1994 model year urban buses effective at time of engine rebuild or...

Code of Federal Regulations, 2011 CFR

2011-07-01

... section. (iii)(A) Pre-rebuild particulate emission levels and projected post-rebuild particulate emission... specified in the following table. The appropriate particulate level, pre-rebuild or post-rebuild, shall be... of engine Pre-rebuild particulate level (g/bhp-hr) Projected post-rebuild particulate level (g/bhp-hr...

Readiness to change and brain damage in patients with chronic alcoholism.

PubMed

Le Berre, Anne-Pascale; Rauchs, Géraldine; La Joie, Renaud; Segobin, Shailendra; Mézenge, Florence; Boudehent, Céline; Vabret, François; Viader, Fausto; Eustache, Francis; Pitel, Anne-Lise; Beaunieux, Hélène

2013-09-30

High motivation to change is a crucial triggering factor to patients' engagement in clinical treatment. This study investigates whether the low readiness to change observed in some alcoholic inpatients at treatment entry could, at least partially, be linked with macrostructural gray matter abnormalities in critical brain regions. Participants comprised 31 alcoholic patients and 27 controls, who underwent 1.5-T magnetic resonance imaging. The Readiness to Change Questionnaire, designed to assess three stages of motivation to change (precontemplation, contemplation and action stages), was completed by all patients, who were then divided into "Action" (i.e., patients in action stage) and "PreAction" (i.e., patients in precontemplation or in contemplation stage) subgroups. The PreAction subgroup, but not the Action subgroup, had gray matter volume deficits compared with controls. Unlike the patients in the Action subgroup, the PreAction patients had gray matter abnormalities in the cerebellum (Crus I), fusiform gyri and frontal cortex. The low level of motivation to modify drinking behavior observed in some alcoholic patients at treatment entry may be related to macrostructural brain abnormalities in regions subtending cognitive, emotional and social abilities. These brain volume deficits may result in impairment of critical abilities such as decision making, executive functions and social cognition skills. Those abilities may be needed to resolve ambivalence toward alcohol addiction and to apply "processes of change", which are essential for activating the desire to change problematic behavior. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Therapeutic effect of captopril, pentoxifylline, and cordyceps sinensis in pre-hepatic portal hypertensive rats.

PubMed

Ahmed, Ahmed F; El-Maraghy, Nabila N; Abdel Ghaney, Rasha H; Elshazly, Shimaa M

2012-01-01

Portal hypertension is an important and potentially fatal complication of liver disease whereby cellular and fibrotic alterations manifest to increase portal venous pressure. The aim of this study is to investigate the effect of captopril, pentoxifylline (PTX), and cordyceps sinensis in pre-hepatic portal hypertensive rats. Wistar male rats were divided at random into 3 main groups: the first group: control rats. The second group: sham-operated rats and the third group: prehepatic portal hypertensive rats (PHPHT) induced by regulated pre-hepatic portal vein ligation. After 14 days, Group 3 was subdivided into 5 subgroups. Subgroup (1): portal vein-ligated (PVL) was killed at once; Subgroup (2): received distilled water for 30 days (untreated PVL group); subgroups 3-5 were treated with captopril (60 mg/kg, orally); PTX (100 mg/kg, orally); and C. sinensis (200 mg/kg, orally), respectively, as a single daily dose for 30 days. Portal pressure, nitric oxide (NO), antioxidant enzymes, Liver enzymes, and creatinine levels were measured to evaluate the status of the liver state. Portal vein ligation produced significant increments in liver enzymes, NO, creatinine and portal pressure concomitant with significant decrements in glutathione content and superoxide dismutase activity. Treatment with captopril, PTX, and C. sinensis resulted in a significant reduction in liver enzymes, NO, creatinine and portal pressure and observable increase in antioxidant enzymes. captopril, PTX, and C. sinensis have promising effect in controlling PHPHT and reducing hyperdynamic circulatory state through reduction of portal pressure and NO level.

The role of vaspin as a predictor of coronary angiography result in SCAD (stable coronary artery disease) patients.

PubMed

Stančík, Matej; Ságová, Ivana; Kantorová, Ema; Mokáň, Marián

2017-05-08

The role of vaspin in the pathogenesis of stable coronary artery disease (SCAD) have been repeatedly addressed in clinical studies. However, from the point of view of clinical practice, the results of earlier studies are still inconclusive. The data of 106 SCAD patients who received coronary angiography and 85 coronary artery disease-free controls were collected and analysed. The patients were divided into subgroups according to their pre-test probability (PTP) and according to the result of coronary angiography. Fasting vaspin concentrations were compared between subgroups of SCAD patients and between target group and controls. The effect of age and smoking on the result of coronary angiography was compared to the effect of vaspin using the binomial regression. We did not find significant difference in vaspin level between target group and controls. Unless the pre-test probability was taken into account, we did not find vaspin difference in the target group, when dividing patients on the basis of presence/absence of significant coronary stenosis. In the subgroup of SCAD patients with PTP between 15% - 65%, those with significant coronary stenoses had higher mean vaspin concentration (0,579 ± 0,898 ng/ml) than patients without significant stenoses. (0,379 ± 0,732 ng/ml) (t = -2595; p = 0,012; d = 0,658; 1-β = 0,850). Age, smoking status and vaspin significantly contributed to the HSCS prediction in binomial regression model in patients with low PTP (OR: 1.1, 4.9, 8.7, respectively). According to our results, vaspin cannot be used as an independent marker for the presence of CAD in general population. However, our results indicate that measuring vaspin in SCAD patients might be clinically useful in patients with PTP below 66%.

Genome-wide analyses of HTLV-1aD strains from Cape Verde, Africa.

PubMed

Zanella, Louise; Pina-Araujo I, Isabel de; Morgado, Mariza G; Vicente, Ana Carolina

2016-09-01

We characterised and reported the first full-length genomes of Human T-cell Lymphotropic Virus Type 1 subgroup HTLV-1aD (CV21 and CV79). This subgroup is one of the major determinants of HTLV-1 infections in North and West Africa, and recombinant strains involving this subgroup have been recently demonstrated. The CV21 and CV79 strains from Cape Verde/Africa were characterised as pure HTLV-1aD genomes, comparative analyses including HTLV-1 subtypes and subgroups revealed HTLV-1aD signatures in the envelope, pol, and pX regions. These genomes provide original information that will contribute to further studies on HTLV-1a epidemiology and evolution.

Altered states of consciousness in epilepsy: a DTI study of the brain.

PubMed

Xie, Fangfang; Xing, Wu; Wang, Xiaoyi; Liao, Weihua; Shi, Wei

2017-08-01

A disturbance in the level of consciousness is a classical clinical sign of several seizure types. Recent studies have shown that altered states of consciousness in seizures are associated with structural and functional changes of several brain regions. Prominent among these are the thalamus, the brain stem and the default mode network, which is part of the consciousness system. Our study used diffusion tensor imaging (DTI) to evaluate these brain regions in patients with three different types of epilepsies that are associated with altered consciousness: complex partial seizures (CPS), primary generalized tonic-clonic seizures (PGTCS) or secondary generalized tonic-clonic seizures (SGTCS). Additionally, this study further explores the probable mechanisms underlying impairment of consciousness in seizures. Conventional MRI and DTI scanning were performed in 51 patients with epilepsy and 51 healthy volunteers. The epilepsy group was in turn subdivided into three subgroups: CPS, PGTCS or SGTCS. Each subgroup comprised 17 patients. Each subject involved in the study underwent a DTI evaluation of the brain to measure the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of nine regions of interest: the postero-superior portion of midbrain, the bilateral dorsal thalamus, the bilateral precuneus/posterior cingulate, the bilateral medial pre-frontal gyri and the bilateral supramarginalgyri. The statistical significance of the measured ADC and FA values between the experimental and control groups was analysed using the paired t-test, and one-way analysis of variance was performed for a comparative analysis between the three subgroups. Statistically significantly higher ADC values ( p < 0.01) were observed in the bilateral dorsal thalamus and postero-superior aspect of the midbrain in the three patient subgroups than in the control group. There were no significant changes in the ADC values ( p > 0.05) in the bilateral precuneus/posterior cingulate, bilateral medial pre-frontal gyri or bilateral supramarginalgyri in the experimental group. Among the three patient subgroups and the ADC values of corresponding brain regions, there were no statistically significant changes. Statistically significantly lower FA values ( p < 0.05) were observed in the bilateral dorsal thalamus of the patients in the three subgroups than in the control group. Significantly lowered FA values from the postero-superior aspect of the mid brain ( p < 0.01) were observed in patients with PGTCS compared with the control group. There were no significant changes in the FA values ( p > 0.05) from the bilateral precuneus/posterior cingulate, bilateral medial frontal gyri or bilateral supramarginalgyri in the experimental group. Among the three patient subgroups and the FA values of the corresponding brain regions, there were no statistically significant changes. In epileptic patients with CPS, PGTCS or SGTCS, there seems to be a long-lasting neuronal dysfunction of the bilateral dorsal thalamus and postero-superior aspect of the midbrain. The thalamus and upper brain stem are likely to play a key role in epileptic patients with impaired consciousness.

Bayesian approach for assessing non-inferiority in a three-arm trial with pre-specified margin.

PubMed

Ghosh, Samiran; Ghosh, Santu; Tiwari, Ram C

2016-02-28

Non-inferiority trials are becoming increasingly popular for comparative effectiveness research. However, inclusion of the placebo arm, whenever possible, gives rise to a three-arm trial which has lesser burdensome assumptions than a standard two-arm non-inferiority trial. Most of the past developments in a three-arm trial consider defining a pre-specified fraction of unknown effect size of reference drug, that is, without directly specifying a fixed non-inferiority margin. However, in some recent developments, a more direct approach is being considered with pre-specified fixed margin albeit in the frequentist setup. Bayesian paradigm provides a natural path to integrate historical and current trials' information via sequential learning. In this paper, we propose a Bayesian approach for simultaneous testing of non-inferiority and assay sensitivity in a three-arm trial with normal responses. For the experimental arm, in absence of historical information, non-informative priors are assumed under two situations, namely when (i) variance is known and (ii) variance is unknown. A Bayesian decision criteria is derived and compared with the frequentist method using simulation studies. Finally, several published clinical trial examples are reanalyzed to demonstrate the benefit of the proposed procedure. Copyright © 2015 John Wiley & Sons, Ltd.

40 CFR 91.413 - Exhaust sample procedure-gaseous components.

Code of Federal Regulations, 2011 CFR

2011-07-01

... that may occur between the pre and post checks is not specified. However, the difference between pre... drift nor the span drift between the pre-analysis and post-analysis checks on any range used may exceed... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM MARINE SPARK-IGNITION ENGINES Gaseous Exhaust Test...

40 CFR 91.413 - Exhaust sample procedure-gaseous components.

Code of Federal Regulations, 2014 CFR

2014-07-01

... that may occur between the pre and post checks is not specified. However, the difference between pre... drift nor the span drift between the pre-analysis and post-analysis checks on any range used may exceed... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM MARINE SPARK-IGNITION ENGINES Gaseous Exhaust Test...

40 CFR 91.413 - Exhaust sample procedure-gaseous components.

Code of Federal Regulations, 2010 CFR

2010-07-01

... that may occur between the pre and post checks is not specified. However, the difference between pre... drift nor the span drift between the pre-analysis and post-analysis checks on any range used may exceed... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM MARINE SPARK-IGNITION ENGINES Gaseous Exhaust Test...

40 CFR 91.413 - Exhaust sample procedure-gaseous components.

Code of Federal Regulations, 2012 CFR

2012-07-01

... that may occur between the pre and post checks is not specified. However, the difference between pre... drift nor the span drift between the pre-analysis and post-analysis checks on any range used may exceed... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM MARINE SPARK-IGNITION ENGINES Gaseous Exhaust Test...

40 CFR 91.413 - Exhaust sample procedure-gaseous components.

Code of Federal Regulations, 2013 CFR

2013-07-01

... that may occur between the pre and post checks is not specified. However, the difference between pre... drift nor the span drift between the pre-analysis and post-analysis checks on any range used may exceed... PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM MARINE SPARK-IGNITION ENGINES Gaseous Exhaust Test...

ARS-Media for Excel

USDA-ARS?s Scientific Manuscript database

ARS-Media for Excel is an ion solution calculator that uses Microsoft Excel to generate recipes of salts for complex ion mixtures specified by the user. Generating salt combinations (recipes) that result in pre-specified target ion values is a linear programming problem. Thus, the recipes are genera...

Subgroup identification of early preterm birth (ePTB): informing a future prospective enrichment clinical trial design.

PubMed

Zhang, Chuanwu; Garrard, Lili; Keighley, John; Carlson, Susan; Gajewski, Byron

2017-01-10

Despite the widely recognized association between the severity of early preterm birth (ePTB) and its related severe diseases, little is known about the potential risk factors of ePTB and the sub-population with high risk of ePTB. Moreover, motivated by a future confirmatory clinical trial to identify whether supplementing pregnant women with docosahexaenoic acid (DHA) has a different effect on the risk subgroup population or not in terms of ePTB prevalence, this study aims to identify potential risk subgroups and risk factors for ePTB, defined as babies born less than 34 weeks of gestation. The analysis data (N = 3,994,872) were obtained from CDC and NCHS' 2014 Natality public data file. The sample was split into independent training and validation cohorts for model generation and model assessment, respectively. Logistic regression and CART models were used to examine potential ePTB risk predictors and their interactions, including mothers' age, nativity, race, Hispanic origin, marital status, education, pre-pregnancy smoking status, pre-pregnancy BMI, pre-pregnancy diabetes status, pre-pregnancy hypertension status, previous preterm birth status, infertility treatment usage status, fertility enhancing drug usage status, and delivery payment source. Both logistic regression models with either 14 or 10 ePTB risk factors produced the same C-index (0.646) based on the training cohort. The C-index of the logistic regression model based on 10 predictors was 0.645 for the validation cohort. Both C-indexes indicated a good discrimination and acceptable model fit. The CART model identified preterm birth history and race as the most important risk factors, and revealed that the subgroup with a preterm birth history and a race designation as Black had the highest risk for ePTB. The c-index and misclassification rate were 0.579 and 0.034 for the training cohort, and 0.578 and 0.034 for the validation cohort, respectively. This study revealed 14 maternal characteristic variables that reliably identified risk for ePTB through either logistic regression model and/or a CART model. Moreover, both models efficiently identify risk subgroups for further enrichment clinical trial design.

Able but unintelligent: including positively stereotyped black subgroups in the stereotype content model.

PubMed

Walzer, Amy S; Czopp, Alexander M

2011-01-01

The stereotype content model (SCM) posits that warmth and competence are the key components underlying judgments about social groups. Because competence can encompass different components (e.g., intelligence, talent) different group members may be perceived to be competent for different reasons. Therefore, we believe it may be important to specify the type of competence being assessed when examining perceptions of groups that are positively stereotyped (i.e., Black athletes and musical Blacks). Consistent with the SCM, these subgroups were perceived as high in competence-talent but not in competence-intelligence and low in warmth. Both the intelligence and talent frame of competence fit in the SCM's social structural hypothesis.

Independent contribution of temporal beta-amyloid deposition to memory decline in the pre-dementia phase of Alzheimer's disease.

PubMed

Chételat, Gaël; Villemagne, Victor L; Pike, Kerryn E; Ellis, Kathryn A; Bourgeat, Pierrick; Jones, Gareth; O'Keefe, Graeme J; Salvado, Olivier; Szoeke, Cassandra; Martins, Ralph N; Ames, David; Masters, Colin L; Rowe, Christopher C

2011-03-01

The relationship between β-amyloid deposition and memory deficits in early Alzheimer's disease is unresolved, as past studies show conflicting findings. The present study aims to determine the relative contribution of regional β-amyloid deposition, hippocampal atrophy and white matter integrity to episodic memory deficits in non-demented older individuals harbouring one of the characteristic hallmarks of Alzheimer's disease, i.e. with β-amyloid pathology. Understanding these relationships is critical for effective therapeutic development. Brain magnetic resonance imaging and [(11)C]Pittsburgh Compound B-positron emission tomography scans were obtained in 136 non-demented individuals aged over 60 years, including 93 healthy elderly and 43 patients with mild cognitive impairment. Voxel-based correlations were computed between a memory composite score and grey matter volume, white matter volume and β-amyloid deposition imaging datasets. Hierarchical linear regression analyses were then performed using values extracted in regions of most significant correlations to determine the relative contribution of each modality to memory deficits. All analyses were conducted pooling all groups together as well as within separate subgroups of cognitively normal elderly, patients with mild cognitive impairment and individuals with high versus low neocortical β-amyloid. Brain areas of highest correlation with episodic memory deficits were the hippocampi for grey matter volume, the perforant path for white matter volume and the temporal neocortex for β-amyloid deposition. When considering these three variables together, only hippocampal volume and temporal β-amyloid deposition provided independent contributions to memory deficits. In contrast to global β-amyloid deposition, temporal β-amyloid deposition was still related to memory independently from hippocampal atrophy within subgroups of cognitively normal elderly, patients with mild cognitive impairment or cases with high neocortical β-amyloid. In the pre-dementia stage of Alzheimer's disease, subtle episodic memory impairment is related to β-amyloid deposition, especially in the temporal neocortex, and independently from hippocampal atrophy, suggesting that both factors should be independently targeted in therapeutic trials aimed at reducing cognitive decline.

40 CFR 1065.530 - Emission test sequence.

Code of Federal Regulations, 2013 CFR

2013-07-01

... temperature continuously to verify that it remains within the pre-test temperature range as specified in... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Emission test sequence. 1065.530... CONTROLS ENGINE-TESTING PROCEDURES Performing an Emission Test Over Specified Duty Cycles § 1065.530...

40 CFR 1065.530 - Emission test sequence.

Code of Federal Regulations, 2012 CFR

2012-07-01

... temperature continuously to verify that it remains within the pre-test temperature range as specified in... 40 Protection of Environment 34 2012-07-01 2012-07-01 false Emission test sequence. 1065.530... CONTROLS ENGINE-TESTING PROCEDURES Performing an Emission Test Over Specified Duty Cycles § 1065.530...

40 CFR 1065.530 - Emission test sequence.

Code of Federal Regulations, 2014 CFR

2014-07-01

... temperature continuously to verify that it remains within the pre-test temperature range as specified in... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Emission test sequence. 1065.530... CONTROLS ENGINE-TESTING PROCEDURES Performing an Emission Test Over Specified Duty Cycles § 1065.530...

42 CFR 418.205 - Special requirements for hospice pre-election evaluation and counseling services.

Code of Federal Regulations, 2013 CFR

2013-10-01

... evaluation and counseling services. 418.205 Section 418.205 Public Health CENTERS FOR MEDICARE & MEDICAID... Covered Services § 418.205 Special requirements for hospice pre-election evaluation and counseling... pre-election evaluation and counseling services as specified in § 418.304(d) may be made to a hospice...

42 CFR 418.205 - Special requirements for hospice pre-election evaluation and counseling services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... evaluation and counseling services. 418.205 Section 418.205 Public Health CENTERS FOR MEDICARE & MEDICAID... Covered Services § 418.205 Special requirements for hospice pre-election evaluation and counseling... pre-election evaluation and counseling services as specified in § 418.304(d) may be made to a hospice...

42 CFR 418.205 - Special requirements for hospice pre-election evaluation and counseling services.

Code of Federal Regulations, 2014 CFR

2014-10-01

... evaluation and counseling services. 418.205 Section 418.205 Public Health CENTERS FOR MEDICARE & MEDICAID... Covered Services § 418.205 Special requirements for hospice pre-election evaluation and counseling... pre-election evaluation and counseling services as specified in § 418.304(d) may be made to a hospice...

Alternative Fuels Data Center: Plug-In Electric Vehicle Deployment Policy

Science.gov Websites

addendum to a pre-existing zoning ordinance to specify permissible use of EVSE in single- and multi-family -ready requirements may include EVSE installation, pre-wiring, or space reservation. California building charging infrastructure. Examples include the scope of EVSE pre-wiring or installation from a

Cloud Applications in Language Teaching: Examining Pre-Service Teachers' Expertise, Perceptions and Integration

ERIC Educational Resources Information Center

Aburezeq, Ibtehal Mahmoud; Dweikat, Fawzi Fayez Ishtaiwa

2017-01-01

This study examined pre-service teachers' expertise, perceptions and integration of cloud applications in teaching of Arabic and English. Questionnaires and semi-structured interviews were used as data collection methods. The findings of the study specified that pre-service teachers did not own sufficient expertise for effective integration of…

40 CFR 86.1330-90 - Test sequence; general requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... fuel and the point at which it is measured shall be specified by the manufacturer. (g) Pre-test engine...-fueled or methanol-fueled diesel engine fuel flows, etc.), pre-test engine performance checks (e.g., verification of actual rated rpm, etc.) and pre-test system calibrations (e.g., inlet and exhaust restrictions...

40 CFR 86.1330-90 - Test sequence; general requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... fuel and the point at which it is measured shall be specified by the manufacturer. (g) Pre-test engine...-fueled or methanol-fueled diesel engine fuel flows, etc.), pre-test engine performance checks (e.g., verification of actual rated rpm, etc.) and pre-test system calibrations (e.g., inlet and exhaust restrictions...

40 CFR 86.1330-90 - Test sequence; general requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... fuel and the point at which it is measured shall be specified by the manufacturer. (g) Pre-test engine...-fueled or methanol-fueled diesel engine fuel flows, etc.), pre-test engine performance checks (e.g., verification of actual rated rpm, etc.) and pre-test system calibrations (e.g., inlet and exhaust restrictions...

40 CFR 86.1330-90 - Test sequence; general requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... fuel and the point at which it is measured shall be specified by the manufacturer. (g) Pre-test engine...-fueled or methanol-fueled diesel engine fuel flows, etc.), pre-test engine performance checks (e.g., verification of actual rated rpm, etc.) and pre-test system calibrations (e.g., inlet and exhaust restrictions...

47 CFR 25.113 - Station construction, launch authority, and operation of spare satellites.

Code of Federal Regulations, 2014 CFR

2014-10-01

... this part, and technical design requirements. Prior to commencing such construction and pre-operational... specify the frequencies the licensee proposes to use for pre-operational testing and the name, address... resulting from such testing. MSS/ATC licensees engaging in pre-operational testing must comply with §§ 5.83...

50 CFR 622.41 - Species specific limitations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... test and evaluate a new BRD design for up to 60 days without being subject to the observer requirements...) [Reserved] (i) Pre-certification. The pre-certification phase allows a person to test and evaluate a new BRD... vessel specified in the application. The RA will issue a pre-certification phase LOA if the BRD design is...

40 CFR 86.1340-90 - Exhaust sample analysis.

Code of Federal Regulations, 2010 CFR

2010-07-01

... may occur between the pre and post checks is not specified. However, the difference between pre... pre-analysis and post-analysis checks on any range used may exceed 3 percent for HC, or 2 percent for... Regulations for New Otto-Cycle and Diesel Heavy-Duty Engines; Gaseous and Particulate Exhaust Test Procedures...

40 CFR 86.1340-90 - Exhaust sample analysis.

Code of Federal Regulations, 2013 CFR

2013-07-01

... may occur between the pre and post checks is not specified. However, the difference between pre... pre-analysis and post-analysis checks on any range used may exceed 3 percent for HC, or 2 percent for... Regulations for New Otto-Cycle and Diesel Heavy-Duty Engines; Gaseous and Particulate Exhaust Test Procedures...

40 CFR 86.1340-90 - Exhaust sample analysis.

Code of Federal Regulations, 2012 CFR

2012-07-01

... may occur between the pre and post checks is not specified. However, the difference between pre... pre-analysis and post-analysis checks on any range used may exceed 3 percent for HC, or 2 percent for... Regulations for New Otto-Cycle and Diesel Heavy-Duty Engines; Gaseous and Particulate Exhaust Test Procedures...

40 CFR 86.1340-90 - Exhaust sample analysis.

Code of Federal Regulations, 2011 CFR

2011-07-01

... may occur between the pre and post checks is not specified. However, the difference between pre... pre-analysis and post-analysis checks on any range used may exceed 3 percent for HC, or 2 percent for... Regulations for New Otto-Cycle and Diesel Heavy-Duty Engines; Gaseous and Particulate Exhaust Test Procedures...

Assessing agreement with relative area under the coverage probability curve.

PubMed

Barnhart, Huiman X

2016-08-15

There has been substantial statistical literature in the last several decades on assessing agreement, and coverage probability approach was selected as a preferred index for assessing and improving measurement agreement in a core laboratory setting. With this approach, a satisfactory agreement is based on pre-specified high satisfactory coverage probability (e.g., 95%), given one pre-specified acceptable difference. In practice, we may want to have quality control on more than one pre-specified differences, or we may simply want to summarize the agreement based on differences up to a maximum acceptable difference. We propose to assess agreement via the coverage probability curve that provides a full spectrum of measurement error at various differences/disagreement. Relative area under the coverage probability curve is proposed for the summary of overall agreement, and this new summary index can be used for comparison of different intra-methods or inter-methods/labs/observers' agreement. Simulation studies and a blood pressure example are used for illustration of the methodology. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Comparison of direct colony method versus extraction method for identification of gram-positive cocci by use of Bruker Biotyper matrix-assisted laser desorption ionization-time of flight mass spectrometry.

PubMed

Alatoom, Adnan A; Cunningham, Scott A; Ihde, Sherry M; Mandrekar, Jayawant; Patel, Robin

2011-08-01

We evaluated Bruker Biotyper (version 2.0) matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) for the identification of 305 clinical isolates of staphylococci, streptococci, and related genera by comparing direct colony testing with preparatory extraction. Isolates were previously identified by use of phenotypic testing and/or 16S rRNA gene sequencing. Manufacturer-specified score cutoffs for genus- and species-level identification were used. After excluding 7 isolates not present in the Biotyper library, the Biotyper correctly identified 284 (95%) and 207 (69%) isolates to the genus and species levels, respectively, using extraction. By using direct colony testing, the Biotyper identified 168 (56%) and 60 (20%) isolates to the genus and species levels, respectively. Overall, more isolates were identified to the genus and species levels with preparatory extraction than with direct colony testing (P < 0.0001). The analysis was repeated after dividing the isolates into two subgroups, staphylococci, streptococci, and enterococci (n = 217) and "related genera" (n = 81). For the former subgroup, the extraction method resulted in the identification of 213 (98%) and 171 (79%) isolates to the genus and species levels, respectively, whereas the direct colony method identified 136 (63%) and 56 (26%) isolates to the genus and species levels, respectively. In contrast, for the subgroup of related genera, the extraction method identified 71 (88%) and 36 (44%) isolates to the genus and species levels, respectively, while the direct colony method identified 32 (40%) and 4 (5%) isolates to the genus and species levels, respectively. For both subgroups, preparatory extraction was superior to direct colony testing for the identification of isolates to the genus and species levels (P < 0.0001). Preparatory extraction is needed for the identification of a substantial proportion of Gram-positive cocci using the Biotyper method according to manufacturer-specified score cutoffs.

40 CFR 1065.530 - Emission test sequence.

Code of Federal Regulations, 2010 CFR

2010-07-01

... to verify that it remains within the pre-test temperature range as specified in § 1065.520(b): (1... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Emission test sequence. 1065.530... CONTROLS ENGINE-TESTING PROCEDURES Performing an Emission Test Over Specified Duty Cycles § 1065.530...

40 CFR 1065.530 - Emission test sequence.

Code of Federal Regulations, 2011 CFR

2011-07-01

... to verify that it remains within the pre-test temperature range as specified in § 1065.520(b): (1... 40 Protection of Environment 33 2011-07-01 2011-07-01 false Emission test sequence. 1065.530... CONTROLS ENGINE-TESTING PROCEDURES Performing an Emission Test Over Specified Duty Cycles § 1065.530...

Tallying Differences between Demographic Subgroups from Multiple Institutions: The Practical Utility of Nonparametric Analysis

ERIC Educational Resources Information Center

Yorke, Mantz

2017-01-01

When analysing course-level data by subgroups based upon some demographic characteristics, the numbers in analytical cells are often too small to allow inferences to be drawn that might help in the enhancement of practices. However, relatively simple analyses can provide useful pointers. This article draws upon a study involving a partnership with…

Identifying HIV care enrollees at-risk for cannabis use disorder.

PubMed

Hartzler, Bryan; Carlini, Beatriz H; Newville, Howard; Crane, Heidi M; Eron, Joseph J; Geng, Elvin H; Mathews, W Christopher; Mayer, Kenneth H; Moore, Richard D; Mugavero, Michael J; Napravnik, Sonia; Rodriguez, Benigno; Donovan, Dennis M

2017-07-01

Increased scientific attention given to cannabis in the United States has particular relevance for its domestic HIV care population, given that evidence exists for both cannabis as a therapeutic agent and cannabis use disorder (CUD) as a barrier to antiretroviral medication adherence. It is critical to identify relative risk for CUD among demographic subgroups of HIV patients, as this will inform detection and intervention efforts. A Center For AIDS Research Network of Integrated Clinical Systems cohort (N = 10,652) of HIV-positive adults linked to care at seven United State sites was examined for this purpose. Based on a patient-report instrument with validated diagnostic threshold for CUD, the prevalence of recent cannabis use and corresponding conditional probabilities for CUD were calculated for the aggregate sample and demographic subgroups. Generalized estimating equations then tested models directly examining patient demographic indices as predictors of CUD, while controlling for history and geography. Conditional probability of CUD among cannabis-using patients was 49%, with the highest conditional probabilities among demographic subgroups of young adults and those with non-specified sexual orientation (67-69%) and the lowest conditional probability among females and those 50+ years of age (42% apiece). Similarly, youthful age and male gender emerged as robust multivariate model predictors of CUD. In the context of increasingly lenient policies for use of cannabis as a therapeutic agent for chronic conditions like HIV/AIDS, current study findings offer needed direction in terms of specifying targeted patient groups in HIV care on whom resources for enhanced surveillance and intervention efforts will be most impactful.

A randomized clinical trial of the effectiveness of mechanical traction for sub-groups of patients with low back pain: study methods and rationale

PubMed Central

2010-01-01

Background Patients with signs of nerve root irritation represent a sub-group of those with low back pain who are at increased risk of persistent symptoms and progression to costly and invasive management strategies including surgery. A period of non-surgical management is recommended for most patients, but there is little evidence to guide non-surgical decision-making. We conducted a preliminary study examining the effectiveness of a treatment protocol of mechanical traction with extension-oriented activities for patients with low back pain and signs of nerve root irritation. The results suggested this approach may be effective, particularly in a more specific sub-group of patients. The aim of this study will be to examine the effectiveness of treatment that includes traction for patients with low back pain and signs of nerve root irritation, and within the pre-defined sub-group. Methods/Design The study will recruit 120 patients with low back pain and signs of nerve root irritation. Patients will be randomized to receive an extension-oriented treatment approach, with or without the addition of mechanical traction. Randomization will be stratified based on the presence of the pre-defined sub-grouping criteria. All patients will receive 12 physical therapy treatment sessions over 6 weeks. Follow-up assessments will occur after 6 weeks, 6 months, and 1 year. The primary outcome will be disability measured with a modified Oswestry questionnaire. Secondary outcomes will include self-reports of low back and leg pain intensity, quality of life, global rating of improvement, additional healthcare utilization, and work absence. Statistical analysis will be based on intention to treat principles and will use linear mixed model analysis to compare treatment groups, and examine the interaction between treatment and sub-grouping status. Discussion This trial will provide a methodologically rigorous evaluation of the effectiveness of using traction for patients with low back pain and signs of nerve root irritation, and will examine the validity of a pre-defined sub-grouping hypothesis. The results will provide evidence to inform non-surgical decision-making for these patients. Trial Registration This trial has been registered with http://ClinicalTrials.gov: NCT00942227 PMID:20433733

Therapeutic Effect of Captopril, Pentoxifylline, and Cordyceps Sinensis in Pre-Hepatic Portal Hypertensive Rats

PubMed Central

Ahmed, Ahmed F.; El-Maraghy, Nabila N.; Ghaney, Rasha H. Abdel; Elshazly, Shimaa M.

2012-01-01

Background/Aim: Portal hypertension is an important and potentially fatal complication of liver disease whereby cellular and fibrotic alterations manifest to increase portal venous pressure. The aim of this study is to investigate the effect of captopril, pentoxifylline (PTX), and cordyceps sinensis in pre-hepatic portal hypertensive rats. Settings and Design: Wister male rats were divided at random into 3 main groups: the first group: control rats. The second group: sham-operated rats and the third group: prehepatic portal hypertensive rats (PHPHT) induced by regulated pre-hepatic portal vein ligation. After 14 days, Group 3 was subdivided into 5 subgroups. Subgroup (1): portal vein-ligated (PVL) was killed at once; Subgroup (2): received distilled water for 30 days (untreated PVL group); subgroups 3-5 were treated with captopril (60 mg/kg, orally); PTX (100 mg/kg, orally); and C. sinensis (200 mg/kg, orally), respectively, as a single daily dose for 30 days. Patients and Methods: Portal pressure, nitric oxide (NO), antioxidant enzymes, Liver enzymes, and creatinine levels were measured to evaluate the status of the liver state. Results: Portal vein ligation produced significant increments in liver enzymes, NO, creatinine and portal pressure concomitant with significant decrements in glutathione content and superoxide dismutase activity. Treatment with captopril, PTX, and C. sinensis resulted in a significant reduction in liver enzymes, NO, creatinine and portal pressure and observable increase in antioxidant enzymes. Conclusions: captopril, PTX, and C. sinensis have promising effect in controlling PHPHT and reducing hyperdynamic circulatory state through reduction of portal pressure and NO level. PMID:22626797

Exercise hemodynamics in Parkinson's disease and autonomic dysfunction.

PubMed

Low, David A; Vichayanrat, Ekawat; Iodice, Valeria; Mathias, Christopher J

2014-05-01

To clarify the characteristics of hemodynamic responses to exercise and orthostasis in Parkinson's disease patients, especially those with autonomic failure. Clinical audit of supine cycling exercise test data (with active standing tests pre- and post-exercise) of Parkinson's patients with autonomic dysfunction. 23 patients (71 ± 7 yr, 7 females) with a confirmed diagnosis of Parkinson's were identified. Group mean systolic blood pressure (SBP) fell during pre-exercise standing (-39 ± 29 mmHg, P < 0.001, 17 patients had orthostatic hypotension (OH)), while heart rate (HR) increased (+13 ± 7 beats min(-1), P < 0.001). SBP (P < 0.001) increased during exercise with a wide variation in responses. SBP increased in 13 patients (INC; +30 ± 14 mmHg) and either did not change or decreased in 10 patients (DEC -12 ± 11 mmHg, P < 0.001 vs INC). The increase in HR was not different between sub-groups (30 ± 12 vs 25 ± 10 beats min(-1), INC vs. DEC, P = 0.29). The size of the pre-exercise stand SBP reduction was greater in DEC vs INC (-64 ± 23 (10 out of 10 had OH) vs -19 ± 16 mmHg (7 out of 13 had OH), respectively, P < 0.001). The HR elevation was not different between sub-groups (13 ± 8 vs 13 ± 4 beats min(-1), DEC vs INC, P = 0.94). Post-exercise SBP/DBP were lower for both sub-groups compared to pre-exercise and the standing SBP reduction post-exercise was not greater relative to pre-exercise in either sub-group. Exercise-induced hypotension can occur in Parkinson's disease patients with autonomic failure with the magnitude of the exercise response being related to the severity of autonomic dysfunction. Exercise does not appear to worsen OH in this sample of Parkinson's patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

A randomized intervention trial of 24-wk dairy consumption on waist circumference, blood pressure, and fasting blood sugar and lipids in Japanese men with metabolic syndrome.

PubMed

Tanaka, Shiro; Uenishi, Kazuhiro; Ishida, Hiromi; Takami, Yasuhiro; Hosoi, Takayuki; Kadowaki, Takashi; Orimo, Hajime; Ohashi, Yasuo

2014-01-01

Dairy foods are postulated to have beneficial effects on blood pressure, body fat, serum lipids, and the incidence of type 2 diabetes. To evaluate the effects of the consumption of milk and dairy products, we performed a randomized dietary intervention trial for 24 wk in Japanese men, aged 20 to 60 y, with 2 or more components of the metabolic syndrome ( UMIN000006353). Subjects were randomized to a control group (n=98) that received dietary intervention focused on weight control supervised by registered dietitians, and a dairy-consumption group (n=102) that received both dietary intervention and regular home dairy delivery of 400 g/d for 24 wk. Co-primary endpoints included waist circumference, blood pressure, fasting blood sugar (FBS), and serum lipids. The dietary intervention decreased energy intake from 2,150 to 1,850 kcal/d in both groups (p<0.01). Mean rates of compliance with the dairy-consumption intervention were over 90%, resulting in increased calcium intake in the dairy-consumption group from 329 to 667 mg/d (p<0.01). Co-primary endpoints improved in both groups, but the degree of improvement was smaller in the dairy-consumption group (one-sided p=0.99). Subgroup analyses specified in the study protocol identified weight and leisure-time physical activity (LTPA) as significant effect modifiers. Differences in changes in systolic blood pressure compared with the control group were 28.0 mmHg (95% CI, 214.0 to 21.9, interaction; p<0.01) in the normal weight group and 25.8 mmHg (211.4 to 20.2, interaction; p=0.02) in the moderate-to-high LTPA group, indicating lower systolic blood pressure in the dairy-consumption group among participants in these subgroups. In conclusion, although effects on the co-primary endpoints of dairy consumption were not shown, dairy consumption lowered systolic blood pressure in the subgroups with normal weight and moderate-to-high LTPA and lowered FBS in the subgroup with normal weight.

[Worrying behaviour in pre-school children aged three to seven years: a factor analysis of the results of a questionnaire].

PubMed

Pilecki, Maciej Wojciech; Kowal, Małgorzata; Woronkowicz, Agnieszka; Sobiecki, Jan; Kryst, Łukasz; Kamińska-Reyman, Jadwiga

2014-01-01

The aims of the study were: 1) the assessment of the interaction between the factors specified for behavioural problems observed in pre-school children based on a factor analysis and 2) the assessment of the relationship the specified factors have with the age and gender of the study group. A factor analysis based on a Principal Component Analysis of the main results of a Disturbing Behaviour Questionnaire (DBQ) completed by pre-school teachers, which includes categories of behaviour observed among pre-school age children that provoke the greatest concern among parents, guardians and educators. Nine-hundred and sixty-one children aged from 2.7 to 7.9 years (mean: 5.4; SD 1.13) from randomly chosen pre-schools in all districts of Krak6w. Based on a screen plot, as well as on a substantive analysis of the results, a decision was taken to employ a four-factor analysis (Lagging behind, Excessive behaviour, Eating-avoidance and Overeating) explaining 68% of the common factor variance. A very high Cronbach's alpha value was returned for the reliability of the individual scales. The conducted analysis of the relationship of the scales with age and gender indicated a greater intensity of disturbing behaviour in boys for the Lagging behind factor, the Excessive behaviour factor and the overall scale for the Disturbing Behaviour Questionnaire (DBQ). These were the scales, along with the Eating-avoidance scale, that were found to be related to age. A greater intensity of disturbing behaviour was found to occur in the younger children. The relationship between the Overeating and Excessive behaviour scales that was found among girls but not among boys indicated that--even at such a young age--the characteristics associated with eating in the context of gender were already present. The authors consider that the coherence of the results obtained and their consistency with other studies ofpre-school age children provide a sound platform for further analyses using the questionnaire described above.

A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation.

PubMed

Abraham, William T; Kuck, Karl-Heinz; Goldsmith, Rochelle L; Lindenfeld, JoAnn; Reddy, Vivek Y; Carson, Peter E; Mann, Douglas L; Saville, Benjamin; Parise, Helen; Chan, Rodrigo; Wiegn, Phi; Hastings, Jeffrey L; Kaplan, Andrew J; Edelmann, Frank; Luthje, Lars; Kahwash, Rami; Tomassoni, Gery F; Gutterman, David D; Stagg, Angela; Burkhoff, Daniel; Hasenfuß, Gerd

2018-05-05

The authors sought to confirm a subgroup analysis of the prior FIX-HF-5 (Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure) study showing that cardiac contractility modulation (CCM) improved exercise tolerance (ET) and quality of life in patients with ejection fractions between 25% and 45%. CCM therapy for New York Heart Association (NYHA) functional class III and IV heart failure (HF) patients consists of nonexcitatory electrical signals delivered to the heart during the absolute refractory period. A total of 160 patients with NYHA functional class III or IV symptoms, QRS duration <130 ms, and ejection fraction ≥25% and ≤45% were randomized to continued medical therapy (control, n = 86) or CCM (treatment, n = 74, unblinded) for 24 weeks. Peak VO 2 (primary endpoint), Minnesota Living With Heart Failure questionnaire, NYHA functional class, and 6-min hall walk were measured at baseline and at 12 and 24 weeks. Bayesian repeated measures linear modeling was used for the primary endpoint analysis with 30% borrowing from the FIX-HF-5 subgroup. Safety was assessed by the percentage of patients free of device-related adverse events with a pre-specified lower bound of 70%. The difference in peak VO 2 between groups was 0.84 (95% Bayesian credible interval: 0.123 to 1.552) ml O 2 /kg/min, satisfying the primary endpoint. Minnesota Living With Heart Failure questionnaire (p < 0.001), NYHA functional class (p < 0.001), and 6-min hall walk (p = 0.02) were all better in the treatment versus control group. There were 7 device-related events, yielding a lower bound of 80% of patients free of events, satisfying the primary safety endpoint. The composite of cardiovascular death and HF hospitalizations was reduced from 10.8% to 2.9% (p = 0.048). CCM is safe, improves exercise tolerance and quality of life in the specified group of HF patients, and leads to fewer HF hospitalizations. (Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure; NCT01381172). Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Childhood maltreatment and pre-pregnancy obesity: a comparison of obese, overweight, and normal weight pregnant women.

PubMed

Nagl, Michaela; Steinig, Jana; Klinitzke, Grit; Stepan, Holger; Kersting, Anette

2016-04-01

Pre-pregnancy overweight and obesity is associated with poor health outcomes for the mother and the child. General population studies suggest that childhood maltreatment is associated with obesity in adulthood. The aim of our study was to examine the association between pre-pregnancy overweight and obesity and a history of childhood abuse or neglect including different stages of severity of abuse and neglect. Three hundred twenty-six normal weight, overweight, or obese pregnant women reported demographic data, height and weight, and general psychological distress at 18-22 weeks of gestation. Childhood maltreatment was assessed using the Childhood Trauma Questionnaire. Associations were examined using logistic regression analyses and a reference group of normal weight women. Fifty percent reported a history of abuse or neglect. After adjusting for age, education, income, marital status, and the number of previous children, pre-pregnancy overweight and obesity were strongly associated with severe physical abuse (overweight: OR = 8.33, 95% CI 1.48-47.03; obesity: OR = 6.31, 95% CI 1.06-37.60). Women with severe physical neglect (OR = 4.25, 95% CI 1.23-14.74) were at increased risk of pregnancy overweight. We found a dose-response relationship between physical abuse and pre-pregnancy overweight and obesity. Whereas other studies report an association between childhood maltreatment and pre-pregnancy obesity, this is the first study that found an association between childhood maltreatment and pre-pregnancy overweight. Considering the severe health risks of pre-pregnancy overweight and obesity and the long-term consequences of childhood maltreatment, affected women constitute a subgroup with special needs in prenatal care. Further research is needed to improve the understanding of the underlying mechanisms.

A chance-constrained stochastic approach to intermodal container routing problems.

PubMed

Zhao, Yi; Liu, Ronghui; Zhang, Xi; Whiteing, Anthony

2018-01-01

We consider a container routing problem with stochastic time variables in a sea-rail intermodal transportation system. The problem is formulated as a binary integer chance-constrained programming model including stochastic travel times and stochastic transfer time, with the objective of minimising the expected total cost. Two chance constraints are proposed to ensure that the container service satisfies ship fulfilment and cargo on-time delivery with pre-specified probabilities. A hybrid heuristic algorithm is employed to solve the binary integer chance-constrained programming model. Two case studies are conducted to demonstrate the feasibility of the proposed model and to analyse the impact of stochastic variables and chance-constraints on the optimal solution and total cost.

A chance-constrained stochastic approach to intermodal container routing problems

PubMed Central

Zhao, Yi; Zhang, Xi; Whiteing, Anthony

2018-01-01

We consider a container routing problem with stochastic time variables in a sea-rail intermodal transportation system. The problem is formulated as a binary integer chance-constrained programming model including stochastic travel times and stochastic transfer time, with the objective of minimising the expected total cost. Two chance constraints are proposed to ensure that the container service satisfies ship fulfilment and cargo on-time delivery with pre-specified probabilities. A hybrid heuristic algorithm is employed to solve the binary integer chance-constrained programming model. Two case studies are conducted to demonstrate the feasibility of the proposed model and to analyse the impact of stochastic variables and chance-constraints on the optimal solution and total cost. PMID:29438389

Experimental Investigations on Subsequent Yield Surface of Pure Copper by Single-Sample and Multi-Sample Methods under Various Pre-Deformation.

PubMed

Liu, Gui-Long; Huang, Shi-Hong; Shi, Che-Si; Zeng, Bin; Zhang, Ke-Shi; Zhong, Xian-Ci

2018-02-10

Using copper thin-walled tubular specimens, the subsequent yield surfaces under pre-tension, pre-torsion and pre-combined tension-torsion are measured, where the single-sample and multi-sample methods are applied respectively to determine the yield stresses at specified offset strain. The rule and characteristics of the evolution of the subsequent yield surface are investigated. Under the conditions of different pre-strains, the influence of test point number, test sequence and specified offset strain on the measurement of subsequent yield surface and the concave phenomenon for measured yield surface are studied. Moreover, the feasibility and validity of the two methods are compared. The main conclusions are drawn as follows: (1) For the single or multi-sample method, the measured subsequent yield surfaces are remarkably different from cylindrical yield surfaces proposed by the classical plasticity theory; (2) there are apparent differences between the test results from the two kinds of methods: the multi-sample method is not influenced by the number of test points, test order and the cumulative effect of residual plastic strain resulting from the other test point, while those are very influential in the single-sample method; and (3) the measured subsequent yield surface may appear concave, which can be transformed to convex for single-sample method by changing the test sequence. However, for the multiple-sample method, the concave phenomenon will disappear when a larger offset strain is specified.

One year clinical outcomes in patients with insulin-treated diabetes mellitus and non-insulin-treated diabetes mellitus compared to non-diabetics after deployment of the bio-engineered COMBO stent.

PubMed

Kalkman, Deborah N; Woudstra, Pier; den Heijer, Peter; Menown, Ian B A; Erglis, Andrejs; Suryapranata, Harry; Arkenbout, Karin E; Iñiguez, Andrés; van 't Hof, Arnoud W J; Muller, Philippe; Tijssen, Jan G; de Winter, Robbert J

2017-01-01

The COMBO stent is a novel sirolimus-eluting stent with a luminal anti-CD34+ antibody layer to promote vessel healing. No data is currently available on clinical outcomes after treatment with this novel bio-engineered device in diabetic patients. We evaluate clinical outcomes at twelve months after COMBO stent placement in patients without diabetes mellitus (non-DM), patients with non-insulin-treated diabetes mellitus (nITDM) and patients with insulin-treated diabetes mellitus (ITDM). This study is a pre-specified subgroup analysis of the 1000 patient all-comers REMEDEE Registry. The primary endpoint is target lesion failure (TLF), which is a combined endpoint consisting of cardiac death, target vessel-myocardial infarction (tv-MI) and target lesion revascularization (TLR) at twelve months follow-up. Kaplan Meier method is used with log rank to compare outcomes between groups. This subgroup analysis includes 807 non-DM, 117 nITDM and 67 ITDM. Kaplan-Meier estimates for TLF at twelve months are 4.4% in non-DM, 6.8% in nITDM and 20.3% in ITDM, p<0.001 (non-DM vs nITDM p=0.244, non-DM vs ITDM p<0.001). This study gives the first insight into the impact of insulin-treated diabetes mellitus on clinical outcome of patients treated with the novel COMBO stent. At one year after COMBO stent placement significantly higher rates of target lesion failure are seen in patients with ITDM compared to patients with nITDM and patients without DM. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

New Medications for Heart Failure

PubMed Central

Gordin, Jonathan S.; Fonarow, Gregg C.

2016-01-01

Heart failure is common and results in substantial morbidity and mortality. Current guideline-based therapies for heart failure with reduced ejection fraction, including beta-blockers, angiotensin converting enzyme (ACE) inhibitors, and aldosterone antagonists aim to interrupt deleterious neurohormonal pathways and have shown significant success in reducing morbidity and mortality associated with heart failure. Continued efforts to further improve outcomes in patients with heart failure with reduced ejection fraction have led to the first new-in-class medications approved for heart failure since 2005, ivabradine and sacubitril/valsartan. Ivabradine targets the If channels in the sinoatrial node of the heart, decreasing heart rate. Sacubitril/valsartan combines a neprilysin inhibitor that increases levels of beneficial vasodilatory peptides with an angiotensin receptor antagonist. On a background of previously approved, guideline-directed medical therapies for heart failure, these medications have shown improved clinical outcomes ranging from decreased hospitalizations in a select group of patients to a reduction in all-cause mortality across all pre-specified subgroups. In this review, we will discuss the previously established guideline-directed medical therapies for heart failure with reduced ejection fraction, the translational research that led to the development of these new therapies, and the results from the major clinical trials of ivabradine and sacubitril/valsartan. PMID:27038558

Agreement Between Deoxyribonucleic Acid Base Composition and Taxometric Classification of Gram-Positive Cocci1

PubMed Central

Silvestri, L. G.; Hill, L. R.

1965-01-01

Silvestri, L. G. (Università Statale, Milan, Italy), and L. R. Hill. Agreement between deoxyribonucleic acid base composition and taxometric classification of gram-positive cocci. J. Bacteriol. 90:136–140. 1965.—It had been previously proposed, from taxometric analyses, that gram-positive, catalase-positive cocci be divided into two subgroups. Thirteen strains, representative of both subgroups, were examined for deoxyribonucleic acid (DNA) base composition, determined from melting temperatures. Per cent GC (guanine + cytosine/total bases) values fell into two groups: 30.8 to 36.5% GC and 69 to 75% GC. Strains with low per cent GC values belonged to the Staphylococcus aureus–S. saprophyticus–S. lactis taxometric subgroups, and those with high per cent GC values belonged to the S. roseus–S. afermentans subgroup. The hypothetical nature of any classification is emphasized, and, in the present work, the hypothesis derived from taxometric analyses of division into two subgroups is confirmed by the study of DNA base ratios. The two subgroups correspond, respectively, to the genera Staphylococcus and Micrococcus. PMID:16562008

An approach to trial design and analysis in the era of non-proportional hazards of the treatment effect.

PubMed

Royston, Patrick; Parmar, Mahesh K B

2014-08-07

Most randomized controlled trials with a time-to-event outcome are designed and analysed under the proportional hazards assumption, with a target hazard ratio for the treatment effect in mind. However, the hazards may be non-proportional. We address how to design a trial under such conditions, and how to analyse the results. We propose to extend the usual approach, a logrank test, to also include the Grambsch-Therneau test of proportional hazards. We test the resulting composite null hypothesis using a joint test for the hazard ratio and for time-dependent behaviour of the hazard ratio. We compute the power and sample size for the logrank test under proportional hazards, and from that we compute the power of the joint test. For the estimation of relevant quantities from the trial data, various models could be used; we advocate adopting a pre-specified flexible parametric survival model that supports time-dependent behaviour of the hazard ratio. We present the mathematics for calculating the power and sample size for the joint test. We illustrate the methodology in real data from two randomized trials, one in ovarian cancer and the other in treating cellulitis. We show selected estimates and their uncertainty derived from the advocated flexible parametric model. We demonstrate in a small simulation study that when a treatment effect either increases or decreases over time, the joint test can outperform the logrank test in the presence of both patterns of non-proportional hazards. Those designing and analysing trials in the era of non-proportional hazards need to acknowledge that a more complex type of treatment effect is becoming more common. Our method for the design of the trial retains the tools familiar in the standard methodology based on the logrank test, and extends it to incorporate a joint test of the null hypothesis with power against non-proportional hazards. For the analysis of trial data, we propose the use of a pre-specified flexible parametric model that can represent a time-dependent hazard ratio if one is present.

The effect of N-acetylcysteine on the incidence of contrast-induced kidney injury: A systematic review and trial sequential analysis.

PubMed

Wang, Nelson; Qian, Pierre; Kumar, Shejil; Yan, Tristan D; Phan, Kevin

2016-04-15

There have been a myriad of studies investigating the effectiveness of N-acetylcysteine (NAC) in the prevention of contrast induced nephropathy (CIN) in patients undergoing coronary angiography (CAG) with or without percutaneous coronary intervention (PCI). However the consensus is still out about the effectiveness of NAC pre-treatment due to vastly mixed results amongst the literature. The aim of this study was to conduct a meta-analysis and trial sequential analysis to determine the effects of pre-operative NAC in lowering the incidence of CIN in patients undergoing CAG and/or PCI. A systematic literature search was performed to include all randomized controlled trials (RCTs) comparing NAC versus control as pretreatment for CAG and/or PCI. A traditional meta-analysis and several subgroup analyses were conducted using traditional meta-analysis with relative risk (RR), trial sequential analysis, and meta-regression analysis. 43 RCTs met our inclusion criteria giving a total of 3277 patients in both control and treatment arms. There was a significant reduction in the risk of CIN in the NAC treated group compared to control (OR 0.666; 95% CI, 0.532-0.834; I2=40.11%; p=0.004). Trial sequential analysis, using a relative risk reduction threshold of 15%, indicates that the evidence is firm. The results of the present paper support the use of NAC in the prevention of CIN in patients undergoing CAG±PCI. Future studies should focus on the benefits of NAC amongst subgroups of high-risk patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Thinking through postoperative cognitive dysfunction: How to bridge the gap between clinical and pre-clinical perspectives.

PubMed

Hovens, Iris B; Schoemaker, Regien G; van der Zee, Eddy A; Heineman, Erik; Izaks, Gerbrand J; van Leeuwen, Barbara L

2012-10-01

Following surgery, patients may experience cognitive decline, which can seriously reduce quality of life. This postoperative cognitive dysfunction (POCD) is mainly seen in the elderly and is thought to be mediated by surgery-induced inflammatory reactions. Clinical studies tend to define POCD as a persisting, generalised decline in cognition, without specifying which cognitive functions are impaired. Pre-clinical research mainly describes early hippocampal dysfunction as a consequence of surgery-induced neuroinflammation. These different approaches to study POCD impede translation between clinical and pre-clinical research outcomes and may hamper the development of appropriate interventions. This article analyses which cognitive domains deteriorate after surgery and which brain areas might be involved. The most important outcomes are: (1) POCD encompasses a wide range of cognitive impairments; (2) POCD affects larger areas of the brain; and (3) individual variation in the vulnerability of neuronal networks to neuroinflammatory mechanisms may determine if and how POCD manifests itself. We argue that, for pre-clinical and clinical research of POCD to advance, the effects of surgery on various cognitive functions and brain areas should be studied. Moreover, in addition to general characteristics, research should take inter-relationships between cognitive complaints and physical and mental characteristics into account. Copyright © 2012 Elsevier Inc. All rights reserved.

Wide differences in mode of delivery within Europe: risk-stratified analyses of aggregated routine data from the Euro-Peristat study.

PubMed

Macfarlane, A J; Blondel, B; Mohangoo, A D; Cuttini, M; Nijhuis, J; Novak, Z; Ólafsdóttir, H S; Zeitlin, J

2016-03-01

To use data from routine sources to compare rates of obstetric intervention in Europe both overall and for subgroups at higher risk of intervention. Retrospective analysis of aggregated routine data. Thirty-one European countries or regions contributing data on mode of delivery to the Euro-Peristat project. Births in participating countries in 2010. Countries provided aggregated data about overall rates of obstetric intervention and about caesarean section rates for specified subgroups. Mode of delivery. Rates of caesarean section ranged from 14.8% to 52.2% of all births and rates of instrumental vaginal delivery ranged from 0.5% to 16.4%. Overall, there was no association between rates of instrumental vaginal delivery and rates of caesarean section, but similarities were observed between some countries that are geographically close and may share common traditions of practice. Associations were observed between caesarean section rates for women with breech and vertex births and with singleton and multiple births but patterns of association for women who had and had not had previous caesarean sections were more complex. The persisting wide variations in caesarean section and instrumental vaginal delivery rates point to a lack of consensus about practice and raise questions for further investigation. Further research is needed to explore the impact of differences in clinical guidelines, healthcare systems and their financing and parents' and professionals' attitudes to care at delivery. © 2015 Royal College of Obstetricians and Gynaecologists.

16 CFR 702.1 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

...-MOSS WARRANTY ACT PRE-SALE AVAILABILITY OF WRITTEN WARRANTY TERMS § 702.1 Definitions. (a) The Act... connection with the sale of a consumer product by a supplier to a buyer which relates to the nature of the... meet a specified level of performance over a specified period of time, or (2) Any undertaking in...

78 FR 47282 - Takes of Marine Mammals Incidental to Specified Activities; Navy Research, Development, Test and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-05

... Director. Post-mission surveys will be conducted from the surface vessel(s) and aircraft used for pre-test... post-test events. Systematic monitoring of the affected area for marine mammals will be conducted prior... Marine Mammals Incidental to Specified Activities; Navy Research, Development, Test and Evaluation...

ARS-Media: A spreadsheet tool for calculating media recipes based on ion-specific constraints

USDA-ARS?s Scientific Manuscript database

ARS-Media is an ion solution calculator that uses Microsoft Excel to generate recipes of salts for complex ion mixtures specified by the user. Generating salt combinations (recipes) that result in pre-specified target ion values is a linear programming problem. Thus, the recipes are generated using ...

Breastfeeding promotion, support and protection: review of six country programmes.

PubMed

Mangasaryan, Nune; Martin, Luann; Brownlee, Ann; Ogunlade, Adebayo; Rudert, Christiane; Cai, Xiaodong

2012-08-01

Reviews of programmes in Bangladesh, Benin, the Philippines, Sri Lanka, Uganda, and Uzbekistan sought to identify health policy and programmatic factors that influenced breastfeeding practices during a 10 to 15 year period. Exclusive breastfeeding rates and trends were analysed in six countries in general and from an equity perspective in two of them. Success factors and challenges were identified in countries with improved and stagnated rates respectively. The disaggregated data analysis showed that progress may be unequal in population subgroups, but if appropriately designed and implemented, a programme can become a "health equalizer" and eliminate discrepancies among different subgroups. Success requires commitment, supportive policies, and comprehensiveness of programmes for breastfeeding promotion, protection and support. Community-based promotion and support was identified as a particularly important component. Although health workers' training on infant feeding support and counselling was prioritized, further improvement of interpersonal counselling and problem solving skills is needed. More attention is advised for pre-service education, including a stronger focus on clinical practice, to ensure knowledge and skills among all health workers. Large-scale communication activities played a significant role, but essential steps were often underemphasized, including identifying social norms and influencing factors, ensuring community participation, and testing of approaches and messages.

Overview of Reviews The prevention of eczema in infants and children: an overview of Cochrane and non-Cochrane reviews

PubMed Central

Foisy, Michelle; Boyle, Robert J.; Chalmers, Joanne R.; Simpson, Eric L.; Williams, Hywel C.

2012-01-01

Background Eczema is the most common inflammatory skin disease of childhood, characterized by an itchy red rash that usually involves the face and skin folds. There is currently no curative treatment for eczema, so the reduction of eczema incidence through disease prevention is a desirable goal. Potential interventions for preventing eczema include exclusive breastfeeding, hydrolysed protein formulas and soy formulas when bottle feeding, maternal antigen avoidance, omega oil supplementation, prebiotics and probiotics. Objectives This overview of reviews aims to present the current body of data from Cochrane and non-Cochrane reviews to provide the most up-to-date evidence on the efficacy and safety of interventions to prevent eczema in infants and children at different risk levels for developing allergic disease. Methods Our pool of Cochrane and non-Cochrane reviews came from the 2010 United Kingdom National Health Service (NHS) Evidence Skin Disorders Annual Evidence Updates Mapping Exercise on Atopic Eczema. This group used a comprehensive search strategy last conducted in August 2010 to identify all systematic reviews on eczema prevention. We identified all reviews that met our pre-specified inclusion criteria, and data were extracted, analysed, compiled into tables and synthesized using quantitative and qualitative methods. Main results Seven systematic reviews containing 39 relevant trials with 11 897 participants were included in this overview. Overall, there was no clear evidence that any of the main interventions reviewed reduced eczema incidence. In subgroup analyses of infants at high risk of allergic disease, an observational study found that exclusive breastfeeding for at least six months compared with introduction of solids at three to six months decreased the incidence of eczema by 60% (risk ratio (RR): 0.40; 95% confidence interval (CI): 0.21, 0.78), and a randomized controlled trial found that prebiotics compared with no prebiotics decreased incidence by 58% (RR: 0.42; 95% CI: 0.21, 0.84). However, each of these findings was based on the results of a single small trial, and no intervention reduced eczema incidence beyond the first two years of life. Although we pre-specified incidence of atopic eczema (i.e. eczema associated with immunoglobulin E (IgE) sensitization) as a primary outcome, data on whether participants diagnosed with eczema were truly atopic were largely lacking from systematic reviews. Similarly, data on atopy, measured using skin prick tests or specific IgE tests to allergens, were not reported in many reviews. No interventions were found to decrease atopy when reported. Adverse events data were generally lacking, but data from a trial of probiotics versus no probiotics showed significantly more spitting up in the first one (RR: 1.88; 95% CI: 1.03, 3.45) and two (RR: 1.69; 95% CI: 1.02, 2.80) months of life, but no overall increase in risk of gastrointestinal symptoms in the first year. Authors’ conclusions Although there is currently no clear evidence showing that any of the interventions examined in this overview prevent eczema in participants not selected for risk of allergic disease, there is some evidence that exclusive breastfeeding for at least six months and prebiotics might reduce eczema incidence in high-risk participants. However, these conclusions are based on limited evidence with methodological shortcomings. Future research on prevention of eczema is needed and should examine different types of hydrolysed formulas, prebiotics and probiotics, as well as enhancement of the skin barrier and other novel approaches in infants at different risk levels for developing allergic disease. PMID:22822349

Methods used and lessons learnt in conducting document reviews of medical and allied health curricula - a key step in curriculum evaluation.

PubMed

Rohwer, Anke; Schoonees, Anel; Young, Taryn

2014-11-02

This paper describes the process, our experience and the lessons learnt in doing document reviews of health science curricula. Since we could not find relevant literature to guide us on how to approach these reviews, we feel that sharing our experience would benefit researchers embarking on similar projects. We followed a rigorous, transparent, pre-specified approach that included the preparation of a protocol, a pre-piloted data extraction form and coding schedule. Data were extracted, analysed and synthesised. Quality checks were included at all stages of the process. The main lessons we learnt related to time and project management, continuous quality assurance, selecting the software that meets the needs of the project, involving experts as needed and disseminating the findings to relevant stakeholders. A complete curriculum evaluation comprises, apart from a document review, interviews with students and lecturers to assess the learnt and taught curricula respectively. Rigorous methods must be used to ensure an objective assessment.

Maternal dental caries and pre-term birth: results from the EPIPAP study.

PubMed

Vergnes, Jean-Noel; Kaminski, Monique; Lelong, Nathalie; Musset, Anne-Marie; Sixou, Michel; Nabet, Cathy

2011-07-01

OBJECTIVE. The aim of this study was to analyse the association between maternal dental caries and pre-term birth (PTB), with a particular focus on the infection-suspected causes of pre-term births. MATERIALS AND METHODS. A secondary analysis was performed on data from the EPIPAP study, a French multi-centre case-control study. Cases were 1107 women giving birth to a singleton live-born infant before 37 weeks of gestation and controls were 1094 women delivering at 37 weeks or more. A sub-group of cases was defined as women with spontaneous labour and/or pre-term premature rupture of membranes (PPROM, n = 620). A full-mouth dental examination was performed after delivery. The main factor of interest was the presence of decay on at least one tooth. RESULTS. Crude associations between presence of tooth decay and PTB or spontaneous PTB/PPROM were significant (OR = 1.21 [1.01-1.45] and OR = 1.25 [1.01-1.55], respectively). After adjustment for two sets of potential confounders (four pre-term birth risk factors and four social characteristics), for periodontitis status and for inter-examiner variability, tooth decay was not significantly associated with either PTB or spontaneous PTB/PPROM (aOR = 1.10 [0.91-1.32] and aOR = 1.14 [0.91-1.42], respectively). CONCLUSIONS. This study failed to demonstrate a significant association between tooth decay and pre-term birth. However, future well-designed studies are needed to further assess the link between dental caries and adverse pregnancy outcomes.

Impact of age, sex, therapeutic intent, race and severity of advanced heart failure on short-term principal outcomes in the MOMENTUM 3 trial.

PubMed

Goldstein, Daniel J; Mehra, Mandeep R; Naka, Yoshifumi; Salerno, Christopher; Uriel, Nir; Dean, David; Itoh, Akinobu; Pagani, Francis D; Skipper, Eric R; Bhat, Geetha; Raval, Nirav; Bruckner, Brian A; Estep, Jerry D; Cogswell, Rebecca; Milano, Carmelo; Fendelander, Lahn; O'Connell, John B; Cleveland, Joseph

2018-01-01

Primary outcomes analysis of the Multicenter Study of MagLev Technology in Patients Undergoing MCS Therapy With HeartMate 3 (MOMENTUM 3) trial short-term cohort demonstrated a higher survival rate free of debilitating stroke and reoperation to replace/remove the device (primary end-point) in patients receiving the HeartMate 3 (HM3) compared with the HeartMate (HMII). In this study we sought to evaluate the individual and interactive effects of pre-specified patient subgroups (age, sex, race, therapeutic intent [bridge to transplant/bridge to candidacy/destination therapy] and severity of illness) on primary end-point outcomes in MOMENTUM 3 patients implanted with HM3 and HMII devices. Cox proportional hazard models were used to analyze patients enrolled in the "as-treated cohort" (n = 289) of the MOMENTUM 3 trial to: (1) determine interaction of various subgroups on primary end-point outcomes; and (2) identify independent variables associated with primary end-point success. Baseline characteristics were well balanced among HM3 (n = 151) and HMII (n = 138) cohorts. No significant interaction between the sub-groups on primary end-point outcomes was observed. Cox multivariable modeling identified age (≤65 years vs >65 years, hazard ratio 0.42 [95% confidence interval 0.22 to 0.78], p = 0.006]) and pump type (HM3 vs HMII, hazard ratio 0.53 [95% confidence interval 0.30 to 0.96], p = 0.034) to be independent predictors of primary outcomes success. After adjusting for age, no significant impact of sex, race, therapeutic intent and INTERMACS profiles on primary outcomes were observed. This analysis of MOMENTUM 3 suggests that younger age (≤65 years) at implant and pump choice are associated with a greater likelihood of primary end-point success. These findings further suggest that characterization of therapeutic intent into discrete bridge-to-transplant and destination therapy categories offers no clear clinical advantage, and should ideally be abandoned. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Sample heterogeneity in unipolar depression as assessed by functional connectivity analyses is dominated by general disease effects.

PubMed

Feder, Stephan; Sundermann, Benedikt; Wersching, Heike; Teuber, Anja; Kugel, Harald; Teismann, Henning; Heindel, Walter; Berger, Klaus; Pfleiderer, Bettina

2017-11-01

Combinations of resting-state fMRI and machine-learning techniques are increasingly employed to develop diagnostic models for mental disorders. However, little is known about the neurobiological heterogeneity of depression and diagnostic machine learning has mainly been tested in homogeneous samples. Our main objective was to explore the inherent structure of a diverse unipolar depression sample. The secondary objective was to assess, if such information can improve diagnostic classification. We analyzed data from 360 patients with unipolar depression and 360 non-depressed population controls, who were subdivided into two independent subsets. Cluster analyses (unsupervised learning) of functional connectivity were used to generate hypotheses about potential patient subgroups from the first subset. The relationship of clusters with demographical and clinical measures was assessed. Subsequently, diagnostic classifiers (supervised learning), which incorporated information about these putative depression subgroups, were trained. Exploratory cluster analyses revealed two weakly separable subgroups of depressed patients. These subgroups differed in the average duration of depression and in the proportion of patients with concurrently severe depression and anxiety symptoms. The diagnostic classification models performed at chance level. It remains unresolved, if subgroups represent distinct biological subtypes, variability of continuous clinical variables or in part an overfitting of sparsely structured data. Functional connectivity in unipolar depression is associated with general disease effects. Cluster analyses provide hypotheses about potential depression subtypes. Diagnostic models did not benefit from this additional information regarding heterogeneity. Copyright © 2017 Elsevier B.V. All rights reserved.

Combining value of information analysis and ethical argumentation in decisions on participation of vulnerable patients in clinical research.

PubMed

van der Wilt, Gert J; Grutters, Janneke P C; Maas, Angela H E M; Rolden, Herbert J A

2018-02-05

The participation of vulnerable patients in clinical research poses apparent ethical dilemmas. Depending on the nature of the vulnerability, their participation may challenge the ethical principles of autonomy, non-maleficence, or justice. On the other hand, non-participation may preclude the building of a knowledge base that is a prerequisite for defining the optimal clinical management of vulnerable patients. Such clinical uncertainty may also incur substantial economic costs. We present the participation of pre-menopausal women with atrial fibrillation in trials of novel oral anticoagulant drugs as a case study. Due to their non-participation in pivotal trials, it is uncertain whether for them, the risks that are associated with these drugs are outweighed by the advantages compared with conventional treatment. We addressed the question whether research of this new class of drugs in this subgroup would be appropriate from both, an ethical as well an economic perspective. We used the method of specifying norms as a wider framework to resolve the apparent ethical dilemma, while incorporating the question whether research of oral anticoagulants in premenopausal women with atrial fibrillation can be justified on economic grounds. For the latter, the results of a value-of-information analysis were used. Further clinical research on NOACs in premenopausal women with atrial fibrillation can be justified on both, ethical and economic grounds. Addressing apparent ethical dilemmas by invoking a method such as specifying norms can improve the quality of public practical reasoning. As such, the method should also prove valuable to committees that have formally been granted the authority to review trial protocols and proposals for scientific research.

Medical specialty selection criteria of Israeli medical students early in their clinical experience: subgroups.

PubMed

Avidan, Alexander; Weissman, Charles; Elchalal, Uriel; Tandeter, Howard; Zisk-Rony, Rachel Yaffa

2018-04-18

Israeli medical school classes include a number of student subgroups. Therefore, interventions aimed at recruiting medical students to the various specialties should to be tailored to each subgroup. Questionnaires, distributed to 6 consecutive 5th-year classes of the Hebrew University - Hadassah School of Medicine, elicited information on criteria for choosing a career specialty, criteria for choosing a residency program and the importance of finding a specialty interesting and challenging when choosing a residency. Completed questionnaires were returned by 540 of 769 (70%) students. The decision processes for choosing a medical specialty and choosing a residency program were different. Family and colleagues had minimal influence on choosing a specialty, while family and their residential locality had much influence on choosing a residency, especially among women. Older age, marriage, and spousal influence were positively associated with choice of a specialty. Two-thirds of the students had completed military service, 20% were attending medical school prior to military service, 5% had completed national service and 9% had entered medical school without serving. Despite the pre-military subgroup being younger and having another 7 years of medical school, internship and military service before residency, they had begun thinking about which specialty to choose, just like the post-military students. When choosing a residency program, post-military women were more influenced by their families and family residential locality than their pre-military counterparts; differences ascribed to the older and often married post-military women having or wanting to begin families. This difference was reinforced by fewer post- than pre-military women willing to wait 2-3 years for a residency in the specialty that interested them most and were willing to begin residency immediately after internship in a specialty that interested them less. Medical school classes are composed of various subgroups, each with its own characteristics. It is important to differentiate between choosing a specialty and a residency program. Choosing a specialty is a uniquely personal decision with some spousal influence among married students. It is of central importance even among pre-military students not slated to begin residency for many years. In contrast, choosing a residency program is influenced by family, where one grew up and other family-related considerations.

Pre-lexical disorders in repetition conduction aphasia.

PubMed

Sidiropoulos, Kyriakos; de Bleser, Ria; Ackermann, Hermann; Preilowski, Bruno

2008-12-01

At the level of clinical speech/language evaluation, the repetition type of conduction aphasia is characterized by repetition difficulties concomitant with reduced short-term memory capacities, in the presence of fluent spontaneous speech as well as unimpaired naming and reading abilities. It is still unsettled which dysfunctions of the pre-lexical processing stage of spoken word recognition contribute to this syndrome and whether there is any relevant top-down impact of the mental lexicon upon the phonetic/phonological level of speech perception. In order to further specify the underlying pathomechanisms, a comprehensive battery of psycholinguistic tests was applied to a patient suffering from repetition conduction aphasia. The obtained results point at a pre-lexical disorder in this subject. To further specify the assumed pre-lexical dysfunction, computer simulations of single-word processing, based upon an interactive activation model (IAM), were conducted. An attenuation of the features-to-phonemes inhibition value was found to simulate the observed profile of psycholinguistic deficits. Conceivably, these pre-lexical disorders interfere with the task-dependent adjustment of the temporal windows of signal analysis, giving rise to compromised sequencing of auditory-verbal information.

A randomized, double-blind, placebo-controlled study of escitalopram in patients with social anxiety disorder in Japan.

PubMed

Asakura, Satoshi; Hayano, Taiji; Hagino, Atsushi; Koyama, Tsukasa

2016-01-01

This randomized, double-blind placebo-controlled study compared the efficacy and tolerability of escitalopram (10 and 20 mg/day) in Japanese patients with social anxiety disorder (SAD). Patients aged 18-64 years with a primary diagnosis of DSM-IV-TR defined SAD, a Liebowitz Social Anxiety Scale Japanese version (LSAS-J) total score ≥60 and a Clinical Global Impression-Severity (CGI-S) score ≥4 at baseline were randomly assigned (1:1:1) to placebo, escitalopram 10 mg or escitalopram 20 mg. The primary endpoint was change from baseline to Week 12 in the LSAS-J total score for both escitalopram 10 mg and 20 mg versus placebo (ANCOVA, FAS, LOCF), using a hierarchical testing procedure. Pre-specified secondary endpoints included LSAS-J sensitivity analyses. This study has the www.japic.or.jp identifier: JapicCTI-121842. For the primary efficacy endpoint, the difference from placebo in the LSAS-J was -3.9 (p = 0.089) for escitalopram 10 mg. Since the superiority of escitalopram 10 mg over placebo was not confirmed, an analysis without multiplicity adjustment was made, which showed a difference for escitalopram 20 mg versus placebo of -9.8 (p < 0.001). In pre-specified sensitivity analyses, the difference versus placebo was -4.9 (p = 0.035) (ANCOVA, FAS, OC) and -5.0 (p = 0.028) (MMRM, FAS) (escitalopram 10 mg) and -10.1 (p < 0.001) (ANCOVA, FAS, OC) and -10.6 (p < 0.001) (MMRM, FAS) (escitalopram 20 mg). Common adverse events (incidence ≥5% and significantly different from placebo) were somnolence, nausea and ejaculation disorder. Escitalopram was efficacious, safe and well tolerated by patients with SAD in Japan. Study limitations are discussed including patient characteristics.

40 CFR 1033.515 - Discrete-mode steady-state emission tests of locomotives and locomotive engines.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the provisions of 40 CFR part 1065, subpart F for general pre-test procedures (including engine and... 1065. (b) Begin the test by operating the locomotive over the pre-test portion of the cycle specified... Sample averagingperiod for emissions 1 Pre-test idle Lowest idle setting 10 to 15 3 Not applicable A Low...

40 CFR 1033.515 - Discrete-mode steady-state emission tests of locomotives and locomotive engines.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the provisions of 40 CFR part 1065, subpart F for general pre-test procedures (including engine and... 1065. (b) Begin the test by operating the locomotive over the pre-test portion of the cycle specified... Sample averagingperiod for emissions 1 Pre-test idle Lowest idle setting 10 to 15 3 Not applicable A Low...

40 CFR 1033.515 - Discrete-mode steady-state emission tests of locomotives and locomotive engines.

Code of Federal Regulations, 2013 CFR

2013-07-01

... the provisions of 40 CFR part 1065, subpart F for general pre-test procedures (including engine and... 1065. (b) Begin the test by operating the locomotive over the pre-test portion of the cycle specified... Sample averagingperiod for emissions 1 Pre-test idle Lowest idle setting 10 to 15 3 Not applicable A Low...

40 CFR 1033.515 - Discrete-mode steady-state emission tests of locomotives and locomotive engines.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the provisions of 40 CFR part 1065, subpart F for general pre-test procedures (including engine and... 1065. (b) Begin the test by operating the locomotive over the pre-test portion of the cycle specified... Sample averagingperiod for emissions 1 Pre-test idle Lowest idle setting 10 to 15 3 Not applicable A Low...

40 CFR 1033.515 - Discrete-mode steady-state emission tests of locomotives and locomotive engines.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the provisions of 40 CFR part 1065, subpart F for general pre-test procedures (including engine and... 1065. (b) Begin the test by operating the locomotive over the pre-test portion of the cycle specified... Sample averagingperiod for emissions 1 Pre-test idle Lowest idle setting 10 to 15 3 Not applicable A Low...

A meta-analysis of interleukin-10-1082 promoter polymorphism associated with gastric cancer risk.

PubMed

Ni, Peihua; Xu, Hong; Xue, Huiping; Lin, Bing; Lu, Yang

2012-04-01

We aimed to explore the role of allele A/G single nucleotide polymorphism (SNP) of gene Interleukin 10 (IL-10) promoter-1082 in the susceptibility to gastric cancer through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were extracted and registered into databases. Twenty studies were ultimately eligible for the meta-analysis of IL-10-1082 A/G SNP. We adopted the most probably appropriate genetic model (dominant model), with the combined group of GG-plus-GA genotypes compared with the AA genotype. Potential sources of heterogeneity were sought out via subgroup analyses and sensitivity analyses, and publication biases were estimated. Between IL-10-1082 GG-plus-GA genotypes with the risk of developing gastric cancer, statistically significant association could be noted with overall gastric cancer, being mainly in Asian subgroup, large sample subgroup, high quality subgroup, intestinal-type subgroup, cardia-type subgroup, and some genotyping method subgroups. Our meta-analysis indicates that IL-10-1082 GG-plus-GA genotypes are associated with the overall risk of developing gastric cancer and seem to be more susceptible to overall gastric cancer in Asian populations. IL-10-1082 GG-plus-GA genotypes are more associated with the pathologically intestinal-type gastric cancer or anatomically cardia-type gastric cancer.

A Meta-Analysis of Interleukin-10-1082 Promoter Polymorphism Associated with Gastric Cancer Risk

PubMed Central

Ni, Peihua; Xu, Hong; Xue, Huiping; Lin, Bing

2012-01-01

We aimed to explore the role of allele A/G single nucleotide polymorphism (SNP) of gene Interleukin 10 (IL-10) promoter-1082 in the susceptibility to gastric cancer through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were extracted and registered into databases. Twenty studies were ultimately eligible for the meta-analysis of IL-10-1082 A/G SNP. We adopted the most probably appropriate genetic model (dominant model), with the combined group of GG-plus-GA genotypes compared with the AA genotype. Potential sources of heterogeneity were sought out via subgroup analyses and sensitivity analyses, and publication biases were estimated. Between IL-10-1082 GG-plus-GA genotypes with the risk of developing gastric cancer, statistically significant association could be noted with overall gastric cancer, being mainly in Asian subgroup, large sample subgroup, high quality subgroup, intestinal-type subgroup, cardia-type subgroup, and some genotyping method subgroups. Our meta-analysis indicates that IL-10-1082 GG-plus-GA genotypes are associated with the overall risk of developing gastric cancer and seem to be more susceptible to overall gastric cancer in Asian populations. IL-10-1082 GG-plus-GA genotypes are more associated with the pathologically intestinal-type gastric cancer or anatomically cardia-type gastric cancer. PMID:22335769

Protein design to understand peptide ligand recognition by tetratricopeptide repeat proteins.

PubMed

Cortajarena, Aitziber L; Kajander, Tommi; Pan, Weilan; Cocco, Melanie J; Regan, Lynne

2004-04-01

Protein design aims to understand the fundamentals of protein structure by creating novel proteins with pre-specified folds. An equally important goal is to understand protein function by creating novel proteins with pre-specified activities. Here we describe the design and characterization of a tetratricopeptide (TPR) protein, which binds to the C-terminal peptide of the eukaryotic chaperone Hsp90. The design emphasizes the importance of both direct, short-range protein-peptide interactions and of long-range electrostatic optimization. We demonstrate that the designed protein binds specifically to the desired peptide and discriminates between it and the similar C-terminal peptide of Hsp70.

Analysis of longitudinal laboratory data in the presence of common selection mechanisms: a view toward greater emphasis on pre-marketing pharmaceutical safety.

PubMed

Schildcrout, Jonathan S; Jenkins, Cathy A; Ostroff, Jack H; Gillen, Daniel L; Harrell, Frank E; Trost, Donald C

2008-05-30

Pharmaceutical safety has received substantial attention in the recent past; however, longitudinal clinical laboratory data routinely collected during clinical trials to derive safety profiles are often used ineffectively. For example, these data are frequently summarized by comparing proportions (between treatment arms) of participants who cross pre-specified threshold values at some time during follow-up. This research is intended, in part, to encourage more effective utilization of these data by avoiding unnecessary dichotomization of continuous data, acknowledging and making use of the longitudinal follow-up, and combining data from multiple clinical trials. However, appropriate analyses require careful consideration of a number of challenges (e.g. selection, comparability of study populations, etc.). We discuss estimation strategies based on estimating equations and maximum likelihood for analyses in the presence of three response history-dependent selection mechanisms: dropout, follow-up frequency, and treatment discontinuation. In addition, because clinical trials' participants usually represent non-random samples from target populations, we describe two sensitivity analysis approaches. All discussions are motivated by an analysis that aims to characterize the dynamic relationship between concentrations of a liver enzyme (alanine aminotransferase) and three distinct doses (no drug, low dose, and high dose) of an nk-1 antagonist across four Phase II clinical trials.

Parental education predicts change in intelligence quotient after childhood epilepsy surgery.

PubMed

Meekes, Joost; van Schooneveld, Monique M J; Braams, Olga B; Jennekens-Schinkel, Aag; van Rijen, Peter C; Hendriks, Marc P H; Braun, Kees P J; van Nieuwenhuizen, Onno

2015-04-01

To know whether change in the intelligence quotient (IQ) of children who undergo epilepsy surgery is associated with the educational level of their parents. Retrospective analysis of data obtained from a cohort of children who underwent epilepsy surgery between January 1996 and September 2010. We performed simple and multiple regression analyses to identify predictors associated with IQ change after surgery. In addition to parental education, six variables previously demonstrated to be associated with IQ change after surgery were included as predictors: age at surgery, duration of epilepsy, etiology, presurgical IQ, reduction of antiepileptic drugs, and seizure freedom. We used delta IQ (IQ 2 years after surgery minus IQ shortly before surgery) as the primary outcome variable, but also performed analyses with pre- and postsurgical IQ as outcome variables to support our findings. To validate the results we performed simple regression analysis with parental education as the predictor in specific subgroups. The sample for regression analysis included 118 children (60 male; median age at surgery 9.73 years). Parental education was significantly associated with delta IQ in simple regression analysis (p = 0.004), and also contributed significantly to postsurgical IQ in multiple regression analysis (p = 0.008). Additional analyses demonstrated that parental education made a unique contribution to prediction of delta IQ, that is, it could not be replaced by the illness-related variables. Subgroup analyses confirmed the association of parental education with IQ change after surgery for most groups. Children whose parents had higher education demonstrate on average a greater increase in IQ after surgery and a higher postsurgical--but not presurgical--IQ than children whose parents completed at most lower secondary education. Parental education--and perhaps other environmental variables--should be considered in the prognosis of cognitive function after childhood epilepsy surgery. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Empirical Bayes estimation of proportions with application to cowbird parasitism rates

USGS Publications Warehouse

Link, W.A.; Hahn, D.C.

1996-01-01

Bayesian models provide a structure for studying collections of parameters such as are considered in the investigation of communities, ecosystems, and landscapes. This structure allows for improved estimation of individual parameters, by considering them in the context of a group of related parameters. Individual estimates are differentially adjusted toward an overall mean, with the magnitude of their adjustment based on their precision. Consequently, Bayesian estimation allows for a more credible identification of extreme values in a collection of estimates. Bayesian models regard individual parameters as values sampled from a specified probability distribution, called a prior. The requirement that the prior be known is often regarded as an unattractive feature of Bayesian analysis and may be the reason why Bayesian analyses are not frequently applied in ecological studies. Empirical Bayes methods provide an alternative approach that incorporates the structural advantages of Bayesian models while requiring a less stringent specification of prior knowledge. Rather than requiring that the prior distribution be known, empirical Bayes methods require only that it be in a certain family of distributions, indexed by hyperparameters that can be estimated from the available data. This structure is of interest per se, in addition to its value in allowing for improved estimation of individual parameters; for example, hypotheses regarding the existence of distinct subgroups in a collection of parameters can be considered under the empirical Bayes framework by allowing the hyperparameters to vary among subgroups. Though empirical Bayes methods have been applied in a variety of contexts, they have received little attention in the ecological literature. We describe the empirical Bayes approach in application to estimation of proportions, using data obtained in a community-wide study of cowbird parasitism rates for illustration. Since observed proportions based on small sample sizes are heavily adjusted toward the mean, extreme values among empirical Bayes estimates identify those species for which there is the greatest evidence of extreme parasitism rates. Applying a subgroup analysis to our data on cowbird parasitism rates, we conclude that parasitism rates for Neotropical Migrants as a group are no greater than those of Resident/Short-distance Migrant species in this forest community. Our data and analyses demonstrate that the parasitism rates for certain Neotropical Migrant species are remarkably low (Wood Thrush and Rose-breasted Grosbeak) while those for others are remarkably high (Ovenbird and Red-eyed Vireo).

Bayesian survival analysis in clinical trials: What methods are used in practice?

PubMed

Brard, Caroline; Le Teuff, Gwénaël; Le Deley, Marie-Cécile; Hampson, Lisa V

2017-02-01

Background Bayesian statistics are an appealing alternative to the traditional frequentist approach to designing, analysing, and reporting of clinical trials, especially in rare diseases. Time-to-event endpoints are widely used in many medical fields. There are additional complexities to designing Bayesian survival trials which arise from the need to specify a model for the survival distribution. The objective of this article was to critically review the use and reporting of Bayesian methods in survival trials. Methods A systematic review of clinical trials using Bayesian survival analyses was performed through PubMed and Web of Science databases. This was complemented by a full text search of the online repositories of pre-selected journals. Cost-effectiveness, dose-finding studies, meta-analyses, and methodological papers using clinical trials were excluded. Results In total, 28 articles met the inclusion criteria, 25 were original reports of clinical trials and 3 were re-analyses of a clinical trial. Most trials were in oncology (n = 25), were randomised controlled (n = 21) phase III trials (n = 13), and half considered a rare disease (n = 13). Bayesian approaches were used for monitoring in 14 trials and for the final analysis only in 14 trials. In the latter case, Bayesian survival analyses were used for the primary analysis in four cases, for the secondary analysis in seven cases, and for the trial re-analysis in three cases. Overall, 12 articles reported fitting Bayesian regression models (semi-parametric, n = 3; parametric, n = 9). Prior distributions were often incompletely reported: 20 articles did not define the prior distribution used for the parameter of interest. Over half of the trials used only non-informative priors for monitoring and the final analysis (n = 12) when it was specified. Indeed, no articles fitting Bayesian regression models placed informative priors on the parameter of interest. The prior for the treatment effect was based on historical data in only four trials. Decision rules were pre-defined in eight cases when trials used Bayesian monitoring, and in only one case when trials adopted a Bayesian approach to the final analysis. Conclusion Few trials implemented a Bayesian survival analysis and few incorporated external data into priors. There is scope to improve the quality of reporting of Bayesian methods in survival trials. Extension of the Consolidated Standards of Reporting Trials statement for reporting Bayesian clinical trials is recommended.

Non-Hierarchical Clustering as a Method to Analyse an Open-Ended Questionnaire on Algebraic Thinking

ERIC Educational Resources Information Center

Di Paola, Benedetto; Battaglia, Onofrio Rosario; Fazio, Claudio

2016-01-01

The problem of taking a data set and separating it into subgroups, where the members of each subgroup are more similar to each other than they are to members outside the subgroup, has been extensively studied in science and mathematics education research. Student responses to written questions and multiple-choice tests have been characterised and…

[Definitions destruction of endothelial cells as a marker of endothelial dysfunction in aging men].

PubMed

Пустовойт, Ганна Л; Ярмола, Тетяна І; Мохначов, Олександр В; Ткаченко, Лідія А; Супруненко, Сергій М

Ukraine occupies the 143 place in the world in life expectancy and the first place in terms of mortality. The main cause of death - cardiovascular diseases - 58%. Recent studies show the important and independent role of endothelium in the development of cardiovascular disease. examination of the endothelium destruction in aging men by determining the level of surface specific antigens of endothelial microparticles. 88 men age from 45 to 76 years. 50 people of the main group had a history of the second type diabetes mellitus (DM-2) combined with arterial hypertension (AH). The control group included 38 men without aforementioned diseases. Also, men were divided into two groups by age: 45-59 years and over 60. in the main subgroup I endothelin level was higher than the control subgroup I: 2,07 ± 0,6 and 1,27 ± 0,25 (p <0.05). In main subgroup II endothelin level was also significantly higher compared with the specified index in control subgroup II: 3,91 ± 0,7 and 1,79 ± 0,27 (p <0.05). Among patients of the main subgroup II endothelin level (3,88 ± 0,7 and 2,04 ± 0,6 (p <0.05)), and triglycerides (2,77 ± 0,08 vs. 1.99 ± 0.05 (p <0.05)) was higher compared with the I subgroup. age androgen deficiency is accompanied by lipid metabolism, development of endothelial dysfunction, insulin resistance, diabetes and hypertension. Reduction of the cardiovascular risk includes measures aimed at normalizing hormonal balance and lipid metabolism in aging men with DM-2 and hypertension.

[Definitions destruction of endothelial cells as a marker of endothelial dysfunction in aging men].

PubMed

Пустовойт, Ганна Л; Ярмола, Тетяна І; Мохначов, Олександр В; Ткаченко, Лідія А; Супруненко, Сергій М

2016-01-01

Ukraine occupies the 143 place in the world in life expectancy and the first place in terms of mortality. The main cause of death - cardiovascular diseases - 58%. Recent studies show the important and independent role of endothelium in the development of cardiovascular disease. examination of the endothelium destruction in aging men by determining the level of surface specific antigens of endothelial microparticles. 88 men age from 45 to 76 years. 50 people of the main group had a history of the second type diabetes mellitus (DM-2) combined with arterial hypertension (AH). The control group included 38 men without aforementioned diseases. Also, men were divided into two groups by age: 45-59 years and over 60. in the main subgroup I endothelin level was higher than the control subgroup I: 2,07 ± 0,6 and 1,27 ± 0,25 (p <0.05). In main subgroup II endothelin level was also significantly higher compared with the specified index in control subgroup II: 3,91 ± 0,7 and 1,79 ± 0,27 (p <0.05). Among patients of the main subgroup II endothelin level (3,88 ± 0,7 and 2,04 ± 0,6 (p <0.05)), and triglycerides (2,77 ± 0,08 vs. 1.99 ± 0.05 (p <0.05)) was higher compared with the I subgroup. age androgen deficiency is accompanied by lipid metabolism, development of endothelial dysfunction, insulin resistance, diabetes and hypertension. Reduction of the cardiovascular risk includes measures aimed at normalizing hormonal balance and lipid metabolism in aging men with DM-2 and hypertension.

The Effectiveness of a Geospatial Technologies-Integrated Curriculum to Promote Climate Literacy

NASA Astrophysics Data System (ADS)

Anastasio, D. J.; Bodzin, A. M.; Peffer, T.; Sahagian, D. L.; Cirucci, L.

2011-12-01

This study examined the effectiveness of a geospatial technologies - integrated climate change curriculum (http://www.ei.lehigh.edu/eli/cc/) to promote climate literacy in an urban school district. Five 8th grade Earth and Space Science classes in an urban middle school (Bethlehem, Pennsylvania) consisting of three different ability level tracks participated in the study. Data gathering methods included pre/posttest assessments, daily classroom observations, daily teacher meetings, and examination of student produced artifacts. Data was gathered using a climate change literacy assessment instrument designed to measure students' climate change content knowledge. The items included distractors that address misunderstandings and knowledge deficits about climate change from the existing literature. Paired-sample t-test analyses were conducted to compare the pre- and post-test assessment results. The results of these analyses were used to compare overall gains as well as ability level track groups. Overall results regarding the use of the climate change curriculum showed significant improvement in urban middle school students' understanding of climate change concepts. Effect sizes were large (ES>0.8) and significant (p<0.001) for the entire assessment and for each ability level subgroup. Findings from classroom observations, assessments embedded in the curriculum, and the examination of all student artifacts revealed that the use of geospatial technologies enable middle school students to improve their knowledge of climate change and improve their spatial thinking and reasoning skills.

Modeling Technology Preparedness as an Antecedent of Mathematic Pre-Service Teachers' Self Efficacy, Perceived Usefulness and Intention toward Use of Information Technology in Nigeria

ERIC Educational Resources Information Center

Shittu, Ahmed Tajudeen; Gambari, Amosa Isiaka; Gimba, W. Rahmatu; Ahmed, Hassan

2016-01-01

This study test a specified model of information technology (IT) preparedness as antecedent of pre-service teachers' self efficacy, perceived usefulness, and intention toward IT use for teaching in Nigeria. Survey method was employed for prosecuting the study. The participants of the study comprise of 200 pre-service teachers studying Mathematics…

Longitudinal Examination of Symptom Profiles among Breast Cancer Survivors

PubMed Central

Avis, Nancy E.; Levine, Beverly; Marshall, Sarah A.; Ip, Edward H.

2017-01-01

Context Identification of cancer patients with similar symptom profiles may facilitate targeted symptom management. Objectives To identify subgroups of breast cancer survivors based on differential experience of symptoms, examine change in subgroup membership over time, and identify relevant characteristics and quality of life (QOL) among subgroups. Methods Secondary analyses of data from 653 breast cancer survivors recruited within 8 months of diagnosis who completed questionnaires at five timepoints. Hidden Markov modeling was used to: 1) formulate symptom profiles based on prevalence and severity of eight symptoms commonly associated with breast cancer, and 2) estimate probabilities of changing subgroup membership over 18 months of follow-up. Ordinal repeated measures were used to: 3) identify patient characteristics related to subgroup membership, and 4) evaluate the relationship between symptom subgroup and QOL. Results A seven-subgroup model provided the best fit: 1) low symptom burden, 2) mild fatigue, 3) mild fatigue and mild pain, 4) moderate fatigue and moderate pain, 5) moderate fatigue and moderate psychological, 6) moderate fatigue, mild pain, mild psychological; and 7) high symptom burden. Seventy percent of survivors remained in the same subgroup over time. In multivariable analyses, chemotherapy and greater illness intrusiveness were significantly related to greater symptom burden, while not being married or partnered, no difficulty paying for basics, and greater social support were protective. Higher symptom burden was associated with lower QOL. Survivors who reported psychological symptoms had significantly lower QOL than did survivors with pain symptoms. Conclusion Cancer survivors can be differentiated by their symptom profiles. PMID:28042076

Examining Moderation Analyses in Propensity Score Methods: Application to Depression and Substance Use

PubMed Central

Green, Kerry M.; Stuart, Elizabeth A.

2014-01-01

Objective This study provides guidance on how propensity score methods can be combined with moderation analyses (i.e., effect modification) to examine subgroup differences in potential causal effects in non-experimental studies. As a motivating example, we focus on how depression may affect subsequent substance use differently for men and women. Method Using data from a longitudinal community cohort study (N=952) of urban African Americans with assessments in childhood, adolescence, young adulthood and midlife, we estimate the influence of depression by young adulthood on substance use outcomes in midlife, and whether that influence varies by gender. We illustrate and compare five different techniques for estimating subgroup effects using propensity score methods, including separate propensity score models and matching for men and women, a joint propensity score model for men and women with matching separately and together by gender, and a joint male/female propensity score model that includes theoretically important gender interactions with matching separately and together by gender. Results Analyses showed that estimating separate models for men and women yielded the best balance and, therefore, is a preferred technique when subgroup analyses are of interest, at least in this data. Results also showed substance use consequences of depression but no significant gender differences. Conclusions It is critical to prespecify subgroup effects before the estimation of propensity scores and to check balance within subgroups regardless of the type of propensity score model used. Results also suggest that depression may affect multiple substance use outcomes in midlife for both men and women relatively equally. PMID:24731233

24 CFR 3280.403 - Standard for windows and sliding glass doors used in manufactured homes.

Code of Federal Regulations, 2014 CFR

2014-04-01

... pressure tests must be conducted at the design wind loads required for components and cladding specified in... certification must be based on tests conducted at the design wind loads specified in § 3280.305(c)(1). (1) All... agency shall conduct pre-production specimen tests in accordance with AAMA 1701.2-95. Further, such...

Long Term Effects on Cognitive Function of Postmenopausal Hormone Therapy Prescribed to Women Aged 50–55 Years

PubMed Central

Espeland, Mark A.; Shumaker, Sally A.; Leng, Iris; Manson, JoAnn E.; Brown, Candice M.; LeBlanc, Erin S.; Vaughan, Leslie; Robinson, Jennifer; Rapp, Stephen R.; Goveas, Joseph S.; Lane, Dorothy; Wactawski-Wende, Jean; Stefanick, Marcia L.; Li, Wenjun; Resnick, Susan M.

2013-01-01

Background Postmenopausal hormone therapy with conjugated equine estrogens (CEE) may adversely affect older women’s cognitive function. It is not known whether this extends to younger women. Methods 1,326 postmenopausal women, who had begun treatment in two randomized placebo-controlled clinical trials of hormone therapy when aged 50–55 years, were assessed with an annual telephone-administered cognitive battery that included measures of global (primary outcome) and domain-specific cognitive functions (verbal memory, attention, executive function, verbal fluency, and working memory). The clinical trials in which they participated had compared 0.625 mg CEE with or without 2.5 mg medroxyprogesterone acetate (MPA) over an average of 7.0 years. Cognitive testing was conducted an average of 7.2 years following the end of the trials, when women had mean age 67.2 years, and repeated one year later. Results Global cognitive function scores from women who had been assigned to CEE-based therapies were similar to those from women assigned to placebo: mean [95% confidence interval] intervention effect of 0.02 [−0.08,0.12]standard deviation units (p=0.66). Similarly, no overall differences were found for any individual cognitive domain (all p>0.15). Pre-specified subgroup analyses found some evidence that CEE-based therapies may have adversely affected verbal fluency among women who had prior hysterectomy or prior use of hormone therapy: mean treatment effects of −0.17 [−0.33, −0.02] and −0.25 [−0.42, −0.08], respectively, however this may be a chance finding. We are not able to address whether initiating hormone therapy during the menopause and maintaining therapy until any symptoms are passed affects cognitive function, either in the short or longer term. Conclusions CEE-based therapies produced no overall sustained benefit or risk to cognitive function when administered to postmenopausal women aged 50–55 years. PMID:23797469

Effect of adding piperacillin-tazobactam to automated dispensing cabinets on promptness of first-dose antibiotics in hospitalized patients.

PubMed

Lo, Amy; Zhu, Juanqi Nikki; Richman, Mark; Joo, Julianne; Chan, Patrick

2014-10-01

Significant improvements in order-to-administration times for critical first doses of i.v. antibiotic therapy through the use of automated dispensing cabinets (ADCs) are reported. In a retrospective pre-post analysis conducted at a large academic medical center, pharmacy and medical records were reviewed to evaluate average times to administration of first doses of i.v. piperacillin-tazobactam therapy during designated periods before and after the addition of selected i.v. antibiotics to ADCs on patient care units. Inpatients who received a specified i.v. piperacillin-tazobactam formulation were included in the analysis. The primary endpoint was the total time from prescribing to administration; the impact of ADC use on other time intervals (e.g., from scanning of orders to administration, from pharmacist verification and release of orders to administration) was also evaluated. A total of 121 subjects were included in the preimplementation (n = 65) and postimplementation (n = 56) samples. There was a significant 1.7-hour reduction in the mean ± S.D. order-to-administration time (from 4.5 ± 4.1 to 2.9 ± 2.5 hours, p = 0.009) for piperacillin-tazobactam first doses with the use of ADCs. Subgroup analyses showed significant reductions in the mean ± S.D. scan-to-administration time (from 3.3 ± 3.4 to 1.7 ± 1.5 hours, p = 0.001) and release-to-administration time (from 2.4 ± 2.4 to 1.4 ± 1.5 hours, p = 0.034). The addition of a piperacillin-tazobactam product and other commonly used i.v. antibiotics to ADCs was associated with a significantly reduced order-to-administration time for piperacillin-tazobactam first doses. This change was accounted for by a significant reduction in the time between order entry and drug administration. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

A systematic review and meta-analysis of pharmacist-led fee-for-services medication review

PubMed Central

Hatah, Ernieda; Braund, Rhiannon; Tordoff, June; Duffull, Stephen B

2014-01-01

Aim The aim was to examine the impact of fee-for-service pharmacist-led medication review on patient outcomes and quantify this according to the type of review undertaken, e.g. adherence support and clinical medication review. Methods Relevant published studies were identified from Medline, Embase and International Pharmaceutical Abstract databases (from inception to February 2011). Study inclusion criteria were fee-for-service medication review, presence of a control group and pre-specified patient outcomes. Outcomes were grouped into primary (changes in biomarkers, hospitalization, and mortality) and secondary outcomes (medication adherence, economic implications and quality of life). Meta-analyses for primary outcomes were conducted using random effects models and secondary outcomes were summarized using descriptive statistics. Results Of the 135 relevant articles located, 21 studies met the inclusion criteria for primary outcomes and 32 for secondary outcomes. Significant results favouring pharmacists' intervention were found for blood pressure (OR 3.50, 95% CI 1.58, 7.75, P = 0.002) and low density lipoprotein (OR 2.35, 95% CI 1.17, 4.72, P = 0.02). Outcomes on hospitalization (OR 0.69, 95% CI 0.39, 1.21, P = 0.19) and mortality (OR 1.50, 95% CI 0.65 to 3.46, P = 0.34) indicated no differences between the groups. On subgroup analysis, clinical medication review (OR 0.46, 95% CI 0.26, 0.83, P = 0.01) but not adherence support review (OR 0.88, 95% CI 0.59, 1.32, P = 0.54) reduced hospitalization. Conclusions The majority of the studies (57.9%) showed improvement in medication adherence. Fee-for-service pharmacist-led medication reviews showed positive benefits on patient outcomes. Interventions that include a clinical review had a significant impact on patient outcomes by attainment of target clinical biomarkers and reduced hospitalization. PMID:23594037

Oncology patient-reported claims: maximising the chance for success.

PubMed

Kitchen, H; Rofail, D; Caron, M; Emery, M-P

2011-01-01

To review Patient Reported Outcome (PRO) labelling claims achieved in oncology in Europe and in the United States and consider the benefits, and challenges faced. PROLabels database was searched to identify oncology products with PRO labelling approved in Europe since 1995 or in the United States since 1998. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) websites and guidance documents were reviewed. PUBMED was searched for articles on PRO claims in oncology. Among all oncology products approved, 22 were identified with PRO claims; 10 in the United States, 7 in Europe, and 5 in both. The language used in the labelling was limited to benefit (e.g. "…resulted in symptom benefits by significantly prolonging time to deterioration in cough, dyspnoea, and pain, versus placebo") and equivalence (e.g. "no statistical differences were observed between treatment groups for global QoL"). Seven products used a validated HRQoL tool; two used symptom tools; two used both; seven used single-item symptom measures (one was unknown). The following emerged as likely reasons for success: ensuring systematic PRO data collection; clear rationale for pre-specified endpoints; adequately powered trials to detect differences and clinically significant changes; adjusting for multiplicity; developing an a priori statistical analysis plan including primary and subgroup analyses, dealing with missing data, pooling multiple-site data; establishing clinical versus statistical significance; interpreting failure to detect change. End-stage patient drop-out rates and cessation of trials due to exceptional therapeutic benefit pose significant challenges to demonstrating treatment PRO improvement. PRO labelling claims demonstrate treatment impact and the trade-off between efficacy and side effects ultimately facilitating product differentiation. Reliable and valid instruments specific to the desired language, claim, and target population are required. Practical considerations include rationale for study endpoints, transparency in assumptions, and attention to subtle variations in data.

Oncology patient-reported claims: maximising the chance for success

PubMed Central

Kitchen, H; Rofail, D; Caron, M; Emery, M-P

2011-01-01

Objectives/purpose: To review Patient Reported Outcome (PRO) labelling claims achieved in oncology in Europe and in the United States and consider the benefits, and challenges faced. Methods: PROLabels database was searched to identify oncology products with PRO labelling approved in Europe since 1995 or in the United States since 1998. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) websites and guidance documents were reviewed. PUBMED was searched for articles on PRO claims in oncology. Results: Among all oncology products approved, 22 were identified with PRO claims; 10 in the United States, 7 in Europe, and 5 in both. The language used in the labelling was limited to benefit (e.g. “…resulted in symptom benefits by significantly prolonging time to deterioration in cough, dyspnoea, and pain, versus placebo”) and equivalence (e.g. “no statistical differences were observed between treatment groups for global QoL”). Seven products used a validated HRQoL tool; two used symptom tools; two used both; seven used single-item symptom measures (one was unknown). The following emerged as likely reasons for success: ensuring systematic PRO data collection; clear rationale for pre-specified endpoints; adequately powered trials to detect differences and clinically significant changes; adjusting for multiplicity; developing an a priori statistical analysis plan including primary and subgroup analyses, dealing with missing data, pooling multiple-site data; establishing clinical versus statistical significance; interpreting failure to detect change. End-stage patient drop-out rates and cessation of trials due to exceptional therapeutic benefit pose significant challenges to demonstrating treatment PRO improvement. Conclusions: PRO labelling claims demonstrate treatment impact and the trade-off between efficacy and side effects ultimately facilitating product differentiation. Reliable and valid instruments specific to the desired language, claim, and target population are required. Practical considerations include rationale for study endpoints, transparency in assumptions, and attention to subtle variations in data. PMID:22276055

A 12-week randomized, double-blind, placebo-controlled multicenter study of choline-stabilized orthosilicic acid in patients with symptomatic knee osteoarthritis.

PubMed

Geusens, Piet; Pavelka, Karel; Rovensky, Jozef; Vanhoof, Johan; Demeester, Nathalie; Calomme, Mario; Vanden Berghe, Dirk

2017-01-05

The aim of this study was to assess the efficacy of choline-stabilized orthosilicic acid (ch-OSA) in patients with symptomatic knee osteoarthritis (OA). In a multicenter, double-blind, placebo-controlled study, 211 patients with knee OA (Kellgren and Lawrence grade II or III) and moderate to moderately severe pain were randomly allocated to ch-OSA or placebo for 12 weeks. The primary outcome was the change in the WOMAC pain subscale from baseline to week 12. Secondary outcomes were changes from baseline to week 12 in WOMAC total, WOMAC stiffness, WOMAC physical function, Subject Global Assessment and levels of cartilage degradation biomarkers C-terminal telopeptide of collagen type II (CTX-II) and cartilage oligomeric matrix protein (COMP). Pre-specified subgroup analyses included the effect of gender. A total of 166 (120 women, 46 men) patients were included in the analysis (87 and 79 in the ch-OSA and placebo group, respectively). In the total study population, no differences were observed between the two treatment groups for the different outcomes but significant treatment x gender interactions were found. In men taking ch-OSA, a significant improvement in WOMAC total, WOMAC stiffness and WOMAC physical function as well as a lower increase in biomarker levels of cartilage degradation was observed, but not in women. The change in WOMAC pain showed a similar positive trend in men taking ch-OSA. After 12 weeks of treatment, no effect was found of ch-OSA in the total study population on clinical parameters and biomarkers, but a gender interaction was observed. In men, ch-OSA was found effective in reducing symptoms of knee OA, which was associated with a slight but significant reduction of biomarkers that are related to cartilage degradation. The study was registered retrospectively: ISRCTN88583133 . Registration date: 2015-10-07.

Edoxaban vs. warfarin in vitamin K antagonist experienced and naive patients with atrial fibrillation†.

PubMed

O'Donoghue, Michelle L; Ruff, Christian T; Giugliano, Robert P; Murphy, Sabina A; Grip, Laura T; Mercuri, Michele F; Rutman, Howard; Shi, Minggao; Kania, Grzegorz; Cermak, Ondrej; Braunwald, Eugene; Antman, Elliott M

2015-06-14

Edoxaban is an oral, once-daily factor Xa inhibitor that is non-inferior to well-managed warfarin in patients with atrial fibrillation (AF) for the prevention of stroke and systemic embolic events (SEEs). We examined the efficacy and safety of edoxaban vs. warfarin in patients who were vitamin K antagonist (VKA) naive or experienced. ENGAGE AF-TIMI 48 randomized 21 105 patients with AF at moderate-to-high risk of stroke to once-daily edoxaban vs. warfarin. Subjects were followed for a median of 2.8 years. The primary efficacy endpoint was stroke or SEE. As a pre-specified subgroup, we analysed outcomes for those with or without prior VKA experience (>60 consecutive days). Higher-dose edoxaban significantly reduced the risk of stroke or SEE in patients who were VKA naive [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.56-0.90] and was similar to warfarin in the VKA experienced (HR 1.01, 95% CI 0.82-1.24; P interaction = 0.028). Lower-dose edoxaban was similar to warfarin for stroke or SEE prevention in patients who were VKA naive (HR 0.92, 95% CI 0.73-1.15), but was inferior to warfarin in those who were VKA experienced (HR 1.31, 95% 1.08-1.60; P interaction = 0.019). Both higher-dose and lower-dose edoxaban regimens significantly reduced the risk of major bleeding regardless of prior VKA experience (P interaction = 0.90 and 0.71, respectively). In patients with AF, edoxaban appeared to demonstrate greater efficacy compared with warfarin in patients who were VKA naive than VKA experienced. Edoxaban significantly reduced major bleeding compared with warfarin regardless of prior VKA exposure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Gene Expression Profiling Differentiates Autism Case–Controls and Phenotypic Variants of Autism Spectrum Disorders: Evidence for Circadian Rhythm Dysfunction in Severe Autism

PubMed Central

Hu, Valerie W.; Sarachana, Tewarit; Kim, Kyung Soon; Nguyen, AnhThu; Kulkarni, Shreya; Steinberg, Mara E.; Luu, Truong; Lai, Yinglei; Lee, Norman H.

2009-01-01

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by delayed/abnormal language development, deficits in social interaction, repetitive behaviors and restricted interests. The heterogeneity in clinical presentation of ASD, likely due to different etiologies, complicates genetic/biological analyses of these disorders. DNA microarray analyses were conducted on 116 lymphoblastoid cell lines (LCL) from individuals with idiopathic autism who are divided into three phenotypic subgroups according to severity scores from the commonly used Autism Diagnostic Interview-Revised questionnaire and age-matched, nonautistic controls. Statistical analyses of gene expression data from control LCL against that of LCL from ASD probands identify genes for which expression levels are either quantitatively or qualitatively associated with phenotypic severity. Comparison of the significant differentially expressed genes from each subgroup relative to the control group reveals differentially expressed genes unique to each subgroup as well as genes in common across subgroups. Among the findings unique to the most severely affected ASD group are 15 genes that regulate circadian rhythm, which has been shown to have multiple effects on neurological as well as metabolic functions commonly dysregulated in autism. Among the genes common to all three subgroups of ASD are 20 novel genes mostly in putative noncoding regions, which appear to associate with androgen sensitivity and which may underlie the strong 4:1 bias toward affected males. PMID:19418574

Migraine and Cardiovascular Disease in Women: the Role of Aspirin – Subgroup Analyses in the Women’s Health Study

PubMed Central

Kurth, Tobias; Diener, Hans-Christoph; Buring, Julie E.

2011-01-01

Background Migraine with aura (MA) has been associated with increased risk of cardiovascular disease (CVD). The role of aspirin on this association remains unclear. Methods Post-hoc subgroup analyses of the Women’s Health Study, a randomized trial testing 100mg aspirin on alternate days in primary prevention of CVD among 39,876 women aged ≥45. Results During 10 years, 998 major CVD events were confirmed in 39,757 women with complete migraine information. Aspirin reduced risk of ischemic stroke (RR=0.76; 95%CI=0.63–0.93) but not other CVD. Migraine or MA did not modify the effect of aspirin on CVD except for myocardial infarction (MI) (p-interaction=0.01). Women with MA on aspirin had increased risk of MI (RR=3.72, 95%CI=1.39–9.95). Further exploratory analyses indicate this is only apparent among women with MA on aspirin who ever smoked or had history of hypertension (p-interaction<0.01). Conclusion In post-hoc subgroup analyses, aspirin had similar protective effects on ischemic stroke for women with or without migraine. By contrast, our data suggest that women with MA on aspirin had increased risk of MI. The small number of outcome events in subgroups, the exploratory nature of our analyses, and lack of plausible mechanisms raise the possibility of a chance finding, which must caution the interpretation. PMID:21673005

The Great Recession worsened blood pressure and blood glucose levels in American adults.

PubMed

Seeman, Teresa; Thomas, Duncan; Merkin, Sharon Stein; Moore, Kari; Watson, Karol; Karlamangla, Arun

2018-03-27

Longitudinal, individual-specific data from the Multi-Ethnic Study of Atherosclerosis (MESA) provide support for the hypothesis that the 2008 to 2010 Great Recession (GR) negatively impacted the health of US adults. Results further advance understanding of the relationship by ( i ) illuminating hypothesized greater negative impacts in population subgroups exposed to more severe impacts of the GR and ( ii ) explicitly controlling for confounding by individual differences in age-related changes in health over time. Analyses overcome limitations of prior work by ( i ) employing individual-level data that avoid concerns about ecological fallacy associated with prior reliance on group-level data, ( ii ) using four waves of data before the GR to estimate and control for underlying individual-level age-related trends, ( iii ) focusing on objective, temporally appropriate health outcomes rather than mortality, and ( iv ) leveraging a diverse cohort to investigate subgroup differences in the GR's impact. Innovative individual fixed-effects modeling controlling for individual-level age-related trajectories yielded substantively important insights: ( i ) significant elevations post-GR for blood pressure and fasting glucose, especially among those on medication pre-GR, and ( ii ) reductions in prevalence and intensity of medication use post-GR. Important differences in the effects of the GR are seen across subgroups, with larger effects among younger adults (who are likely still in the labor force) and older homeowners (whose declining home wealth likely reduced financial security, with less scope for recouping losses during their lifetime); least affected were older adults without a college degree (whose greater reliance on Medicare and Social Security likely provided more protection from the recession).

Bridging the gap: a review of dose investigations in paediatric investigation plans

PubMed Central

Hampson, Lisa V; Herold, Ralf; Posch, Martin; Saperia, Julia; Whitehead, Anne

2014-01-01

Aims In the EU, development of new medicines for children should follow a prospectively agreed paediatric investigation plan (PIP). Finding the right dose for children is crucial but challenging due to the variability of pharmacokinetics across age groups and the limited sample sizes available. We examined strategies adopted in PIPs to support paediatric dosing recommendations to identify common assumptions underlying dose investigations and the attempts planned to verify them in children. Methods We extracted data from 73 PIP opinions recently adopted by the Paediatric Committee of the European Medicines Agency. These opinions represented 79 medicinal development programmes and comprised a total of 97 dose investigation studies. We identified the design of these dose investigation studies, recorded the analyses planned and determined the criteria used to define target doses. Results Most dose investigation studies are clinical trials (83 of 97) that evaluate a single dosing rule. Sample sizes used to investigate dose are highly variable across programmes, with smaller numbers used in younger children (< 2 years). Many studies (40 of 97) do not pre-specify a target dose criterion. Of those that do, most (33 of 57 studies) guide decisions using pharmacokinetic data alone. Conclusions Common assumptions underlying dose investigation strategies include dose proportionality and similar exposure−response relationships in adults and children. Few development programmes pre-specify steps to verify assumptions in children. There is scope for the use of Bayesian methods as a framework for synthesizing existing information to quantify prior uncertainty about assumptions. This process can inform the design of optimal drug development strategies. PMID:24720849

Bayesian methods including nonrandomized study data increased the efficiency of postlaunch RCTs.

PubMed

Schmidt, Amand F; Klugkist, Irene; Klungel, Olaf H; Nielen, Mirjam; de Boer, Anthonius; Hoes, Arno W; Groenwold, Rolf H H

2015-04-01

Findings from nonrandomized studies on safety or efficacy of treatment in patient subgroups may trigger postlaunch randomized clinical trials (RCTs). In the analysis of such RCTs, results from nonrandomized studies are typically ignored. This study explores the trade-off between bias and power of Bayesian RCT analysis incorporating information from nonrandomized studies. A simulation study was conducted to compare frequentist with Bayesian analyses using noninformative and informative priors in their ability to detect interaction effects. In simulated subgroups, the effect of a hypothetical treatment differed between subgroups (odds ratio 1.00 vs. 2.33). Simulations varied in sample size, proportions of the subgroups, and specification of the priors. As expected, the results for the informative Bayesian analyses were more biased than those from the noninformative Bayesian analysis or frequentist analysis. However, because of a reduction in posterior variance, informative Bayesian analyses were generally more powerful to detect an effect. In scenarios where the informative priors were in the opposite direction of the RCT data, type 1 error rates could be 100% and power 0%. Bayesian methods incorporating data from nonrandomized studies can meaningfully increase power of interaction tests in postlaunch RCTs. Copyright © 2015 Elsevier Inc. All rights reserved.

Escitalopram: superior to citalopram or a chiral chimera?

PubMed

Svensson, Staffan; Mansfield, Peter R

2004-01-01

Escitalopram is the active isomer of the antidepressant citalopram. In theory single-isomer drugs may be superior but few have been found to have clinically significant advantages. The manufacturer claims that escitalopram has more efficacy and a faster onset of effect than citalopram. The purpose of this study was to assess how far these claims are justified. Relevant trial reports were requested from H. Lundbeck A/S and the Swedish drug regulatory authority. The trials consisted of a pooled analysis of 1,321 patients from one unpublished, one partly published and one published eight-week trial, as well as a 24-week trial with 357 patients published as a poster. The studies compared escitalopram with placebo and/or citalopram in outpatients aged or=18 years who met specified criteria for depression. The trials' quality was assessed with Moncrieff et al.'s quality assessment instrument and the results compared with the claims from the advertisements. The advertising claims are not justified because they are based on secondary outcomes, non-intention-to-treat analyses and arbitrarily defined subgroups. The subgroup results are inconsistent. Methodological flaws in the trials could account for the differences found. Even if the differences claimed were real they appear too small to justify higher prices. On the evidence available to us the manufacturer's claims of superiority for escitalopram over citalopram are unwarranted. The Swedish and Danish drug regulatory authorities reached similar conclusions. This highlights the need for wider dissemination of national authorities' statements to other countries affected by the European Union's mutual recognition procedure. Copyright 2004 S. Karger AG, Basel

Discovery of nitrate-CPK-NLP signalling in central nutrient-growth networks

PubMed Central

Liu, Kun-hsiang; Niu, Yajie; Konishi, Mineko; Wu, Yue; Du, Hao; Sun Chung, Hoo; Li, Lei; Boudsocq, Marie; McCormack, Matthew; Maekawa, Shugo; Ishida, Tetsuya; Zhang, Chao; Shokat, Kevan; Yanagisawa, Shuichi; Sheen, Jen

2018-01-01

Nutrient signalling integrates and coordinates gene expression, metabolism and growth. However, its primary molecular mechanisms remain incompletely understood in plants and animals. Here we report novel Ca2+ signalling triggered by nitrate with live imaging of an ultrasensitive biosensor in Arabidopsis leaves and roots. A nitrate-sensitized and targeted functional genomic screen identifies subgroup III Ca2+-sensor protein kinases (CPKs) as master regulators orchestrating primary nitrate responses. A chemical switch with the engineered CPK10(M141G) kinase enables conditional analyses of cpk10,30,32 to define comprehensive nitrate-associated regulatory and developmental programs, circumventing embryo lethality. Nitrate-CPK signalling phosphorylates conserved NIN-LIKE PROTEIN (NLP) transcription factors (TFs) to specify reprogramming of gene sets for downstream TFs, transporters, N-assimilation, C/N-metabolism, redox, signalling, hormones, and proliferation. Conditional cpk10,30,32 and nlp7 similarly impair nitrate-stimulated system-wide shoot growth and root establishment. The nutrient-coupled Ca2+ signalling network integrates transcriptome and cellular metabolism with shoot-root coordination and developmental plasticity in shaping organ biomass and architecture. PMID:28489820

Discovery of nitrate-CPK-NLP signalling in central nutrient-growth networks.

PubMed

Liu, Kun-Hsiang; Niu, Yajie; Konishi, Mineko; Wu, Yue; Du, Hao; Sun Chung, Hoo; Li, Lei; Boudsocq, Marie; McCormack, Matthew; Maekawa, Shugo; Ishida, Tetsuya; Zhang, Chao; Shokat, Kevan; Yanagisawa, Shuichi; Sheen, Jen

2017-05-18

Nutrient signalling integrates and coordinates gene expression, metabolism and growth. However, its primary molecular mechanisms remain incompletely understood in plants and animals. Here we report unique Ca 2+ signalling triggered by nitrate with live imaging of an ultrasensitive biosensor in Arabidopsis leaves and roots. A nitrate-sensitized and targeted functional genomic screen identifies subgroup III Ca 2+ -sensor protein kinases (CPKs) as master regulators that orchestrate primary nitrate responses. A chemical switch with the engineered mutant CPK10(M141G) circumvents embryo lethality and enables conditional analyses of cpk10 cpk30 cpk32 triple mutants to define comprehensive nitrate-associated regulatory and developmental programs. Nitrate-coupled CPK signalling phosphorylates conserved NIN-LIKE PROTEIN (NLP) transcription factors to specify the reprogramming of gene sets for downstream transcription factors, transporters, nitrogen assimilation, carbon/nitrogen metabolism, redox, signalling, hormones and proliferation. Conditional cpk10 cpk30 cpk32 and nlp7 mutants similarly impair nitrate-stimulated system-wide shoot growth and root establishment. The nutrient-coupled Ca 2+ signalling network integrates transcriptome and cellular metabolism with shoot-root coordination and developmental plasticity in shaping organ biomass and architecture.

How to define severely injured patients? -- an Injury Severity Score (ISS) based approach alone is not sufficient.

PubMed

Paffrath, Thomas; Lefering, Rolf; Flohé, Sascha

2014-10-01

Multiple injured patients, polytrauma or severely injured patients are terms used as synonyms in international literature describing injured patients with a high risk of mortality and cost consuming therapeutic demands. In order to advance the definition of these terms, we analysed a large trauma registry. In detail, we compared critically ill trauma patients first specified on a pure anatomical base according to the ISS or NISS, second in the original "polytrauma definition" with two body regions affected and finally all of them combined with a physiological component. Records that were collected in the TraumaRegister DGU(®) of the German Trauma Society (Deutsche Gesellschaft für Unfallchirurgie, DGU) between 1993 and 2011 (92,479 patients) were considered for this study. All patients with primary admission from scene with a minimum hospital stay of 48 h and an Injury Severity Score (ISS)≥ 16 were included. Pre-hospital and early admission data were used to determine physiological risk factors and calculate individual risk of death using the Revised Injury Severity Classification (RISC). 45,350 patients met inclusion criteria. The overall hospital mortality rate was 20.4%. The predicted mortality according to the RISC-Score was 21.6%. 36,897 patients (81.4%) had injuries in several body regions. The prevalence of the five physiological risk factors varied between 17% (high age) and 34% (unconsciousness). There were 17,617 patients (38.8%) without any risk factor present on admission, while 30.6% (n=13,890) of the patients had one and 30.5% (n=13,843) had two or more factors present. Patients with ISS ≥ 16 but no physiological risk factor present had a very low mortality rate of 3.1% (542 of 17,617). With an increasing number of physiological factors there was an almost linear increase in mortality up to an 86% rate in patients with all five factors present. The 'polytrauma' definition of Butcher and colleagues with AIS ≥ 3 in at least two different body regions would apply to only 56.2% of patients in the present group with ISS ≥ 16. The mortality in this subgroup is only marginally higher (21.8%; 5559 of 25,494) than in the group of patients with only one severely affected body region (18.5%; 3675 of 19,875). In our opinion the principle of sharpening an anatomically based definition by a defined physiological problem will help to specify the really critically ill trauma patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Comparative Study of Teaching Efficacy in Pre-Service and In-Service Teachers in Korean Early Childhood Education and Care (ECEC)

ERIC Educational Resources Information Center

Seo, SoJung; Moon, HyukJun

2013-01-01

The main purpose of this study was to investigate the differences between pre-service and in-service teachers in terms of their levels of teaching efficacy and teaching professionalism. In addition, the patterns in predictors of teachers' teaching efficacy were compared between the two subgroups of this study. Five hundred and seventy-three…

Resistance to bond degradation between dual-cure resin cements and pre-treated sintered CAD-CAM dental ceramics

PubMed Central

Osorio, Raquel; Monticelli, Francesca; Osorio, Estrella; Toledano, Manuel

2012-01-01

Objective: To evaluate the bond stability of resin cements when luted to glass-reinforced alumina and zirconia CAD/CAM dental ceramics. Study design: Eighteen glass-infiltrated alumina and eighteen densely sintered zirconia blocks were randomly conditioned as follows: Group 1: No treatment; Group 2: Sandblasting (125 µm Al2O3-particles); and Group 3: Silica-coating (50 µm silica-modified Al2O3-particles). Composite samples were randomly bonded to the pre-treated ceramic surfaces using different resin cements: Subgroup 1: Clearfil Esthetic Cement (CEC); Subgroup 2: RelyX Unicem (RXU); and Subgroup 3: Calibra (CAL). After 24 h, bonded specimens were cut into 1 ± 0.1 mm2 sticks. One-half of the beams were tested for microtensile bond strength (MTBS). The remaining one-half was immersed in 10 % NaOCl aqueous solution (NaOClaq) for 5 h before testing. The fracture pattern and morphology of the debonded surfaces were assessed with a field emission gun scanning electron microscope (FEG-SEM). A multiple ANOVA was conducted to analyze the contributions of ceramic composition, surface treatment, resin cement type, and chemical challenging to MTBS. The Tukey test was run for multiple comparisons (p < 0.05). Results: After 24 h, CEC luted to pre-treated zirconia achieved the highest MTBS. Using RXU, alumina and zirconia registered comparable MTBS. CAL failed prematurely, except when luted to sandblasted zirconia. After NaOClaq storage, CEC significantly lowered MTBS when luted to zirconia or alumina. RXU decreased MTBS only when bonded to silica-coated alumina. CAL recorded 100 % of pre-testing failures. Micromorphological alterations were evident after NaOClaq immersion. Conclusions: Resin-ceramic interfacial longevity depended on cement selection rather than on surface pre-treatments. The MDP-containing and the self-adhesive resin cements were both suitable for luting CAD/CAM ceramics. Despite both cements being prone to degradation, RXU luted to zirconia or untreated or sandblasted alumina showed the most stable interfaces. CAL experimented spontaneous debonding in all tested groups. Key words:CAD/CAM ceramic, alumina, zirconia, resin cement, surface pre-treatment, sandblasting, silica-coating, chemical aging, bond degradation, microtensile bond strength. PMID:22322517

Effects of personalized colorectal cancer risk information on laypersons' interest in colorectal cancer screening: The importance of individual differences.

PubMed

Han, Paul K J; Duarte, Christine W; Daggett, Susannah; Siewers, Andrea; Killam, Bill; Smith, Kahsi A; Freedman, Andrew N

2015-10-01

To evaluate how personalized quantitative colorectal cancer (CRC) risk information affects laypersons' interest in CRC screening, and to explore factors influencing these effects. An online pre-post experiment was conducted in which a convenience sample (N=578) of laypersons, aged >50, were provided quantitative personalized estimates of lifetime CRC risk, calculated by the National Cancer Institute Colorectal Cancer Risk Assessment Tool (CCRAT). Self-reported interest in CRC screening was measured immediately before and after CCRAT use; sociodemographic characteristics and prior CRC screening history were also assessed. Multivariable analyses assessed participants' change in interest in screening, and subgroup differences in this change. Personalized CRC risk information had no overall effect on CRC screening interest, but significant subgroup differences were observed. Change in screening interest was greater among individuals with recent screening (p=.015), higher model-estimated cancer risk (p=.0002), and lower baseline interest (p<.0001), with individuals at highest baseline interest demonstrating negative (not neutral) change in interest. Effects of quantitative personalized CRC risk information on laypersons' interest in CRC screening differ among individuals depending on prior screening history, estimated cancer risk, and baseline screening interest. Personalized cancer risk information has personalized effects-increasing and decreasing screening interest in different individuals. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Breastfeeding Promotion, Support and Protection: Review of Six Country Programmes

PubMed Central

Mangasaryan, Nune; Martin, Luann; Brownlee, Ann; Ogunlade, Adebayo; Rudert, Christiane; Cai, Xiaodong

2012-01-01

Reviews of programmes in Bangladesh, Benin, the Philippines, Sri Lanka, Uganda, and Uzbekistan sought to identify health policy and programmatic factors that influenced breastfeeding practices during a 10 to 15 year period. Exclusive breastfeeding rates and trends were analysed in six countries in general and from an equity perspective in two of them. Success factors and challenges were identified in countries with improved and stagnated rates respectively. The disaggregated data analysis showed that progress may be unequal in population subgroups, but if appropriately designed and implemented, a programme can become a “health equalizer” and eliminate discrepancies among different subgroups. Success requires commitment, supportive policies, and comprehensiveness of programmes for breastfeeding promotion, protection and support. Community-based promotion and support was identified as a particularly important component. Although health workers’ training on infant feeding support and counselling was prioritized, further improvement of interpersonal counselling and problem solving skills is needed. More attention is advised for pre-service education, including a stronger focus on clinical practice, to ensure knowledge and skills among all health workers. Large-scale communication activities played a significant role, but essential steps were often underemphasized, including identifying social norms and influencing factors, ensuring community participation, and testing of approaches and messages. PMID:23016128

Shunting normal pressure hydrocephalus: the predictive value of combined clinical and CT data.

PubMed

Vanneste, J; Augustijn, P; Tan, W F; Dirven, C

1993-03-01

The value of an ordinal global scale derived from combined clinical and CT data (clin/CT scale) to predict the clinical outcome in 112 patients shunted for presumed normal pressure hydrocephalus (NPH) was analysed. The clinical data were retrospectively collected, all CT scans were re-evaluated, and the clin/CT scale was determined blind to the results of further ancillary tests and to the post-surgical outcome. The scale ranked three classes of prediction: on the basis of clinical and CT characteristics, improvement after shunting was probable, possible, or improbable. The predictive value of the clin/CT scale for the subgroup of communicating NPH was established for two different strategies, depending on the strictness of selection criteria for shunting. In the subgroup of patients with presumed communicating NPH, the prevalence of shunt responsiveness was 29%; the best strategy was to shunt only patients with probable shunt-responsive NPH: the sensitivity was 0.54, the specificity 0.84, and the predictive accuracy 0.75, with a limited number of ineffective shunts (11%) and missed improvements (13%). The study illustrates its need to assess the pre-test probability of NPH based on combined clinical and CT data, before establishing the clinical usefulness of an ancillary test.

Shunting normal pressure hydrocephalus: the predictive value of combined clinical and CT data.

PubMed Central

Vanneste, J; Augustijn, P; Tan, W F; Dirven, C

1993-01-01

The value of an ordinal global scale derived from combined clinical and CT data (clin/CT scale) to predict the clinical outcome in 112 patients shunted for presumed normal pressure hydrocephalus (NPH) was analysed. The clinical data were retrospectively collected, all CT scans were re-evaluated, and the clin/CT scale was determined blind to the results of further ancillary tests and to the post-surgical outcome. The scale ranked three classes of prediction: on the basis of clinical and CT characteristics, improvement after shunting was probable, possible, or improbable. The predictive value of the clin/CT scale for the subgroup of communicating NPH was established for two different strategies, depending on the strictness of selection criteria for shunting. In the subgroup of patients with presumed communicating NPH, the prevalence of shunt responsiveness was 29%; the best strategy was to shunt only patients with probable shunt-responsive NPH: the sensitivity was 0.54, the specificity 0.84, and the predictive accuracy 0.75, with a limited number of ineffective shunts (11%) and missed improvements (13%). The study illustrates its need to assess the pre-test probability of NPH based on combined clinical and CT data, before establishing the clinical usefulness of an ancillary test. PMID:8459240

Longitudinal Examination of Symptom Profiles Among Breast Cancer Survivors.

PubMed

Avis, Nancy E; Levine, Beverly; Marshall, Sarah A; Ip, Edward H

2017-04-01

Identification of cancer patients with similar symptom profiles may facilitate targeted symptom management. To identify subgroups of breast cancer survivors based on differential experience of symptoms, examine change in subgroup membership over time, and identify relevant characteristics and quality of life (QOL) among subgroups. Secondary analyses of data from 653 breast cancer survivors recruited within eight months of diagnosis who completed questionnaires at five time points. Hidden Markov modeling was used to 1) formulate symptom profiles based on prevalence and severity of eight symptoms commonly associated with breast cancer and 2) estimate probabilities of changing subgroup membership over 18 months of follow-up. Ordinal repeated measures were used to 3) identify patient characteristics related to subgroup membership and 4) evaluate the relationship between symptom subgroup and QOL. A seven-subgroup model provided the best fit: 1) low symptom burden, 2) mild fatigue, 3) mild fatigue and mild pain, 4) moderate fatigue and moderate pain, 5) moderate fatigue and moderate psychological, 6) moderate fatigue, mild pain, mild psychological, and 7) high symptom burden. Seventy percent of survivors remained in the same subgroup over time. In multivariable analyses, chemotherapy and greater illness intrusiveness were significantly related to greater symptom burden, while not being married or partnered, no difficulty paying for basics, and greater social support were protective. Higher symptom burden was associated with lower QOL. Survivors who reported psychological symptoms had significantly lower QOL than did survivors with pain symptoms. Cancer survivors can be differentiated by their symptom profiles. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

The clinical usefulness of the new LPE specifier for subtyping adolescents with conduct disorder in the DSM 5.

PubMed

Jambroes, Tijs; Jansen, Lucres M C; Vermeiren, Robert R J M; Doreleijers, Theo A H; Colins, Olivier F; Popma, Arne

2016-08-01

In DSM 5, conduct disorder (CD) has been expanded with a new specifier 'with Limited Prosocial Emotions' (LPE) in addition to the age-of-onset (AoO) subtyping, and is thought to identify a severe antisocial subgroup of CD. However, research in clinical practice has been scarce. Therefore, the current study will examine differences in clinical symptoms between subtypes of CD, based on both subtyping schemes. Subsequently, it will investigate whether the LPE specifier explains unique variance in aggression, added to the AoO subtyping. A sample of 145 adolescents with CD (51 % male, mean age 15.0) from a closed treatment institution participated in this study. CD diagnoses and AoO subtype were assessed using a structured diagnostic interview. The LPE specifier was assessed using the callous-unemotional dimension of the Youth Psychopathy Traits Inventory (YPI). Self-reported proactive and reactive aggression, rule-breaking behavior and internalizing problems within the subtypes were compared. Youth with childhood-onset CD and LPE showed significantly more aggression than adolescent-onset CD without LPE (proactive aggression: F = 3.1, p < 0.05, reactive aggression: F = 3.7, p < 0.05). Hierarchical regression revealed that the LPE specifier uniquely explained 7 % of the variance in reactive aggression, additionally to the AoO subtyping. For proactive aggression, the interaction between AoO and the LPE added 4.5 % to the explained variance. Although the LPE specifier may help to identify a more aggressive subtype of CD in adolescents, the incremental utility seems to be limited. Therefore, clinical relevance of the LPE specifier in high-risk adolescent samples still needs to be investigated thoroughly.

Resistance profiles to antimicrobial agents in bacteria isolated from acute endodontic infections: systematic review and meta-analysis.

PubMed

Lang, Pauline M; Jacinto, Rogério C; Dal Pizzol, Tatiane S; Ferreira, Maria Beatriz C; Montagner, Francisco

2016-11-01

Infected root canal or acute apical abscess exudates can harbour several species, including Fusobacterium, Porphyromonas, Prevotella, Parvimonas, Streptococcus, Treponema, Olsenella and not-yet cultivable species. A systematic review and meta-analysis was performed to assess resistance rates to antimicrobial agents in clinical studies that isolated bacteria from acute endodontic infections. Electronic databases and the grey literature were searched up to May 2015. Clinical studies in humans evaluating the antimicrobial resistance of primary acute endodontic infection isolates were included. PRISMA guidelines were followed. A random-effect meta-analysis was employed. The outcome was described as the pooled resistance rates for each antimicrobial agent. Heterogeneity and sensitivity analyses were performed. Subgroup analyses were conducted based upon report or not of the use of antibiotics prior to sampling as an exclusion factor (subgroups A and B, respectively). Data from seven studies were extracted. Resistance rates for 15 different antimicrobial agents were evaluated (range, 3.5-40.0%). Lower resistance rates were observed for amoxicillin/clavulanic acid and amoxicillin; higher resistance rates were detected for tetracycline. Resistance rates varied according to previous use of an antimicrobial agent as demonstrated by the subgroup analyses. Heterogeneity was observed for the resistance profiles of penicillin G in subgroup A and for amoxicillin, clindamycin, metronidazole and tetracycline in subgroup B. Sensitivity analyses demonstrated that resistance rates changed for metronidazole, clindamycin, tetracycline and amoxicillin. These findings suggest that clinical isolates had low resistance to β-lactams. Further well-designed studies are needed to clarify whether the differences in susceptibility among the antimicrobial agents may influence clinical responses to treatment. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

The cardiovascular safety trials of DPP-4 inhibitors, GLP-1 agonists, and SGLT2 inhibitors.

PubMed

Secrest, Matthew H; Udell, Jacob A; Filion, Kristian B

2017-04-01

In this paper, we review the results of large, double-blind, placebo-controlled randomized trials mandated by the US Food and Drug Administration to examine the cardiovascular safety of newly-approved antihyperglycemic agents in patients with type 2 diabetes. The cardiovascular effects of dipeptidyl peptidase-4 (DPP-4) inhibitors remain controversial: while these drugs did not reduce or increase the risk of primary, pre-specified composite cardiovascular outcomes, one DPP-4 inhibitor (saxagliptin) increased the risk of hospitalization for heart failure in the overall population; another (alogliptin) demonstrated inconsistent effects on heart failure hospitalization across subgroups of patients, and a third (sitagliptin) demonstrated no effect on heart failure. Evidence for cardiovascular benefits of glucagon-like peptide-1 (GLP-1) agonists has been similarly heterogeneous, with liraglutide and semaglutide reducing the risk of composite cardiovascular outcomes, but lixisenatide having no reduction or increase in cardiovascular risk. The effect of GLP-1 agonists on retinopathy remains a potential concern. In the only completed trial to date to assess a sodium-glucose cotransporter-2 (SGLT2) inhibitor, empagliflozin reduced the risk of composite cardiovascular endpoints, predominantly through its impact on cardiovascular mortality and heart failure hospitalization. Copyright © 2017 Elsevier Inc. All rights reserved.

Behavior-Based Language Generation for Believable Agents,

DTIC Science & Technology

1995-03-01

retaining only those aspects of the agent that are essential to express its personality and its role in the work of which it is part.1 While full realism is...must contain a type and a role feature. The type provides information about the expected elements of the group and the level of the group in the...linguistic hierarchy, for example morpheme, word, phrase, or clause. The role specifies the group’s function within its parent group. All subgroups

Modulation of Coronary Heart Disease Risk by Insulin Resistance in Subjects With Normal Glucose Tolerance or Prediabetes

PubMed Central

Ariel, Danit; Reaven, Gerald

2014-01-01

Aims/hypothesis This study is based on the hypothesis that: 1)coronary heart disease (CHD) risk is accentuated in the insulin resistant subset of persons with normal glucose tolerance (NGT) or prediabetes (PreDM); 2)the prevalence of insulin resistance, and associated abnormalities, is greater in subjects with PreDM; and 3)insulin resistance is the major contributor to increased CHD risk in these individuals. Methods A 75 g oral glucose challenge was used to classify volunteers as having NGT or PreDM. Steady-state plasma glucose (SSPG) concentrations during the insulin suppression test subdivided both groups into insulin sensitive (IS=SSPG <8.4 mmol/L) or resistant (IR=SSPG ≥8.4 mmol/L). Measurements were made of demographic characteristics, blood pressure, and lipid and lipoprotein concentrations, and comparisons made between the subgroups. Results Subjects with PreDM (n=127) were somewhat older, more likely to be non-Hispanic men, with increased adiposity than those with NGT (n=315). In addition, they had higher FPG concentrations, were insulin resistant (SSPG concentration; 11.4 vs. 7.2 mmol/L), with higher blood pressures, and a significantly more adverse CHD risk lipid profile (p<0.001). Twice as many subjects with PreDM were IR (72% vs. 35 %), and the CHD risk profile was significantly worse in the IR subgroups in those with either NGT or PreDM. Conclusions/interpretation CHD risk profile is significantly more adverse in subjects with PreDM as compared to individuals with NGT. However, glucose tolerance status is not the only determinant of CHD risk in nondiabetic individuals, and differences in degree of insulin resistance significantly modulate CHD risk in subjects with NGT or PreDM. PMID:25358836

Diversity and evolutionary history of lettuce necrotic yellows virus in Australia and New Zealand.

PubMed

Higgins, Colleen M; Chang, Wee-Leong; Khan, Subuhi; Tang, Joe; Elliott, Carol; Dietzgen, Ralf G

2016-02-01

Lettuce necrotic yellows virus (LNYV) is the type member of the genus Cytorhabdovirus, family Rhabdoviridae, and causes a severe disease of lettuce (Lactuca sativa L.). This virus has been described as endemic to Australia and New Zealand, with sporadic reports of a similar virus in Europe. Genetic variability studies of plant-infecting rhabdoviruses are scarce. We have extended a previous study on the variability of the LNYV nucleocapsid gene, comparing sequences from isolates sampled from both Australia and New Zealand, as well as analysing symptom expression on Nicotiana glutinosa. Phylogenetic and BEAST analyses confirm separation of LNYV isolates into two subgroups (I and II) and suggest that subgroup I is slightly older than subgroup II. No correlation was observed between isolate subgroup and disease symptoms on N. glutinosa. The origin of LNYV remains unclear; LNYV may have moved between native and weed hosts within Australia or New Zealand before infecting lettuce or may have appeared as a result of at least two incursions, with the first coinciding with the beginning of European agriculture in the region. The apparent extinction of subgroup I in Australia may have been due to less-efficient dispersal than that which has occurred for subgroup II - possibly a consequence of suboptimal interactions with plant and/or insect hosts. Introduction of subgroup II to New Zealand appears to be more recent. More-detailed epidemiological studies using molecular tools are needed to fully understand how LNYV interacts with its hosts and to determine where the virus originated.

Acoustic Features Influence Musical Choices Across Multiple Genres.

PubMed

Barone, Michael D; Bansal, Jotthi; Woolhouse, Matthew H

2017-01-01

Based on a large behavioral dataset of music downloads, two analyses investigate whether the acoustic features of listeners' preferred musical genres influence their choice of tracks within non-preferred, secondary musical styles. Analysis 1 identifies feature distributions for pairs of genre-defined subgroups that are distinct. Using correlation analysis, these distributions are used to test the degree of similarity between subgroups' main genres and the other music within their download collections. Analysis 2 explores the issue of main-to-secondary genre influence through the production of 10 feature-influence matrices, one per acoustic feature, in which cell values indicate the percentage change in features for genres and subgroups compared to overall population averages. In total, 10 acoustic features and 10 genre-defined subgroups are explored within the two analyses. Results strongly indicate that the acoustic features of people's main genres influence the tracks they download within non-preferred, secondary musical styles. The nature of this influence and its possible actuating mechanisms are discussed with respect to research on musical preference, personality, and statistical learning.

Distributional benefit analysis of a national air quality rule.

PubMed

Post, Ellen S; Belova, Anna; Huang, Jin

2011-06-01

Under Executive Order 12898, the U.S. Environmental Protection Agency (EPA) must perform environmental justice (EJ) reviews of its rules and regulations. EJ analyses address the hypothesis that environmental disamenities are experienced disproportionately by poor and/or minority subgroups. Such analyses typically use communities as the unit of analysis. While community-based approaches make sense when considering where polluting sources locate, they are less appropriate for national air quality rules affecting many sources and pollutants that can travel thousands of miles. We compare exposures and health risks of EJ-identified individuals rather than communities to analyze EPA's Heavy Duty Diesel (HDD) rule as an example national air quality rule. Air pollutant exposures are estimated within grid cells by air quality models; all individuals in the same grid cell are assigned the same exposure. Using an inequality index, we find that inequality within racial/ethnic subgroups far outweighs inequality between them. We find, moreover, that the HDD rule leaves between-subgroup inequality essentially unchanged. Changes in health risks depend also on subgroups' baseline incidence rates, which differ across subgroups. Thus, health risk reductions may not follow the same pattern as reductions in exposure. These results are likely representative of other national air quality rules as well.

Evolution of specifier proteins in glucosinolate-containing plants

PubMed Central

2012-01-01

Background The glucosinolate-myrosinase system is an activated chemical defense system found in plants of the Brassicales order. Glucosinolates are stored separately from their hydrolytic enzymes, the myrosinases, in plant tissues. Upon tissue damage, e.g. by herbivory, glucosinolates and myrosinases get mixed and glucosinolates are broken down to an array of biologically active compounds of which isothiocyanates are toxic to a wide range of organisms. Specifier proteins occur in some, but not all glucosinolate-containing plants and promote the formation of biologically active non-isothiocyanate products upon myrosinase-catalyzed glucosinolate breakdown. Results Based on a phytochemical screening among representatives of the Brassicales order, we selected candidate species for identification of specifier protein cDNAs. We identified ten specifier proteins from a range of species of the Brassicaceae and assigned each of them to one of the three specifier protein types (NSP, nitrile-specifier protein, ESP, epithiospecifier protein, TFP, thiocyanate-forming protein) after heterologous expression in Escherichia coli. Together with nine known specifier proteins and three putative specifier proteins found in databases, we subjected the newly identified specifier proteins to phylogenetic analyses. Specifier proteins formed three major clusters, named AtNSP5-cluster, AtNSP1-cluster, and ESP/TFP cluster. Within the ESP/TFP cluster, specifier proteins grouped according to the Brassicaceae lineage they were identified from. Non-synonymous vs. synonymous substitution rate ratios suggested purifying selection to act on specifier protein genes. Conclusions Among specifier proteins, NSPs represent the ancestral activity. The data support a monophyletic origin of ESPs from NSPs. The split between NSPs and ESPs/TFPs happened before the radiation of the core Brassicaceae. Future analyses have to show if TFP activity evolved from ESPs at least twice independently in different Brassicaceae lineages as suggested by the phylogeny. The ability to form non-isothiocyanate products by specifier protein activity may provide plants with a selective advantage. The evolution of specifier proteins in the Brassicaceae demonstrates the plasticity of secondary metabolism within an activated plant defense system. PMID:22839361

42 CFR 418.205 - Special requirements for hospice pre-election evaluation and counseling services.

Code of Federal Regulations, 2011 CFR

2011-10-01

... evaluation and counseling services. 418.205 Section 418.205 Public Health CENTERS FOR MEDICARE & MEDICAID... Services § 418.205 Special requirements for hospice pre-election evaluation and counseling services. (a... evaluation and counseling services as specified in § 418.304(d) may be made to a hospice on behalf of a...

42 CFR 418.205 - Special requirements for hospice pre-election evaluation and counseling services.

Code of Federal Regulations, 2010 CFR

2010-10-01

... evaluation and counseling services. 418.205 Section 418.205 Public Health CENTERS FOR MEDICARE & MEDICAID... Services § 418.205 Special requirements for hospice pre-election evaluation and counseling services. (a... evaluation and counseling services as specified in § 418.304(d) may be made to a hospice on behalf of a...

40 CFR 86.341-79 - Diesel engine dynamometer test run.

Code of Federal Regulations, 2012 CFR

2012-07-01

... and sample probes as required; (2) Observe pre-test procedure, § 86.339; (3) Read and record the... observed torque for the rated and intermediate speeds; (8) Read and record all pre-test data specified in... 40 Protection of Environment 19 2012-07-01 2012-07-01 false Diesel engine dynamometer test run. 86...

40 CFR 86.341-79 - Diesel engine dynamometer test run.

Code of Federal Regulations, 2013 CFR

2013-07-01

... and sample probes as required; (2) Observe pre-test procedure, § 86.339; (3) Read and record the... observed torque for the rated and intermediate speeds; (8) Read and record all pre-test data specified in... 40 Protection of Environment 19 2013-07-01 2013-07-01 false Diesel engine dynamometer test run. 86...

40 CFR 86.341-79 - Diesel engine dynamometer test run.

Code of Federal Regulations, 2010 CFR

2010-07-01

... and sample probes as required; (2) Observe pre-test procedure, § 86.339; (3) Read and record the... observed torque for the rated and intermediate speeds; (8) Read and record all pre-test data specified in... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Diesel engine dynamometer test run. 86...

40 CFR 86.341-79 - Diesel engine dynamometer test run.

Code of Federal Regulations, 2011 CFR

2011-07-01

... and sample probes as required; (2) Observe pre-test procedure, § 86.339; (3) Read and record the... observed torque for the rated and intermediate speeds; (8) Read and record all pre-test data specified in... 40 Protection of Environment 18 2011-07-01 2011-07-01 false Diesel engine dynamometer test run. 86...

Pre-wired systems prove their worth.

PubMed

2012-03-01

The 'new generation' of modular wiring systems from Apex Wiring Solutions have been specified for two of the world's foremost teaching hospitals - the Royal London and St Bartholomew's Hospital, as part of a pounds sterling 1 billion redevelopment project, to cut electrical installation times, reduce on-site waste, and provide a pre-wired, factory-tested, power and lighting system. HEJ reports.

Evaluation of a bespoke training to increase uptake by midwifery teams of NICE Guidance for membrane sweeping to reduce induction of labour: a stepped wedge cluster randomised design.

PubMed

Kenyon, Sara; Dann, Sophie; Hope, Lucy; Clarke, Paula; Hogan, Amanda; Jenkinson, David; Hemming, Karla

2017-07-27

National guidance recommends pregnant women are offered membrane sweeping at term to reduce induction of labour. Local audit suggested this was not being undertaken routinely across two maternity units in the West Midlands, UK between March and November 2012. Bespoke training session for midwifery teams (nine community and one antenatal clinic) was developed to address identified barriers to encourage offer of membrane sweeping, together with an information leaflet for women and appointment of a champion within each team. The timing of training session on membrane sweeping to ten midwifery teams was randomly allocated using a stepped wedge cluster randomised design. All women who gave birth in the Trusts after 39 + 3/40 weeks gestation within the study time period were eligible. Relevant anonymised data were extracted from maternity notes for three months before and after training. Data were analysed using a generalised linear mixed model, allowing for clustering and adjusting for temporal effects. Primary outcomes were number of women offered and accepting membrane sweeping and average number of sweeps per woman. Sub-group comparisons were undertaken for adherence to Trust guidance and potential influence of pre-specified maternal characteristics. Data included whether sweeping was offered but declined and no record of membrane sweeping. Training was given to all teams as planned. Analyses included data from 2787 of the 2864 (97%) eligible low-risk women over 39 + 4 weeks pregnant. Characteristics of the women were similar before and after training. No evidence of difference in proportion of women being offered and accepting membrane sweeping (44.4% before training versus 46.8% after training (adjusted relative risk [aRR] = 0.90, 95% confidence interval [CI] = 0.71-1.13), nor in average number of sweeps per woman (0.603 versus 0.627, aRR = 0.83, 95% CI = 0.67-1.01). No differences in any secondary outcomes nor influence of maternal characteristics were demonstrated. The midwives evaluated training positively. This stepped wedge cluster trial enabled randomised evaluation within a natural roll-out and demonstrates the importance of robust evaluation in circumstances in which it is rarely undertaken. While the midwives evaluated the training positively, it did not appear to change practice. ISRCTN14300475 . Registered on 23 August 2016.

Clustering of self-organizing map identifies five distinct medulloblastoma subgroups.

PubMed

Cao, Changjun; Wang, Wei; Jiang, Pucha

2016-01-01

Medulloblastoma is one the most malignant paediatric brain tumours. Molecular subgrouping these medulloblastomas will not only help identify specific cohorts for certain treatment but also improve confidence in prognostic prediction. Currently, there is a consensus of the existences of four distinct subtypes of medulloblastoma. We proposed a novel bioinformatics method, clustering of self-organizing map, to determine the subgroups and their molecular diversity. Microarray expression profiles of 46 medulloblastoma samples were analysed and five clusters with distinct demographics, clinical outcome and transcriptional profiles were identified. The previously reported Wnt subgroup was identified as expected. Three other novel subgroups were proposed for later investigation. Our findings underscore the value of SOM clustering for discovering the medulloblastoma subgroups. When the suggested subdivision has been confirmed in large cohorts, this method should serve as a part of routine classification of clinical samples.

Non-anaplastic peripheral T cell lymphoma in children and adolescents-an international review of 143 cases.

PubMed

Mellgren, K; Attarbaschi, A; Abla, O; Alexander, S; Bomken, S; Bubanska, E; Chiang, A; Csóka, M; Fedorova, A; Kabickova, E; Kapuscinska-Kemblowska, L; Kobayashi, R; Krenova, Z; Meyer-Wentrup, F; Miakova, N; Pillon, M; Plat, G; Uyttebroeck, A; Williams, D; Wróbel, G; Kontny, U

2016-08-01

Peripheral T cell lymphomas (PTCL) are rare in children and adolescents, and data about outcome and treatment results are scarce. The present study is a joint, international, retrospective analysis of 143 reported cases of non-anaplastic PTCL in patients <19 years of age, with a focus on treatment and outcome features. One hundred forty-three patients, between 0.3 and 18.7 years old, diagnosed between 2000 and 2015 were included in the study. PTCL not otherwise specified was the largest subgroup, followed by extranodal NK/T cell lymphoma, hepatosplenic T cell lymphoma (HS TCL), and subcutaneous panniculitis-like T cell lymphoma (SP TCL). Probability of overall survival (pOS) at 5 years for the whole group was 0.56 ± 0.05, and probability of event-free survival was (pEFS) 0.45 ± 0.05. Patients with SP TCL had a good outcome with 5-year pOS of 0.78 ± 0.1 while patients with HS TCL were reported with 5-year pOS of only 0.13 ± 0.12. Twenty-five percent of the patients were reported to have a pre-existing condition, and this group had a dismal outcome with 5-year pOS of 0.29 ± 0.09. The distribution of non-anaplastic PTCL subtypes in pediatric and adolescent patients differs from what is reported in adult patients. Overall outcome depends on the subtype with some doing better than others. Pre-existing conditions are frequent and associated with poor outcomes. There is a clear need for subtype-based treatment recommendations for children and adolescents with PTCL.

Systematic review of model-based analyses reporting the cost-effectiveness and cost-utility of cardiovascular disease management programs.

PubMed

Maru, Shoko; Byrnes, Joshua; Whitty, Jennifer A; Carrington, Melinda J; Stewart, Simon; Scuffham, Paul A

2015-02-01

The reported cost effectiveness of cardiovascular disease management programs (CVD-MPs) is highly variable, potentially leading to different funding decisions. This systematic review evaluates published modeled analyses to compare study methods and quality. Articles were included if an incremental cost-effectiveness ratio (ICER) or cost-utility ratio (ICUR) was reported, it is a multi-component intervention designed to manage or prevent a cardiovascular disease condition, and it addressed all domains specified in the American Heart Association Taxonomy for Disease Management. Nine articles (reporting 10 clinical outcomes) were included. Eight cost-utility and two cost-effectiveness analyses targeted hypertension (n=4), coronary heart disease (n=2), coronary heart disease plus stoke (n=1), heart failure (n=2) and hyperlipidemia (n=1). Study perspectives included the healthcare system (n=5), societal and fund holders (n=1), a third party payer (n=3), or was not explicitly stated (n=1). All analyses were modeled based on interventions of one to two years' duration. Time horizon ranged from two years (n=1), 10 years (n=1) and lifetime (n=8). Model structures included Markov model (n=8), 'decision analytic models' (n=1), or was not explicitly stated (n=1). Considerable variation was observed in clinical and economic assumptions and reporting practices. Of all ICERs/ICURs reported, including those of subgroups (n=16), four were above a US$50,000 acceptability threshold, six were below and six were dominant. The majority of CVD-MPs was reported to have favorable economic outcomes, but 25% were at unacceptably high cost for the outcomes. Use of standardized reporting tools should increase transparency and inform what drives the cost-effectiveness of CVD-MPs. © The European Society of Cardiology 2014.

Relative Age Effects Across and Within Female Sport Contexts: A Systematic Review and Meta-Analysis.

PubMed

Smith, Kristy L; Weir, Patricia L; Till, Kevin; Romann, Michael; Cobley, Stephen

2018-06-01

Subtle differences in chronological age within sport (bi-) annual-age groupings can contribute to immediate participation and long-term attainment discrepancies; known as the relative age effect. Voluminous studies have examined relative age effects in male sport; however, their prevalence and context-specific magnitude in female sport remain undetermined. The objective of this study was to determine the prevalence and magnitude of relative age effects in female sport via examination of published data spanning 1984-2016. Registered with PROSPERO (No. 42016053497) and using Preferred Reporting Items for Systematic Reviews and Meta-analysis systematic search guidelines, 57 studies were identified, containing 308 independent samples across 25 sports. Distribution data were synthesised using odds ratio meta-analyses, applying an invariance random-effects model. Follow-up subgroup category analyses examined whether relative age effect magnitudes were moderated by age group, competition level, sport type, sport context and study quality. When comparing the relatively oldest (quartile 1) vs. youngest (quartile 4) individuals across all female sport contexts, the overall pooled estimate identified a significant but small relative age effect (odds ratio = 1.25; 95% confidence interval 1.21-1.30; p = 0.01; odds ratio adjusted = 1.21). Subgroup analyses revealed the relative age effect magnitude was higher in pre-adolescent (≤ 11 years) and adolescent (12-14 years) age groups and at higher competition levels. Relative age effect magnitudes were higher in team-based and individual sport contexts associated with high physiological demands. The findings highlight relative age effects are prevalent across the female sport contexts examined. Relative age effect magnitude is moderated by interactions between developmental stages, competition level and sport context demands. Modifications to sport policy, organisational and athlete development system structure, as well as practitioner intervention are recommended to prevent relative age effect-related participation and longer term attainment inequalities.

Psychotherapeutic Treatment for Anorexia Nervosa: A Systematic Review and Network Meta-Analysis

PubMed Central

Zeeck, Almut; Herpertz-Dahlmann, Beate; Friederich, Hans-Christoph; Brockmeyer, Timo; Resmark, Gaby; Hagenah, Ulrich; Ehrlich, Stefan; Cuntz, Ulrich; Zipfel, Stephan; Hartmann, Armin

2018-01-01

Background: The aim of the study was a systematic review of studies evaluating psychotherapeutic treatment approaches in anorexia nervosa and to compare their efficacy. Weight gain was chosen as the primary outcome criterion. We also aimed to compare treatment effects according to service level (inpatient vs. outpatient) and age group (adolescents vs. adults). Methods:The data bases PubMed, Cochrane Library, Web of Science, Cinahl, and PsychInfo were used for a systematic literature search (until Feb 2017). Search terms were adapted for data base, combining versions of the search terms anorexia, treat*/therap* and controlled trial. Studies were selected using pre-defined in- and exclusion criteria. Data were extracted by two independent coders using piloted forms. Network-meta-analyses were conducted on all RCTs. For a comparison of service levels and age groups, standard mean change (SMC) statistics were used and naturalistic, non-randomized studies included. Results: Eighteen RCTs (trials on adults: 622 participants; trials on adolescents: 625 participants) were included in the network meta-analysis. SMC analyses were conducted with 38 studies (1,164 participants). While family-based approaches dominate interventions for adolescents, individual psychotherapy dominates in adults. There was no superiority of a specific approach. Weight gains were more rapid in adolescents and inpatient treatment. Conclusions: Several specialized psychotherapeutic interventions have been developed and can be recommended for AN. However, adult and adolescent patients should be distinguished, as groups differ in terms of treatment approaches considered suitable as well as treatment response. Future trials should replicate previous findings and be multi-center trials with large sample sizes to allow for subgroup analyses. Patient assessment should include variables that can be considered relevant moderators of treatment outcome. It is desirable to explore adaptive treatment strategies for subgroups of patients with AN. Identifying and addressing maintaining factors in AN remains a major challenge. PMID:29765338

Effect of soya protein on blood pressure: a meta-analysis of randomised controlled trials.

PubMed

Dong, Jia-Yi; Tong, Xing; Wu, Zhi-Wei; Xun, Peng-Cheng; He, Ka; Qin, Li-Qiang

2011-08-01

Observational studies have indicated that soya food consumption is inversely associated with blood pressure (BP). Evidence from randomised controlled trials (RCT) on the BP-lowering effects of soya protein intake is inconclusive. We aimed to evaluate the effectiveness of soya protein intake in lowering BP. The PubMed database was searched for published RCT in the English language through to April 2010, which compared a soya protein diet with a control diet. We conducted a random-effects meta-analysis to examine the effects of soya protein on BP. Subgroup and meta-regression analyses were performed to explore possible explanations for heterogeneity among trials. Meta-analyses of twenty-seven RCT showed a mean decrease of 2·21 mmHg (95 % CI - 4·10, - 0·33; P = 0·021) for systolic BP (SBP) and 1·44 mmHg (95 % CI - 2·56, - 0·31; P = 0·012) for diastolic BP (DBP), comparing the participants in the soya protein group with those in the control group. Soya protein consumption significantly reduced SBP and DBP in both hypertensive and normotensive subjects, and the reductions were markedly greater in hypertensive subjects. Significant and greater BP reductions were also observed in trials using carbohydrate, but not milk products, as the control diet. Meta-regression analyses further revealed a significantly inverse association between pre-treatment BP and the level of BP reductions. In conclusion, soya protein intake, compared with a control diet, significantly reduces both SBP and DBP, but the BP reductions are related to pre-treatment BP levels of subjects and the type of control diet used as comparison.

Molecular heterogeneity at the network level: high-dimensional testing, clustering and a TCGA case study.

PubMed

Städler, Nicolas; Dondelinger, Frank; Hill, Steven M; Akbani, Rehan; Lu, Yiling; Mills, Gordon B; Mukherjee, Sach

2017-09-15

Molecular pathways and networks play a key role in basic and disease biology. An emerging notion is that networks encoding patterns of molecular interplay may themselves differ between contexts, such as cell type, tissue or disease (sub)type. However, while statistical testing of differences in mean expression levels has been extensively studied, testing of network differences remains challenging. Furthermore, since network differences could provide important and biologically interpretable information to identify molecular subgroups, there is a need to consider the unsupervised task of learning subgroups and networks that define them. This is a nontrivial clustering problem, with neither subgroups nor subgroup-specific networks known at the outset. We leverage recent ideas from high-dimensional statistics for testing and clustering in the network biology setting. The methods we describe can be applied directly to most continuous molecular measurements and networks do not need to be specified beforehand. We illustrate the ideas and methods in a case study using protein data from The Cancer Genome Atlas (TCGA). This provides evidence that patterns of interplay between signalling proteins differ significantly between cancer types. Furthermore, we show how the proposed approaches can be used to learn subtypes and the molecular networks that define them. As the Bioconductor package nethet. staedler.n@gmail.com or sach.mukherjee@dzne.de. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Association of Gestational Hypertensive Disorders with Retinopathy of prematurity: A Systematic Review and Meta-analysis.

PubMed

Chan, Priscilla Y L; Tang, Shu-Min; Au, Sunny C L; Rong, Shi-Song; Lau, Henry H W; Ko, Simon T C; Ng, Danny S C; Chen, Li Jia; Yam, Jason C S

2016-08-05

The role of gestational hypertensive disorders, which includes both pre-eclampsia and gestational hypertension, in the development of retinopathy of prematurity (ROP) has been controversial. Therefore, this systematic review and meta-analysis is to evaluate the association between gestational hypertensive disoders and ROP. Eligible studies published up to June 5, 2016 were identified from MEDLINE and EMBASE that evaluated the association between the two conditions. Totally 1142 published records were retrieved for screening, 925 of them eligible for detailed evaluation. Finally 19 studies involving 45281 infants with 5388 cases of ROP met our criteria for meta-analysis. Gestational hypertensive disorders were not associated with ROP (unadjusted OR: 0.89; P = 0.38; adjusted OR: 1.35; P = 0.18). Subgroup analyses also revealed no significant association between ROP with pre-eclampsia (unadjusted OR: 0.85; P = 0.29; adjusted OR:1.29; P = 0.28) or with gestational hypertension (unadjusted OR: 1.10; P = 0.39; adjusted OR: 1.25; P = 0.60) separately. Sensitivity analysis indicated our results were robust. We concluded no significant association between gestational hypertensive disorders and ROP. More large scale well-conducted prospective cohorts on the topic are needed.

Trait anxiety mediates the effect of stress exposure on post-traumatic stress disorder and depression risk in cardiac surgery patients.

PubMed

Kok, Lotte; Sep, Milou S; Veldhuijzen, Dieuwke S; Cornelisse, Sandra; Nierich, Arno P; van der Maaten, Joost; Rosseel, Peter M; Hofland, Jan; Dieleman, Jan M; Vinkers, Christiaan H; Joëls, Marian; van Dijk, Diederik; Hillegers, Manon H

2016-12-01

Post-traumatic stress disorder (PTSD) and depression are common after cardiac surgery. Lifetime stress exposure and personality traits may influence the development of these psychiatric conditions. Self-reported rates of PTSD and depression and potential determinants (i.e., trait anxiety and stress exposure) were established 1.5 to 4 years after cardiac surgery. Data was available for 1125 out of 1244 (90.4%) participants. Multivariable linear regressions were conducted to investigate mediating and/or moderating effects of trait anxiety on the relationship between stress exposure, and PTSD and depression. Pre-planned subgroup analyses were performed for both sexes. PTSD and depression symptoms were present in 10.2% and 13.1% of the participants, respectively. Trait anxiety was a full mediator of the association between stress exposure and depression in both the total cohort and female and male subgroups. Moreover, trait anxiety partially mediated the relationship between stress exposure and PTSD in the full cohort and the male subgroup, whereas trait anxiety fully mediated this relationship in female patients. Trait anxiety did not play a moderating role in the total patient sample, nor after stratification on gender. The unequal distribution of male (78%) and female patients (22%) might limit the generalizability of our findings. Furthermore, risk factors were investigated retrospectively and with variable follow-up time. In cardiac surgery patients, trait anxiety was found to be an important mediator of postoperative PTSD and depression. Prospective research is necessary to verify whether these factors are reliable screening measures of individuals' vulnerability for psychopathology development after cardiac surgery. Copyright © 2016 Elsevier B.V. All rights reserved.

Commognitive Analysis of Undergraduate Mathematics Students' First Encounter with the Subgroup Test

ERIC Educational Resources Information Center

Ioannou, Marios

2018-01-01

This study analyses learning aspects of undergraduate mathematics students' first encounter with the subgroup test, using the commognitive theoretical framework. It focuses on students' difficulties as these are related to the object-level and metalevel mathematical learning in group theory, and, when possible, highlights any commognitive…

Adult Developmental Dyslexia in a Shallow Orthography: Are There Subgroups?

ERIC Educational Resources Information Center

Laasonen, Marja; Service, Elisabet; Lipsanen, Jari; Virsu, Veijo

2012-01-01

The existence and stability of subgroups among adult dyslexic readers of a shallow orthography was explored by comparing three different cluster analyses based on previously suggested combinations of two variables. These were oral reading speed versus accuracy, word versus pseudoword reading speed, and phonological awareness versus rapid naming.…

Efficacy and safety of enzalutamide in patients 75 years or older with chemotherapy-naive metastatic castration-resistant prostate cancer: results from PREVAIL.

PubMed

Graff, J N; Baciarello, G; Armstrong, A J; Higano, C S; Iversen, P; Flaig, T W; Forer, D; Parli, T; Phung, D; Tombal, B; Beer, T M; Sternberg, C N

2016-02-01

Prostate cancer disproportionately affects older men. Because age affects treatment decisions, it is important to understand the efficacy and tolerability of therapies for advanced prostate cancer in elderly men. This analysis describes efficacy and safety outcomes in men aged ≥75 years who received enzalutamide, an androgen receptor inhibitor, in the phase III PREVAIL trial. PREVAIL was a randomised, double-blind, multinational study of oral enzalutamide 160 mg/day (N = 872) versus placebo (N = 845) in chemotherapy-naive men with metastatic castration-resistant prostate cancer. Overall survival (OS) and radiographic progression-free survival (rPFS) were coprimary end points. Subgroup analysis of men aged ≥75 years (elderly) and men aged <75 years was pre-specified for the coprimary end points and adverse events (AEs). Among 609 elderly patients (35%) who participated in PREVAIL, median treatment duration was 16.6 and 5.0 months in the enzalutamide and placebo arms, respectively. In the elderly subgroup, OS was greater with enzalutamide than with placebo [32.4 months (95% confidence interval (CI) 27.7-not yet reached] versus 25.1 months (95% CI 22.6-28.0); hazard ratio (HR) = 0.61 (95% CI 0.47-0.79); P = 0.0001], as was rPFS [not yet reached (95% CI 12.3-not yet reached) versus 3.7 months (95% CI 3.6-5.3); HR = 0.17 (95% CI 0.12-0.24); P < 0.0001]. Irrespective of treatment assignment, incidence of AEs was similar between the two age groups, except for an overall higher incidence of falls among elderly patients than younger patients [84/609 (13.8%) versus 62/1106 (5.6%)] and among elderly patients receiving enzalutamide than those receiving placebo [61/317 (19.2%) versus 23/292 (7.9%)]. Elderly men benefited from treatment with enzalutamide in terms of OS and rPFS. Enzalutamide was well tolerated in the elderly subgroup and those aged <75 years. Age and enzalutamide treatment were associated with a higher incidence of falls. NCT01212991, ClinicalTrials.gov. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Linagliptin plus metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycemia.

PubMed

Ross, Stuart A; Caballero, A Enrique; Del Prato, Stefano; Gallwitz, Baptist; Lewis-D'Agostino, Diane; Bailes, Zelie; Thiemann, Sandra; Patel, Sanjay; Woerle, Hans-Juergen; von Eynatten, Maximilian

2016-11-01

Few studies of oral glucose-lowering drugs exist in newly diagnosed type 2 diabetes (T2D) patients with marked hyperglycemia, and insulin is often proposed as initial treatment. We evaluated the oral initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in this population. We performed a pre-specified subgroup analysis of a randomized study in which newly diagnosed T2D patients with glycated hemoglobin A1c (HbA1c) 8.5%-12.0% received linagliptin/metformin or linagliptin monotherapy. Subgroups of baseline HbA1c, age, body-mass index (BMI), renal function, race, and ethnicity were evaluated, with efficacy measured by HbA1c change from baseline after 24 weeks. HbA1c reductions from baseline (mean 9.7%) at week 24 in the overall population were an adjusted mean -2.81% ± 0.12% with linagliptin/metformin (n = 132) and -2.02% ± 0.13% with linagliptin (n = 113); treatment difference -0.79% (95% CI -1.13 to -0.46, P < 0.0001). In patients with baseline HbA1c ≥9.5%, HbA1c reduction was -3.37% with linagliptin/metformin (n = 76) and -2.53% with linagliptin (n = 61); difference -0.84% (95% CI -1.32 to -0.35). In those with baseline HbA1c <9.5%, HbA1c reduction was -2.08% with linagliptin/metformin (n = 56) and -1.39% with linagliptin (n = 52); difference -0.69% (95% CI -1.23 to -0.15). Changes in HbA1c and treatment differences between the linagliptin/metformin and linagliptin groups were of similar magnitudes to the overall population across patient subgroups based on age, BMI, renal function, and race. Drug-related adverse events occurred in 8.8% and 5.7% of linagliptin/metformin and linagliptin patients, respectively; no severe hypoglycemia occurred. Linagliptin/metformin combination in newly diagnosed T2D patients with marked hyperglycemia was well tolerated and elicited substantial improvements in glycemic control regardless of baseline HbA1c, age, BMI, renal function, or race. Thus, newly diagnosed, markedly hyperglycemic patients may be effectively treated by combinations of oral agents. www.clinicaltrials.gov identifier is NCT01512979.

Trends in stunting and overweight in Peruvian pre-schoolers from 1991 to 2011: findings from the Demographic and Health Surveys.

PubMed

Urke, Helga Bjørnøy; Mittelmark, Maurice B; Valdivia, Martín

2014-11-01

To examine trends in stunting and overweight in Peruvian children, using 2006 WHO Multicentre Growth Reference Study criteria. Trend analyses using nationally representative cross-sectional surveys from Demographic and Health Surveys (1991-2011). We performed logistic regression analyses of stunting and overweight trends in sociodemographic groups (sex, age, urban-rural residence, region, maternal education and household wealth), adjusted for sampling design effects (strata, clusters and sampling weights). Peru. Children aged 0-59 months surveyed in 1991-92 (n 7999), 1996 (n 14 877), 2000 (n 11 754), 2007-08 (n 8232) and 2011 (n 8186). Child stunting declined (F(1, 5149) = 174·8, P ≤ 0·00) and child overweight was stable in the period 1991-2011 (F(1, 5147) = 0·4, P ≤ 0·54). Over the study period, levels of stunting were highest in rural compared with urban areas, the Andean and Amazon regions compared with the Coast, among children of low-educated mothers and among children living in households in the poorest wealth quintile. The trend in overweight rose among males in coastal areas (F(1, 2250) = 4·779, P ≤ 0·029) and among males in the richest wealth quintile (F(1, 1730) = 5·458, P ≤ 0·020). The 2011 levels of stunting and overweight were eight times and three and a half times higher, respectively, than the expected levels from the 2006 WHO growth standards. The trend over the study period in stunting declined in most sociodemographic subgroups. The trend in overweight was stable in most sociodemographic subgroups.

Does consideration and assessment of effects on health equity affect the conclusions of systematic reviews? A methodology study.

PubMed

Welch, Vivian; Petticrew, Mark; Ueffing, Erin; Benkhalti Jandu, Maria; Brand, Kevin; Dhaliwal, Bharbhoor; Kristjansson, Elizabeth; Smylie, Janet; Wells, George Anthony; Tugwell, Peter

2012-01-01

Tackling health inequities both within and between countries remains high on the agenda of international organizations including the World Health Organization and local, regional and national governments. Systematic reviews can be a useful tool to assess effects on equity in health status because they include studies conducted in a variety of settings and populations. This study aims to describe the extent to which the impacts of health interventions on equity in health status are considered in systematic reviews, describe methods used, and assess the implications of their equity related findings for policy, practice and research. We conducted a methodology study of equity assessment in systematic reviews. Two independent reviewers extracted information on the reporting and analysis of impacts of health interventions on equity in health status in a group of 300 systematic reviews collected from all systematic reviews indexed in one month of MEDLINE, using a pre-tested data collection form. Any differences in data extraction were resolved by discussion. Of the 300 systematic reviews, 224 assessed the effectiveness of interventions on health outcomes. Of these 224 reviews, 29 systematic reviews assessed effects on equity in health status using subgroup analysis or targeted analyses of vulnerable populations. Of these, seven conducted subgroup analyses related to health equity which were reported in insufficient detail to judge their credibility. Of these 29 reviews, 18 described implications for policy and practice based on assessment of effects on health equity. The quality and completeness of reporting should be enhanced as a priority, because without this policymakers and practitioners will continue lack the evidence base they need to inform decision-making about health inequity. Furthermore, there is a need to develop methods to systematically consider impacts on equity in health status that is currently lacking in systematic reviews.

Does improved access to diagnostic imaging results reduce hospital length of stay? A retrospective study

PubMed Central

2010-01-01

Background One year after the introduction of Information and Communication Technology (ICT) to support diagnostic imaging at our hospital, clinicians had faster and better access to radiology reports and images; direct access to Computed Tomography (CT) reports in the Electronic Medical Record (EMR) was particularly popular. The objective of this study was to determine whether improvements in radiology reporting and clinical access to diagnostic imaging information one year after the ICT introduction were associated with a reduction in the length of patients' hospital stays (LOS). Methods Data describing hospital stays and diagnostic imaging were collected retrospectively from the EMR during periods of equal duration before and one year after the introduction of ICT. The post-ICT period was chosen because of the documented improvement in clinical access to radiology results during that period. The data set was randomly split into an exploratory part used to establish the hypotheses, and a confirmatory part. The data was used to compare the pre-ICT and post-ICT status, but also to compare differences between groups. Results There was no general reduction in LOS one year after ICT introduction. However, there was a 25% reduction for one group - patients with CT scans. This group was heterogeneous, covering 445 different primary discharge diagnoses. Analyses of subgroups were performed to reduce the impact of this divergence. Conclusion Our results did not indicate that improved access to radiology results reduced the patients' LOS. There was, however, a significant reduction in LOS for patients undergoing CT scans. Given the clinicians' interest in CT reports and the results of the subgroup analyses, it is likely that improved access to CT reports contributed to this reduction. PMID:20819224

Systematic Review of Cognitive Function in Euthymic Bipolar Disorder and Pre-Surgical Temporal Lobe Epilepsy.

PubMed

Bostock, Emmanuelle C S; Kirkby, Kenneth C; Garry, Michael I; Taylor, Bruce V M

2017-01-01

Bipolar disorder (BD) and temporal lobe epilepsy (TLE) overlap in domains including epidemiology, treatment response, shared neurotransmitter involvement and temporal lobe pathology. Comparison of cognitive function in both disorders may indicate temporal lobe mediated processes relevant to BD. This systematic review examines neuropsychological test profiles in euthymic bipolar disorder type I (BD-I) and pre-surgical TLE and compares experimental designs used. A search of PubMed, PsychINFO, and Scopus using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted. Inclusion criteria were comparison group or pre- to post-surgical patients; reported neuropsychological tests; participants aged 18-60 years. Fifty six studies met criteria: 27 BD-I; 29 TLE. Deficits in BD-I compared to healthy controls (HC) were in executive function, attention span and verbal memory. Deficits in TLE compared to HC were in executive function and memory. In the pre- to post-surgical comparisons, verbal memory in left temporal lobe (LTL) and, less consistently, visuospatial memory in right temporal lobe (RTL) epilepsy declined following surgery. BD-I studies used comprehensive test batteries in well-defined euthymic patients compared to matched HC groups. TLE studies used convenience samples pre- to post-surgery, comparing LTL and RTL subgroups, few included comparisons to HC (5 studies). TLE studies typically examined a narrow range of known temporal lobe-mediated neuropsychological functions, particularly verbal and visuospatial memory. Both disorders exhibit deficits in executive function and verbal memory suggestive of both frontal and temporal lobe involvement. However, deficits in TLE are measured pre- to post-surgery and not controlled at baseline pre-surgery. Further research involving a head-to-head comparison of the two disorders on a broad range of neuropsychological tests is needed to clarify the nature and extent of cognitive deficits and potential overlaps.

Automatic Dynamic Aircraft Modeler (ADAM) for the Computer Program NASTRAN

NASA Technical Reports Server (NTRS)

Griffis, H.

1985-01-01

Large general purpose finite element programs require users to develop large quantities of input data. General purpose pre-processors are used to decrease the effort required to develop structural models. Further reduction of effort can be achieved by specific application pre-processors. Automatic Dynamic Aircraft Modeler (ADAM) is one such application specific pre-processor. General purpose pre-processors use points, lines and surfaces to describe geometric shapes. Specifying that ADAM is used only for aircraft structures allows generic structural sections, wing boxes and bodies, to be pre-defined. Hence with only gross dimensions, thicknesses, material properties and pre-defined boundary conditions a complete model of an aircraft can be created.

A photometric study of the Orion OB 1 association. 3: Subgroup analyses

NASA Technical Reports Server (NTRS)

Warren, W. H., Jr.; Hesser, J. E.

1977-01-01

The four principal subgroups of the association were examined in detail using individual distances and reddening values determined for their B type members. Subgroup 1a appeared not to show a spread in age nor did it show a systematic distance increase with right ascension when fainter members were considered. An eastwardly increase in distance was found for subgroup 1b but the reddening law for the east Belt appeared normal. Small subclusterings in the vicinity of the Orion Nebula appeared not to differ in the evolutionary state but their ages were considerably greater than those of stars in the nebulae and its associated cluster.

European regulatory use and impact of subgroup evaluation in marketing authorisation applications.

PubMed

Tanniou, Julien; Teerenstra, Steven; Hassan, Sagal; Elferink, Andre; van der Tweel, Ingeborg; Gispen-de Wied, Christine; Roes, Kit C B

2017-12-01

Marketing authorisation application dossiers relating to medicinal products containing new active substances and evaluated by the European Medicines Agency (EMA) over the period 2012-2015 were examined. Major objections and other concerns relating to efficacy and safety of the day 80 assessment reports were reviewed. Overall, approved products have more subgroup concerns than nonapproved products, which seems to be a consistent pattern. Subgroup analyses are mainly assessed to have the insurance that subgroups of patients that might lack a positive benefit: risk ratio will not be wrongly included in the approved treatment indication. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Pain patients' experiences of validation and invalidation from physicians before and after multimodal pain rehabilitation: Associations with pain, negative affectivity, and treatment outcome.

PubMed

Edlund, Sara M; Wurm, Matilda; Holländare, Fredrik; Linton, Steven J; Fruzzetti, Alan E; Tillfors, Maria

2017-10-01

Validating and invalidating responses play an important role in communication with pain patients, for example regarding emotion regulation and adherence to treatment. However, it is unclear how patients' perceptions of validation and invalidation relate to patient characteristics and treatment outcome. The aim of this study was to investigate the occurrence of subgroups based on pain patients' perceptions of validation and invalidation from their physicians. The stability of these perceptions and differences between subgroups regarding pain, pain interference, negative affectivity and treatment outcome were also explored. A total of 108 pain patients answered questionnaires regarding perceived validation and invalidation, pain severity, pain interference, and negative affectivity before and after pain rehabilitation treatment. Two cluster analyses using perceived validation and invalidation were performed, one on pre-scores and one on post-scores. The stability of patient perceptions from pre- to post-treatment was investigated, and clusters were compared on pain severity, pain interference, and negative affectivity. Finally, the connection between perceived validation and invalidation and treatment outcome was explored. Three clusters emerged both before and after treatment: (1) low validation and heightened invalidation, (2) moderate validation and invalidation, and (3) high validation and low invalidation. Perceptions of validation and invalidation were generally stable over time, although there were individuals whose perceptions changed. When compared to the other two clusters, the low validation/heightened invalidation cluster displayed significantly higher levels of pain interference and negative affectivity post-treatment but not pre-treatment. The whole sample significantly improved on pain interference and depression, but treatment outcome was independent of cluster. Unexpectedly, differences between clusters on pain interference and negative affectivity were only found post-treatment. This appeared to be due to the pre- and post-heightened invalidation clusters not containing the same individuals. Therefore, additional analyses were conducted to investigate the individuals who changed clusters. Results showed that patients scoring high on negative affectivity ended up in the heightened invalidation cluster post-treatment. Taken together, most patients felt understood when communicating with their rehabilitation physician. However, a smaller group of patients experienced the opposite: low levels of validation and heightened levels of invalidation. This group stood out as more problematic, reporting greater pain interference and negative affectivity when compared to the other groups after treatment. Patient perceptions were typically stable over time, but some individuals changed cluster, and these movements seemed to be related to negative affectivity and pain interference. These results do not support a connection between perceived validation and invalidation from physicians (meeting the patients pre- and post-treatment) and treatment outcome. Overall, our results suggest that there is a connection between negative affectivity and pain interference in the patients, and perceived validation and invalidation from the physicians. In clinical practice, it is important to pay attention to comorbid psychological problems and level of pain interference, since these factors may negatively influence effective communication. A focus on decreasing invalidating responses and/or increasing validating responses might be particularly important for patients with high levels of psychological problems and pain interference. Copyright © 2017. Published by Elsevier B.V.

Factors Associated with Exclusive Breastfeeding of Preterm Infants. Results from a Prospective National Cohort Study

PubMed Central

Maastrup, Ragnhild; Hansen, Bo Moelholm; Kronborg, Hanne; Bojesen, Susanne Norby; Hallum, Karin; Frandsen, Annemi; Kyhnaeb, Anne; Svarer, Inge; Hallström, Inger

2014-01-01

Background and Aim Evidence-based knowledge of how to guide the mothers of preterm infants in breastfeeding establishment is contradictive or sparse. The aim was to investigate the associations between pre-specified clinical practices for facilitating breastfeeding, and exclusive breastfeeding at discharge as well as adequate duration thereof. Methods A prospective survey based on questionnaires was conducted with a Danish national cohort, comprised of 1,221 mothers and their 1,488 preterm infants with a gestational age of 24–36 weeks. Adjusted for covariates, the pre-specified clinical practices were analysed by multiple logistic regression analyses. Results At discharge 68% of the preterm infants were exclusively breastfed and 17% partially. Test-weighing the infant, and minimizing the use of a pacifier, showed a protective effect to exclusive breastfeeding at discharge (OR 0.6 (95% CI 0.4–0.8) and 0.4 (95% CI 0.3–0.6), respectively). The use of nipple shields (OR 2.3 (95% CI 1.6–3.2)) and the initiation of breast milk expression later than 48 hours postpartum (OR 4.9 (95% CI 1.9–12.6)) were associated with failure of exclusive breastfeeding at discharge. The clinical practices associated with an inadequate breastfeeding duration were the initiation of breast milk expression at 12–24 hours (OR 1.6 (95% CI 1.0–2.4)) and 24–48 hours (OR 1.8 (95% CI 1.0–3.1)) vs. before six hours postpartum, and the use of nipple shields (OR 1.4 (95% CI 1.1–1.9)). Conclusion Early initiation of breast milk pumping before 12 hours postpartum may increase breastfeeding rates, and it seems that the use of nipple shields should be restricted. The use of test-weighing and minimizing the use of a pacifier may promote the establishment of exclusive breastfeeding, but more research is needed regarding adequate support to the mother when test-weighing is ceased, as more of these mothers ceased exclusive breastfeeding at an early stage after discharge. PMID:24586513

Weighing up the weighted case mix tool (WCMT): a psychometric investigation using confirmatory factor analysis.

PubMed

Duane, B G; Humphris, G; Richards, D; Okeefe, E J; Gordon, K; Freeman, R

2014-12-01

To assess the use of the WCMT in two Scottish health boards and to consider the impact of simplifying the tool to improve efficient use. A retrospective analysis of routine WCMT data (47,276 cases). Public Dental Service (PDS) within NHS Lothian and Highland. The WCMT consists of six criteria. Each criterion is measured independently on a four-point scale to assess patient complexity and the dental care for the disabled/impaired patient. Psychometric analyses on the data-set were conducted. Conventional internal consistency coefficients were calculated. Latent variable modelling was performed to assess the 'fit' of the raw data to a pre-specified measurement model. A Confirmatory Factor Analysis (CFA) was used to test three potential changes to the existing WCMT that included, the removal of the oral risk factor question, the removal of original weightings for scoring the Tool, and collapsing the 4-point rating scale to three categories. The removal of the oral risk factor question had little impact on the reliability of the proposed simplified CMT to discriminate between levels of patient complexity. The removal of weighting and collapsing each item's rating scale to three categories had limited impact on reliability of the revised tool. The CFA analysis provided strong evidence that a new, proposed simplified Case Mix Tool (sCMT) would operate closely to the pre-specified measurement model (the WMCT). A modified sCMT can demonstrate, without reducing reliability, a useful measure of the complexity of patient care. The proposed sCMT may be implemented within primary care dentistry to record patient complexity as part of an oral health assessment.

Bridging the gap: a review of dose investigations in paediatric investigation plans.

PubMed

Hampson, Lisa V; Herold, Ralf; Posch, Martin; Saperia, Julia; Whitehead, Anne

2014-10-01

In the EU, development of new medicines for children should follow a prospectively agreed paediatric investigation plan (PIP). Finding the right dose for children is crucial but challenging due to the variability of pharmacokinetics across age groups and the limited sample sizes available. We examined strategies adopted in PIPs to support paediatric dosing recommendations to identify common assumptions underlying dose investigations and the attempts planned to verify them in children. We extracted data from 73 PIP opinions recently adopted by the Paediatric Committee of the European Medicines Agency. These opinions represented 79 medicinal development programmes and comprised a total of 97 dose investigation studies. We identified the design of these dose investigation studies, recorded the analyses planned and determined the criteria used to define target doses. Most dose investigation studies are clinical trials (83 of 97) that evaluate a single dosing rule. Sample sizes used to investigate dose are highly variable across programmes, with smaller numbers used in younger children (< 2 years). Many studies (40 of 97) do not pre-specify a target dose criterion. Of those that do, most (33 of 57 studies) guide decisions using pharmacokinetic data alone. Common assumptions underlying dose investigation strategies include dose proportionality and similar exposure-response relationships in adults and children. Few development programmes pre-specify steps to verify assumptions in children. There is scope for the use of Bayesian methods as a framework for synthesizing existing information to quantify prior uncertainty about assumptions. This process can inform the design of optimal drug development strategies. © 2014 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

On Parametrization of the Linear GL(4,C) and Unitary SU(4) Groups in Terms of Dirac Matrices

NASA Astrophysics Data System (ADS)

Red'Kov, Victor M.; Bogush, Andrei A.; Tokarevskaya, Natalia G.

2008-02-01

Parametrization of 4 × 4-matrices G of the complex linear group GL(4,C) in terms of four complex 4-vector parameters (k,m,n,l) is investigated. Additional restrictions separating some subgroups of GL(4,C) are given explicitly. In the given parametrization, the problem of inverting any 4 × 4 matrix G is solved. Expression for determinant of any matrix G is found: det G = F(k,m,n,l). Unitarity conditions G+ = G-1 have been formulated in the form of non-linear cubic algebraic equations including complex conjugation. Several simplest solutions of these unitarity equations have been found: three 2-parametric subgroups G1, G2, G3 - each of subgroups consists of two commuting Abelian unitary groups; 4-parametric unitary subgroup consis! ting of a product of a 3-parametric group isomorphic SU(2) and 1-parametric Abelian group. The Dirac basis of generators Λk, being of Gell-Mann type, substantially differs from the basis λi used in the literature on SU(4) group, formulas relating them are found - they permit to separate SU(3) subgroup in SU(4). Special way to list 15 Dirac generators of GL(4,C) can be used {Λk} = {μiÅνjÅ(μiVνj = KÅL ÅM )}, which permit to factorize SU(4) transformations according to S = eiaμ eibνeikKeilLeimM, where two first factors commute with each other and are isomorphic to SU(2) group, the three last ones are 3-parametric groups, each of them consisting of three Abelian commuting unitary subgroups. Besides, the structure of fifteen Dirac matrices Λk permits to separate twenty 3-parametric subgroups in SU(4) isomorphic to SU(2); those subgroups might be used as bigger elementary blocks in constructing of a general transformation SU(4). It is shown how one can specify the present approach for the pseudounitary group SU(2,2) and SU(3,1).

Effect of the application of surface treatments before and after sintering on the flexural strength, phase transformation and surface topography of zirconia.

PubMed

Kurtulmus-Yilmaz, Sevcan; Aktore, Huseyin

2018-05-01

To evaluate the effects of airborne-particle abrasion (APA) and Er,Cr:YSGG laser irradiation on 4-point-flexural strength, phase transformation and morphologic changes of zirconia ceramics treated at pre-sintered or post-sintered stage. Three hundred and forty-two bar shaped zirconia specimens were milled with different sizes according to the flexural strength test (n = 10), X-ray diffraction (XRD) (n = 4) and field emission scanning electron microscope (FE-SEM) (n = 4) analyses. For each test protocol, specimens were divided into 4 main groups whether the surface treatments applied before or after sintering and whether the specimens received heat treatment or not as pre-sintered, post-sintered no-heat and post-sintered heat-treated groups, and a group was served as control. Main groups were further divided into 6 equal subgroups according to surface treatment method applied (2 W-, 3 W-, 4 W-, 5 W-, 6 W-laser irradiations and APA). Surface treatments were applied to pre-sintered groups before sintering and to post-sintered groups after sintering. Post-sintered heat-treated groups were subjected to veneer ceramic firing simulation after surface treatments. Flexural strength and flexural modulus values were statistically analysed and monoclinic phase content was calculated. Weibull analysis was used to evaluate strength reliability and fractographic analysis was conducted. Highest flexural strength values were detected at post-sintered no-heat APA and 4W-laser groups (P < 0.05). Pre-sintered groups showed statistically lower flexural strength values. Heat treatment decreased the strength of the specimens. Monoclinic phase content was only detected at post-sintered no-heat groups and the highest amount was detected at APA group. Rougher surfaces and deeper irregularities were detected at FE-SEM images pre-sintered groups. Application of surface treatments at pre-sintered stage may be detrimental for zirconia ceramics in terms of flexural strength. Treating the surface of zirconia ceramic before sintering process is not recommended due to significant decrease in flexural strength values. 2 W-4 W Er,Cr:YSGG laser irradiations can be regarded as alternative surface treatment methods when zirconia restoration would be subjected to veneer ceramic firing procedures. Copyright © 2018 Elsevier Ltd. All rights reserved.

SeqSIMLA2_exact: simulate multiple disease sites in large pedigrees with given disease status for diseases with low prevalence.

PubMed

Yao, Po-Ju; Chung, Ren-Hua

2016-02-15

It is difficult for current simulation tools to simulate sequence data in a pre-specified pedigree structure and pre-specified affection status. Previously, we developed a flexible tool, SeqSIMLA2, for simulating sequence data in either unrelated case-control or family samples with different disease and quantitative trait models. Here we extended the tool to efficiently simulate sequences with multiple disease sites in large pedigrees with a given disease status for each pedigree member, assuming that the disease prevalence is low. SeqSIMLA2_exact is implemented with C++ and is available at http://seqsimla.sourceforge.net. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Issues for Universities Working with K-12 Institutions Implementing Prepackaged Pre-Engineering Curricula Such as Project Lead the Way

ERIC Educational Resources Information Center

Reid, Kenneth J.; Feldhaus, Charles R.

2007-01-01

The implementation of pre-engineering, standard curricula in K-12 schools is growing at a rapid pace. One such curriculum model, Project Lead the Way, consists of six standardized courses requiring significant training for teachers, specified laboratory equipment, standard topics, exams, etc. Schools implementing Project Lead the Way implement an…

Atypical squamous and glandular cells of undetermined significance (ASCUS and AGUS) of the uterine cervix.

PubMed

Cenci, M; Vecchione, A

2000-01-01

ASCUS (Atypical Squamous Cells of Undetermined Significance) and AGUS (Atypical Glandular Cells of Undetermined Significance), or AGCUS, are two acronyms introduced in 1988 by The Bethesda System (TBS) for reporting borderline cytological changes in cervical cytology. ASCUS and AGUS categories should be subclassified. Five ASCUS subgroups were proposed: 1) ASCUS due to processing defects, 2) with "mature" cytoplasm, 3) in post-menopausal women (a--in the setting of atrophy and b--with estrogen stimulation), 4) atypical metaplasia, and 5) ASCUS with keratinized cytoplasm. AGUS subgroups may be subcategorized in endometrial or endocervical on the basis of origin. Endocervical AGUS should be further qualified, but the analysis of atypical glandular cells may be really difficult and the conclusive diagnosis is frequently "AGUS not otherwise specified". The subclassification of ASCUS and AGUS is useful for an appropriate clinical management, but pertinent patient information (such as age, date of last menstrual period, mechanical therapies, tamoxifen therapy, and others) is needed to avoid an overdiagnosis and consequently an overtreatment. In fact various subgroups require different clinical management. Therefore, an effective communication between cytopathologists and referring physicians is essential in the analysis of squamous and glandular atypias.

Quantifying, displaying and accounting for heterogeneity in the meta-analysis of RCTs using standard and generalised Q statistics

PubMed Central

2011-01-01

Background Clinical researchers have often preferred to use a fixed effects model for the primary interpretation of a meta-analysis. Heterogeneity is usually assessed via the well known Q and I2 statistics, along with the random effects estimate they imply. In recent years, alternative methods for quantifying heterogeneity have been proposed, that are based on a 'generalised' Q statistic. Methods We review 18 IPD meta-analyses of RCTs into treatments for cancer, in order to quantify the amount of heterogeneity present and also to discuss practical methods for explaining heterogeneity. Results Differing results were obtained when the standard Q and I2 statistics were used to test for the presence of heterogeneity. The two meta-analyses with the largest amount of heterogeneity were investigated further, and on inspection the straightforward application of a random effects model was not deemed appropriate. Compared to the standard Q statistic, the generalised Q statistic provided a more accurate platform for estimating the amount of heterogeneity in the 18 meta-analyses. Conclusions Explaining heterogeneity via the pre-specification of trial subgroups, graphical diagnostic tools and sensitivity analyses produced a more desirable outcome than an automatic application of the random effects model. Generalised Q statistic methods for quantifying and adjusting for heterogeneity should be incorporated as standard into statistical software. Software is provided to help achieve this aim. PMID:21473747

A comparison of three clustering methods for finding subgroups in MRI, SMS or clinical data: SPSS TwoStep Cluster analysis, Latent Gold and SNOB.

PubMed

Kent, Peter; Jensen, Rikke K; Kongsted, Alice

2014-10-02

There are various methodological approaches to identifying clinically important subgroups and one method is to identify clusters of characteristics that differentiate people in cross-sectional and/or longitudinal data using Cluster Analysis (CA) or Latent Class Analysis (LCA). There is a scarcity of head-to-head comparisons that can inform the choice of which clustering method might be suitable for particular clinical datasets and research questions. Therefore, the aim of this study was to perform a head-to-head comparison of three commonly available methods (SPSS TwoStep CA, Latent Gold LCA and SNOB LCA). The performance of these three methods was compared: (i) quantitatively using the number of subgroups detected, the classification probability of individuals into subgroups, the reproducibility of results, and (ii) qualitatively using subjective judgments about each program's ease of use and interpretability of the presentation of results.We analysed five real datasets of varying complexity in a secondary analysis of data from other research projects. Three datasets contained only MRI findings (n = 2,060 to 20,810 vertebral disc levels), one dataset contained only pain intensity data collected for 52 weeks by text (SMS) messaging (n = 1,121 people), and the last dataset contained a range of clinical variables measured in low back pain patients (n = 543 people). Four artificial datasets (n = 1,000 each) containing subgroups of varying complexity were also analysed testing the ability of these clustering methods to detect subgroups and correctly classify individuals when subgroup membership was known. The results from the real clinical datasets indicated that the number of subgroups detected varied, the certainty of classifying individuals into those subgroups varied, the findings had perfect reproducibility, some programs were easier to use and the interpretability of the presentation of their findings also varied. The results from the artificial datasets indicated that all three clustering methods showed a near-perfect ability to detect known subgroups and correctly classify individuals into those subgroups. Our subjective judgement was that Latent Gold offered the best balance of sensitivity to subgroups, ease of use and presentation of results with these datasets but we recognise that different clustering methods may suit other types of data and clinical research questions.

Psychopathic Traits of Dutch Adolescents in Residential Care: Identifying Subgroups

ERIC Educational Resources Information Center

Nijhof, Karin S.; Vermulst, Ad; Scholte, Ron H. J.; van Dam, Coleta; Veerman, Jan Willem; Engels, Rutger C. M. E.

2011-01-01

The present study examined whether a sample of 214 (52.8% male, M age = 15.76, SD = 1.29) institutionalized adolescents could be classified into subgroups based on psychopathic traits. Confirmatory Factor Analyses revealed a relationship between the subscales of the Youth Psychopathic traits Inventory (YPI) and the three latent constructs of the…

High School Graduation Rates across English Learner Student Subgroups in Arizona. REL 2017-205

ERIC Educational Resources Information Center

Huang, Min; Haas, Eric; Zhu, Niufeng; Tran, Loan

2016-01-01

Recent studies have documented differences in academic achievement between current and former English learner students. These differences validate calls for more focused analyses of achievement across English learner student subgroups. Specifically, there is interest in examining variation in academic success based on the amount of time a student…

Analysis of categorical moderators in mixed-effects meta-analysis: Consequences of using pooled versus separate estimates of the residual between-studies variances.

PubMed

Rubio-Aparicio, María; Sánchez-Meca, Julio; López-López, José Antonio; Botella, Juan; Marín-Martínez, Fulgencio

2017-11-01

Subgroup analyses allow us to examine the influence of a categorical moderator on the effect size in meta-analysis. We conducted a simulation study using a dichotomous moderator, and compared the impact of pooled versus separate estimates of the residual between-studies variance on the statistical performance of the Q B (P) and Q B (S) tests for subgroup analyses assuming a mixed-effects model. Our results suggested that similar performance can be expected as long as there are at least 20 studies and these are approximately balanced across categories. Conversely, when subgroups were unbalanced, the practical consequences of having heterogeneous residual between-studies variances were more evident, with both tests leading to the wrong statistical conclusion more often than in the conditions with balanced subgroups. A pooled estimate should be preferred for most scenarios, unless the residual between-studies variances are clearly different and there are enough studies in each category to obtain precise separate estimates. © 2017 The British Psychological Society.

Acoustic Features Influence Musical Choices Across Multiple Genres

PubMed Central

Barone, Michael D.; Bansal, Jotthi; Woolhouse, Matthew H.

2017-01-01

Based on a large behavioral dataset of music downloads, two analyses investigate whether the acoustic features of listeners' preferred musical genres influence their choice of tracks within non-preferred, secondary musical styles. Analysis 1 identifies feature distributions for pairs of genre-defined subgroups that are distinct. Using correlation analysis, these distributions are used to test the degree of similarity between subgroups' main genres and the other music within their download collections. Analysis 2 explores the issue of main-to-secondary genre influence through the production of 10 feature-influence matrices, one per acoustic feature, in which cell values indicate the percentage change in features for genres and subgroups compared to overall population averages. In total, 10 acoustic features and 10 genre-defined subgroups are explored within the two analyses. Results strongly indicate that the acoustic features of people's main genres influence the tracks they download within non-preferred, secondary musical styles. The nature of this influence and its possible actuating mechanisms are discussed with respect to research on musical preference, personality, and statistical learning. PMID:28725200

Incidence and prevalence of diabetic ketoacidosis (DKA) among adults with type 1 diabetes mellitus (T1D): a systematic literature review.

PubMed

Fazeli Farsani, Soulmaz; Brodovicz, Kimberly; Soleymanlou, Nima; Marquard, Jan; Wissinger, Erika; Maiese, Brett A

2017-08-01

To summarise incidence and prevalence of diabetic ketoacidosis (DKA) in adults with type 1 diabetes (T1D) for the overall patient population and different subgroups (age, sex, geographical region, ethnicity and type of insulin administration). Systematic literature review (SLR). Medline (via PubMed) and Embase (1 January 2000 to 23 June 2016). Peer-reviewed observational studies with reported data on the incidence or prevalence of DKA in T1D adults were included. A single reviewer completed the study screening and selection process and a second reviewer performed an additional screening of approximately 20% of the publications; two reviewers independently conducted the quality assessment; the results were narratively synthesised. Out of 1082 articles, 19 met the inclusion and exclusion criteria, with two additional studies identified that did not specify the patient age range and are therefore not included in the SLR. Overall, eight studies reported incidence with a range of 0-56 per 1000 person-years (PYs), with one outlying study reporting an incidence of 263 per 1000 PYs. Eleven studies reported prevalence with a range of 0-128 per 1000 people. Prevalence of DKA decreased with increasing age. Subgroup analyses were performed using data from no more than two studies per subgroup. There was a higher prevalence of DKA reported in women, non-whites and patients treated with insulin injections compared with men, whites and patients using continuous subcutaneous insulin infusion pumps, respectively. To our knowledge, this is the first SLR on the epidemiology of DKA in T1D adults. Despite an increasing prevalence of T1D in recent years, DKA in adults has been poorly characterised. In an era when the benefit-risk profiles of new antidiabetic therapies are being evaluated, including the potential risk of DKA, there is a clear need to better elucidate the expected rate of DKA among T1D adults. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Low-Mass Stellar Content of the Scorpius-Centaurus OB Association

NASA Technical Reports Server (NTRS)

Yorke, H.; Kunkel, M.; Brander, W.; Zinnecker, H.; Neuhauser, R.; Schmitt, J.; Mayor, M.; Udry, S.

2000-01-01

Based on ROSAT observations and data obtained with ground-based telescopes, we have carried out an extensive study of the low-mass pre-main-sequence population in Upper Scorpius, the youngest subgroup of the Scorpius-Centaurus OB association.

Medulloblastoma in China: Clinicopathologic Analyses of SHH, WNT, and Non-SHH/WNT Molecular Subgroups Reveal Different Therapeutic Responses to Adjuvant Chemotherapy

PubMed Central

Ren, Yong; Yao, Yu; Li, Kay Ka-Wai; Ng, Ho-Keung; Mao, Ying; Zhou, Liang-Fu; Zhong, Ping

2014-01-01

Medulloblastoma (MB) is one of the most common primary central nervous system tumors in children. Data is lacking of a large cohort of medulloblastoma patients in China. Also, our knowledge on the sensitivity of different molecular subgroups of MB to adjuvant radiation therapy (RT) or chemotherapy (CHT) is still limited. The authors performed a retrospective study of 173 medulloblastoma patients treated at two institutions from 2002 to 2011. Formalin-fixed paraffin embedded (FFPE) tissues were available in all the cases and sections were stained to classify histological and molecular subgroups. Univariate and multivariate analyses were used to investigate prognostic factors. Of 173 patients, there were 118 children and 55 adults, 112 males and 61 females. Estimated 5-year overall survival (OS) rates for all patients, children and adults were 52%, 48% and 63%, respectively. After multivariate analysis, postoperative primary radiation therapy (RT) and chemotherapy (CHT) were revealed as favorable prognostic factors influencing OS and EFS. Postoperative primary chemotherapy (CHT) was found significantly improving the survival of children (p<0.001) while it was not a significant prognostic factor for adult patients. Moreover, patients in WNT subtype had better OS (p = 0.028) than others (SHH and Non-SHH/WNT subtypes) given postoperative adjuvant therapies. Postoperative primary RT was found to be a strong prognostic factor influencing the survival in all histological and molecular subgroups (p<0.001). Postoperative primary CHT was found significantly to influence the survival of classic medulloblastoma (CMB) (OS p<0.001, EFS p<0.001), SHH subgroup (OS p = 0.020, EFS p = 0.049) and WNT subgroup (OS p = 0.003, EFS p = 0.016) but not in desmoplastic/nodular medulloblastoma (DMB) (OS p = 0.361, EFS p = 0.834) and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055). Our study showed postoperative primary CHT significantly influence the survival of CMB, SHH subgroup and WNT subgroup but not in DMB and Non-SHH/WNT subgroup of MB. PMID:24932704

Anorexia nervosa and bulimia nervosa: A meta-analysis of executive functioning.

PubMed

Hirst, Rayna B; Beard, Charlotte L; Colby, Katrina A; Quittner, Zoe; Mills, Brent M; Lavender, Jason M

2017-12-01

Research investigating the link between eating disorder (ED) diagnosis and executive dysfunction has had conflicting results, yet no meta-analyses have examined the overall association of ED pathology with executive functioning (EF). Effect sizes were extracted from 32 studies comparing ED groups (27 of anorexia nervosa, 9 of bulimia nervosa) with controls to determine the grand mean effect on EF. Analyses included effects for individual EF measures, as well as an age-based subgroup analysis. There was a medium effect of ED diagnosis on executive functioning, with bulimia nervosa demonstrating a larger effect (Hedges's g=-0.70) than anorexia nervosa (g=-0.41). Within anorexia nervosa studies, subgroup analyses were conducted for age and diagnostic subtype. The effect of anorexia nervosa on EF was largest in adults; however, subgroup differences for age were not significant. Anorexia and bulimia nervosa are associated with EF deficits, which are particularly notable for individuals with bulimia nervosa. The present analysis includes recommendations for future studies regarding study design and EF measurement. Copyright © 2017 Elsevier Ltd. All rights reserved.

Military Transition Assistance Program (TAP): An Overview

DTIC Science & Technology

2017-03-15

Title II of P.L. 112-56) which made a pre-separation counseling program mandatory for all servicemembers who have served at least 180 continuous days...anticipated retirement date or 12-month period preceding the anticipated separation date. It also specifies that pre-separation counseling should...in the development, management oversight, and strategic planning of TAP. TAP Counseling Requirements Over time, Congress has increased the

Education Level Is a Strong Prognosticator in the Subgroup Aged More Than 50 Years Regardless of the Molecular Subtype of Breast Cancer: A Study Based on the Nationwide Korean Breast Cancer Registry Database.

PubMed

Hwang, Ki-Tae; Noh, Woochul; Cho, Se-Heon; Yu, Jonghan; Park, Min Ho; Jeong, Joon; Lee, Hyouk Jin; Kim, Jongjin; Oh, Sohee; Kim, Young A

2017-10-01

This study investigated the role of the education level (EL) as a prognostic factor for breast cancer and analyzed the relationship between the EL and various confounding factors. The data for 64,129 primary breast cancer patients from the Korean Breast Cancer Registry were analyzed. The EL was classified into two groups according to the education period; the high EL group (≥ 12 years) and low EL group (< 12 years). Survival analyses were performed with respect to the overall survival between the two groups. A high EL conferred a superior prognosis compared to a low EL in the subgroup aged > 50 years (hazard ratio, 0.626; 95% confidence interval [CI], 0.577 to 0.678) but not in the subgroup aged ≤ 50 years (hazard ratio, 0.941; 95% CI, 0.865 to 1.024). The EL was a significant independent factor in the subgroup aged > 50 years according to multivariate analyses. The high EL group showed more favorable clinicopathologic features and a higher proportion of patients in this group received lumpectomy, radiation therapy, and endocrine therapy. In the high EL group, a higher proportion of patients received chemotherapy in the subgroups with unfavorable clinicopathologic features. The EL was a significant prognosticator across all molecular subtypes of breast cancer. The EL is a strong independent prognostic factor for breast cancer in the subgroup aged > 50 years regardless of the molecular subtype, but not in the subgroup aged ≤ 50 years. Favorable clinicopathologic features and active treatments can explain the main causality of the superior prognosis in the high EL group.

Education Level Is a Strong Prognosticator in the Subgroup Aged More Than 50 Years Regardless of the Molecular Subtype of Breast Cancer: A Study Based on the Nationwide Korean Breast Cancer Registry Database

PubMed Central

Hwang, Ki-Tae; Noh, Woochul; Cho, Se-Heon; Yu, Jonghan; Park, Min Ho; Jeong, Joon; Lee, Hyouk Jin; Kim, Jongjin; Oh, Sohee; Kim, Young A

2017-01-01

Purpose This study investigated the role of the education level (EL) as a prognostic factor for breast cancer and analyzed the relationship between the EL and various confounding factors. Materials and Methods The data for 64,129 primary breast cancer patients from the Korean Breast Cancer Registry were analyzed. The EL was classified into two groups according to the education period; the high EL group (≥ 12 years) and low EL group (< 12 years). Survival analyses were performed with respect to the overall survival between the two groups. Results A high EL conferred a superior prognosis compared to a low EL in the subgroup aged > 50 years (hazard ratio, 0.626; 95% confidence interval [CI], 0.577 to 0.678) but not in the subgroup aged ≤ 50 years (hazard ratio, 0.941; 95% CI, 0.865 to 1.024). The EL was a significant independent factor in the subgroup aged > 50 years according to multivariate analyses. The high EL group showed more favorable clinicopathologic features and a higher proportion of patients in this group received lumpectomy, radiation therapy, and endocrine therapy. In the high EL group, a higher proportion of patients received chemotherapy in the subgroups with unfavorable clinicopathologic features. The EL was a significant prognosticator across all molecular subtypes of breast cancer. Conclusion The EL is a strong independent prognostic factor for breast cancer in the subgroup aged > 50 years regardless of the molecular subtype, but not in the subgroup aged ≤ 50 years. Favorable clinicopathologic features and active treatments can explain the main causality of the superior prognosis in the high EL group. PMID:28161933

Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis.

PubMed

Rowan, Kathryn M; Angus, Derek C; Bailey, Michael; Barnato, Amber E; Bellomo, Rinaldo; Canter, Ruth R; Coats, Timothy J; Delaney, Anthony; Gimbel, Elizabeth; Grieve, Richard D; Harrison, David A; Higgins, Alisa M; Howe, Belinda; Huang, David T; Kellum, John A; Mouncey, Paul R; Music, Edvin; Peake, Sandra L; Pike, Francis; Reade, Michael C; Sadique, M Zia; Singer, Mervyn; Yealy, Donald M

2017-06-08

After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT. We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics. We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation. In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics. (Funded by the National Institute of General Medical Sciences and others; PRISM ClinicalTrials.gov number, NCT02030158 .).

Histopathological subgroups in knee osteoarthritis.

PubMed

Wyatt, L A; Moreton, B J; Mapp, P I; Wilson, D; Hill, R; Ferguson, E; Scammell, B E; Walsh, D A

2017-01-01

Osteoarthritis (OA) is a heterogeneous, multi-tissue disease. We hypothesised that different histopathological features characterise different stages during knee OA progression, and that discrete subgroups can be defined based on validated measures of OA histopathological features. Medial tibial plateaux and synovium were from 343 post-mortem (PM) and 143 OA arthroplasty donations. A 'chondropathy/osteophyte' group (n = 217) was classified as PM cases with osteophytes or macroscopic medial tibiofemoral chondropathy lesions ≥grade 3 to represent pre-surgical (early) OA. 'Non-arthritic' controls (n = 48) were identified from the remaining PM cases. Mankin histopathological scores were subjected to Rasch analysis and supplemented with histopathological scores for subchondral bone marrow replacement and synovitis. Item weightings were derived by principle components analysis (PCA). Histopathological subgroups were sought using latent class analysis (LCA). Chondropathy, synovitis and osteochondral pathology were each associated with OA at arthroplasty, but each was also identified in some 'non-arthritic' controls. Tidemark breaching in the chondropathy/osteophyte group was greater than in non-arthritic controls. Three histopathological subgroups were identified, characterised as 'mild OA', or 'severe OA' with mild or moderate/severe synovitis. Presence and severity of synovitis helps define distinct histopathological OA subgroups. The absence of a discrete 'normal' subgroup indicates a pathological continuum between normality and OA status. Identifying specific pathological processes and their clinical correlates in OA subgroups has potential to accelerate the development of more effective therapies. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Time-based and event-based prospective memory in autism spectrum disorder: the roles of executive function and theory of mind, and time-estimation.

PubMed

Williams, David; Boucher, Jill; Lind, Sophie; Jarrold, Christopher

2013-07-01

Prospective memory (remembering to carry out an action in the future) has been studied relatively little in ASD. We explored time-based (carry out an action at a pre-specified time) and event-based (carry out an action upon the occurrence of a pre-specified event) prospective memory, as well as possible cognitive correlates, among 21 intellectually high-functioning children with ASD, and 21 age- and IQ-matched neurotypical comparison children. We found impaired time-based, but undiminished event-based, prospective memory among children with ASD. In the ASD group, time-based prospective memory performance was associated significantly with diminished theory of mind, but not with diminished cognitive flexibility. There was no evidence that time-estimation ability contributed to time-based prospective memory impairment in ASD.

Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response.

PubMed

van Vollenhoven, Ronald F; Petri, Michelle A; Cervera, Ricard; Roth, David A; Ji, Beulah N; Kleoudis, Christi S; Zhong, Z John; Freimuth, William

2012-08-01

To identify factors that predict response to belimumab treatment in the phase 3 BLISS trials of autoantibody-positive systemic lupus erythematosus (SLE) and further analyse clinical efficacy in various patient subsets. The BLISS trials compared belimumab 1 and 10 mg/kg versus placebo, all plus standard SLE therapy, over 52 or 76 weeks. Pooled subgroup analyses of week 52 SLE responder index rates (the primary endpoint in both trials) were performed based on demographic characteristics and baseline disease activity indicators. Pooled multivariate analysis was performed to determine predictors of response and treatment effect. Pooled univariate and multivariate analyses (N=1684) identified baseline factors associated with an increased benefit of belimumab versus placebo. These factors included the Safety Of Estrogens In Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) ≥10, low complement, anti-dsDNA positivity and corticosteroid use. Efficacy outcomes were assessed in the low complement/anti-dsDNA-positive and SELENA-SLEDAI ≥10 subgroups. Week 52 SLE Responder Index rates in the low complement/anti-dsDNA-positive subgroup were 31.7%, 41.5% (p=0.002) and 51.5% (p<0.001) with placebo and belimumab 1 mg/kg and 10 mg/kg, respectively; corresponding rates in the SELENA-SLEDAI ≥10 subgroup were 44.3%, 58.0% (p<0.001) and 63.2% (p<0.001). Further analysis of secondary endpoints in the low complement/anti-dsDNA-positive subgroup showed that compared with placebo, belimumab produced greater benefits regarding severe flares, corticosteroid use and health-related quality of life. These findings suggest that belimumab has greater therapeutic benefit than standard therapy alone in patients with higher disease activity, anti-dsDNA positivity, low complement or corticosteroid treatment at baseline. CLINICALTRIALS.GOV: identifiers NCT00424476 and NCT00410384.

Is Blood Eosinophil Count a Predictor of Response to Bronchodilators in Chronic Obstructive Pulmonary Disease? Results from Post Hoc Subgroup Analyses.

PubMed

Iqbal, Ahmar; Barnes, Neil C; Brooks, Jean

2015-10-01

Chronic obstructive pulmonary disease (COPD) patients with blood eosinophil (EOS) count ≥ 2% benefit from exacerbation reductions with inhaled corticosteroids (ICSs). We conducted post hoc analyses to determine if EOS count ≥ 2% is a marker for greater responsiveness to the bronchodilators umeclidinium (UMEC; long-acting muscarinic antagonist), vilanterol (VI; long-acting β2-agonist) or UMEC/VI combination. Effects of once-daily UMEC/VI 62.5/25, UMEC 62.5 and VI 25 µg versus placebo on trough forced expiratory volume in one second (FEV1), Transition Dyspnoea Index (TDI), St George's Respiratory Questionnaire (SGRQ) scores and adverse event (AE) incidences in four completed, 6-month studies were assessed by EOS subgroup. Trough FEV1 was also evaluated by ICS use and EOS subgroup. Analyses were performed using a repeated measures model. At baseline, 2437 of 4647 (52%) patients had EOS count ≥ 2%. Overall, ≈ 50% of patients used ICSs. At day 169, no notable variations were observed in trough FEV1 least squares mean differences between EOS subgroups versus placebo for UMEC/VI, UMEC and VI; results according to ICS use were similar. No differences were reported between EOS subgroups in TDI and SGRQ scores on day 168, or for incidences of AEs, serious AEs and AEs leading to withdrawal. Response to UMEC/VI, UMEC and VI in terms of trough FEV1, dyspnoea and health-related quality of life was similar for COPD patients with baseline EOS counts ≥ 2 or <2%. EOS count did not appear to predict bronchodilator response in either ICS users or non-users.

An evaluation of inferential procedures for adaptive clinical trial designs with pre-specified rules for modifying the sample size.

PubMed

Levin, Gregory P; Emerson, Sarah C; Emerson, Scott S

2014-09-01

Many papers have introduced adaptive clinical trial methods that allow modifications to the sample size based on interim estimates of treatment effect. There has been extensive commentary on type I error control and efficiency considerations, but little research on estimation after an adaptive hypothesis test. We evaluate the reliability and precision of different inferential procedures in the presence of an adaptive design with pre-specified rules for modifying the sampling plan. We extend group sequential orderings of the outcome space based on the stage at stopping, likelihood ratio statistic, and sample mean to the adaptive setting in order to compute median-unbiased point estimates, exact confidence intervals, and P-values uniformly distributed under the null hypothesis. The likelihood ratio ordering is found to average shorter confidence intervals and produce higher probabilities of P-values below important thresholds than alternative approaches. The bias adjusted mean demonstrates the lowest mean squared error among candidate point estimates. A conditional error-based approach in the literature has the benefit of being the only method that accommodates unplanned adaptations. We compare the performance of this and other methods in order to quantify the cost of failing to plan ahead in settings where adaptations could realistically be pre-specified at the design stage. We find the cost to be meaningful for all designs and treatment effects considered, and to be substantial for designs frequently proposed in the literature. © 2014, The International Biometric Society.

Commognitive Analysis of Undergraduate Mathematics Students' Responses in Proving Subgroup's Non-Emptiness

ERIC Educational Resources Information Center

Ioannou, Marios

2016-01-01

Proving that a given set is indeed a subgroup, one needs to show that it is non-empty, and closed under operation and inverses. This study focuses on the first condition, analysing students' responses to this task. Results suggest that there are three distinct problematic responses: the total absence of proving this condition, the problematic…

Tobacco price increase and smoking behaviour changes in various subgroups: a nationwide longitudinal 7-year follow-up study among a middle-aged Japanese population

PubMed Central

Fujiwara, Takeo; Shinozaki, Tomohiro

2017-01-01

Objective Few longitudinal studies have examined the effect of tobacco price increase on both cessation among smokers and relapse among quitters. Our objective was to investigate the differential impact of the tobacco price increase on the changes in smoking status in the total population and various subgroups. Methods We analysed data from a Japanese nationally representative longitudinal study of 30 773 individuals aged 50–59 years (weighted sum of discrete-time number = 215 411) with smoking information, using inverse probability weighting to account for non-response at follow-up. Generalised estimating equation models were used to calculate the odds ratios (ORs) for smoking behavioural changes (cessation among smokers and relapse among quitters), using discrete-time design. Stratified analyses were conducted according to demographic, socioeconomic and health behavioural characteristics. Results From 2005 to 2012, current smoker prevalence among the middle-aged Japanese population decreased from 30.5% to 24.3%. Of all the factors surveyed, only the tobacco price increase in 2010 (up by 37%, the highest increase during the period) was significantly associated with both cessation among smokers (OR 2.14, 95% confidence interval 1.90 to 2.41) and prevention of relapse among quitters (0.60, 0.46 to 0.77). Regarding the subgroup analysis, the tobacco price increase was associated with a significant reduction in relapse in the lowest income, recent quitters and very poor health subgroups. However, different associations were observed for cessation; a significant association between price increase and cessation was observed among all subgroups except for the heavy smoker and recently unemployed subgroups. Conclusions We confirmed that the tobacco price rise was associated with increasing cessation and decreasing relapse concurrently. Furthermore, this price rise was associated with favourable smoking changes in nearly all population subgroups; a large differential impact was not observed across the various subgroups. PMID:26880743

Relamorelin: A Novel Gastrocolokinetic Synthetic Ghrelin Agonist

PubMed Central

Camilleri, Michael; Acosta, Andres

2015-01-01

Synthetic ghrelin agonists, predominantly small molecules, are being developed as prokinetic agents that may prove useful in the treatment of gastrointestinal motility disorders. Relamorelin (RM-131) is a pentapeptide synthetic ghrelin analog that activates the growth hormone secretagogue (GHS)-1a (also called the ghrelin) receptor with approximately 6-fold greater potency than natural ghrelin. The ability of relamorelin to stimulate growth hormone (GH) release is comparable to that of native ghrelin. Relamorelin has enhanced efficacy and plasma stability compared to native ghrelin. In this review, we discuss the pharmacokinetics, pharmacodynamics and potential indications for relamorelin. Relamorelin is administered subcutaneously, dosed daily or twice daily. Relamorelin is being studied for the treatment of patients with gastrointestinal motility disorders. Phase IIA pharmacodynamic studies have demonstrated acceleration of gastric emptying in patients with type 1 diabetes mellitus (T1DM) and type 2 DM (T2DM) and upper gastrointestinal symptoms. In a phase IIA study in patients with diabetic gastroparesis, relamorelin accelerated gastric emptying and significantly improved vomiting frequency compared to placebo and improved other symptoms of gastroparesis in a pre-specified subgroup of patients with vomiting at baseline. In patients with chronic idiopathic constipation with defined transit profile at baseline, relamorelin relieved constipation and accelerated colonic transit compared to placebo. These characteristics suggest that this new ghrelin analog shows great promise to relieve patients with upper or lower gastrointestinal motility disorders. PMID:25545036

Boomerang: A Method for Recursive Reclassification

PubMed Central

Devlin, Sean M.; Ostrovnaya, Irina; Gönen, Mithat

2016-01-01

Summary While there are many validated prognostic classifiers used in practice, often their accuracy is modest and heterogeneity in clinical outcomes exists in one or more risk subgroups. Newly available markers, such as genomic mutations, may be used to improve the accuracy of an existing classifier by reclassifying patients from a heterogenous group into a higher or lower risk category. The statistical tools typically applied to develop the initial classifiers are not easily adapted towards this reclassification goal. In this paper, we develop a new method designed to refine an existing prognostic classifier by incorporating new markers. The two-stage algorithm called Boomerang first searches for modifications of the existing classifier that increase the overall predictive accuracy and then merges to a pre-specified number of risk groups. Resampling techniques are proposed to assess the improvement in predictive accuracy when an independent validation data set is not available. The performance of the algorithm is assessed under various simulation scenarios where the marker frequency, degree of censoring, and total sample size are varied. The results suggest that the method selects few false positive markers and is able to improve the predictive accuracy of the classifier in many settings. Lastly, the method is illustrated on an acute myeloid leukemia dataset where a new refined classifier incorporates four new mutations into the existing three category classifier and is validated on an independent dataset. PMID:26754051

[The drug of the month: everolimus (Afinitor) for the treatment of metastatic breast cancer].

PubMed

Jerusalem, G; Rorive, A; Collignon, J

2014-09-01

Sequential endocrine treatments are recommended for estrogen receptor (ER) positive human epidermal growth factor receptor 2 (HER 2) negative metastatic breast cancers except in the case of symptomatic visceral disease. However, patients who suffer from disease progression while receiving a non-steroidal aromatase inhibitor (NSAI) have a very poor prognosis with standard endocrine therapy alone. Recently, based onthe results of the BOLERO 2 trial, the mammalian target of rapamycin (mTOR) inhibitor everolimus, combined with exemestane, a steroidal aromatase inhibitor, has been approved in Europe and the US for patients suffering from ER positive HER2 negative advanced breast cancer previously treated by a NSAI. The median progression-free survival (PFS) increased from 3.2 to 7.8 months in patients receiving everolimus and exemestane compared to placebo and exemestane. The magnitude of benefit was consistent in all pre-specified subgroups. Side effects were manageable and the quality of life was at least maintained. Everolimus has also beenrecently studied in HER2 positive locally advanced or metastatic disease in heavily pretreated patients (BOLERO 3 trial). This trial met its primary endpoint. The median PFS was increased in patients receiving trastuzumab, vinorelbine and everolimus compared to patients receiving trastuzumab, vinorelbine and placebo. We review pharmacological data and side effects of the drug. We also review the most important clinical trials leading to reimbursement of everolimus in metastatic breast cancer.

Prevention of haematoma progression by tranexamic acid in intracerebral haemorrhage patients with and without spot sign on admission scan: a statistical analysis plan of a pre-specified sub-study of the TICH-2 trial.

PubMed

Ovesen, Christian; Jakobsen, Janus Christian; Gluud, Christian; Steiner, Thorsten; Law, Zhe; Flaherty, Katie; Dineen, Rob A; Bath, Philip M; Sprigg, Nikola; Christensen, Hanne

2018-06-13

We present the statistical analysis plan of a prespecified Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH)-2 sub-study aiming to investigate, if tranexamic acid has a different effect in intracerebral haemorrhage patients with the spot sign on admission compared to spot sign negative patients. The TICH-2 trial recruited above 2000 participants with intracerebral haemorrhage arriving in hospital within 8 h after symptom onset. They were included irrespective of radiological signs of on-going haematoma expansion. Participants were randomised to tranexamic acid versus matching placebo. In this subgroup analysis, we will include all participants in TICH-2 with a computed tomography angiography on admission allowing adjudication of the participants' spot sign status. Primary outcome will be the ability of tranexamic acid to limit absolute haematoma volume on computed tomography at 24 h (± 12 h) after randomisation among spot sign positive and spot sign negative participants, respectively. Within all outcome measures, the effect of tranexamic acid in spot sign positive/negative participants will be compared using tests of interaction. This sub-study will investigate the important clinical hypothesis that spot sign positive patients might benefit more from administration of tranexamic acid compared to spot sign negative patients. Trial registration ISRCTN93732214 ( http://www.isrctn.com ).

Dynamic transcriptional symmetry-breaking in pre-implantation mammalian embryo development revealed by single-cell RNA-seq.

PubMed

Shi, Junchao; Chen, Qi; Li, Xin; Zheng, Xiudeng; Zhang, Ying; Qiao, Jie; Tang, Fuchou; Tao, Yi; Zhou, Qi; Duan, Enkui

2015-10-15

During mammalian pre-implantation embryo development, when the first asymmetry emerges and how it develops to direct distinct cell fates remain longstanding questions. Here, by analyzing single-blastomere transcriptome data from mouse and human pre-implantation embryos, we revealed that the initial blastomere-to-blastomere biases emerge as early as the first embryonic cleavage division, following a binomial distribution pattern. The subsequent zygotic transcriptional activation further elevated overall blastomere-to-blastomere biases during the two- to 16-cell embryo stages. The trends of transcriptional asymmetry fell into two distinct patterns: for some genes, the extent of asymmetry was minimized between blastomeres (monostable pattern), whereas other genes, including those known to be lineage specifiers, showed ever-increasing asymmetry between blastomeres (bistable pattern), supposedly controlled by negative or positive feedbacks. Moreover, our analysis supports a scenario in which opposing lineage specifiers within an early blastomere constantly compete with each other based on their relative ratio, forming an inclined 'lineage strength' that pushes the blastomere onto a predisposed, yet flexible, lineage track before morphological distinction. © 2015. Published by The Company of Biologists Ltd.

In Vitro Retentive Effect of Groove, Sandblasting, and Cement Type on Stainless Steel Crowns in Primary Molars.

PubMed

Pathak, Sidhant; Shashibhushan, K K; Bharath, K P; Poornima, P; Reddy, V V Subba

2015-01-01

The purpose of this study was to evaluate and compare the effect of placing vertical grooves, sandblasting, and luting cements on the retention of stainless steel crowns (SSCs). Eighty extracted primary molars were mounted in acrylic blocks. Specimens were divided into Group 1 (RelyX U200) and Group 2 (Smart Cem2). Teeth in each group were further subdivided into Subgroup A (no vertical grooves and no sandblasting), Subgroup B (vertical grooves), Subgroup C (sandblasting of crowns), and Subgroup D (vertical grooves and sandblasting of crowns). After cementation, SSCs were pulled off using a universal testing machine. One-way analysis of variance was used for statistical analyses. In Groups 1 and 2, the highest retentive strengths were found in Subgroup D (1,124 and 783 kPa, respectively), followed by Subgroup C (1,066 and 748 kPa, respectively), Subgroup A (762 and 356 kPa, respectively), and Subgroup B (743 and 314 kPa, respectively). Retentive strength in Group one was significantly higher than in Group two; Subgroups A and B were significantly lower than C and D. RelyX U200 showed higher retentive strength than Smart Cem2. Sandblasting increased the retention strength, whereas a vertical groove had no significant effect on retention.

Subtyping attention-deficit/hyperactivity disorder using temperament dimensions: toward biologically based nosologic criteria.

PubMed

Karalunas, Sarah L; Fair, Damien; Musser, Erica D; Aykes, Kamari; Iyer, Swathi P; Nigg, Joel T

2014-09-01

Psychiatric nosology is limited by behavioral and biological heterogeneity within existing disorder categories. The imprecise nature of current nosologic distinctions limits both mechanistic understanding and clinical prediction. We demonstrate an approach consistent with the National Institute of Mental Health Research Domain Criteria initiative to identify superior, neurobiologically valid subgroups with better predictive capacity than existing psychiatric categories for childhood attention-deficit/hyperactivity disorder (ADHD). To refine subtyping of childhood ADHD by using biologically based behavioral dimensions (i.e., temperament), novel classification algorithms, and multiple external validators. A total of 437 clinically well-characterized, community-recruited children, with and without ADHD, participated in an ongoing longitudinal study. Baseline data were used to classify children into subgroups based on temperament dimensions and examine external validators including physiological and magnetic resonance imaging measures. One-year longitudinal follow-up data are reported for a subgroup of the ADHD sample to address stability and clinical prediction. Parent/guardian ratings of children on a measure of temperament were used as input features in novel community detection analyses to identify subgroups within the sample. Groups were validated using 3 widely accepted external validators: peripheral physiological characteristics (cardiac measures of respiratory sinus arrhythmia and pre-ejection period), central nervous system functioning (via resting-state functional connectivity magnetic resonance imaging), and clinical outcomes (at 1-year longitudinal follow-up). The community detection algorithm suggested 3 novel types of ADHD, labeled as mild (normative emotion regulation), surgent (extreme levels of positive approach-motivation), and irritable (extreme levels of negative emotionality, anger, and poor soothability). Types were independent of existing clinical demarcations including DSM-5 presentations or symptom severity. These types showed stability over time and were distinguished by unique patterns of cardiac physiological response, resting-state functional brain connectivity, and clinical outcomes 1 year later. Results suggest that a biologically informed temperament-based typology, developed with a discovery-based community detection algorithm, provides a superior description of heterogeneity in the ADHD population than does any current clinical nosologic criteria. This demonstration sets the stage for more aggressive attempts at a tractable, biologically based nosology.

Factor structure and measurement invariance of the Health Education Impact Questionnaire: Does the subjectivity of the response perspective threaten the contextual validity of inferences?

PubMed

Elsworth, Gerald R; Nolte, Sandra; Osborne, Richard H

2015-01-01

On-going evidence is required to support the validity of inferences about change and group differences in the evaluation of health programs, particularly when self-report scales requiring substantial subjectivity in response generation are used as outcome measures. Following this reasoning, the aim of this study was to replicate the factor structure and investigate the measurement invariance of the latest version of the Health Education Impact Questionnaire, a widely used health program evaluation measure. An archived dataset of responses to the most recent version of the English-language Health Education Impact Questionnaire that uses four rather than six response options (N = 3221) was analysed using exploratory structural equation modelling and confirmatory factor analysis appropriate for ordered categorical data. Metric and scalar invariance were studied following recent recommendations in the literature to apply fully invariant unconditional models with minimum constraints necessary for model identification. The original eight-factor structure was replicated and all but one of the scales (Self Monitoring and Insight) was found to consist of unifactorial items with reliability of ⩾0.8 and satisfactory discriminant validity. Configural, metric and scalar invariance were established across pre-test to post-test and population sub-groups (sex, age, education, ethnic background). The results support the high level of interest in the Health Education Impact Questionnaire, particularly for use as a pre-test/post-test measure in experimental studies, other pre-post evaluation designs and system-level monitoring and evaluation.

Impact of angiotensin-converting enzyme gene polymorphism on neurohormonal responses to high- versus low-dose enalapril in advanced heart failure.

PubMed

Tang, W H Wilson; Vagelos, Randall H; Yee, Yin-Gail; Fowler, Michael B

2004-11-01

The impact of angiotensin-converting enzyme (ACE) gene polymorphism on neurohormonal dose response to ACE inhibitor therapy is unclear. ACE Insertion (I) or Deletion (D) genotype was determined in 74 patients with chronic heart failure who were randomly assigned to receive either high-dose or low-dose enalapril over a period of 6 months. Monthly pre-enalapril and post-enalapril neurohormone levels (serum ACE activity (sACE), plasma angiotensin II (A-II), plasma renin activity (PRA), and serum aldosterone (ALDO) were compared between genotype subgroups and between patients who received high- or low-dose enalapril within each genotype subgroup. At baseline, predose/postdose sACE and postdose PRA were significantly higher in the DD genotype. At 6-month follow-up, postdose sACE was reduced in a dose-dependent fashion in all three genotypes (P < .05). However, predose and postdose ALDO and A-II levels did not differ between each genotype subgroup at baseline or by enalapril dose within each genotype subgroup. ALDO escape and A-II reactivation were not affected by ACE genotype or enalapril dosage. Predose sACE were consistently higher in the DD genotype when compared with ID or II subgroups. Despite a dose-dependent suppression of sACE, there were no observed statistically significant differences in ALDO and A-II suppression or escape with escalating doses of enalapril within each subgroup.

Diagnostic and psychosocial differences in psychiatrically hospitalized military service members with single versus multiple suicide attempts.

PubMed

Kochanski-Ruscio, Kristen M; Carreno-Ponce, Jaime T; DeYoung, Kathryn; Grammer, Geoffrey; Ghahramanlou-Holloway, Marjan

2014-04-01

Individuals with multiple versus single suicide attempts present a more severe clinical picture and may be at greater risk for suicide. Yet group differences within military samples have been vastly understudied. The objective is to determine demographic, diagnostic, and psychosocial differences, based on suicide attempt status, among military inpatients admitted for suicide-related events. A retrospective chart review design was used with a total of 423 randomly selected medical records of psychiatric admissions to a military hospital from 2001 to 2006. Chi-square analyses indicated that individuals with multiple versus single suicide attempts were significantly more likely to have documented childhood sexual abuse (p =.025); problem substance use (p=.001); mood disorder diagnosis (p=.005); substance disorder diagnosis (p =.050); personality disorder not otherwise specified diagnosis (p =.018); and Axis II traits or diagnosis (p=.038) when compared to those with a single attempt history. Logistic regression analyses showed that males with multiple suicide attempts were more likely to have problem substance use (p=.005) and a mood disorder diagnosis (p =.002), while females with a multiple attempt history were more likely to have a history of childhood sexual (p =.027). Clinically meaningful differences among military inpatients with single versus multiple suicide attempts exist. Targeted Department of Defense suicide prevention and intervention efforts that address the unique needs of these two specific at-risk subgroups are additionally needed. Published by Elsevier Inc.

Adaptive designs for subpopulation analysis optimizing utility functions.

PubMed

Graf, Alexandra C; Posch, Martin; Koenig, Franz

2015-01-01

If the response to treatment depends on genetic biomarkers, it is important to identify predictive biomarkers that define (sub-)populations where the treatment has a positive benefit risk balance. One approach to determine relevant subpopulations are subgroup analyses where the treatment effect is estimated in biomarker positive and biomarker negative groups. Subgroup analyses are challenging because several types of risks are associated with inference on subgroups. On the one hand, by disregarding a relevant subpopulation a treatment option may be missed due to a dilution of the treatment effect in the full population. Furthermore, even if the diluted treatment effect can be demonstrated in an overall population, it is not ethical to treat patients that do not benefit from the treatment when they can be identified in advance. On the other hand, selecting a spurious subpopulation increases the risk to restrict an efficacious treatment to a too narrow fraction of a potential benefiting population. We propose to quantify these risks with utility functions and investigate nonadaptive study designs that allow for inference on subgroups using multiple testing procedures as well as adaptive designs, where subgroups may be selected in an interim analysis. The characteristics of such adaptive and nonadaptive designs are compared for a range of scenarios. © 2014 The Authors. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Report on the Achievements of Subgroup 19 on Activation Cross Sections of the WPEC, OECD-NEA

NASA Astrophysics Data System (ADS)

Plompen, A. J. M.; Smith, D. L.; Semkova, V. M.

2005-05-01

Subgroup 19 on Activation Cross Sections of the Working Party on Evaluation Cooperation of the OECD-NEA has recently concluded its activities. The goal of the subgroup was to generate a large set of new measured activation cross sections relevant to nuclear applications and make these data available to the nuclear science community. In addition, modeling efforts and sensitivity studies were undertaken to evaluate the use of measured data and model calculations for the prediction of unknown cross sections. The latter addresses the potential of model calculations to satisfy issues on the High Priority Request List when no measured data are available. In the course of the activities of the subgroup over ninety reaction channels were studied experimentally. All except the most recent of these data have been compiled into EXFOR format by members of the subgroup and submitted to OECD- NEA. As a result most of these data can now be retrieved online from the data centers. A systematic comparison was made with the new evaluated data files JEF3.0/EAF2003, JENDL3.3, and ENDF/B-VI.8 and with the current status of the global parameter systematics of the model code TALYS-0.57. In addition, a considerable number of locally optimized parameter sets were developed. Both the global and local approaches emphasize the use of consistent physics modelling for all important reaction channels and nuclides involved in the decay. Comparison of the two approaches allows assessment of the effort required when model estimates to a certain accuracy must be made. Parameter sensitivity studies were undertaken to further assess the accuracy requirements on model parameters if target uncertainties for the cross sections have been specified. The value of this approach has demonstrated itself and indicates the need for model codes that fit all available experimental data in order to connect the data covariance with the covariance of the model predictions. The work of the subgroup was a joint effort between IRMM, ANL, FZ-Jülich, INRNE Sofia, NIPNE Bucharest, IEP and Atomki Debrecen, JAERI, and Tohoku University. A comprehensive review of the subgroup activities will be presented.

Modeling the Interrelationships among Pre-Service Science Teachers' Understanding and Acceptance of Evolution, Their Views on Nature of Science and Self-Efficacy Beliefs regarding Teaching Evolution

ERIC Educational Resources Information Center

Akyol, Gulsum; Tekkaya, Ceren; Sungur, Semra; Traynor, Anne

2012-01-01

This study proposed a path model of relationships among understanding and acceptance of evolution, views on nature of science, and self-efficacy beliefs regarding teaching evolution. A total of 415 pre-service science teachers completed a series of self-report instruments for the specified purpose. After the estimation of scale scores using…

Measuring stigma among abortion providers: assessing the Abortion Provider Stigma Survey instrument.

PubMed

Martin, Lisa A; Debbink, Michelle; Hassinger, Jane; Youatt, Emily; Eagen-Torkko, Meghan; Harris, Lisa H

2014-01-01

We explored the psychometric properties of 15 survey questions that assessed abortion providers' perceptions of stigma and its impact on providers' professional and personal lives referred to as the Abortion Provider Stigma Survey (APSS). We administered the survey to a sample of abortion providers recruited for the Providers' Share Workshop (N = 55). We then completed analyses using Stata SE/12.0. Exploratory factor analysis, which resulted in 13 retained items and identified three subscales: disclosure management, resistance and resilience, and discrimination. Stigma was salient in abortion provider's lives: they identified difficulties surrounding disclosure (66%) and felt unappreciated by society (89%). Simultaneously, workers felt they made a positive contribution to society (92%) and took pride in their work (98%). Paired t-test analyses of the pre- and post-Workshop APSS scores showed no changes in the total score. However, the Disclosure Management subscale scores were significantly lower (indicating decreased stigma) for two subgroups of participants: those over the age of 30 and those with children. This analysis is a promising first step in the development of a quantitative tool for capturing abortion providers' experiences of and responses to pervasive abortion stigma.

Caesarean delivery and subsequent pregnancy interval: a systematic review and meta-analysis

PubMed Central

2013-01-01

Background Caesarean delivery has increased worldwide, however, the effects on fertility are largely unknown. This systematic review aims to compare subsequent sub-fertility (time to next pregnancy or birth) among women with a Caesarean delivery to women with a vaginal delivery. Methods Systematic review of the literature including seven databases: CINAHL; the Cochrane Library; Embase; Medline; PubMed; SCOPUS and Web of Knowledge (1945 - October 2012), using detailed search-strategies and reference list cross-checking. Cohort, case–control and cross-sectional studies were included. Two assessors reviewed titles, abstracts, and full articles using standardised data abstraction forms and assessed study quality. Results 11 articles were eligible for inclusion in the systematic review, of these five articles which adjusted for confounders were combined in a meta-analysis, totalling 750,407 women using fixed-effect models. Previous Caesarean delivery was associated with an increased risk of sub-fertility [pooled odds ratio (OR) 0.90; 95% CI 0.86, 0.93]. Subgroup analyses by parity [primiparous women: OR 0.91; 95% CI 0.87, 0.96; not limited to primiparous women: OR 0.81; 95% CI 0.73, 0.90]; by publication date (pre-2000: OR 0.80, 95% CI 0.68, 0.94; post-2000: OR 0.90, 95% CI 0.86, 0.94); by length of follow-up (<10 years: OR 0.81, 95% CI 0.73, 0.90; >10 years: OR 0.91, 95% CI 0.87, 0.96); by indication for mode of delivery (specified: 0.92, 95% CI 0.88, 0.97; not specified: OR 0.81, 95% CI 0.73, 0.90); by cohort size (<35,000: OR 0.79, 95% CI 0.67, 0.92; >35,000: OR 0.90, 95% CI 0.87, 0.95), by definition of sub-fertility used divided into (birth interval [BI]: OR 0.89, 95% CI 0.84, 0.94; inter-pregnancy interval [IPI]: OR 0.91, 95% CI 0.85, 0.97; and categorical measures: OR 0.81, 95% CI 0.73, 0.90); continuous measures: OR 0.91, 95% CI 0.87, 0.96) were performed. Results of the six studies not included in the meta-analysis (which did not adjust for confounders) are presented individually. Conclusions The meta-analysis shows an increased waiting time to next pregnancy and risk of sub-fertility among women with a previous Caesarean delivery. However, included studies are limited by poor epidemiological methods such as variations in the definition of time to next pregnancy, lack of confounding adjustment, or details of the indication for Caesarean delivery. Further research of a more robust methodological quality to better explore any underlying causes of sub-fertility and maternal intent to delay childbearing is warranted. PMID:23981569

A cross-species bi-clustering approach to identifying conserved co-regulated genes.

PubMed

Sun, Jiangwen; Jiang, Zongliang; Tian, Xiuchun; Bi, Jinbo

2016-06-15

A growing number of studies have explored the process of pre-implantation embryonic development of multiple mammalian species. However, the conservation and variation among different species in their developmental programming are poorly defined due to the lack of effective computational methods for detecting co-regularized genes that are conserved across species. The most sophisticated method to date for identifying conserved co-regulated genes is a two-step approach. This approach first identifies gene clusters for each species by a cluster analysis of gene expression data, and subsequently computes the overlaps of clusters identified from different species to reveal common subgroups. This approach is ineffective to deal with the noise in the expression data introduced by the complicated procedures in quantifying gene expression. Furthermore, due to the sequential nature of the approach, the gene clusters identified in the first step may have little overlap among different species in the second step, thus difficult to detect conserved co-regulated genes. We propose a cross-species bi-clustering approach which first denoises the gene expression data of each species into a data matrix. The rows of the data matrices of different species represent the same set of genes that are characterized by their expression patterns over the developmental stages of each species as columns. A novel bi-clustering method is then developed to cluster genes into subgroups by a joint sparse rank-one factorization of all the data matrices. This method decomposes a data matrix into a product of a column vector and a row vector where the column vector is a consistent indicator across the matrices (species) to identify the same gene cluster and the row vector specifies for each species the developmental stages that the clustered genes co-regulate. Efficient optimization algorithm has been developed with convergence analysis. This approach was first validated on synthetic data and compared to the two-step method and several recent joint clustering methods. We then applied this approach to two real world datasets of gene expression during the pre-implantation embryonic development of the human and mouse. Co-regulated genes consistent between the human and mouse were identified, offering insights into conserved functions, as well as similarities and differences in genome activation timing between the human and mouse embryos. The R package containing the implementation of the proposed method in C ++ is available at: https://github.com/JavonSun/mvbc.git and also at the R platform https://www.r-project.org/ jinbo@engr.uconn.edu. © The Author 2016. Published by Oxford University Press.

Efficacy of aripiprazole augmentation in Japanese patients with major depressive disorder: a subgroup analysis and Montgomery-Åsberg Depression Rating Scale and Hamilton Rating Scale for Depression item analyses of the Aripiprazole Depression Multicenter Efficacy study.

PubMed

Ozaki, Norio; Otsubo, Tempei; Kato, Masaki; Higuchi, Teruhiko; Ono, Hiroaki; Kamijima, Kunitoshi

2015-01-01

Results from this randomized, placebo-controlled study of aripiprazole augmentation to antidepressant therapy (ADT) in Japanese patients with major depressive disorder (MDD) (the Aripiprazole Depression Multicenter Efficacy [ADMIRE] study) revealed that aripiprazole augmentation was superior to ADT alone and was well tolerated. In subgroup analyses, we investigated the influence of demographic- and disease-related factors on the observed responses. We also examined how individual symptom improvement was related to overall improvement in MDD. Data from the ADMIRE study were analyzed. Subgroup analyses were performed on the primary outcome measures: the mean change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from the end of selective serotonin reuptake inhibitor (SSRI)/serotonin norepinephrine reuptake inhibitor (SNRI) treatment to the end of the randomized treatment. Changes in the MADRS total scores were consistently greater with aripiprazole than placebo in each of the subgroups. Efficacy was not related to sex, age, number of adequate ADT trials in the current episode, MDD diagnosis, number of depressive episodes, duration of the current episode, age at first depressive episode, time since the first depressive episode, type of SSRI/SNRI, or severity at the end of SSRI/SNRI treatment phase. Compared to placebo, aripiprazole resulted in significant and rapid improvement on seven of the 10 MADRS items, including sadness. These post-hoc analyses indicated that aripiprazole was effective for a variety of Japanese patients with MDD who had exhibited inadequate responses to ADT. Additionally, we suggest that aripiprazole significantly and rapidly improved the core depressive symptoms. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Health care expenditures among Asian American subgroups.

PubMed

Chen, Jie; Vargas-Bustamante, Arturo; Ortega, Alexander N

2013-06-01

Using two nationally representative data sets, this study examined health care expenditure disparities between Caucasians and different Asian American subgroups. Multivariate analyses demonstrate that Asian Americans, as a group, have significantly lower total expenditures compared with Caucasians. Results also point to considerable heterogeneities in health care spending within Asian American subgroups. Findings suggest that language assistance programs would be effective in reducing disparities among Caucasians and Asian American subgroups with the exception of Indians and Filipinos, who tend to be more proficient in English. Results also indicate that citizenship and nativity were major factors associated with expenditure disparities. Socioeconomic status, however, could not explain expenditure disparities. Results also show that Asian Americans have lower physician and pharmaceutical costs but not emergency department or hospital expenditures. These findings suggest the need for culturally competent policies specific to Asian American subgroups and the necessity to encourage cost-effective treatments among Asian Americans.

Health Care Expenditures Among Asian American Subgroups

PubMed Central

Chen, Jie; Vargas-Bustamante, Arturo; Ortega, Alexander N.

2014-01-01

Using two nationally representative data sets, this study examined health care expenditure disparities between Caucasians and different Asian American subgroups. Multivariate analyses demonstrate that Asian Americans, as a group, have significantly lower total expenditures compared with Caucasians. Results also point to considerable heterogeneities in health care spending within Asian American subgroups. Findings suggest that language assistance programs would be effective in reducing disparities among Caucasians and Asian American subgroups with the exception of Indians and Filipinos, who tend to be more proficient in English. Results also indicate that citizenship and nativity were major factors associated with expenditure disparities. Socioeconomic status, however, could not explain expenditure disparities. Results also show that Asian Americans have lower physician and pharmaceutical costs but not emergency department or hospital expenditures. These findings suggest the need for culturally competent policies specific to Asian American subgroups and the necessity to encourage cost-effective treatments among Asian Americans. PMID:23223329

Recovery of lipid metabolic alterations in hepatitis C patients after viral clearance: Incomplete restoration with accelerated ω-oxidation.

PubMed

Chang, Su-Wei; Cheng, Mei-Ling; Shiao, Ming-Shi; Yeh, Chau-Ting; Wang, Chao-Hung; Fan, Chun-Ming; Chiu, Cheng-Tang; Chang, Ming-Ling

2018-03-02

How hepatitis C virus (HCV)-associated lipid metabolic alterations recover after sustained virological response (SVR) remains elusive. The aforementioned recovery pattern was investigated. In a prospective cohort study of 438 chronic hepatitis C (CHC) patients with SVR after anti-HCV therapy, 164 sex- and age-matched genotype I (G1) and G2 patients underwent paired-serum liquid chromatography-tandem mass spectrometry analyses before and 24 weeks after therapy. Subjects without CHC served as controls (n = 100). CHC patients had lower baseline lipid levels than controls. Among CHC patients, pre-therapy total cholesterol levels were positively associated with HCV RNA levels; G1 patients had higher pre-therapy HCV RNA levels than G2 patients. Repeated measures analysis of variance of CHC patients showed that lathosterol, lanosterol, total hydroxysphingomyelin, and total phosphatidylcholines levels, and total dicarboxyacylcarnitine/total acylcarnitine (indicators of ω-oxidation) and pre-β-lipoprotein ratios elevated 24 weeks after therapy compared with the levels before therapy. Levels of total lysophosphatidylcholines and α- and β-lipoprotein ratios decreased. Subgroup analyses showed elevated 7-dehydrocholesterol and lanosterol levels, particularly in G2 and male patients, who had broader spectra of altered phosphatidylcholines and acylcarnitines than G1 and female patients, respectively. Compared with controls, CHC patients had higher post-therapy levels of total lysophosphatidylcholines and hydroxysphingomyelins and ratios of total dicarboxyacylcarnitines/total acylcarnitines but lower cholesterol levels. At 24 weeks after therapy, accelerated cholesterol biosynthesis, hepatic lipid export, ω-oxidation, and decreased systemic inflammation were noted in CHC patients with SVR, with greater efficiency in G2 and male patients. Regardless, HCV-associated lipid metabolic alterations required >24 weeks for restoration or were incompletely reversible after SVR. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Understanding Definitions of Minimally Verbal across Instruments: Evidence for Subgroups within Minimally Verbal Children and Adolescents with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Bal, Vanessa Hus; Katz, Terry; Bishop, Somer L.; Krasileva, Kate

2016-01-01

Background: Minimally verbal (MV) children with autism spectrum disorder (ASD) are often assumed to be profoundly cognitively impaired and excluded from analyses due to challenges completing standardized testing protocols. A literature aimed at increasing understanding of this subgroup is emerging; however, the many methods used to define MV…

Comparative sequence analyses of sixteen reptilian paramyxoviruses

USGS Publications Warehouse

Ahne, W.; Batts, W.N.; Kurath, G.; Winton, J.R.

1999-01-01

Viral genomic RNA of Fer-de-Lance virus (FDLV), a paramyxovirus highly pathogenic for reptiles, was reverse transcribed and cloned. Plasmids with significant sequence similarities to the hemagglutinin-neuraminidase (HN) and polymerase (L) genes of mammalian paramyxoviruses were identified by BLAST search. Partial sequences of the FDLV genes were used to design primers for amplification by nested polymerase chain reaction (PCR) and sequencing of 518-bp L gene and 352-bp HN gene fragments from a collection of 15 previously uncharacterized reptilian paramyxoviruses. Phylogenetic analyses of the partial L and HN sequences produced similar trees in which there were two distinct subgroups of isolates that were supported with maximum bootstrap values, and several intermediate isolates. Within each subgroup the nucleotide divergence values were less than 2.5%, while the divergence between the two subgroups was 20-22%. This indicated that the two subgroups represent distinct virus species containing multiple virus strains. The five intermediate isolates had nucleotide divergence values of 11-20% and may represent additional distinct species. In addition to establishing diversity among reptilian paramyxoviruses, the phylogenetic groupings showed some correlation with geographic location, and clearly demonstrated a low level of host species-specificity within these viruses. Copyright (C) 1999 Elsevier Science B.V.

The impact of ethnicity, family income, and parental education on children's health and use of health services.

PubMed Central

Flores, G; Bauchner, H; Feinstein, A R; Nguyen, U S

1999-01-01

OBJECTIVES: This study characterized ethnic disparities for children in demographics, health status, and use of services; explored whether ethnic subgroups (Puerto Rican, Cuban, and Mexican) have additional distinctive differences; and determined whether disparities are explained by differences in family income and parental education. METHODS: Bivariate and multivariate analyses of data on 99,268 children from the 1989-91 National Health Interview Surveys were conducted. RESULTS: Native American, Black, and Hispanic children are poorest (35%, 41% below poverty level vs 10% of Whites), least healthy (66%-74% in excellent or very good health vs 85% of Whites), and have the least well educated parents. Compared with Whites, non-White children average fewer doctor visits and are more likely to have excessive intervals between visits. Hispanic subgroup differences in demographics, health, and use of services equal or surpass differences among major ethnic groups. In multivariate analyses, almost all ethnic group disparities persisted after adjustment for family income, parental education, and other relevant covariates. CONCLUSIONS: Major ethnic groups and subgroups of children differ strikingly in demographics, health, and use of services; subgroup differences are easily overlooked; and most disparities persist even after adjustment for family income and parental education. PMID:10394317

Gait Biomechanics in Participants, Six Months after First-time Lateral Ankle Sprain.

PubMed

Doherty, C; Bleakley, C; Hertel, J; Caulfield, B; Ryan, J; Delahunt, E

2016-06-01

No research currently exists predicating a link between the injury-affiliated sensorimotor deficits of acute ankle sprain and those of chronic ankle instability during gait. This analysis evaluates participants with a 6-month history of ankle sprain injury to affirm this link. 69 participants with a 6-month history of acute first-time lateral ankle sprain were divided into subgroups ('chronic ankle instability' and 'coper') based on their self-reported disability and compared to 20 non-injured participants during a gait task. Lower extremity kinematic and kinetic data were collected from 200 ms pre- to 200 ms post-heel strike (period 1) and from 200 ms pre- to 200 ms post-toe off (period 2). The 'chronic ankle instability' subgroup (who reported greater disability) displayed increased knee flexion during period 1. During period 2, this subgroup exhibited greater total displacement at their ankle joint and greater extensor dominance at their knee. That many of these features are present, both in individuals with acute ankle sprain and those with chronic ankle instability may advocate a link between acute deficits and long-term outcome. Clinicians must be aware that the sensorimotor deficits of ankle sprain may persevere beyond the acute stage of injury and be cognizant of the capacity for impairments to pervade proximally. © Georg Thieme Verlag KG Stuttgart · New York.

The Australasian Resuscitation in Sepsis Evaluation (ARISE) trial statistical analysis plan.

PubMed

Delaney, Anthony P; Peake, Sandra L; Bellomo, Rinaldo; Cameron, Peter; Holdgate, Anna; Howe, Belinda; Higgins, Alisa; Presneill, Jeffrey; Webb, Steve

2013-09-01

The Australasian Resuscitation in Sepsis Evaluation (ARISE) study is an international, multicentre, randomised, controlled trial designed to evaluate the effectiveness of early goal-directed therapy compared with standard care for patients presenting to the emergency department with severe sepsis. In keeping with current practice, and considering aspects of trial design and reporting specific to non-pharmacological interventions, our plan outlines the principles and methods for analysing and reporting the trial results. The document is prepared before completion of recruitment into the ARISE study, without knowledge of the results of the interim analysis conducted by the data safety and monitoring committee and before completion of the two related international studies. Our statistical analysis plan was designed by the ARISE chief investigators, and reviewed and approved by the ARISE steering committee. We reviewed the data collected by the research team as specified in the study protocol and detailed in the study case report form. We describe information related to baseline characteristics, characteristics of delivery of the trial interventions, details of resuscitation, other related therapies and other relevant data with appropriate comparisons between groups. We define the primary, secondary and tertiary outcomes for the study, with description of the planned statistical analyses. We have developed a statistical analysis plan with a trial profile, mock-up tables and figures. We describe a plan for presenting baseline characteristics, microbiological and antibiotic therapy, details of the interventions, processes of care and concomitant therapies and adverse events. We describe the primary, secondary and tertiary outcomes with identification of subgroups to be analysed. We have developed a statistical analysis plan for the ARISE study, available in the public domain, before the completion of recruitment into the study. This will minimise analytical bias and conforms to current best practice in conducting clinical trials.

Treatment of scalp psoriasis with clobetasol-17 propionate 0.05% shampoo: a study on daily clinical practice.

PubMed

Bovenschen, H J; Van de Kerkhof, P C M

2010-04-01

Safety and clinical effectiveness of clobetasol-17 propionate 0.05% shampoo have been shown in patients with scalp psoriasis. First, to evaluate treatment satisfaction, user convenience safety and effectiveness of clobetasol-17 propionate 0.05% shampoo treatment in daily clinical practice. Second, to identify subgroup variables that may predict treatment success or failure. A total of 56 patients with scalp psoriasis were treated with short-contact clobetasol-17 propionate 0.05% shampoo once daily for 4 weeks. Data on treatment satisfaction, user convenience, safety and effectiveness were assessed on a 7-point Likert scale using postal questionnaires. Subgroup analyses were performed to identify variables that may predict treatment outcome. A total of 41 patients returned both questionnaires (73%). Positive treatment satisfaction and user convenience were reported by 66% and 79% of patients respectively. Patient-rated indicators for disease severity improved by 39-46% (P < 0.05%). No major side-effects were reported. Subgroup analyses did not reveal any statistically significant patient variable that may predict treatment outcome. However, a tendency towards improved treatment satisfaction was observed in patients who had received fewer topical antipsoriatic treatments previously (P > 0.05). Short-contact treatment with clobetasol-17 propionate 0.05% shampoo has high user convenience and patient satisfaction rates. Moreover, the treatment is well-tolerated and efficacious from patients' perspective. Subgroup analyses did not reveal factors predicting treatment outcome, although treatment success tended to be more evident in patients who had received fewer treatments previously.

The Eucalyptus grandis R2R3-MYB transcription factor family: evidence for woody growth-related evolution and function.

PubMed

Soler, Marçal; Camargo, Eduardo Leal Oliveira; Carocha, Victor; Cassan-Wang, Hua; San Clemente, Hélène; Savelli, Bruno; Hefer, Charles A; Paiva, Jorge A Pinto; Myburg, Alexander A; Grima-Pettenati, Jacqueline

2015-06-01

The R2R3-MYB family, one of the largest transcription factor families in higher plants, controls a wide variety of plant-specific processes including, notably, phenylpropanoid metabolism and secondary cell wall formation. We performed a genome-wide analysis of this superfamily in Eucalyptus, one of the most planted hardwood trees world-wide. A total of 141 predicted R2R3-MYB sequences identified in the Eucalyptus grandis genome sequence were subjected to comparative phylogenetic analyses with Arabidopsis thaliana, Oryza sativa, Populus trichocarpa and Vitis vinifera. We analysed features such as gene structure, conserved motifs and genome location. Transcript abundance patterns were assessed by RNAseq and validated by high-throughput quantitative PCR. We found some R2R3-MYB subgroups with expanded membership in E. grandis, V. vinifera and P. trichocarpa, and others preferentially found in woody species, suggesting diversification of specific functions in woody plants. By contrast, subgroups containing key genes regulating lignin biosynthesis and secondary cell wall formation are more conserved across all of the species analysed. In Eucalyptus, R2R3-MYB tandem gene duplications seem to disproportionately affect woody-preferential and woody-expanded subgroups. Interestingly, some of the genes belonging to woody-preferential subgroups show higher expression in the cambial region, suggesting a putative role in the regulation of secondary growth. © 2014 The Authors New Phytologist © 2014 New Phytologist Trust.

Antecedents and consequences of binge eating episodes in women with an eating disorder.

PubMed

Kjelsås, E; Børsting, I; Gudde, C Buch

2004-03-01

The aim of this study was to explore antecedents and sequelae of binge eating episodes. A sample of eating disorders (n = 154 women) was selected from a total of 1849 female respondents (out of 2500) recruited as part of a general population-based survey. Included participants met DSM-III-R criteria for anorexia nervosa (AN), bulimia nervosa (BN) or eating disorder not otherwise specified (EDNOS) based on the Survey for Eating Disorders (SEDs). Preliminary criteria for binge eating disorder (BED) were added. Results indicated that the most frequently reported antecedents and consequences of binge eating were emotional and physiological factors. There were significant differences between the different ED subgroups in their frequency of binge eating episodes. Regarding antecedents of a binge eating episode, the SEDs-defined ED subgroups had overall differences in frequency on "stomach feeling". In particular, the BN-group reported "euphoria" more frequently than the BED and EDNOS-groups. Concerning consequences of a binge eating episode, there were overall differences between the ED subgroups on "fall asleep", and in addition a borderline significance was found for "disturbed by others" (p = 0.059). None of the eight women in the AN group reported "euphoria" as a factor that terminated a binge eating episode. The findings may have important implications with regard to prevention and treatment of ED.

Detection of unusual strains of RV in patients with acute diarrhoea in Mexico.

PubMed

del R González-Losa, Maria; Rodríguez-Angulo, Elsa; Manzano-Cabrera, Luis; Mejía-Cámara, Javier; Puerto-Solís, Marylin

2005-04-01

Group A rotaviruses are a major cause of acute gastroenteritis in infants. Human strains with a short RNA pattern generally exhibit subgroup I, G2, P1B[4] specificity, those with a long RNA pattern show subgroup II, G1, G3 or G4, P1A[8] specificity. The presence of strains with unusual specificities has been reported worldwide over the last decade. To determine antigenic diversity among rotaviruses isolated from patients with diarrhoea. A laboratory-based survey study was carried out with faecal samples from patients with acute gastroenteritis form January to April 2000. To classify the samples PAGE and ELISA with specific antibodies to serotype G and P and RT-PCR were carried out. Twenty one specimens from patients with dehydrating diarrhoea had unusual specifies. Nine specimens had unusual combination of long pattern and subgroup I. Twelve specimens with short pattern belong to G1 serotype. As far as the serotypes and genotypes concern 11 samples were P1A, P[4] and one specimen was P1A, P[9]. These results demonstrated the unexpected presence of unusual strains of rotavirus in Mexico. Detection of strains with both human and animal characteristics may indicate interspecies transmission of RV between humans and animals.

Putting habit into practice, and practice into habit: a process evaluation and exploration of the acceptability of a habit-based dietary behaviour change intervention.

PubMed

Gardner, Benjamin; Sheals, Kate; Wardle, Jane; McGowan, Laura

2014-10-30

Forming 'habit' - defined as a learned process that generates automatic responses to contextual cues - has been suggested as a mechanism for behaviour maintenance, but few studies have applied habit theory to behaviour change. This study used process evaluation data, taken from a randomised controlled trial of a healthy child-feeding intervention for parents previously shown to be effective, to explore the applicability to dietary behaviour change of predictions and recommendations drawn from habit theory. The intervention supported parents in pursuing child-feeding habit goals in three domains (giving fruit and vegetables, water, healthy snacks), over four fortnightly home visits. We explored whether (a) the habit-formation model was acceptable to participants, (b) better-specified habit-formation goals yielded greater habit gains, and (c) habit gains were sustained (d) even when subsequent, new habit goals were pursued. Qualitative and quantitative data were taken from 57 parents randomised to the intervention arm, and so analyses presented here used a pre-post intervention design. Thematic analysis of post-intervention qualitative interviews evaluated acceptability, and self-reported habit goals were content-analysed. ANOVAs explored changes in habit strength, recorded at home visits and one- and two-month follow-ups, across time and goals. Participants understood and engaged positively with the habit-formation approach. Although many seemingly poorly-specified habit goals were set, goal characteristics had minimal impact on habit strength, which were achieved within two weeks for all behaviours (p's < .001), and were maintained or had increased further by the final follow-up. The habit-formation model appears to be an acceptable and fruitful basis for dietary behaviour change.

Liver transplantation nearly normalizes brain spontaneous activity and cognitive function at 1 month: a resting-state functional MRI study.

PubMed

Cheng, Yue; Huang, Lixiang; Zhang, Xiaodong; Zhong, Jianhui; Ji, Qian; Xie, Shuangshuang; Chen, Lihua; Zuo, Panli; Zhang, Long Jiang; Shen, Wen

2015-08-01

To investigate the short-term brain activity changes in cirrhotic patients with Liver transplantation (LT) using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method. Twenty-six cirrhotic patients as transplant candidates and 26 healthy controls were included in this study. The assessment was repeated for a sub-group of 12 patients 1 month after LT. ReHo values were calculated to evaluate spontaneous brain activity and whole brain voxel-wise analysis was carried to detect differences between groups. Correlation analyses were performed to explore the relationship between the change of ReHo with the change of clinical indexes pre- and post-LT. Compared to pre-LT, ReHo values increased in the bilateral inferior frontal gyrus (IFG), right inferior parietal lobule (IPL), right supplementary motor area (SMA), right STG and left middle frontal gyrus (MFG) in patients post-LT. Compared to controls, ReHo values of post-LT patients decreased in the right precuneus, right SMA and increased in bilateral temporal pole, left caudate, left MFG, and right STG. The changes of ReHo in the right SMA, STG and IFG were correlated with change of digit symbol test (DST) scores (P < 0.05 uncorrected). This study found that, at 1 month after LT, spontaneous brain activity of most brain regions with decreased ReHo in pre-LT was substantially improved and nearly normalized, while spontaneous brain activity of some brain regions with increased ReHo in pre-LT continuously increased. ReHo may provide information on the neural mechanisms of LT' effects on brain function.

A Randomized Comparison of Reservoir-Based Polymer-Free Amphilimus-Eluting Stents Versus Everolimus-Eluting Stents With Durable Polymer in Patients With Diabetes Mellitus: The RESERVOIR Clinical Trial.

PubMed

Romaguera, Rafael; Gómez-Hospital, Joan A; Gomez-Lara, Josep; Brugaletta, Salvatore; Pinar, Eduardo; Jiménez-Quevedo, Pilar; Gracida, Montserrat; Roura, Gerard; Ferreiro, Jose L; Teruel, Luis; Montanya, Eduard; Fernandez-Ortiz, Antonio; Alfonso, Fernando; Valgimigli, Marco; Sabate, Manel; Cequier, Angel

2016-01-11

The aim of this study was to compare the efficacy of amphilimus-eluting stents (AES) with that of everolimus-eluting stents (EES) in patients with diabetes mellitus (DM). The AES is a polymer-free drug-eluting stent that elutes sirolimus formulated with an amphiphilic carrier from laser-dug wells. This technology could be associated with a high efficacy in patients with DM. This was a multicenter, randomized, noninferiority trial. Patients with DM medically treated with oral glucose-lowering agents or insulin and de novo coronary lesions were randomized in a 1:1 fashion to AES or EES. The primary endpoint was the neointimal (NI) volume obstruction assessed by optical coherence tomography at 9-month follow-up. A total of 116 lesions in 112 patients were randomized. Overall, 40% were insulin-treated patients, with a median HbA1c of 7.3% (interquartile range: 6.7% to 8.0%). The primary endpoint, NI volume obstruction, was 11.97 ± 5.94% for AES versus 16.11 ± 18.18% for EES, meeting the noninferiority criteria (p = 0.0003). Pre-specified subgroup analyses showed a significant interaction between stent type and glycemic control (p = 0.02), with a significant reduction in NI hyperplasia in the AES group in patients with the higher HbA1c (p = 0.03). By quantitative coronary angiography, in-stent late loss was 0.14 ± 0.24 for AES versus 0.24 ± 0.57 mm for EES (p = 0.27), with a larger minimal lumen diameter at follow-up for AES (p = 0.02), mainly driven by 2 cases of occlusive restenosis in the EES group. AES are noninferior to EES for the coronary revascularization of patients with DM. These results suggest a high efficacy of the AES and may support the potential benefit of this stent in patients with DM. (A Randomized Comparison of Reservoir-Based Polymer-Free Amphilimus-Eluting Stents Versus Everolimus-Eluting Stents With Durable Polymer in Patients With Diabetes Mellitus [RESERVOIR]; NCT01710748). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

SELF-MANAGEMENT COUNSELING IN PATIENTS WITH HEART FAILURE: PRIMARY RESULTS FROM THE HEART FAILURE ADHERENCE AND RETENTION TRIAL (HART)

PubMed Central

Powell, Lynda H.; Calvin, James E.; Richardson, Dejuran; Janssen, Imke; Mendes de Leon, Carlos F.; Flynn, Kristin J.; Grady, Kathleen L.; Rucker-Whitaker, Cheryl S.; Eaton, Claudia; Avery, Elizabeth

2013-01-01

Context Activating patients with heart failure (HF) to adhere to physician advice has not translated into clinical benefit, but past trials have had methodologic limitations. Objective To determine the value of self-management counseling plus HF education, over HF education alone, on the primary endpoint of death or HF hospitalization. Design, Setting, and Patients A single center behavioral efficacy trial in 902 patients with mild to moderate systolic or diastolic dysfunction, randomized between 2001–2004. Interventions All patients were offered 18 contacts and 18 HF educational tip sheets over the course of 1 year. Patients randomized to education received tip sheets in the mail and phone calls to check comprehension. Patients randomized to self-management received tip sheets in groups and were taught self-management skills to implement the advice. Main Outcome Measure Death or HF hospitalization, blindly adjudicated by cardiologists. Intent-to-treat results were analyzed as time-to-event and accelerated failure time models were used for non-proportional hazards. Results Patients were an average of 63.6 years, 47% female, 40% minority, 52% with family income <$30,000/year, and 23% with diastolic dysfunction. The self-management arm was no different from the education arm on the primary endpoint (Wilcoxon p=0.58). Post-hoc analyses on pre-specified subgroups revealed a significant income x treatment interaction (log-logistic estimate=0.64, p=0.02). Patients with income <$30,000 in self-management had a slower time to event than those in education (p=0.05) and were no different than higher income patients in either treatment arm. Conclusions The addition of self-management counseling to HF education does not reduce death or HF hospitalizations in patients with mild to moderate HF. Future trials should evaluate tailored outpatient HF management featuring ongoing education and comprehension checks for all, augmented by group-based skill development for those more economically disadvantaged. Such an approach may be a cost-effective, timely, and simple option for reducing HF costs. PMID:20858878

Victimization and health risk factors among weapon-carrying youth.

PubMed

Stayton, Catherine; McVeigh, Katharine H; Olson, E Carolyn; Perkins, Krystal; Kerker, Bonnie D

2011-11-01

To compare health risks of 2 subgroups of weapon carriers: victimized and nonvictimized youth. 2003-2007 NYC Youth Risk Behavior Surveys were analyzed using bivariate analyses and multinomial logistic regression. Among NYC teens, 7.5% reported weapon carrying without victimization; 6.9% reported it with victimization. Both subgroups were more likely than non-weapon carriers to binge drink, use marijuana, smoke, fight, and have multiple sex partners; weapon carriers with victimization also experienced persistent sadness and attempted suicide. Subgroups of weapon carriers have distinct profiles. Optimal response should pair disciplinary action with screening for behavioral and mental health concerns and victimization.

Racial/ethnic differences in correlates of psychological distress among five Asian-American subgroups and non-Hispanic Whites.

PubMed

Park, Hyunjeong; Choi, Eunsuk; Wenzel, Jennifer A

2018-05-29

Despite their vastly different historical backgrounds, unique languages and variable pre- and post-immigration experiences, Asian-Americans are considered to share stressors surrounding immigration, but there is a gap in describing manifestations of possible mental distress. Thus, the purpose of this study was to explore and compare differences in factors associated with psychological distress among Asian subgroups including Chinese, Filipino, Vietnamese, Korean, Japanese, and non-Hispanic Whites. Using a cross-sectional study design, California Health Interview Survey (CHIS) 2011/2012 data were analyzed. The sample consisted of 29,142 participants: 25,645 non-Hispanic Whites, 3497 non-Hispanic Asian-Americans, 1156 Chinese, 471 Filipinos, 864 Vietnamese, 704 Koreans, and 302 Japanese. Sociodemographic characteristics included gender, age group, marital status, education, poverty level, working status, health insurance, level of acculturation, social cohesion, neighborhood safety, and civic engagement. Physical health status included disability and chronic illness. Psychological distress was evaluated using the Kessler 6 (K6) scale. Results showed that psychological distress levels ranged between 1.96 and 4.52 (p < .05) out of 24 and associated factors were significantly different among the five Asian subgroups and non-Hispanic Whites. The current study highlights the differences in characteristics of psychological distress among Asian subgroups. It underscores the significance of understanding individualized cultural and historical background in each Asian subgroup and subsequently developing and applying appropriate interventions for those groups. In addition, different influencing factors should be applied to assess and prioritize the needs of Asian subgroups to improve psychological distress. The study also warrants further investigation and careful description of each Asian subgroups.

A serious game for children with Attention Deficit Hyperactivity Disorder: Who benefits the most?

PubMed Central

Franken, Ingmar H. A.; Maras, Athanasios

2018-01-01

Objective The aim of the current study was to identify which subgroups of children with Attention Deficit Hyperactivity Disorder (ADHD) benefitted the most from playing a Serious Game (SG) intervention shown in a randomized trial to improve behavioral outcomes. Method Pre-intervention characteristics [i.e., gender, age, intellectual level of functioning, medication use, computer experience, ADHD subtype, severity of inattention problems, severity of hyperactivity/impulsivity problems, comorbid Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) symptoms] were explored as potential moderators in a Virtual Twins (VT) analysis to identify subgroups for whom the SG intervention was most effective. Primary outcome measures were parent-reported time management, planning/organizing and cooperation skills. Results Two subgroups were identified. Girls (n = 26) were identified as the subgroup that was most likely to show greater improvements in planning/organizing skills as compared to the estimated treatment effect of the total group of participants. Furthermore, among the boys, those (n = 47) with lower baseline levels of hyperactivity and higher levels of CD symptoms showed more improvements in their planning/organizing skills when they played the SG intervention as compared to the estimated treatment effect of the total group of participants. Conclusion Using a VT analysis two subgroups of children with ADHD, girls, and boys with both higher levels of CD and lower levels of hyperactivity, were identified. These subgroups mostly benefit from playing the SG intervention developed to improve ADHD related behavioral problems. Our results imply that these subgroups have a higher chance of treatment success. PMID:29543891

Program for Weibull Analysis of Fatigue Data

NASA Technical Reports Server (NTRS)

Krantz, Timothy L.

2005-01-01

A Fortran computer program has been written for performing statistical analyses of fatigue-test data that are assumed to be adequately represented by a two-parameter Weibull distribution. This program calculates the following: (1) Maximum-likelihood estimates of the Weibull distribution; (2) Data for contour plots of relative likelihood for two parameters; (3) Data for contour plots of joint confidence regions; (4) Data for the profile likelihood of the Weibull-distribution parameters; (5) Data for the profile likelihood of any percentile of the distribution; and (6) Likelihood-based confidence intervals for parameters and/or percentiles of the distribution. The program can account for tests that are suspended without failure (the statistical term for such suspension of tests is "censoring"). The analytical approach followed in this program for the software is valid for type-I censoring, which is the removal of unfailed units at pre-specified times. Confidence regions and intervals are calculated by use of the likelihood-ratio method.

Participation of the elderly, women, and minorities in pivotal trials supporting 2011-2013 U.S. Food and Drug Administration approvals.

PubMed

Downing, Nicholas S; Shah, Nilay D; Neiman, Joseph H; Aminawung, Jenerius A; Krumholz, Harlan M; Ross, Joseph S

2016-04-14

Pivotal trials, the clinical studies that inform U.S. Food and Drug Administration (FDA) approval decisions, provide the foundational evidence supporting the safety and efficacy of novel therapeutics. We determined the representation of the elderly, women, and patients from racial and ethnic minorities in pivotal trials and whether the FDA is making subgroup efficacy analyses among these subpopulations available to the public. We conducted a cross-sectional study of novel therapeutics approved by the FDA between 2011 and 2013. Using publicly available FDA documents, we collected information on the demographic characteristics of pivotal trial participants (age ≥65 years, sex [male, female], race [white, black, Asian, other], and ethnicity [Hispanic, non-Hispanic]) and determined the availability of subgroup analyses by age, sex, race, and ethnicity. We identified 86 novel therapeutic that were approved by the FDA between 2011 and 2013 for 92 indications on the basis of 206 pivotal trials. The median age of pivotal trial patients was 53.1 years (interquartile range 40.6-60.6), and the mean proportion of patients ≥65 years of age was 28.9 % (95 % CI 23.5-34.4 %). Similar proportions of pivotal trial participants were male (mean 50.3 %, 95 % CI 45.3-55.2 %) and female (mean 49.7 %, 95 % CI 44.7-54.7 %). Most participants were white (mean 79.2 %, 95 % CI 75.9-82.6 %), while the mean proportion of black patients was 7.4 % (95 % CI 5.5-9.3 %), that of Asian patients was 7.4 % (95 % CI 5.2-9.7 %), and that of patients of other races was 5.9 % (95 % CI 4.4-7.5 %). Information about ethnicity was available for only 59.8 % of indications, and where such data were available, the mean proportion of Hispanic participants was 13.3 % (95 % CI 10.3-16.3 %). FDA reviewers performed and made available subgroup efficacy analyses by age, sex, and race for at least one of the pivotal trials used as the basis of approval for over 80 % of indications. Although women are equally represented in pivotal trials supporting recent novel therapeutic approvals by the FDA, elderly patients and those from racial and ethnic minorities are underrepresented. FDA reviewers generally perform subgroup efficacy analyses by age, sex, and race and make these subgroup analyses available to the public.

Heterogeneity in chronic fatigue syndrome - empirically defined subgroups from the PACE trial.

PubMed

Williams, T E; Chalder, T; Sharpe, M; White, P D

2017-06-01

Chronic fatigue syndrome is likely to be a heterogeneous condition. Previous studies have empirically defined subgroups using combinations of clinical and biological variables. We aimed to explore the heterogeneity of chronic fatigue syndrome. We used baseline data from the PACE trial, which included 640 participants with chronic fatigue syndrome. Variable reduction, using a combination of clinical knowledge and principal component analyses, produced a final dataset of 26 variables for 541 patients. Latent class analysis was then used to empirically define subgroups. The most statistically significant and clinically recognizable model comprised five subgroups. The largest, 'core' subgroup (33% of participants), had relatively low scores across all domains and good self-efficacy. A further three subgroups were defined by: the presence of mood disorders (21%); the presence of features of other functional somatic syndromes (such as fibromyalgia or irritable bowel syndrome) (21%); or by many symptoms - a group which combined features of both of the above (14%). The smallest 'avoidant-inactive' subgroup was characterized by physical inactivity, belief that symptoms were entirely physical in nature, and fear that they indicated harm (11%). Differences in the severity of fatigue and disability provided some discriminative validation of the subgroups. In addition to providing further evidence for the heterogeneity of chronic fatigue syndrome, the subgroups identified may aid future research into the important aetiological factors of specific subtypes of chronic fatigue syndrome and the development of more personalized treatment approaches.

The Contribution of Personality and Refugee Camp Experience to Callous and Unemotional Traits Among Immigrant Adolescents in the United States: Implications for the DSM-5 "Limited Prosocial Emotions" Specifier.

PubMed

Latzman, Robert D; Malikina, Mariya V; Hecht, Lisa K; Lilienfeld, Scott O; Chan, Wing Yi

2016-04-01

Callous and Unemotional (C&U) traits characterize a group of adolescents who engage and persist in especially severe antisocial behaviors. These traits have been included in DSM-5 within a "Limited Prosocial Emotions" (LPE) specifier for Conduct Disorder. To investigate the generalizability of this specifier to non-Western cultures, we examined associations among Big Five personality, refugee camp experience, and C&U traits among 81 immigrant adolescents from non-Western cultures. Adolescents with refugee camp history endorsed higher levels of Uncaring than other adolescents. Personality traits explained 6 (Unemotional) to 18 % (Callousness) of the variance in C&U traits. The association between Neuroticism and Callousness held only for adolescents with a refugee camp history. Our results corroborate the importance of considering personality to understand C&U traits and the LPE specifier. Results also raise questions regarding the applicability of C&U traits to non-Western adolescents with varying pre-immigration experiences, and raise the possibility that the LPE specifier is vulnerable to false-positive identifications among such individuals.

Breakup of New Orleans Households after Hurricane Katrina

ERIC Educational Resources Information Center

Rendall, Michael S.

2011-01-01

Theory and evidence on disaster-induced population displacement have focused on individual and population-subgroup characteristics. Less is known about impacts on households. I estimate excess incidence of household breakup resulting from Hurricane Katrina by comparing a probability sample of pre-Katrina New Orleans resident adult household heads…

26 CFR 1.1502-98 - Coordination with section 383.

Code of Federal Regulations, 2010 CFR

2010-04-01

... business credits from a pre-change consolidated return year to a post-change consolidated return year, the... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Coordination with section 383. 1.1502-98... example, subgroups with respect to the carryover of general business credits, minimum tax credits, unused...

Dose-related beneficial and harmful effects of gabapentin in postoperative pain management – post hoc analyses from a systematic review with meta-analyses and trial sequential analyses

PubMed Central

Fabritius, Maria Louise; Wetterslev, Jørn; Mathiesen, Ole; Dahl, Jørgen B

2017-01-01

Background During the last 15 years, gabapentin has become an established component of postoperative pain treatment. Gabapentin has been employed in a wide range of doses, but little is known about the optimal dose, providing the best balance between benefit and harm. This systematic review with meta-analyses aimed to explore the beneficial and harmful effects of various doses of gabapentin administered to surgical patients. Materials and methods Data in this paper were derived from an original review, and the subgroup analyses were predefined in an International Prospective Register of Systematic Reviews published protocol: PROSPERO (ID: CRD42013006538). The methods followed Cochrane guidelines. The Cochrane Library’s CENTRAL, PubMed, EMBASE, Science Citation Index Expanded, Google Scholar, and FDA database were searched for relevant trials. Randomized clinical trials comparing gabapentin versus placebo were included. Four different dose intervals were investigated: 0–350, 351–700, 701–1050, and >1050 mg. Primary co-outcomes were 24-hour morphine consumption and serious adverse events (SAEs), with emphasis put on trials with low risk of bias. Results One hundred and twenty-two randomized clinical trials, with 8466 patients, were included. Sixteen were overall low risk of bias. No consistent increase in morphine-sparing effect was observed with increasing doses of gabapentin from the trials with low risk of bias. Analyzing all trials, the smallest and the highest dose subgroups demonstrated numerically the most prominent reduction in morphine consumption. Twenty-seven trials reported 72 SAEs, of which 83% were reported in the >1050 mg subgroup. No systematic increase in SAEs was observed with increasing doses of gabapentin. Conclusion Data were sparse, and the small number of trials with low risk of bias is a major limitation for firm conclusions. Taking these limitations into account, we were not able to demonstrate a clear relationship between the dosage of gabapentin and opioid-sparing or harmful effects. These subgroup analyses are exploratory and hypothesis-generating for future trialists. PMID:29138592

Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Lihua; Cui, Jingkun; Tang, Fengjiao

Purpose: Studies of the association between ataxia telangiectasia–mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings. Methods and Materials: Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted. Results: The meta-analysis was conducted on the ATMmore » polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries. Conclusions: Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries was dependent on the incidence of the injury. These support the evidence of an association between the rs1801516 polymorphism and acute radiation injuries, encouraging further research of this topic.« less

Factors impacting the efficacy of venlafaxine extended release 75–225 mg/day in patients with major depressive disorder: exploratory post hoc subgroup analyses of a randomized, double-blind, placebo-controlled study in Japan

PubMed Central

Watanabe, Yoshinori; Asami, Yuko; Hirano, Yoko; Kuribayashi, Kazuhiko; Itamura, Rio; Imaeda, Takayuki

2018-01-01

Purpose To explore the potential factors impacting the efficacy of venlafaxine extended release (ER) and treatment differences between 75 mg/day and 75–225 mg/day dose in patients with major depressive disorder (MDD). Methods We performed exploratory post hoc subgroup analyses of a randomized, double-blind, placebo-controlled study conducted in Japan. A total of 538 outpatients aged 20 years or older with a primary diagnosis of MDD who experienced single or recurrent episodes were randomized into three groups: fixed-dose, flexible-dose, or placebo. Venlafaxine ER was initiated at 37.5 mg/day and titrated to 75 mg/day for both fixed-dose and flexible-dose group, and to 225 mg/day for flexible-dose group (if well tolerated). Efficacy endpoints were changes from baseline at Week 8 using the Hamilton Rating Scale for Depression–17 items (HAM-D17) total score, Hamilton Rating Scale for Depression–6 items score, and Montgomery–Asberg Depression Rating Scale total score. The following factors were considered in the subgroup analyses: sex, age, HAM-D17 total score at baseline, duration of MDD, duration of current depressive episode, history of previous depressive episodes, history of previous medications for MDD, and CYP2D6 phenotype. For each subgroup, an analysis of covariance model was fitted and the adjusted mean of the treatment effect and corresponding 95% CI were computed. Due to the exploratory nature of the investigation, no statistical hypothesis testing was used. Results Venlafaxine ER improved symptoms of MDD compared with placebo in most subgroups. The subgroup with a long duration of MDD (>22 months) consistently showed greater treatment benefits in the flexible-dose group than in the fixed-dose group. Conclusion These results suggest that a greater treatment response to venlafaxine ER (up to 225 mg/day) can be seen in patients with a longer duration of MDD. Further investigations are needed to identify additional factors impacting the efficacy of venlafaxine ER. PMID:29844674

Factors impacting the efficacy of venlafaxine extended release 75-225 mg/day in patients with major depressive disorder: exploratory post hoc subgroup analyses of a randomized, double-blind, placebo-controlled study in Japan.

PubMed

Watanabe, Yoshinori; Asami, Yuko; Hirano, Yoko; Kuribayashi, Kazuhiko; Itamura, Rio; Imaeda, Takayuki

2018-01-01

To explore the potential factors impacting the efficacy of venlafaxine extended release (ER) and treatment differences between 75 mg/day and 75-225 mg/day dose in patients with major depressive disorder (MDD). We performed exploratory post hoc subgroup analyses of a randomized, double-blind, placebo-controlled study conducted in Japan. A total of 538 outpatients aged 20 years or older with a primary diagnosis of MDD who experienced single or recurrent episodes were randomized into three groups: fixed-dose, flexible-dose, or placebo. Venlafaxine ER was initiated at 37.5 mg/day and titrated to 75 mg/day for both fixed-dose and flexible-dose group, and to 225 mg/day for flexible-dose group (if well tolerated). Efficacy endpoints were changes from baseline at Week 8 using the Hamilton Rating Scale for Depression-17 items (HAM-D 17 ) total score, Hamilton Rating Scale for Depression-6 items score, and Montgomery-Asberg Depression Rating Scale total score. The following factors were considered in the subgroup analyses: sex, age, HAM-D 17 total score at baseline, duration of MDD, duration of current depressive episode, history of previous depressive episodes, history of previous medications for MDD, and CYP2D6 phenotype. For each subgroup, an analysis of covariance model was fitted and the adjusted mean of the treatment effect and corresponding 95% CI were computed. Due to the exploratory nature of the investigation, no statistical hypothesis testing was used. Venlafaxine ER improved symptoms of MDD compared with placebo in most subgroups. The subgroup with a long duration of MDD (>22 months) consistently showed greater treatment benefits in the flexible-dose group than in the fixed-dose group. These results suggest that a greater treatment response to venlafaxine ER (up to 225 mg/day) can be seen in patients with a longer duration of MDD. Further investigations are needed to identify additional factors impacting the efficacy of venlafaxine ER.

Effect of cocoa on blood pressure.

PubMed

Ried, Karin; Fakler, Peter; Stocks, Nigel P

2017-04-25

High blood pressure is an important risk factor for cardiovascular disease, contributing to about 50% of cardiovascular events worldwide and 37% of cardiovascular-related deaths in Western populations. Epidemiological studies suggest that cocoa-rich products reduce the risk of cardiovascular disease. Flavanols found in cocoa have been shown to increase the formation of endothelial nitric oxide which promotes vasodilation and therefore blood pressure reduction. Here we update previous meta-analyses on the effect of cocoa on blood pressure. To assess the effects on blood pressure of chocolate or cocoa products versus low-flavanol products or placebo in adults with or without hypertension when consumed for two weeks or longer. This is an updated version of the review initially published in 2012. In this updated version, we searched the following electronic databases from inception to November 2016: Cochrane Hypertension Group Specialised Register, CENTRAL, MEDLINE and Embase. We also searched international trial registries, and the reference lists of review articles and included trials. Randomised controlled trials (RCTs) investigating the effects of chocolate or cocoa products on systolic and diastolic blood pressure in adults for a minimum of two weeks duration. Two review authors independently extracted data and assessed the risks of bias in each trial. We conducted random-effects meta-analyses on the included studies using Review Manager 5. We explored heterogeneity with subgroup analyses by baseline blood pressure, flavanol content of control group, blinding, age and duration. Sensitivity analyses explored the influence of unusual study design. Thirty-five trials (including 40 treatment comparisons) met the inclusion criteria. Of these, we added 17 trials (20 treatment comparisons) to the 18 trials (20 treatment comparisons) in the previous version of this updated review.Trials provided participants with 30 to 1218 mg of flavanols (mean = 670 mg) in 1.4 to 105 grams of cocoa products per day in the active intervention group. The control group received either a flavanol-free product (n = 26 treatment comparisons) or a low-flavanol-containing cocoa powder (range 6.4 to 88 mg flavanols (mean = 55 mg, 13 treatment comparisons; 259 mg, 1 trial).Meta-analyses of the 40 treatment comparisons involving 1804 mainly healthy participants revealed a small but statistically significant blood pressure-reducing effect of flavanol-rich cocoa products compared with control in trials of two to 18 weeks duration (mean nine weeks):Mean difference systolic blood pressure (SBP) (95% confidence interval (CI): -1.76 (-3.09 to -0.43) mmHg, P = 0.009, n = 40 treatment comparisons, 1804 participants;Mean difference diastolic blood pressure (DBP) (95% CI): -1.76 (-2.57 to -0.94) mmHg, P < 0.001, n = 39 treatment comparisons, 1772 participants.Baseline blood pressure may play a role in the effect of cocoa on blood pressure. While systolic blood pressure was reduced significantly by 4 mmHg in hypertensive people (n = 9 treatment comparisons, 401 participants), and tended to be lowered in prehypertensive people (n= 8 treatment comparisons, 340 participants), there was no significant difference in normotensive people (n = 23 treatment comparisons, 1063 participants); however, the test for subgroup differences was of borderline significance (P = 0.08; I 2 = 60%), requiring further research to confirm the findings.Subgroup meta-analysis by blinding suggested a trend towards greater blood pressure reduction in unblinded trials compared to double-blinded trials, albeit statistically not significant. Further research is needed to confirm whether participant expectation may influence blood pressure results. Subgroup analysis by type of control (flavanol-free versus low-flavanol control) did not reveal a significant difference.Whether the age of participants plays a role in the effect of cocoa on blood pressure, with younger participants responding with greater blood pressure reduction, needs to be further investigated.Sensitivity analysis excluding trials with authors employed by trials sponsoring industry (33 trials, 1482 participants) revealed a small reduction in effect size, indicating some reporting bias.Due to the remaining heterogeneity, which we could not explain in terms of blinding, flavanol content of the control groups, age of participants, or study duration, we downgraded the quality of the evidence from high to moderate.Results of subgroup analyses should be interpreted with caution and need to be confirmed or refuted in trials using direct randomised comparisons.Generally, cocoa products were highly tolerable, with adverse effects including gastrointestinal complaints and nausea being reported by 1% of participants in the active cocoa intervention group and 0.4% of participants in the control groups (moderate-quality evidence). This review provides moderate-quality evidence that flavanol-rich chocolate and cocoa products cause a small (2 mmHg) blood pressure-lowering effect in mainly healthy adults in the short term.These findings are limited by the heterogeneity between trials, which could not be explained by prespecified subgroup analyses, including blinding, flavanol content of the control groups, age of participants, or study duration. However, baseline blood pressure may play a role in the effect of cocoa on blood pressure; subgroup analysis of trials with (pre)hypertensive participants revealed a greater blood pressure-reducing effect of cocoa compared to normotensive participants with borderline significance.Long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events and to assess potential adverse effects associated with chronic ingestion of cocoa products.

HTLV-1 subgroups associated with the risk of HAM/TSP are related to viral and host gene expression in peripheral blood mononuclear cells, independent of the transactivation functions of the viral factors.

PubMed

Yasuma, Keiko; Matsuzaki, Toshio; Yamano, Yoshihisa; Takashima, Hiroshi; Matsuoka, Masao; Saito, Mineki

2016-08-01

Among human T cell leukemia virus type 1 (HTLV-1)-infected individuals, the risk of developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) across lifetime differs between ethnic groups. There is an association between HTLV-1 tax gene subgroups (subgroup-A or subgroup-B) and the risk of HAM/TSP in the Japanese population. In this study, we investigated the full-length proviral genome sequences of various HTLV-1-infected cell lines and patient samples. The functional differences in the viral transcriptional regulators Tax and HTLV-1 bZIP factor (HBZ) between each subgroup and the relationships between subgroups and the clinical and laboratory characteristics of HAM/TSP patients were evaluated. The results of these analyses indicated the following: (1) distinct nucleotide substitutions corresponding to each subgroup were associated with nucleotide substitutions in viral structural, regulatory, and accessory genes; (2) the HBZ messenger RNA (mRNA) expression in HTLV-1-infected cells was significantly higher in HAM/TSP patients with subgroup-B than in those with subgroup-A; (3) a positive correlation was observed between the expression of HBZ mRNA and its target Foxp3 mRNA in HAM/TSP patients with subgroup-B, but not in patients with subgroup-A; (4) no clear differences were noted in clinical and laboratory characteristics between HAM/TSP patients with subgroup-A and subgroup-B; and (5) no functional differences were observed in Tax and HBZ between each subgroup based on reporter gene assays. Our results indicate that although different HTLV-1 subgroups are characterized by different patterns of viral and host gene expression in HAM/TSP patients via independent mechanisms of direct transcriptional regulation, these differences do not significantly affect the clinical and laboratory characteristics of HAM/TSP patients.

Near N-S paleo-extension in the western Deccan region, India: Does it link strike-slip tectonics with India-Seychelles rifting?

NASA Astrophysics Data System (ADS)

Misra, Achyuta Ayan; Bhattacharya, Gourab; Mukherjee, Soumyajit; Bose, Narayan

2014-09-01

This is the first detailed report and analyses of deformation from the W part of the Deccan large igneous province (DLIP), Maharashtra, India. This deformation, related to the India-Seychelles rifting during Late Cretaceous-Early Paleocene, was studied, and the paleostress tensors were deduced. Near N-S trending shear zones, lineaments, and faults were already reported without significant detail. An E-W extension was envisaged by the previous workers to explain the India-Seychelles rift at ~64 Ma. The direction of extension, however, does not match with their N-S brittle shear zones and also those faults (sub-vertical, ~NE-SW/~NW-SE, and few ~N-S) we report and emphasize in this work. Slickenside-bearing fault planes, brittle shear zones, and extension fractures in meso-scale enabled us to estimate the paleostress tensors (directions and relative magnitudes). The field study was complemented by remote sensing lineament analyses to map dykes and shear zones. Dykes emplaced along pre-existing ~N-S to ~NE-SW/~NW-SE shears/fractures. This information was used to derive regional paleostress trends. A ~NW-SE/NE-SW minimum compressive stress in the oldest Kalsubai Subgroup and a ~N-S direction for the younger Lonavala, Wai, and Salsette Subgroups were deciphered. Thus, a ~NW/NE to ~N-S extension is put forward that refutes the popular view of E-W India-Seychelles extension. Paleostress analyses indicate that this is an oblique rifted margin. Field criteria suggest only ~NE-SW and ~NW-SE, with some ~N-S strike-slip faults/brittle shear zones. We refer this deformation zone as the "Western Deccan Strike-slip Zone" (WDSZ). The observed deformation was matched with offshore tectonics deciphered mainly from faults interpreted on seismic profiles and from magnetic seafloor spreading anomalies. These geophysical findings too indicate oblique rifting in this part of the W Indian passive margin. We argue that the Seychelles microcontinent separated from India only after much of the DLIP erupted. Further studies of magma-rich passive margins with respect to timing and architecture of deformation and emplacement of volcanics are required.

Aspirin for primary prevention of cardiovascular events: meta-analysis of randomized controlled trials and subgroup analysis by sex and diabetes status.

PubMed

Xie, Manling; Shan, Zhilei; Zhang, Yan; Chen, Sijing; Yang, Wei; Bao, Wei; Rong, Ying; Yu, Xuefeng; Hu, Frank B; Liu, Liegang

2014-01-01

To evaluate the benefits and harms of aspirin for the primary prevention of CVD and determine whether the effects vary by sex and diabetes status. We searched Medline, Embase, and Cochrane databases for randomized controlled trials comparing the effects of aspirin with placebo or control in people with no pre-existing CVD. Two investigators independently extracted data and assessed the study quality. Analyses were performed using Stata version 12. Fourteen trials (107,686 participants) were eligible. Aspirin was associated with reductions in major cardiovascular events (risk ratio, 0.90; 95% confidence interval, 0.85-0.95), myocardial infarction (0.86; 0.75-0.93), ischemic stroke (0.86; 0.75-0.98) and all-cause mortality (0.94; 0.89-0.99). There were also increases in hemorrhagic stroke (1.34; 1.01-1.79) and major bleeding (1.55; 1.35-1.78) with aspirin. The number needed to treat to prevent 1 major cardiovascular event over a mean follow-up of 6.8 years was 284. By comparison, the numbers needed to harm to cause 1 major bleeding is 299. In subgroup analyses, pooled results demonstrated a reduction in myocardial infarction among men (0.71; 0.59-0.85) and ischemic stroke among women (0.77; 0.63-0.93). Aspirin use was associated with a reduction (0.65; 0.51-0.82) in myocardial infarction among diabetic men. In meta-regression analyses, the results suggested that aspirin therapy might be associated with a decrease in stroke among diabetic women and a decrease in MI among diabetic men and risk reductions achieved with low doses (75 mg/day) were as large as those obtained with higher doses (650 mg/day). The use of low-dose aspirin was beneficial for primary prevention of CVD and the decision regarding an aspirin regimen should be made on an individual patient basis. The effects of aspirin therapy varied by sex and diabetes status. A clear benefit of aspirin in the primary prevention of CVD in people with diabetes needs more trials.

Aspirin for Primary Prevention of Cardiovascular Events: Meta-Analysis of Randomized Controlled Trials and Subgroup Analysis by Sex and Diabetes Status

PubMed Central

Zhang, Yan; Chen, Sijing; Yang, Wei; Bao, Wei; Rong, Ying; Yu, Xuefeng; Hu, Frank B.; Liu, Liegang

2014-01-01

Objective To evaluate the benefits and harms of aspirin for the primary prevention of CVD and determine whether the effects vary by sex and diabetes status. Methods We searched Medline, Embase, and Cochrane databases for randomized controlled trials comparing the effects of aspirin with placebo or control in people with no pre-existing CVD. Two investigators independently extracted data and assessed the study quality. Analyses were performed using Stata version 12. Results Fourteen trials (107,686 participants) were eligible. Aspirin was associated with reductions in major cardiovascular events (risk ratio, 0.90; 95% confidence interval, 0.85–0.95), myocardial infarction (0.86; 0.75–0.93), ischemic stroke (0.86; 0.75–0.98) and all-cause mortality (0.94; 0.89–0.99). There were also increases in hemorrhagic stroke (1.34; 1.01–1.79) and major bleeding (1.55; 1.35–1.78) with aspirin. The number needed to treat to prevent 1 major cardiovascular event over a mean follow-up of 6.8 years was 284. By comparison, the numbers needed to harm to cause 1 major bleeding is 299. In subgroup analyses, pooled results demonstrated a reduction in myocardial infarction among men (0.71; 0.59–0.85) and ischemic stroke among women (0.77; 0.63–0.93). Aspirin use was associated with a reduction (0.65; 0.51–0.82) in myocardial infarction among diabetic men. In meta-regression analyses, the results suggested that aspirin therapy might be associated with a decrease in stroke among diabetic women and a decrease in MI among diabetic men and risk reductions achieved with low doses (75 mg/day) were as large as those obtained with higher doses (650 mg/day). Conclusions The use of low-dose aspirin was beneficial for primary prevention of CVD and the decision regarding an aspirin regimen should be made on an individual patient basis. The effects of aspirin therapy varied by sex and diabetes status. A clear benefit of aspirin in the primary prevention of CVD in people with diabetes needs more trials. PMID:25360605

Global epigenetic profiling identifies methylation subgroups associated with recurrence-free survival in meningioma

PubMed Central

Olar, Adriana; Wani, Khalida M; Wilson, Charmaine D; Zadeh, Gelareh; DeMonte, Franco; Jones, David TW; Pfister, Stefan M; Sulman, Erik P; Aldape, Kenneth D

2017-01-01

Meningioma is the most common primary brain tumor and carries a substantial risk of local recurrence. Methylation profiles of meningioma and their clinical implications are not well understood. We hypothesized that aggressive meningiomas have unique DNA methylation patterns that could be used to better stratify patient management. Samples (n=140) were profiled using the Illumina HumanMethylation450 BeadChip. Unsupervised modeling on a training set (n=89) identified 2 molecular methylation subgroups of meningioma (MM) with significantly different recurrence free survival (RFS) times between the groups: a prognostically unfavorable subgroup (MM-UNFAV) and a prognostically favorable subgroup (MM-FAV). This finding was validated in the remaining 51 samples and led to a baseline meningioma methylation classifier (bMMC) defined by 283 CpG loci (283-bMMC). To further optimize a recurrence predictor, probes subsumed within the baseline classifier were subject to additional modeling using a similar training/validation approach, leading to a 64-CpG loci meningioma methylation predictor (64-MMP). After adjustment for relevant clinical variables [WHO grade, mitotic index, Simpson grade, sex, location, and copy number aberrations (CNA)] multivariable analyses for RFS showed that the baseline methylation classifier was not significant (p=0.0793). The methylation predictor however was significantly associated with tumor recurrence (p<0.0001). CNA were extracted from the 450k intensity profiles. Tumor samples in the MM-UNFAV subgroup showed an overall higher proportion of CNAs compared to the MM-FAV subgroup tumors and the CNAs were complex in nature. CNAs in the MM-UNFAV subgroup included recurrent losses of 1p, 6q, 14q and 18q, and gain of 1q, all of which were previously identified as indicators of poor outcome. In conclusion, our analyses demonstrate robust DNA methylation signatures in meningioma that correlate with CNAs and stratify patients by recurrence risk. PMID:28130639

Using existing questionnaires in latent class analysis: should we use summary scores or single items as input? A methodological study using a cohort of patients with low back pain.

PubMed

Nielsen, Anne Molgaard; Vach, Werner; Kent, Peter; Hestbaek, Lise; Kongsted, Alice

2016-01-01

Latent class analysis (LCA) is increasingly being used in health research, but optimal approaches to handling complex clinical data are unclear. One issue is that commonly used questionnaires are multidimensional, but expressed as summary scores. Using the example of low back pain (LBP), the aim of this study was to explore and descriptively compare the application of LCA when using questionnaire summary scores and when using single items to subgrouping of patients based on multidimensional data. Baseline data from 928 LBP patients in an observational study were classified into four health domains (psychology, pain, activity, and participation) using the World Health Organization's International Classification of Functioning, Disability, and Health framework. LCA was performed within each health domain using the strategies of summary-score and single-item analyses. The resulting subgroups were descriptively compared using statistical measures and clinical interpretability. For each health domain, the preferred model solution ranged from five to seven subgroups for the summary-score strategy and seven to eight subgroups for the single-item strategy. There was considerable overlap between the results of the two strategies, indicating that they were reflecting the same underlying data structure. However, in three of the four health domains, the single-item strategy resulted in a more nuanced description, in terms of more subgroups and more distinct clinical characteristics. In these data, application of both the summary-score strategy and the single-item strategy in the LCA subgrouping resulted in clinically interpretable subgroups, but the single-item strategy generally revealed more distinguishing characteristics. These results 1) warrant further analyses in other data sets to determine the consistency of this finding, and 2) warrant investigation in longitudinal data to test whether the finer detail provided by the single-item strategy results in improved prediction of outcomes and treatment response.

Clinical effects of pre-adjusted edgewise orthodontic brackets: a systematic review and meta-analysis.

PubMed

Papageorgiou, Spyridon N; Konstantinidis, Ioannis; Papadopoulou, Konstantina; Jäger, Andreas; Bourauel, Christoph

2014-06-01

Fixed-appliance treatment is a major part of orthodontic treatment, but clinical evidence remains scarce. Objective of this systematic review was to investigate how the therapeutic effects and side-effects of brackets used during the fixed-appliance orthodontic treatment are affected by their characteristics. SEARCH METHODS AND SELECTION CRITERIA: We searched MEDLINE and 18 other databases through April 2012 without restrictions for randomized controlled trials and quasi-randomized controlled trials investigating any bracket characteristic. After duplicate selection and extraction procedures, risk of bias was assessed also in duplicate according to Cochrane guidelines and quality of evidence according to the Grades of Recommendation. Assessment, Development and Evaluation approach. Random-effects meta-analyses, subgroup analyses, and sensitivity analyses were performed with the corresponding 95 per cent confidence intervals (CI) and 95 per cent prediction intervals (PI). We included 25 trials on 1321 patients, with most comparing self-ligated (SL) and conventional brackets. Based on the meta-analyses, the duration of orthodontic treatment was on average 2.01 months longer among patients with SL brackets (95 per cent CI: 0.45 to 3.57). The 95 per cent PIs for a future trial indicated that the difference could be considerable (-1.46 to 5.47 months). Treatment characteristics, outcomes, and side-effects were clinically similar between SL and conventional brackets. For most bracket characteristics, evidence is insufficient. Some meta-analyses included trials with high risk of bias, but sensitivity analyses indicated robustness. Based on existing evidence, no clinical recommendation can be made regarding the bracket material or different ligation modules. For SL brackets, no conclusive benefits could be proven, while their use was associated with longer treatment durations.

The whole-genome landscape of medulloblastoma subtypes.

PubMed

Northcott, Paul A; Buchhalter, Ivo; Morrissy, A Sorana; Hovestadt, Volker; Weischenfeldt, Joachim; Ehrenberger, Tobias; Gröbner, Susanne; Segura-Wang, Maia; Zichner, Thomas; Rudneva, Vasilisa A; Warnatz, Hans-Jörg; Sidiropoulos, Nikos; Phillips, Aaron H; Schumacher, Steven; Kleinheinz, Kortine; Waszak, Sebastian M; Erkek, Serap; Jones, David T W; Worst, Barbara C; Kool, Marcel; Zapatka, Marc; Jäger, Natalie; Chavez, Lukas; Hutter, Barbara; Bieg, Matthias; Paramasivam, Nagarajan; Heinold, Michael; Gu, Zuguang; Ishaque, Naveed; Jäger-Schmidt, Christina; Imbusch, Charles D; Jugold, Alke; Hübschmann, Daniel; Risch, Thomas; Amstislavskiy, Vyacheslav; Gonzalez, Francisco German Rodriguez; Weber, Ursula D; Wolf, Stephan; Robinson, Giles W; Zhou, Xin; Wu, Gang; Finkelstein, David; Liu, Yanling; Cavalli, Florence M G; Luu, Betty; Ramaswamy, Vijay; Wu, Xiaochong; Koster, Jan; Ryzhova, Marina; Cho, Yoon-Jae; Pomeroy, Scott L; Herold-Mende, Christel; Schuhmann, Martin; Ebinger, Martin; Liau, Linda M; Mora, Jaume; McLendon, Roger E; Jabado, Nada; Kumabe, Toshihiro; Chuah, Eric; Ma, Yussanne; Moore, Richard A; Mungall, Andrew J; Mungall, Karen L; Thiessen, Nina; Tse, Kane; Wong, Tina; Jones, Steven J M; Witt, Olaf; Milde, Till; Von Deimling, Andreas; Capper, David; Korshunov, Andrey; Yaspo, Marie-Laure; Kriwacki, Richard; Gajjar, Amar; Zhang, Jinghui; Beroukhim, Rameen; Fraenkel, Ernest; Korbel, Jan O; Brors, Benedikt; Schlesner, Matthias; Eils, Roland; Marra, Marco A; Pfister, Stefan M; Taylor, Michael D; Lichter, Peter

2017-07-19

Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.

Interpreting weightings of the peer assessment rating index and the discrepancy index across contexts on Chinese patients.

PubMed

Liu, Siqi; Oh, Heesoo; Chambers, David William; Xu, Tianmin; Baumrind, Sheldon

2018-04-06

Determine optimal weightings of Peer Assessment Rating (PAR) index and Discrepancy Index (DI) for malocclusion severity assessment in Chinese orthodontic patients. Sixty-nine Chinese orthodontists assessed a full set of pre-treatment records from a stratified random sample of 120 subjects gathered from six university orthodontic centres. Using professional judgment as the outcome variable, multiple regression analyses were performed to derive customized weighting systems for the PAR index and DI, for all subjects and each Angle classification subgroup. Professional judgment was consistent, with an Intraclass Correlation Coefficient (ICC) of 0.995. The PAR index or DI can be reliably measured, with ICC = 0.959 and 0.990, respectively. The predictive accuracy of PAR index was greatly improved by the Chinese weighting process (from r = 0.431 to r = 0.788) with almost equal distribution in each Angle classification subgroup. The Chinese-weighted DI showed a higher predictive accuracy, at P = 0.01, compared with the PAR index (r = 0.851 versus r = 0.788). A better performance was found in the Class II group (r = 0.890) when compared to Class I (r = 0.736) and III (r = 0.785) groups. The Chinese-weighted PAR index and DI were capable of predicting 62 per cent and 73 per cent of total variance in the professional judgment of malocclusion severity in Chinese patients. Differential prediction across Angle classifications merits attention since different weighting formulas were found.

[Satisfaction according to health care insurance systems in an emergency department].

PubMed

Dávila, F A; Herrera, J S; Yasnó, D A; Forero, L C; Alvarado, M V

Health satisfaction is a fundamental measure of the quality of health services. This study aims to validate and analyse the results of a quality of care questionnaire to assess the level of satisfaction of patients attended in the emergency department of a high complexity hospital. Observational, cross-sectional study, with a questionnaire designed to assess the quality of service and satisfaction at the end of care in the emergency department. Descriptive statistics of scale were established and presented, as well as determining the construct validity, overall reliability, internal and concurrent validity of an overall against a uni-dimensional scale. A total of 5,961 records were reviewed, most of them (77.3%) reported by patients in the Mandatory Health Plan. High levels of satisfaction overall and by subgroups were found. There were no significant differences between subgroups, with 86.8 for those with Pre-paid Medical Care Plan and 84.4 for mandatory health plan. Cronbach's alpha for the questionnaire was 0.90. The questionnaire proved to be reliable and valid in determining the quality and satisfaction with care. The results showed high levels of satisfaction overall and in the domains. A low consistency between the results of the multidimensional and unidimensional satisfaction scales suggests that there were aspects of satisfaction not investigated on the multidimensional scale. Ecologically-designed before and after studies are required to evaluate the effectiveness of interventions in satisfaction. Copyright © 2016 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

Do residents’ perceptions of being well-placed and objective presence of local amenities match? A case study in West Central Scotland, UK

PubMed Central

2013-01-01

Background Recently there has been growing interest in how neighbourhood features, such as the provision of local facilities and amenities, influence residents’ health and well-being. Prior research has measured amenity provision through subjective measures (surveying residents’ perceptions) or objective (GIS mapping of distance) methods. The latter may provide a more accurate measure of physical access, but residents may not use local amenities if they do not perceive them as ‘local’. We believe both subjective and objective measures should be explored, and use West Central Scotland data to investigate correspondence between residents’ subjective assessments of how well-placed they are for everyday amenities (food stores, primary and secondary schools, libraries, pharmacies, public recreation), and objective GIS-modelled measures, and examine correspondence by various sub-groups. Methods ArcMap was used to map the postal locations of ‘Transport, Health and Well-being 2010 Study’ respondents (n = 1760), and the six amenities, and the presence/absence of each of them within various straight-line and network buffers around respondents’ homes was recorded. SPSS was used to investigate whether objective presence of an amenity within a specified buffer was perceived by a respondent as being well-placed for that amenity. Kappa statistics were used to test agreement between measures for all respondents, and by sex, age, social class, area deprivation, car ownership, dog ownership, walking in the local area, and years lived in current home. Results In general, there was poor agreement (Kappa <0.20) between perceptions of being well-placed for each facility and objective presence, within 800 m and 1000 m straight-line and network buffers, with the exception of pharmacies (at 1000 m straight-line) (Kappa: 0.21). Results varied between respondent sub-groups, with some showing better agreement than others. Amongst sub-groups, at 800 m straight-line buffers, the highest correspondence between subjective and objective measures was for pharmacies and primary schools, and at 1000 m, for pharmacies, primary schools and libraries. For road network buffers under 1000 m, agreement was generally poor. Conclusion Respondents did not necessarily regard themselves as well-placed for specific amenities when these amenities were present within specified boundaries around their homes, with some exceptions; the picture is not clear-cut with varying findings between different amenities, buffers, and sub-groups. PMID:23651734

Factors associated with perceived risk in automotive employees at increased risk of colorectal cancer.

PubMed

Vernon, S W; Myers, R E; Tilley, B C; Li, S

2001-01-01

Risk perception may be an important motivator of health-related behaviors. To develop effective risk communication messages, it is important to understand both the patterns of association between perceived risk and health-related behaviors as well as the correlates of risk perception. Very little is known about whether correlates of risk perception are similar in cross-sectional data compared with prospective data. Furthermore, there are scant data on consistency of correlates of risk perception across groups who vary in objective medical risk. If correlates differ, it would underscore the need to tailor intervention messages based on subgroup characteristics as well as increase awareness of the limitations of basing intervention messages only on cross-sectional data. We analyzed data on a subset of 5042 employees who participated in The Next Step Trial, a randomized health promotion trial to encourage colorectal cancer screening and dietary change. We restricted our analysis to only those automotive workers who were white, male, and did not have colorectal cancer (4477/5042) and who returned surveys both at baseline (2,684/4,477) and at year 2 of follow-up (1955/2684). Initial analyses detected interactions between a history of polyps and several of the other covariates. Therefore, univariate and multivariable analyses were conducted separately for men with and without a personal history of colorectal polyps. Within each of the four subgroups (those with or without polyps in the baseline or follow-up analyses), we examined associations between perceived risk measured at baseline (cross-sectional analyses) and at year 2 of follow-up (prospective analyses) in relation to intervention group status, demographic, medical history, psychosocial, and worksite characteristics measured at baseline. To assess the predictive ability of the models, we computed sensitivity and specificity as measures of each model's ability to correctly classify men into their respective subgroup. Although there was no association between perceived risk and intervention group status in the four subgroups analyzed, we included intervention group status as a covariate in all analyses. At baseline (cross-sectional analyses) among men with and without a history of polyps, perceived risk was positively associated with family history of colorectal polyps or cancer, family support for screening, and worry about being diagnosed with colorectal cancer. In addition, for men without polyps, perceived risk was positively associated with being a current smoker. At year 2 of follow-up (prospective analyses) for men with and without polyps, perceived risk at year 2 was positively associated with family history and baseline perceived risk and was negatively associated with having a normal screening examination or no examinations during the trial. In addition, for men with polyps, perceived risk was positively associated with belief in the salience and coherence of screening and with intention to be screened and was negatively associated with access to screening at the worksite. Specificity was higher than sensitivity in three of four subgroups and was >65% in all subgroups. Except for family history, messages to influence perceived risk would emphasize different factors, depending on whether associations were based on baseline or follow-up data and depending on whether men reported a personal history of polyps. For example, although intervention messages using baseline data would emphasize the same factors for men with or without polyps, messages based on follow-up data would emphasize psychosocial characteristics, such as salience and coherence of screening and intention for men with a history of polyps but not for men without. Our findings support the need to delineate subgroups in the study population to target and tailor health-related messages based on respondent characteristics. Our findings also underscore the need to base health-related messages on prospective data as well as cross-sectional data to better address health-related beliefs and behaviors.

The DeepMIP Contribution to PMIP4: Experimental Design for Model Simulations of the EECO, PETM, and pre-PETM (version 1.0)

NASA Technical Reports Server (NTRS)

Lunt, Daniel J.; Huber, Matthew; Anagnostou, Eleni; Baatsen, Michiel L. J.; Caballero, Rodrigo; DeConto, Rob; Dijkstra, Henk A.; Donnadieu, Yannick; Evans, David; Feng, Ran;

Publishing interim results of randomised clinical trials in peer-reviewed journals.

PubMed

Counsell, Nicholas; Biri, Despina; Fraczek, Joanna; Hackshaw, Allan

2017-02-01

Interim analyses of randomised controlled trials are sometimes published before the final results are available. In several cases, the treatment effects were noticeably different after patient recruitment and follow-up completed. We therefore conducted a literature review of peer-reviewed journals to compare the reported treatment effects between interim and final publications and to examine the magnitude of the difference. We performed an electronic search of MEDLINE from 1990 to 2014 (keywords: 'clinical trial' OR 'clinical study' AND 'random*' AND 'interim' OR 'preliminary'), and we manually identified the corresponding final publication. Where the electronic search produced a final report in which the abstract cited interim results, we found the interim publication. We also manually searched every randomised controlled trial in eight journals, covering a range of impact factors and general medical and specialist publications (1996-2014). All paired articles were checked to ensure that the same comparison between interventions was available in both. In all, 63 studies are included in our review, and the same quantitative comparison was available in 58 of these. The final treatment effects were smaller than the interim ones in 39 (67%) trials and the same size or larger in 19 (33%). There was a marked reduction, defined as a ≥20% decrease in the size of the treatment effect from interim to final analysis, in 11 (19%) trials compared to a marked increase in 3 (5%), p = 0.057. The magnitude of percentage change was larger in trials where commercial support was reported, and increased as the proportion of final events at the interim report decreased in trials where commercial support was reported (interaction p = 0.023). There was no evidence of a difference between trials that stopped recruitment at the interim analysis where this was reported as being pre-specified versus those that were not pre-specified (interaction p = 0.87). Published interim trial results were more likely to be associated with larger treatment effects than those based on the final report. Publishing interim results should be discouraged, in order to have reliable estimates of treatment effects for clinical decision-making, regulatory authority reviews and health economic analyses. Our work should be expanded to include conference publications and manual searches of additional journal publications.

Tobacco price increase and smoking behaviour changes in various subgroups: a nationwide longitudinal 7-year follow-up study among a middle-aged Japanese population.

PubMed

Tabuchi, Takahiro; Fujiwara, Takeo; Shinozaki, Tomohiro

2017-01-01

Few longitudinal studies have examined the effect of tobacco price increase on both cessation among smokers and relapse among quitters. Our objective was to investigate the differential impact of the tobacco price increase on the changes in smoking status in the total population and various subgroups. We analysed data from a Japanese nationally representative longitudinal study of 30 773 individuals aged 50-59 years (weighted sum of discrete-time number = 215 411) with smoking information, using inverse probability weighting to account for non-response at follow-up. Generalised estimating equation models were used to calculate the odds ratios (ORs) for smoking behavioural changes (cessation among smokers and relapse among quitters), using discrete-time design. Stratified analyses were conducted according to demographic, socioeconomic and health behavioural characteristics. From 2005 to 2012, current smoker prevalence among the middle-aged Japanese population decreased from 30.5% to 24.3%. Of all the factors surveyed, only the tobacco price increase in 2010 (up by 37%, the highest increase during the period) was significantly associated with both cessation among smokers (OR 2.14, 95% confidence interval 1.90 to 2.41) and prevention of relapse among quitters (0.60, 0.46 to 0.77). Regarding the subgroup analysis, the tobacco price increase was associated with a significant reduction in relapse in the lowest income, recent quitters and very poor health subgroups. However, different associations were observed for cessation; a significant association between price increase and cessation was observed among all subgroups except for the heavy smoker and recently unemployed subgroups. We confirmed that the tobacco price rise was associated with increasing cessation and decreasing relapse concurrently. Furthermore, this price rise was associated with favourable smoking changes in nearly all population subgroups; a large differential impact was not observed across the various subgroups. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Corrosion of post-tensioned tendons with deficient grout : final report.

DOT National Transportation Integrated Search

2016-10-20

Recent corrosion failures of post-tensioned (PT) tendons in the Ringling Causeway Bridge (and corrosion development of PT tendons elsewhere in Florida) utilizing pre-packaged low-bleed specified grout products have spurred the need to evaluate what m...

Association analyses of vitamin D-binding protein gene with compression strength index variation in Caucasian nuclear families.

PubMed

Xu, X-H; Xiong, D-H; Liu, X-G; Guo, Y; Chen, Y; Zhao, J; Recker, R R; Deng, H-W

2010-01-01

This study was conducted to test whether there exists an association between vitamin D-binding protein (DBP) gene and compression strength index (CSI) phenotype. Candidate gene association analyses were conducted in total sample, male subgroup, and female subgroup, respectively. Two single-nucleotide polymorphisms (SNPs) with significant association results were found in males, suggesting the importance of DBP gene polymorphisms on the variation in CSI especially in Caucasian males. CSI of the femoral neck (FN) is a newly developed phenotype integrating information about bone size, body size, and bone mineral density. It is considered to have the potential to improve the performance of risk assessment for hip fractures because it is based on a combination of phenotypic traits influencing hip fractures rather than a single trait. CSI is under moderate genetic determination (with a heritability of approximately 44% found in this study), but the relevant genetic study is still rather scarce. Based on the known physiological role of DBP in bone biology and the relatively high heritability of CSI, we tested 12 SNPs of the DBP gene for association with CSI variation in 405 Caucasian nuclear families comprising 1,873 subjects from the Midwestern US. Association analyses were performed in the total sample, male and female subgroups, respectively. Significant associations with CSI were found with two SNPs (rs222029, P = 0.0019; rs222020, P = 0.0042) for the male subgroup. Haplotype-based association tests corroborated the single-SNP results. Our findings suggest that the DBP gene might be one of the genetic factors influencing CSI phenotype in Caucasians, especially in males.

Individual patient data meta-analysis of trials investigating the effectiveness of intra-articular glucocorticoid injections in patients with knee or hip osteoarthritis: an OA Trial Bank protocol for a systematic review

PubMed Central

2013-01-01

Background Based on small to moderate effect sizes for the wide range of symptomatic treatments in osteoarthritis (OA), and on the heterogeneity of OA patients, treatment guidelines for OA have stressed the need for research on clinical predictors of response to different treatments. A meta-analysis to quantify the effect modified by the predictors using individual patient data (IPD) is suggested. The initiative to collect and analyze IPD in OA research is commenced by the OA Trial Bank. The study aims are therefore: to evaluate the efficacy of intra-articular glucocorticoids for knee or hip OA in specific subgroups of patients with severe pain and (mild) inflammatory signs, over both short-term and long-term follow-up, using IPD from existing studies; to reach consensus on the rules for cooperation in a consortium; and to develop and explore the methodological issues of meta-analysis with individual OA patient data. Methods/Design For the current IPD analysis we will collect and synthesize IPD from randomized trials studying the effect of intra-articular glucocorticoid injections in patients with hip or knee OA. Subgroup analyses will be performed for the primary outcome of pain at both short-term and long-term follow-up, in the subgroups of patients with and without severe pain and with and without inflammatory signs. Discussion This study protocol includes the first study of the OA Trial Bank, an international collaboration that initiates meta-analyses on predefined subgroups of OA patients from existing literature. This approach ensures a widely supported initiative and is therefore likely to be successful in data collection of existing trials. The collaboration developed (that is, the OA Trial Bank) may also lead to future IPD analyses on subgroups of patients with several intervention strategies applied in OA patients. PMID:23830482

Individual patient data meta-analysis of trials investigating the effectiveness of intra-articular glucocorticoid injections in patients with knee or hip osteoarthritis: an OA Trial Bank protocol for a systematic review.

PubMed

van Middelkoop, Marienke; Dziedzic, Krysia S; Doherty, Michael; Zhang, Weiya; Bijlsma, Johannes W; McAlindon, Timothy E; Lohmander, Stefan L; Bierma-Zeinstra, Sita M A

2013-07-05

Based on small to moderate effect sizes for the wide range of symptomatic treatments in osteoarthritis (OA), and on the heterogeneity of OA patients, treatment guidelines for OA have stressed the need for research on clinical predictors of response to different treatments. A meta-analysis to quantify the effect modified by the predictors using individual patient data (IPD) is suggested. The initiative to collect and analyze IPD in OA research is commenced by the OA Trial Bank. The study aims are therefore: to evaluate the efficacy of intra-articular glucocorticoids for knee or hip OA in specific subgroups of patients with severe pain and (mild) inflammatory signs, over both short-term and long-term follow-up, using IPD from existing studies; to reach consensus on the rules for cooperation in a consortium; and to develop and explore the methodological issues of meta-analysis with individual OA patient data. For the current IPD analysis we will collect and synthesize IPD from randomized trials studying the effect of intra-articular glucocorticoid injections in patients with hip or knee OA. Subgroup analyses will be performed for the primary outcome of pain at both short-term and long-term follow-up, in the subgroups of patients with and without severe pain and with and without inflammatory signs. This study protocol includes the first study of the OA Trial Bank, an international collaboration that initiates meta-analyses on predefined subgroups of OA patients from existing literature. This approach ensures a widely supported initiative and is therefore likely to be successful in data collection of existing trials. The collaboration developed (that is, the OA Trial Bank) may also lead to future IPD analyses on subgroups of patients with several intervention strategies applied in OA patients.

Novel molecular subgroups for clinical classification and outcome prediction in childhood medulloblastoma: a cohort study.

PubMed

Schwalbe, Edward C; Lindsey, Janet C; Nakjang, Sirintra; Crosier, Stephen; Smith, Amanda J; Hicks, Debbie; Rafiee, Gholamreza; Hill, Rebecca M; Iliasova, Alice; Stone, Thomas; Pizer, Barry; Michalski, Antony; Joshi, Abhijit; Wharton, Stephen B; Jacques, Thomas S; Bailey, Simon; Williamson, Daniel; Clifford, Steven C

2017-07-01

International consensus recognises four medulloblastoma molecular subgroups: WNT (MB WNT ), SHH (MB SHH ), group 3 (MB Grp3 ), and group 4 (MB Grp4 ), each defined by their characteristic genome-wide transcriptomic and DNA methylomic profiles. These subgroups have distinct clinicopathological and molecular features, and underpin current disease subclassification and initial subgroup-directed therapies that are underway in clinical trials. However, substantial biological heterogeneity and differences in survival are apparent within each subgroup, which remain to be resolved. We aimed to investigate whether additional molecular subgroups exist within childhood medulloblastoma and whether these could be used to improve disease subclassification and prognosis predictions. In this retrospective cohort study, we assessed 428 primary medulloblastoma samples collected from UK Children's Cancer and Leukaemia Group (CCLG) treatment centres (UK), collaborating European institutions, and the UKCCSG-SIOP-PNET3 European clinical trial. An independent validation cohort (n=276) of archival tumour samples was also analysed. We analysed samples from patients with childhood medulloblastoma who were aged 0-16 years at diagnosis, and had central review of pathology and comprehensive clinical data. We did comprehensive molecular profiling, including DNA methylation microarray analysis, and did unsupervised class discovery of test and validation cohorts to identify consensus primary molecular subgroups and characterise their clinical and biological significance. We modelled survival of patients aged 3-16 years in patients (n=215) who had craniospinal irradiation and had been treated with a curative intent. Seven robust and reproducible primary molecular subgroups of childhood medulloblastoma were identified. MB WNT remained unchanged and each remaining consensus subgroup was split in two. MB SHH was split into age-dependent subgroups corresponding to infant (<4·3 years; MB SHH-Infant ; n=65) and childhood patients (≥4·3 years; MB SHH-Child ; n=38). MB Grp3 and MB Grp4 were each split into high-risk (MB Grp3-HR [n=65] and MB Grp4-HR [n=85]) and low-risk (MB Grp3-LR [n=50] and MB Grp4-LR [n=73]) subgroups. These biological subgroups were validated in the independent cohort. We identified features of the seven subgroups that were predictive of outcome. Cross-validated subgroup-dependent survival models, incorporating these novel subgroups along with secondary clinicopathological and molecular features and established disease risk-factors, outperformed existing disease risk-stratification schemes. These subgroup-dependent models stratified patients into four clinical risk groups for 5-year progression-free survival: favourable risk (54 [25%] of 215 patients; 91% survival [95% CI 82-100]); standard risk (50 [23%] patients; 81% survival [70-94]); high-risk (82 [38%] patients; 42% survival [31-56]); and very high-risk (29 [13%] patients; 28% survival [14-56]). The discovery of seven novel, clinically significant subgroups improves disease risk-stratification and could inform treatment decisions. These data provide a new foundation for future research and clinical investigations. Cancer Research UK, The Tom Grahame Trust, Star for Harris, Action Medical Research, SPARKS, The JGW Patterson Foundation, The INSTINCT network (co-funded by The Brain Tumour Charity, Great Ormond Street Children's Charity, and Children with Cancer UK). Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome, and Fibromyalgia Syndrome

PubMed Central

Light, A.R.; Bateman, L.; Jo, D.; Hughen, R. W.; VanHaitsma, T.A.; White, A.T.; Light, K.C.

2011-01-01

Objectives To determine mRNA expression differences in genes involved in signaling and modulating sensory fatigue, and muscle pain in patients with Chronic Fatigue Syndrome (CFS) and Fibromyalgia Syndrome (FM) at baseline, and following moderate exercise. Design Forty eight Patients with CFS-only, or CFS with comorbid FM, 18 Patients with FM that did not meet criteria for CFS, and 49 healthy Controls underwent moderate exercise (25 minutes at 70% maximum age predicted heart-rate). Visual-analogue measures of fatigue and pain were taken before, during, and after exercise. Blood samples were taken before, and 0.5, 8, 24, and 48 hours after exercise. Leukocytes were immediately isolated from blood, number coded for blind processing and analyses, and flash frozen. Using real-time, quantitative PCR, the amount of mRNA for 13 genes (relative to control genes) involved in sensory, adrenergic, and immune functions was compared between groups at baseline, and following exercise. Changes in amounts of mRNA were correlated with behavioral measures, and functional clinical assessments. Results No gene expression changes occurred following exercise in Controls. In 71% of CFS patients, moderate exercise increased most sensory and adrenergic receptor’s and one cytokine gene’s transcription for 48 hours. These post-exercise increases correlated with behavioral measures of fatigue and pain. In contrast, for the other 29% of CFS patients, adrenergic α-2A receptor’s transcription was decreased at all time points after exercise; other genes were not altered. History of orthostatic intolerance was significantly more common in the α-2A decrease subgroup. FM only patients showed no post-exercise alterations in gene expression, but their pre-exercise baseline mRNA for two sensory ion channels and one cytokine were significantly higher than Controls. Conclusions At least two subgroups of CFS patients can be identified by gene expression changes following exercise. The larger subgroup showed increases in mRNA for sensory and adrenergic receptors and a cytokine. The smaller subgroup contained most of the CFS patients with orthostatic intolerance, showed no post-exercise increases in any gene, and was defined by decreases in mRNA for α-2A. FM only patients can be identified by baseline increases in 3 genes. Post-exercise increases for 4 genes meet published criteria as an objective biomarker for CFS, and could be useful in guiding treatment selection for different subgroups. PMID:21615807

A simple algorithm for the identification of clinical COPD phenotypes.

PubMed

Burgel, Pierre-Régis; Paillasseur, Jean-Louis; Janssens, Wim; Piquet, Jacques; Ter Riet, Gerben; Garcia-Aymerich, Judith; Cosio, Borja; Bakke, Per; Puhan, Milo A; Langhammer, Arnulf; Alfageme, Inmaculada; Almagro, Pere; Ancochea, Julio; Celli, Bartolome R; Casanova, Ciro; de-Torres, Juan P; Decramer, Marc; Echazarreta, Andrés; Esteban, Cristobal; Gomez Punter, Rosa Mar; Han, MeiLan K; Johannessen, Ane; Kaiser, Bernhard; Lamprecht, Bernd; Lange, Peter; Leivseth, Linda; Marin, Jose M; Martin, Francis; Martinez-Camblor, Pablo; Miravitlles, Marc; Oga, Toru; Sofia Ramírez, Ana; Sin, Don D; Sobradillo, Patricia; Soler-Cataluña, Juan J; Turner, Alice M; Verdu Rivera, Francisco Javier; Soriano, Joan B; Roche, Nicolas

2017-11-01

This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (COPD) patients to clinical phenotypes identified by cluster analyses.Data from 2409 COPD patients of French/Belgian COPD cohorts were analysed using cluster analysis resulting in the identification of subgroups, for which clinical relevance was determined by comparing 3-year all-cause mortality. Classification and regression trees (CARTs) were used to develop an algorithm for allocating patients to these subgroups. This algorithm was tested in 3651 patients from the COPD Cohorts Collaborative International Assessment (3CIA) initiative.Cluster analysis identified five subgroups of COPD patients with different clinical characteristics (especially regarding severity of respiratory disease and the presence of cardiovascular comorbidities and diabetes). The CART-based algorithm indicated that the variables relevant for patient grouping differed markedly between patients with isolated respiratory disease (FEV 1 , dyspnoea grade) and those with multi-morbidity (dyspnoea grade, age, FEV 1 and body mass index). Application of this algorithm to the 3CIA cohorts confirmed that it identified subgroups of patients with different clinical characteristics, mortality rates (median, from 4% to 27%) and age at death (median, from 68 to 76 years).A simple algorithm, integrating respiratory characteristics and comorbidities, allowed the identification of clinically relevant COPD phenotypes. Copyright ©ERS 2017.

[Patient first - The impact of characteristics of target populations on decisions about therapy effectiveness of complex interventions: Psychological variables to assess effectiveness in interdisciplinary multimodal pain therapy].

PubMed

Kaiser, Ulrike; Sabatowski, Rainer; Balck, Friedrich

2017-08-01

The assessment of treatment effectiveness in public health settings is ensured by indicators that reflect the changes caused by specific interventions. These indicators are also applied in benchmarking systems. The selection of constructs should be guided by their relevance for affected patients (patient reported outcomes). The interdisciplinary multimodal pain therapy (IMPT) is a complex intervention based on a biopsychosocial understanding of chronic pain. For quality assurance purposes, psychological parameters (depression, general anxiety, health-related quality of life) are included in standardized therapy assessment in pain medicine (KEDOQ), which can also be used for comparative analyses in a benchmarking system. The aim of the present study was to investigate the relevance of depressive symptoms, general anxiety and mental quality of life in patients undergoing IMPT under real life conditions. In this retrospective, one-armed and exploratory observational study we used secondary data of a routine documentation of IMST in routine care, applying several variables of the German Pain Questionnaire and the facility's comprehensive basic documentation. 352 participants with IMPT (from 2006 to 2010) were included, and the follow-up was performed over two years with six assessments. Because of statistically heterogeneous characteristics a complex analysis consisting of factor and cluster analyses was applied to build subgroups. These subgroups were explored to identify differences in depressive symptoms (HADS-D), general anxiety (HADS-A), and mental quality of life (SF 36 PSK) at the time of therapy admission and their development estimated by means of effect sizes. Analyses were performed using SPSS 21.0®. Six subgroups were derived and mainly proved to be clinically and psychologically normal, with the exception of one subgroup that consistently showed psychological impairment for all three parameters. The follow-up of the total study population revealed medium or large effects; changes in the subgroups were consistently caused by two subgroups, while the other four showed little or no change. In summary, only a small proportion of the target population (20 %) demonstrated clinically relevant scores in the psychological parameters applied. When selecting indicators for quality assurance, the heterogeneity of the target populations as well as conceptual and methodological aspects should be considered. The characteristics of the parameters intended, along with clinical and personal relevance of indicators for patients, should be investigated by specific procedures such as patient surveys and statistical analyses. Copyright © 2017. Published by Elsevier GmbH.

Derivation and validation of in-hospital mortality prediction models in ischaemic stroke patients using administrative data.

PubMed

Lee, Jason; Morishima, Toshitaka; Kunisawa, Susumu; Sasaki, Noriko; Otsubo, Tetsuya; Ikai, Hiroshi; Imanaka, Yuichi

2013-01-01

Stroke and other cerebrovascular diseases are a major cause of death and disability. Predicting in-hospital mortality in ischaemic stroke patients can help to identify high-risk patients and guide treatment approaches. Chart reviews provide important clinical information for mortality prediction, but are laborious and limiting in sample sizes. Administrative data allow for large-scale multi-institutional analyses but lack the necessary clinical information for outcome research. However, administrative claims data in Japan has seen the recent inclusion of patient consciousness and disability information, which may allow more accurate mortality prediction using administrative data alone. The aim of this study was to derive and validate models to predict in-hospital mortality in patients admitted for ischaemic stroke using administrative data. The sample consisted of 21,445 patients from 176 Japanese hospitals, who were randomly divided into derivation and validation subgroups. Multivariable logistic regression models were developed using 7- and 30-day and overall in-hospital mortality as dependent variables. Independent variables included patient age, sex, comorbidities upon admission, Japan Coma Scale (JCS) score, Barthel Index score, modified Rankin Scale (mRS) score, and admissions after hours and on weekends/public holidays. Models were developed in the derivation subgroup, and coefficients from these models were applied to the validation subgroup. Predictive ability was analysed using C-statistics; calibration was evaluated with Hosmer-Lemeshow χ(2) tests. All three models showed predictive abilities similar or surpassing that of chart review-based models. The C-statistics were highest in the 7-day in-hospital mortality prediction model, at 0.906 and 0.901 in the derivation and validation subgroups, respectively. For the 30-day in-hospital mortality prediction models, the C-statistics for the derivation and validation subgroups were 0.893 and 0.872, respectively; in overall in-hospital mortality prediction these values were 0.883 and 0.876. In this study, we have derived and validated in-hospital mortality prediction models for three different time spans using a large population of ischaemic stroke patients in a multi-institutional analysis. The recent inclusion of JCS, Barthel Index, and mRS scores in Japanese administrative data has allowed the prediction of in-hospital mortality with accuracy comparable to that of chart review analyses. The models developed using administrative data had consistently high predictive abilities for all models in both the derivation and validation subgroups. These results have implications in the role of administrative data in future mortality prediction analyses. Copyright © 2013 S. Karger AG, Basel.

Overview of the 2016 U.S. Food and Drug Administration Circulatory System Devices Advisory Panel Meeting on the Absorb Bioresorbable Vascular Scaffold System.

PubMed

Steinvil, Arie; Rogers, Toby; Torguson, Rebecca; Waksman, Ron

2016-09-12

This study aims to describe the discussions and recommendations made during the U.S. Food and Drug Administration (FDA) Circulatory System Device Panel pre-market approval application for the Absorb Bioresorbable Vascular Scaffold (BVS) System. The Absorb BVS System is a first-of-its-kind fully bioresorbable percutaneous coronary intervention technology. The absorb BVS was studied in the ABSORB III (A Clinical Evaluation of Absorb BVS, the Everolimus Eluting Bioresorbable Vascular Scaffold in the Treatment of Subjects with de Novo Native Coronary Artery Lesions) trial, the pivotal U.S. investigational device exemption trial. Observational report of the FDA Circulatory System Device Panel pre-market approval application meeting held on March 15, 2016. The U.S. FDA Circulatory System Device Panel members reviewed the ABSROB III trial outcomes and additional post hoc analyses presented by the sponsor and the FDA. The ABSORB III trial met the primary endpoint of noninferiority of Absorb BVS compared with the control, XIENCE drug-eluting stent, for target lesion failure at 1 year. Although a higher numerical trend for adverse outcomes was reported for the Absorb BVS, there were no statistical differences between Absorb BVS and XIENCE for any safety or effectiveness components for target lesion failure or for the secondary pre-specified outcomes. Panel members raised concerns with regard to the ABSORB III results and post hoc analyses focusing mainly on the noninferiority design of the trial, the apparent safety issues of the Absorb BVS in small vessels, the mismatch of visually versus intravascular imaging assessed vessel size found in ABSORB III and its implications on the adequate device labeling, the safety of Absorb BVS in specific patient and lesion subsets, and the post-approval commitments of the sponsor. Following panel discussions and the evidence presented, the panel voted for approval of the device. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The fine scale genetic structure of the British population

PubMed Central

Davison, Dan; Boumertit, Abdelhamid; Day, Tammy; Hutnik, Katarzyna; Royrvik, Ellen C; Cunliffe, Barry; Lawson, Daniel J; Falush, Daniel; Freeman, Colin; Pirinen, Matti; Myers, Simon; Robinson, Mark; Donnelly, Peter; Bodmer, Walter

2015-01-01

Summary Fine-scale genetic variation between human populations is interesting as a signature of historical demographic events and because of its potential for confounding disease studies. We use haplotype-based statistical methods to analyse genome-wide SNP data from a carefully chosen geographically diverse sample of 2,039 individuals from the United Kingdom (UK). This reveals a rich and detailed pattern of genetic differentiation with remarkable concordance between genetic clusters and geography. The regional genetic differentiation and differing patterns of shared ancestry with 6,209 individuals from across Europe carry clear signals of historical demographic events. We estimate the genetic contribution to SE England from Anglo-Saxon migrations to be under half, identify the regions not carrying genetic material from these migrations, suggest significant pre-Roman but post-Mesolithic movement into SE England from the Continent, and show that in non-Saxon parts of the UK there exist genetically differentiated subgroups rather than a general “Celtic” population. PMID:25788095

Preparing novice teachers to develop basic reading and spelling skills in children.

PubMed

Spear-Swerling, Louise; Brucker, Pamela Owen

2004-12-01

This study examined the word-structure knowledge of novice teachers and the progress of children tutored by a subgroup of the teachers. Teachers' word-structure knowledge was assessed using three tasks: graphophonemic segmentation, classification of pseudowords by syllable type, and classification of real words as phonetically regular or irregular. Tutored children were assessed on several measures of basic reading and spelling skills. Novice teachers who received word-structure instruction outperformed a comparison group of teachers in word-structure knowledge at post-test. Tutored children improved significantly from pre-test to post-test on all assessments. Teachers' post-test knowledge on the graphophonemic segmentation and irregular words tasks correlated significantly with tutored children's progress in decoding phonetically regular words; error analyses indicated links between teachers' patterns of word-structure knowledge and children's patterns of decoding progress. The study suggests that word-structure knowledge is important to effective teaching of word decoding and underscores the need to include this information in teacher preparation.

Priorities for research in child maltreatment, intimate partner violence and resilience to violence exposures: results of an international Delphi consensus development process.

PubMed

Wathen, C Nadine; MacGregor, Jennifer C D; Hammerton, Joanne; Coben, Jeffrey H; Herrman, Helen; Stewart, Donna E; MacMillan, Harriet L

2012-08-21

Intimate partner violence (IPV) and child maltreatment (CM) are major global public health problems. The Preventing Violence Across the Lifespan (PreVAiL) Research Network, an international group of over 60 researchers and national and international knowledge-user partners in CM and IPV, sought to identify evidence-based research priorities in IPV and CM, with a focus on resilience, using a modified Delphi consensus development process. Review of existing empirical evidence, PreVAiL documents and team discussion identified a starting list of 20 priorities in the following categories: resilience to violence exposure (RES), CM, and IPV, as well as priorities that cross-cut the content areas (CC), and others specific to research methodologies (RM) in violence research. PreVAiL members (N = 47) completed two online survey rounds, and one round of discussions via three teleconference calls to rate, rank and refine research priorities. Research priorities were: to examine key elements of promising or successful programmes in RES/CM/IPV to build intervention pilot work; CC: to integrate violence questions into national and international surveys, and RM: to investigate methods for collecting and collating datasets to link data and to conduct pooled, meta and sub-group analyses to identify promising interventions for particular groups. These evidence-based research priorities, developed by an international team of violence, gender and mental health researchers and knowledge-user partners, are of relevance for prevention and resilience-oriented research in the areas of IPV and CM.

Reduction in outpatient antibiotic sales for pre-school children: interrupted time series analysis of weekly antibiotic sales data in Sweden 1992-2002.

PubMed

Högberg, Liselotte; Oke, Thimothy; Geli, Patricia; Lundborg, Cecilia Stålsby; Cars, Otto; Ekdahl, Karl

2005-07-01

The aim of this study was to use detailed weekly data on outpatient antibiotic sales for pre-school children in Sweden to test for the significance of trends during 1992-2002. We also report on the special features found in weekly antibiotic data, and how the interrupted time series (ITS) design can adjust for this. Weekly data on the total number of dispensed outpatient antibiotic prescriptions to pre-school children were studied, as well as the individual subgroups commonly used to treat respiratory tract infections in children: narrow-spectrum penicillins, broad-spectrum penicillins and macrolides. In parallel, monthly data of paracetamol sales of paediatric dosages were analysed to reflect trends in symptomatic treatment. An ITS model controlling for seasonality and autocorrelation was used to examine the datasets for significant level and trend shifts. A significant increase in mean and change in level could be found in the total antibiotic data in 1997, also reflected in broad-spectrum penicillin data where a similar trend break occurred in 1996. For macrolides, a trend break with a decrease in mean was noted in 1996, but no trend breaks were found in narrow-spectrum penicillin data. In contrast to the general decreasing trends in antibiotic sales, the yearly over-the-counter sales of paracetamol in paediatric preparations increased during the same period, with no identified trend breaks. The overall decrease in antibiotic sales and increase in paediatric paracetamol sales might suggest that symptomatic treatment in the home has increased, as antibiotics are less commonly prescribed.

Priorities for research in child maltreatment, intimate partner violence and resilience to violence exposures: results of an international Delphi consensus development process

PubMed Central

2012-01-01

Background Intimate partner violence (IPV) and child maltreatment (CM) are major global public health problems. The Preventing Violence Across the Lifespan (PreVAiL) Research Network, an international group of over 60 researchers and national and international knowledge-user partners in CM and IPV, sought to identify evidence-based research priorities in IPV and CM, with a focus on resilience, using a modified Delphi consensus development process. Methods Review of existing empirical evidence, PreVAiL documents and team discussion identified a starting list of 20 priorities in the following categories: resilience to violence exposure (RES), CM, and IPV, as well as priorities that cross-cut the content areas (CC), and others specific to research methodologies (RM) in violence research. PreVAiL members (N = 47) completed two online survey rounds, and one round of discussions via three teleconference calls to rate, rank and refine research priorities. Results Research priorities were: to examine key elements of promising or successful programmes in RES/CM/IPV to build intervention pilot work; CC: to integrate violence questions into national and international surveys, and RM: to investigate methods for collecting and collating datasets to link data and to conduct pooled, meta and sub-group analyses to identify promising interventions for particular groups. Conclusions These evidence-based research priorities, developed by an international team of violence, gender and mental health researchers and knowledge-user partners, are of relevance for prevention and resilience-oriented research in the areas of IPV and CM. PMID:22908894

Does Consideration and Assessment of Effects on Health Equity Affect the Conclusions of Systematic Reviews? A Methodology Study

PubMed Central

Welch, Vivian; Petticrew, Mark; Ueffing, Erin; Benkhalti Jandu, Maria; Brand, Kevin; Dhaliwal, Bharbhoor; Kristjansson, Elizabeth; Smylie, Janet; Wells, George Anthony; Tugwell, Peter

2012-01-01

Introduction Tackling health inequities both within and between countries remains high on the agenda of international organizations including the World Health Organization and local, regional and national governments. Systematic reviews can be a useful tool to assess effects on equity in health status because they include studies conducted in a variety of settings and populations. This study aims to describe the extent to which the impacts of health interventions on equity in health status are considered in systematic reviews, describe methods used, and assess the implications of their equity related findings for policy, practice and research. Methods We conducted a methodology study of equity assessment in systematic reviews. Two independent reviewers extracted information on the reporting and analysis of impacts of health interventions on equity in health status in a group of 300 systematic reviews collected from all systematic reviews indexed in one month of MEDLINE, using a pre-tested data collection form. Any differences in data extraction were resolved by discussion. Results Of the 300 systematic reviews, 224 assessed the effectiveness of interventions on health outcomes. Of these 224 reviews, 29 systematic reviews assessed effects on equity in health status using subgroup analysis or targeted analyses of vulnerable populations. Of these, seven conducted subgroup analyses related to health equity which were reported in insufficient detail to judge their credibility. Of these 29 reviews, 18 described implications for policy and practice based on assessment of effects on health equity. Conclusion The quality and completeness of reporting should be enhanced as a priority, because without this policymakers and practitioners will continue lack the evidence base they need to inform decision-making about health inequity. Furthermore, there is a need to develop methods to systematically consider impacts on equity in health status that is currently lacking in systematic reviews. PMID:22427804

Pre-Literacy Skills of Subgroups of Children with Speech Sound Disorders

ERIC Educational Resources Information Center

Raitano, Nancy A.; Pennington, Bruce F.; Tunick, Rachel A.; Boada, Richard; Shriberg, Lawrence D.

2004-01-01

Background: The existing literature has conflicting findings about the literacy outcome of children with speech sound disorders (SSD), which may be due to the heterogeneity within SSD. Previous studies have documented that two important dimensions of heterogeneity are the presence of a comorbid language impairment (LI) and the persistence of SSD,…

West Virginia's Progress Toward Universal Prekindergarten. Summary. Issues & Answers. REL 2009-No. 070

ERIC Educational Resources Information Center

Cavalluzzo, Linda; Clinton, Yvette; Holian, Laura; Marr, Linda; Taylor, Lydotta

2009-01-01

The report examines rates of participation in West Virginia's universal, voluntary prekindergarten (PreK) program from 2002-03 to 2006-07. It describes the share of seats provided by collaborative partners and public school systems and analyzes participation rates by demographic and socioeconomic subgroup and county characteristics. Reported…

West Virginia's Progress toward Universal Prekindergarten. Issues & Answers. REL 2009-No. 070

ERIC Educational Resources Information Center

Cavalluzzo, Linda; Clinton, Yvette; Holian, Laura; Marr, Linda; Taylor, Lydotta

2009-01-01

The report examines rates of participation in West Virginia's universal, voluntary prekindergarten (PreK) program from 2002-03 to 2006-07. It describes the share of seats provided by collaborative partners and public school systems and analyzes participation rates by demographic and socioeconomic subgroup and county characteristics. Reported…

Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the Hippocampus, Amygdala, and Striatum Following Long-Term Spatial Memory Retrieval

PubMed Central

VanElzakker, Michael B.; Zoladz, Phillip R.; Thompson, Vanessa M.; Park, Collin R.; Halonen, Joshua D.; Spencer, Robert L.; Diamond, David M.

2011-01-01

We have studied the influence of pre-training psychological stress on the expression of c-fos mRNA following long-term spatial memory retrieval. Rats were trained to learn the location of a hidden escape platform in the radial-arm water maze, and then their memory for the platform location was assessed 24 h later. Rat brains were extracted 30 min after the 24-h memory test trial for analysis of c-fos mRNA. Four groups were tested: (1) Rats given standard training (Standard); (2) Rats given cat exposure (Predator Stress) 30 min prior to training (Pre-Training Stress); (3) Rats given water exposure only (Water Yoked); and (4) Rats given no water exposure (Home Cage). The Standard trained group exhibited excellent 24 h memory which was accompanied by increased c-fos mRNA in the dorsal hippocampus and basolateral amygdala (BLA). The Water Yoked group exhibited no increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group were classified into two subgroups: good and bad memory performers. Neither of the two Pre-Training Stress subgroups exhibited a significant change in c-fos mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with good memory exhibited significantly greater c-fos mRNA expression in the dorsolateral striatum (DLS) compared to stressed rats with bad memory. This finding suggests that stressed rats with good memory used their DLS to generate a non-spatial (cue-based) strategy to learn and subsequently retrieve the memory of the platform location. Collectively, these findings provide evidence at a molecular level for the involvement of the hippocampus and BLA in the retrieval of spatial memory and contribute novel observations on the influence of pre-training stress in activating the DLS in response to long-term memory retrieval. PMID:21738501

Expectancy after the first treatment and response to acupuncture for menopausal hot flashes.

PubMed

Ee, Carolyn C; Thuraisingam, Sharmala; Pirotta, Marie V; French, Simon D; Xue, Charlie C; Teede, Helena J

2017-01-01

Evidence on the impact of expectancy on acupuncture treatment response is conflicting. This secondary analysis of a randomized sham-controlled trial on acupuncture for menopausal hot flashes investigated whether treatment expectancy score was associated with hot flash score at end-of-treatment. Secondary analyses investigated whether there were associations between other pre-specified factors and hot flash score. Women experiencing moderately-severe hot flashes were randomized to receive 10 sessions of real or sham acupuncture over eight weeks. Hot flash score was collected using a seven-day hot flash diary, and expectancy using the modified Credibility and Expectancy Questionnaire immediately after the first treatment. Linear mixed-effects models with random intercepts were used to identify associations between expectancy score and hot flash score at end-of-treatment. Regression was also used to identify associations between pre-specified factors of interest and hot flash score. Because there was no difference between real and sham acupuncture for the primary outcome of hot flash score, both arms were combined in the analysis. 285 women returned the Credibility and Expectancy Questionnaire, and 283 women completed both expectancy measures. We found no evidence for an association between expectancy and hot flash score at end-of-treatment for individual cases in either acupuncture or sham group. Hot flash scores at end-of-treatment were 8.1 (95%CI, 3.0 to 13.2; P = 0.002) points lower in regular smokers compared to those who had never smoked, equivalent to four fewer moderate hot flashes a day. In our study of acupuncture for menopausal hot flashes, higher expectancy after the first treatment did not predict better treatment outcomes. Future research may focus on other determinants of outcomes in acupuncture such as therapist attention. The relationship between smoking and hot flashes is poorly understood and needs further exploration.

Forecasting the Onset Time of Volcanic Eruptions Using Ground Deformation Data

NASA Astrophysics Data System (ADS)

Blake, S.; Cortes, J. A.

2016-12-01

The pre-eruptive inflation of the ground surface is a well-known phenomenon at many volcanoes. In a number of intensively studied cases, elevation and/or radial tilt increase with time (t) towards a limiting value by following a decaying exponential with characteristic timescale τ (Kilauea and Mauna Loa: Dvorak and Okamura 1987, Lengliné et al., 2008) or, after sufficiently long times, by following the sum of two such functions such that two timescales, τ1 and τ2, are required to describe the temporal pattern of inflation (Axial Seamount: Nooner and Chadwick, 2009). We have used the Levenberg-Marquardt non-linear fit algorithm to analyse data for 18 inflation periods at Krafla volcano, Iceland, (Björnsson and Eysteinsson, 1998) and found the same functional relationship. Pooling all of the available data from 25 eruptions at 4 volcanoes shows that the duration of inflation before an eruption or shallow intrusion (t*) is comparable to τ (or the longer of τ1 and τ2) and follows an almost 1:1 linear relationship (r2 0.8). We also find that this scaling is replicated by Monte Carlo simulations of physics-based forward models of hydraulically connected dual magma chamber systems which erupt when the chamber pressure reaches a threshold value. These results lead to a new forecasting method which we describe and assess here: if τ can be constrained during an on-going inflation period, then the statistical distribution of t*/τ values calibrated from other pre-eruptive inflation periods allows the probability of an eruption starting before (or after) a specified time to be estimated. The time at which there is a specified probability of an eruption starting can also be forecast. These approaches rely on fitting deformation data up to time t in order to obtain τ(t) which is then used to forecast t*. Forecasts can be updated after each new deformation measurement.

The association between histological, macroscopic and magnetic resonance imaging assessed synovitis in end-stage knee osteoarthritis: a cross-sectional study.

PubMed

Riis, R G C; Gudbergsen, H; Simonsen, O; Henriksen, M; Al-Mashkur, N; Eld, M; Petersen, K K; Kubassova, O; Bay Jensen, A C; Damm, J; Bliddal, H; Arendt-Nielsen, L; Boesen, M

2017-02-01

To investigate the association between magnetic resonance imaging (MRI), macroscopic and histological assessments of synovitis in end-stage knee osteoarthritis (KOA). Synovitis of end-stage osteoarthritic knees was assessed using non-contrast-enhanced (CE), contrast-enhanced magnetic resonance imaging (CE-MRI) and dynamic contrast-enhanced (DCE)-MRI prior to (TKR) and correlated with microscopic and macroscopic assessments of synovitis obtained intraoperatively. Multiple bivariate correlations were used with a pre-specified threshold of 0.70 for significance. Also, multiple regression analyses with different subsets of MRI-variables as explanatory variables and the histology score as outcome variable were performed with the intention to find MRI-variables that best explain the variance in histological synovitis (i.e., highest R 2 ). A stepped approach was taken starting with basic characteristics and non-CE MRI-variables (model 1), after which CE-MRI-variables were added (model 2) with the final model also including DCE-MRI-variables (model 3). 39 patients (56.4% women, mean age 68 years, Kellgren-Lawrence (KL) grade 4) had complete MRI and histological data. Only the DCE-MRI variable MExNvoxel (surrogate of the volume and degree of synovitis) and the macroscopic score showed correlations above the pre-specified threshold for acceptance with histological inflammation. The maximum R 2 -value obtained in Model 1 was R 2  = 0.39. In Model 2, where the CE-MRI-variables were added, the highest R 2  = 0.52. In Model 3, a four-variable model consisting of the gender, one CE-MRI and two DCE-MRI-variables yielded a R 2  = 0.71. DCE-MRI is correlated with histological synovitis in end-stage KOA and the combination of CE and DCE-MRI may be a useful, non-invasive tool in characterising synovitis in KOA. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Prognostic impact of age in children and adolescents with acute lymphoblastic leukemia: data from the trials ALL-BFM 86, 90, and 95.

PubMed

Möricke, A; Zimmermann, M; Reiter, A; Gadner, H; Odenwald, E; Harbott, J; Ludwig, W-D; Riehm, H; Schrappe, M

2005-01-01

Large progress has been made in the treatment of acute lymphoblastic leukemia (ALL) of childhood and adolescence over the past 30 years. Eighty percent of the patients can be cured, but clinical subgroups with a dismal outcome can still be identified. In this study, we investigated the association of age with prognosis in 5 181 patients with ALL under 18 years (y) of age enrolled in the three consecutive treatment trials ALL-BFM 86, 90 and 95 in more than 80 centers. Event-free survival (pEFS) of the total group was significantly associated with age. The most unfavorable outcome was found in infancy and the best results were achieved at toddler and pre-school age. Beyond 5 y of age, survival probability decreased (pEFS at 8 y: < 1 y = 0.45; 1-5 y = 0.82; 6-9 y = 0.75; 10-14 y = 0.63; > or = 15 y = 0.59). The proportion of T-ALL as compared to precursor B-cell ALL (pB-ALL) was lower in younger children, due to an incidence peak of pB-ALL in toddlers and at pre-school age compared to a constant incidence of T-ALL. Within the T-ALL group, no correlation of age with sex, initial white blood cell count, CNS disease, or early treatment response was found. Children under 10 y of age had a slightly lower relapse rate compared to older patients. Within pB-ALL patients, the proportion as well as the absolute incidence of TEL/AML1 rearrangement and DNA index of > or = 1.16 was higher in the younger children. A lower proportion of BCR/ABL-positive ALL was observed in the age group of < 6 y when compared to patients aged > or = 6 y, but the absolute incidence was constant across the age groups after the first year of life. More than half of the infants had a CD10-negative pB-ALL. The incidence was constant after a peak in the first year of life, yet the percentage of CD10 negativity increased with rising age in this subgroup. Adolescents with pB-ALL had a significantly higher proportion of prednisone poor-responders. Accordingly, outcome was worse in older patients. This pattern was also evident in the biologically heterogeneous group of patients with a DNA index of > or = 1.16. In contrast, no significant age-related outcome differences could be shown within TEL/AML1- or BCR/ABL-positive patients, as well as within CD10-negative pB-ALL beyond infant age. Analysis of the pB-ALL group in a Cox's regression model including age and the above-listed biological factors revealed age < 1 year and > or = 10 years as independent risk factors. This is in line with the poorer prognosis of these age groups in the pB-ALL subgroup without specific biological characteristics. This subgroup also had an incidence peak at toddler age, presumably containing other favorable biological subsets. An independent prognostic impact of age in pediatric ALL cannot be excluded by this study. However, our analyses show that the age-associated different prognosis in childhood ALL is at least partly related to the different distribution of relevant prognostic subgroups between the age groups.

Polymorphisms in Tumor Necrosis Factor-α Are Associated With Higher Anxiety Levels in Women After Breast Cancer Surgery.

PubMed

Miaskowski, Christine; Elboim, Charles; Paul, Steven M; Mastick, Judy; Cooper, Bruce A; Levine, Jon D; Aouizerat, Bradley E

2016-02-01

Before and after breast cancer surgery, women have reported varying anxiety levels. Recent evidence has suggested that anxiety has a genetic basis and is associated with inflammation. The purposes of the present study were to identify the subgroups of women with distinct anxiety trajectories; to evaluate for differences in the phenotypic characteristics between these subgroups; and to evaluate for associations between polymorphisms in cytokine genes and subgroup membership. Patients with breast cancer (n = 398) were recruited before surgery and followed up for 6 months. The patients completed the Spielberger State Anxiety Inventory and provided a blood sample for genomic analyses. Growth mixture modeling was used to identify the subgroups of patients with distinct anxiety trajectories. Two distinct anxiety subgroups were identified. The women in the higher anxiety subgroup were younger and had a lower functional status score. Two single nucleotide polymorphisms in tumor necrosis factor-α (rs1799964, rs3093662) were associated with the higher anxiety subgroup. The results of the present exploratory study suggest that polymorphisms in cytokine genes could partially explain the interindividual variability in anxiety. The determination of phenotypic and molecular markers associated with greater levels of anxiety can assist clinicians to identify high-risk patients and initiate appropriate interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

The association between congenital anomalies and autism spectrum disorders in a Finnish national birth cohort.

PubMed

Timonen-Soivio, Laura; Vanhala, Raija; Malm, Heli; Leivonen, Susanna; Jokiranta, Elina; Hinkka-Yli-Salomäki, Susanna; Gissler, Mika; Brown, Alan S; Sourander, Andre

2015-01-01

The first aim of this study was to evaluate the association between different subgroups of autism spectrum disorders (ASDs) (childhood autism, Asperger syndrome, and pervasive developmental disorder/pervasive developmental disorder - not otherwise specified [PDD/PDD-NOS]) and congenital anomalies. Second, we assessed the association among intellectually disabled children with ASDs in the subgroups of childhood autism and PDD/PDD-NOS. Nationwide population-based register data for children with a diagnosis of ASD (n=4449; 3548 males, 901 females) were collected during years 1987-2000 from the Finnish Hospital Discharge Register. Data on congenital anomalies were derived from the National Register of Congenital Malformations. Conditional logistic regression models were used as a statistical method. The association between ASD subgroups and congenital anomalies was stratified by the presence or absence of intellectual disability. Congenital anomalies occurred more frequently in all subgroups of ASD than in comparison participants (adjusted odds ratio [OR] for major congenital anomalies 1.8, 95% confidence interval [CI] 1.5-2.2, p<0.001). The association between congenital anomalies and childhood autism (OR 2.4, 95% CI 1.6-3.6, p<0.001) and between congenital anomalies and PDD/PDD-NOS (OR 3.7, 95% CI 2.4-5.7, p<0.001) among children with an intellectual disability was strong but remained significant also without intellectual disability (childhood autism: OR 1.7, 95% CI 1.3-2.3, p<0.001; PDD/PDD-NOS: OR 2.3, 95% CI 1.9-2.8, p<0.001). The results suggest a significant association between ASDs and congenital anomalies regardless of the ASD subgroup. The association between childhood autism and PDD/PDD-NOS and congenital anomalies is stronger among children with intellectual disability is stronger than among those without intellectual disability. These results may have relevance in examining early risk factors in autism during fetal neurodevelopment. © 2014 Mac Keith Press.

Lower extremity revascularization using directional atherectomy: 12-month prospective results of the DEFINITIVE LE study.

PubMed

McKinsey, James F; Zeller, Thomas; Rocha-Singh, Krishna J; Jaff, Michael R; Garcia, Lawrence A

2014-08-01

The aim of this study was to assess the safety and effectiveness of directional atherectomy (DA) for endovascular treatment of peripheral arterial disease (PAD) in infrainguinal arteries in patients with claudication or critical limb ischemia. To date, no prospective, multicenter, independently-adjudicated study has evaluated the effectiveness and durability of DA in the treatment of PAD. Previous DA studies have not been prospectively powered to evaluate any differences in outcomes in patients with and without diabetes. DEFINITIVE LE (Determination of EFfectiveness of the SilverHawk(®) PerIpheral Plaque ExcisioN System (SIlverHawk Device) for the Treatment of Infrainguinal VEssels / Lower Extremities) prospectively enrolled subjects at 47 multinational centers with an infrainguinal lesion length up to 20 cm. Primary endpoints were defined as primary patency at 12 months for claudicants and freedom from major unplanned amputation for critical limb ischemia (CLI) subjects. A pre-specified statistical hypothesis evaluated noninferiority of primary patency in diabetic versus nondiabetic claudicants. Independent angiographic and sonographic core laboratories assessed outcomes, and events were adjudicated by a clinical events committee. A total of 800 subjects were enrolled. The 12-month primary patency was 78% (95% confidence interval: 74.0% to 80.6%) in claudicants, with a 77% rate in the diabetic subgroup versus 78% in the nondiabetic subgroup (noninferior, p < 0.001). The rate of freedom from major unplanned amputation of the target limb at 12 months in CLI subjects was 95% (95% confidence interval: 90.7% to 97.4%). Periprocedural adverse events included embolization (3.8%), perforation (5.3%), and abrupt closure (2.0%). The bail-out stent rate was 3.2%. The DEFINITIVE LE study demonstrated that DA is a safe and effective treatment modality at 12 months for a diverse patient population with either claudication or CLI. Furthermore, DA was shown to be noninferior for treating PAD in patients with diabetes compared with those without diabetes. (Study of SilverHawk/TurboHawk in Lower Extremity Vessels [DEFINITIVE LE]; NCT00883246). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Using cost-analyses to inform health professions education - The economic cost of pre-clinical failure.

PubMed

Foo, Jonathan; Ilic, Dragan; Rivers, George; Evans, Darrell J R; Walsh, Kieran; Haines, Terry P; Paynter, Sophie; Morgan, Prue; Maloney, Stephen

2017-12-07

Student failure creates additional economic costs. Knowing the cost of failure helps to frame its economic burden relative to other educational issues, providing an evidence-base to guide priority setting and allocation of resources. The Ingredients Method is a cost-analysis approach which has been previously applied to health professions education research. In this study, the Ingredients Method is introduced, and applied to a case study, investigating the cost of pre-clinical student failure. The four step Ingredients Method was introduced and applied: (1) identify and specify resource items, (2) measure volume of resources in natural units, (3) assign monetary prices to resource items, and (4) analyze and report costs. Calculations were based on a physiotherapy program at an Australian university. The cost of failure was £5991 per failing student, distributed across students (70%), the government (21%), and the university (8%). If the cost of failure and attrition is distributed among the remaining continuing cohort, the cost per continuing student educated increases from £9923 to £11,391 per semester. The economics of health professions education is complex. Researchers should consider both accuracy and feasibility in their costing approach, toward the goal of better informing cost-conscious decision-making.

Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme.

PubMed

Johansen, Odd Erik; Neubacher, Dietmar; von Eynatten, Maximilian; Patel, Sanjay; Woerle, Hans-Juergen

2012-01-10

This study investigated the cardiovascular (CV) safety profile of the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin versus comparator treatments. This was a pre-specified meta-analysis of CV events in linagliptin or comparator-treated patients with type 2 diabetes mellitus (T2DM) from eight Phase 3 studies. All suspected CV events were prospectively adjudicated by a blinded independent expert committee. The primary endpoint was a composite of CV death, stroke, myocardial infarction, and hospitalization for unstable angina. Three secondary composite endpoints derived from the adjudicated CV events were also pre-specified. Risk estimates were calculated using several statistical methods including Cox regression analysis. Of 5239 treated patients (mean ± SD HbA1c 65 ± 10 mmol/mol [8.0 ± 0.9%], age 58 ± 10 years, BMI 29 ± 5 kg/m2), 3319 received linagliptin once daily (5 mg, 3159; 10 mg, 160) and 1920 received comparators (placebo, 977; glimepiride 1-4 mg, 781; voglibose 0.6 mg, 162). Cumulative exposure (patient-years) was 2060 for linagliptin and 1372 for comparators. Primary CV events occurred in 11 (0.3%) patients receiving linagliptin and 23 (1.2%) receiving comparators. The hazard ratio (HR) for the primary endpoint showed significantly lower risk with linagliptin than comparators (HR 0.34 [95% confidence interval (CI) 0.16-0.70]) as did estimates for all secondary endpoints (HR ranging from 0.34 to 0.55 [all upper 95% CIs < 1.0]). These results from a large Phase 3 programme support the hypothesis that linagliptin may have CV benefits in patients with T2DM. © 2012 Johansen et al; licensee BioMed Central Ltd.

Study protocol of a mixed-methods evaluation of a cluster randomized trial to improve the safety of NSAID and antiplatelet prescribing: data-driven quality improvement in primary care.

PubMed

Grant, Aileen; Dreischulte, Tobias; Treweek, Shaun; Guthrie, Bruce

2012-08-28

Trials of complex interventions are criticized for being 'black box', so the UK Medical Research Council recommends carrying out a process evaluation to explain the trial findings. We believe it is good practice to pre-specify and publish process evaluation protocols to set standards and minimize bias. Unlike protocols for trials, little guidance or standards exist for the reporting of process evaluations. This paper presents the mixed-method process evaluation protocol of a cluster randomized trial, drawing on a framework designed by the authors. This mixed-method evaluation is based on four research questions and maps data collection to a logic model of how the data-driven quality improvement in primary care (DQIP) intervention is expected to work. Data collection will be predominately by qualitative case studies in eight to ten of the trial practices, focus groups with patients affected by the intervention and quantitative analysis of routine practice data, trial outcome and questionnaire data and data from the DQIP intervention. We believe that pre-specifying the intentions of a process evaluation can help to minimize bias arising from potentially misleading post-hoc analysis. We recognize it is also important to retain flexibility to examine the unexpected and the unintended. From that perspective, a mixed-methods evaluation allows the combination of exploratory and flexible qualitative work, and more pre-specified quantitative analysis, with each method contributing to the design, implementation and interpretation of the other.As well as strengthening the study the authors hope to stimulate discussion among their academic colleagues about publishing protocols for evaluations of randomized trials of complex interventions. DATA-DRIVEN QUALITY IMPROVEMENT IN PRIMARY CARE TRIAL REGISTRATION: ClinicalTrials.gov: NCT01425502.

A randomized placebo-controlled phase 3 trial of an antisense oligonucleotide, drisapersen, in Duchenne muscular dystrophy.

PubMed

Goemans, Nathalie; Mercuri, Eugenio; Belousova, Elena; Komaki, Hirofumi; Dubrovsky, Alberto; McDonald, Craig M; Kraus, John E; Lourbakos, Afrodite; Lin, Zhengning; Campion, Giles; Wang, Susanne X; Campbell, Craig

2018-01-01

This 48-week, randomized, placebo-controlled phase 3 study (DMD114044; NCT01254019) evaluated efficacy and safety of subcutaneous drisapersen 6 mg/kg/week in 186 ambulant boys aged ≥5 years, with Duchenne muscular dystrophy (DMD) resulting from an exon 51 skipping amenable mutation. Drisapersen was generally well tolerated, with injection-site reactions and renal events as most commonly reported adverse events. A nonsignificant treatment difference (P = 0.415) in the change from baseline in six-minute walk distance (6MWD; primary efficacy endpoint) of 10.3 meters in favor of drisapersen was observed at week 48. Key secondary efficacy endpoints (North Star Ambulatory Assessment, 4-stair climb ascent velocity, and 10-meter walk/run velocity) gave consistent findings. Lack of statistical significance was thought to be largely due to greater data variability and subgroup heterogeneity. The increased standard deviation alone, due to less stringent inclusion/exclusion criteria, reduced the statistical power from pre-specified 90% to actual 53%. Therefore, a post-hoc analysis was performed in 80 subjects with a baseline 6MWD 300-400 meters and ability to rise from floor. A statistically significant improvement in 6MWD of 35.4 meters (P = 0.039) in favor of drisapersen was observed in this subpopulation. Results suggest that drisapersen could have benefit in a less impaired population of DMD subjects. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Risk Factors for Suicidal Ideation in People at Risk for Huntington's Disease.

PubMed

Anderson, Karen E; Eberly, Shirley; Groves, Mark; Kayson, Elise; Marder, Karen; Young, Anne B; Shoulson, Ira

2016-12-15

Suicidal ideation (SI) and attempts are increased in Huntington's disease (HD), making risk factor assessment a priority. To determine whether, hopelessness, irritability, aggression, anxiety, CAG expansion status, depression, and motor signs/symptoms were associated with Suicidal Ideation (SI) in those at risk for HD. Behavioral and neurological data were collected from subjects in an observational study. Subject characteristics were calculated by CAG status and SI. Logistic regression models were adjusted for demographics. Separate logistic regressions were used to compare SI and non-SI subjects. A combined logistic regression model, including 4 pre-specified predictors, (hopelessness, irritability, aggression, anxiety) was used to assess the relationship of SI to these predictors. 801 subjects were assessed, 40 were classified as having SI, 6.3% of CAG mutation expansion carriers had SI, compared with 4.3% of non- CAG mutation expansion carriers (p = 0.2275). SI subjects had significantly increased depression (p < 0.0001), hopelessness (p < 0.0001), irritability (p < 0.0001), aggression (p = 0.0089), and anxiety (p < 0.0001), and an elevated motor score (p = 0.0098). Impulsivity, assessed in a subgroup of subjects, was also associated with SI (p = 0.0267). Hopelessness and anxiety remained significant in combined model (p < 0.001; p < 0.0198, respectively) even when motor score was included. Behavioral symptoms were significantly higher in those reporting SI. Hopelessness and anxiety showed a particularly strong association with SI. Risk identification could assist in assessment of suicidality in this group.

Association of hospitalization for neurosurgical operations in Magnet hospitals with mortality and length-of-stay

PubMed Central

Missios, Symeon; Bekelis, Kimon

2017-01-01

Background The association of Magnet hospital status with improved surgical outcomes remains an issue of debate. Objective To investigate whether hospitalization in a Magnet hospital is associated with improved outcomes for patients undergoing neurosurgical operations. Methods A cohort study was executed using all patients undergoing neurosurgical operations in New York registered in the Statewide Planning and Research Cooperative System (SPARCS) database from 2009–2013. We examined the association of Magnet status hospitalization after neurosurgical operations with inpatient case-fatality, and length of stay (LOS). We employed an instrumental variable analysis to simulate a randomized trial. Results Overall, 190,787 patients underwent neurosurgical operations. Of these, 68,046 (35.7%) were hospitalized in Magnet hospitals, and 122,741 (64.3%) in non-Magnet institutions. Instrumental variable analysis demonstrated that hospitalization in Magnet hospitals was associated with decreased case-fatality (Adjusted difference, −0.8%; −95% CI, −0.7% to −0.6%), and LOS (Adjusted difference, −1.9; 95% CI, −2.2 to −1.5) in comparison to non-Magnet hospitals. These associations were also observed in propensity score adjusted mixed effects models. These associations persisted in pre-specified subgroups of patients undergoing spine surgery, craniotomy for tumor resection, or neurovascular interventions. Conclusions We identified an association of Magnet hospitals with lower case-fatality, and shorter LOS in a comprehensive New York State patient cohort undergoing neurosurgical procedures. PMID:28472336

4G/5G Variant of Plasminogen Activator Inhibitor-1 Gene and Severe Pregnancy-Induced Hypertension: Subgroup Analyses of Variants of Angiotensinogen and Endothelial Nitric Oxide Synthase

PubMed Central

Kobashi, Gen; Ohta, Kaori; Yamada, Hideto; Hata, Akira; Minakami, Hisanori; Sakuragi, Noriaki; Tamashiro, Hiko; Fujimoto, Seiichiro

2009-01-01

Background Pregnancy-induced hypertension (PIH) is a common cause of perinatal mortality. It is believed to result from the interaction of several factors, including those related to the blood coagulation system. We performed genotyping and subgroup analyses to determine if the 4G/5G genotypes of the plasminogen activator inhibitor-1 gene (PAI-1) play a role in the pathogenesis of PIH, and to evaluate possible interactions of the PAI-1 polymorphisms with those of the angiotensinogen gene (AGT) and the endothelial nitric oxide synthase gene (NOS3). Methods An association study of PAI-1 polymorphism, and subgroup analyses of common variants of AGT and NOS3, among 128 patients with PIH and 376 healthy pregnant controls. Results No significant differences were found between the cases and controls in the frequencies of allele 4G or the 4G/4G genotype. In subgroup analyses, after adjustment for multiple comparison, a significant association with the AGT TT genotype was found among women with the PAI-1 4G/4G genotype, and an association with the NOS3 GA+AA genotype was found among women with the 5G/5G or 4G/5G genotypes. Conclusions Our findings suggest that there are at least 2 pathways in the pathogenesis of severe PIH. However, with respect to early prediction and prevention of severe PIH, although the PAI-1 4G/4G genotype alone was not a risk factor for severe PIH, the fact that PAI-1 genotypes are associated with varying risks for severe PIH suggests that PAI-1 genotyping of pregnant women, in combination with other tests, may be useful in the development of individualized measures that may prevent severe PIH. PMID:19838007

Bioinformatic Analyses of Subgroup-A Members of the Wheat bZIP Transcription Factor Family and Functional Identification of TabZIP174 Involved in Drought Stress Response

PubMed Central

Li, Xueyin; Feng, Biane; Zhang, Fengjie; Tang, Yimiao; Zhang, Liping; Ma, Lingjian; Zhao, Changping; Gao, Shiqing

2016-01-01

Extensive studies in Arabidopsis and rice have demonstrated that Subgroup-A members of the bZIP transcription factor family play important roles in plant responses to multiple abiotic stresses. Although common wheat (Triticum aestivum) is one of the most widely cultivated and consumed food crops in the world, there are limited investigations into Subgroup A of the bZIP family in wheat. In this study, we performed bioinformatic analyses of the 41 Subgroup-A members of the wheat bZIP family. Phylogenetic and conserved motif analyses showed that most of the Subgroup-A bZIP proteins involved in abiotic stress responses of wheat, Arabidopsis, and rice clustered in Clade A1 of the phylogenetic tree, and shared a majority of conserved motifs, suggesting the potential importance of Clade-A1 members in abiotic stress responses. Gene structure analysis showed that TabZIP genes with close phylogenetic relationships tended to possess similar exon–intron compositions, and the positions of introns in the hinge regions of the bZIP domains were highly conserved, whereas introns in the leucine zipper regions were at variable positions. Additionally, eleven groups of homologs and two groups of tandem paralogs were also identified in Subgroup A of the wheat bZIP family. Expression profiling analysis indicated that most Subgroup-A TabZIP genes were responsive to abscisic acid and various abiotic stress treatments. TabZIP27, TabZIP74, TabZIP138, and TabZIP174 proteins were localized in the nucleus of wheat protoplasts, whereas TabZIP9-GFP fusion protein was simultaneously present in the nucleus, cytoplasm, and cell membrane. Transgenic Arabidopsis overexpressing TabZIP174 displayed increased seed germination rates and primary root lengths under drought treatments. Overexpression of TabZIP174 in transgenic Arabidopsis conferred enhanced drought tolerance, and transgenic plants exhibited lower water loss rates, higher survival rates, higher proline, soluble sugar, and leaf chlorophyll contents, as well as more stable osmotic potential under drought conditions. Additionally, overexpression of TabZIP174 increased the expression of stress-responsive genes (RD29A, RD29B, RAB18, DREB2A, COR15A, and COR47). The improved drought resistance might be attributed to the increased osmotic adjustment capacity. Our results indicate that TabZIP174 may participate in regulating plant response to drought stress and holds great potential for genetic improvement of abiotic stress tolerance in crops. PMID:27899926

A meta-analysis of the effect of neuromuscular training on the prevention of the anterior cruciate ligament injury in female athletes.

PubMed

Yoo, Jae Ho; Lim, Bee Oh; Ha, Mina; Lee, Soo Won; Oh, Soo Jin; Lee, Yong Seuk; Kim, Jin Goo

2010-06-01

Female athletes are more prone to anterior cruciate ligament (ACL) injury than their male counterparts, presumably because of anatomical, hormonal, and neuromuscular differences. Of these three, only the neuromuscular component can be modified by preventive exercise. We aimed to evaluate the effect of a neuromuscular protocol on the prevention of ACL injury by performing meta-analysis, and to identify essential factors by subgroup analysis. An extensive literature review was conducted to identify relevant studies, and eventually, only seven randomized controlled trials or prospective cohort studies were included in the analysis. The odds ratios (OR) and the confidence interval (CI) for the overall effects of training and of potentially contributory factors were estimated. The OR and the 95% CI for the overall effect of the preventive training were 0.40 and [0.27, 0.60], respectively. Subgroup analysis revealed that an age under 18, soccer rather than handball, pre- and in-season training rather than either pre- or in-season training, and the plyometrics and strengthening components rather than balancing were significant. Meta-analysis showed that pre- and in-season neuromuscular training with an emphasis on plyometrics and strengthening exercises was effective at preventing ACL injury in female athletes, especially in those under 18 years of age. Further study is required to develop a relevant training program protocol of appropriate intensity.

Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial.

PubMed

Keohane, Denis; Schwartz, Jeffrey; Gundapaneni, Balarama; Stewart, Michelle; Amass, Leslie

2017-03-01

Tafamidis, a non-NSAID highly specific transthyretin stabilizer, delayed neurologic disease progression as measured by Neuropathy Impairment Score-Lower Limbs (NIS-LL) in an 18-month, double-blind, placebo-controlled randomized trial in 128 patients with early-stage transthyretin V30M familial amyloid polyneuropathy (ATTRV30M-FAP). The current post hoc analyses aimed to further evaluate the effects of tafamidis in delaying ATTRV30M-FAP progression in this trial. Pre-specified, repeated-measures analysis of change from baseline in NIS-LL in this trial (ClinicalTrials.gov NCT00409175) was repeated with addition of baseline as covariate and multiple imputation analysis for missing data by treatment group. Change in NIS-LL plus three small-fiber nerve tests (NIS-LL + Σ3) and NIS-LL plus seven nerve tests (NIS-LL + Σ7) were assessed without baseline as covariate. Treatment outcomes over the NIS-LL, Σ3, Σ7, modified body mass index and Norfolk Quality of Life-Diabetic Neuropathy Total Quality of Life Score were also examined using multivariate analysis techniques. Neuropathy progression based on NIS-LL change from baseline to Month 18 remained significantly reduced for tafamidis versus placebo in the baseline-adjusted and multiple imputation analyses. NIS-LL + Σ3 and NIS-LL + Σ7 captured significant treatment group differences. Multivariate analyses provided strong statistical evidence for a superior tafamidis treatment effect. These supportive analyses confirm that tafamidis delays neurologic progression in early-stage ATTRV30M-FAP. NCT00409175.

Patterns of Alcohol Use Among Canadian Military Personnel and Their Associations With Health and Well-Being.

PubMed

Richer, Isabelle; Lee, Jennifer E C; Born, Jennifer

2016-04-07

Heavy drinking increases the risk of injury, adverse physical and mental health outcomes, and loss of productivity. Nonetheless, patterns of alcohol use and related symptomatology among military personnel remain poorly understood. A latent class analysis (LCA) was used to explore the presence of subgroups of alcohol users among Canadian Armed Forces (CAF) Regular Forces members. Correlates of empirically derived subgroups were further explored. Analyses were performed on a subsample of alcohol users who participated in a 2008/09 cross-sectional survey of a stratified random sample of currently serving CAF Regular Force members (N = 1980). Multinomial logistic regression models were conducted to verify physical and mental health differences across subgroups of alcohol users. All analyses were adjusted for complex survey design. A 4-class solution was considered the best fit for the data. Subgroups were labeled as follows: Class 1 - Infrequent drinkers (27.2%); Class 2 - Moderate drinkers (41.5%); Class 3 - Regular binge drinkers with minimal problems (14.8%); and Class 4 - Problem drinkers (16.6%). Significant differences by age, sex, marital status, element, rank, recent serious injuries, chronic conditions, psychological distress, posttraumatic stress disorder, and depression symptoms were found across the subgroups. Problem drinkers demonstrated the most degraded physical and mental health. Findings highlight the heterogeneity of alcohol users and heavy drinkers among CAF members and the need for tailored interventions addressing high-risk alcohol use. Results have the potential to inform prevention strategies and screening efforts. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

A Physics-Based Temperature Stabilization Criterion for Thermal Testing

NASA Technical Reports Server (NTRS)

Rickman, Steven L.; Ungar, Eugene K.

2009-01-01

Spacecraft testing specifications differ greatly in the criteria they specify for stability in thermal balance tests. Some specify a required temperature stabilization rate (the change in temperature per unit time, dT/dt), some specify that the final steady-state temperature be approached to within a specified difference, delta T , and some specify a combination of the two. The particular values for temperature stabilization rate and final temperature difference also vary greatly between specification documents. A one-size-fits-all temperature stabilization rate requirement does not yield consistent results for all test configurations because of differences in thermal mass and heat transfer to the environment. Applying a steady-state temperature difference requirement is problematic because the final test temperature is not accurately known a priori, especially for powered configurations. In the present work, a simplified, lumped-mass analysis has been used to explore the applicability of these criteria. A new, user-friendly, physics-based approach is developed that allows the thermal engineer to determine when an acceptable level of temperature stabilization has been achieved. The stabilization criterion can be predicted pre-test but must be refined during test to allow verification that the defined level of temperature stabilization has been achieved.

Outcomes in endoscopic sinus surgery: olfaction, nose scale and quality of life in a prospective cohort study.

PubMed

Andrews, P J; Poirrier, A-L; Lund, V J; Choi, D

2016-12-01

To determine the efficacy of endoscopic sinus surgery (ESS) on olfactory function in chronic rhinosinusitis patients with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) and to compare the nasal obstruction and symptom evaluation (NOSE) scale before and after surgery. A prospective cohort study SETTING: Royal National Throat and Nose and Ear Hospital, London UK. One hundred and thirteen patients with CRS; 60 CRSwNP and 53 CRSsNP. Olfaction was measured using both the University of Pennsylvania Smell Investigation Test (UPSIT) and the 'sense of smell' visual analogue scale (VAS). The NOSE scale, the sinonasal outcome test (SNOT 22) and the Lund-Kennedy (LK) surgeon reported scores were also measured pre- and postoperatively at 6 months. The UPSIT psychophysical measurement significantly improved following ESS in the CRSwNP subgroup as did the patients perceived VAS sense of smell. However, in the CRSsNP subgroup, the improved VAS and UPSIT measurements were not significant. The NOSE, SNOT 22 and LK scores all improved significantly. The olfactory improvement as measured by the UPSIT correlated to the SNOT-22, but a correlation between the NOSE score and UPSIT was not found. Endoscopic sinus surgery significantly improved the patient's perceived and measured sense of smell in the CRSwNP subgroup which is the most surgically responsive CRS subgroup. Additionally, improved olfaction in the CRSwNP subgroup is most likely to improve the patient's quality of life. Endoscopic sinus surgery significantly improved the NOSE scale in both CRS subgroups at 6 months following surgery. © 2016 John Wiley & Sons Ltd.

Application of attachment modes in the control of large space structures

NASA Technical Reports Server (NTRS)

Craig, Roy R., Jr.

1989-01-01

Various ways are examined to obtain reduced order mathematical models of structures for use in dynamic response analyses and in controller design studies. Attachment modes are deflection shapes of a structure subjected to specified unit load distributions. Attachment modes are frequently employed to supplement free-interface normal modes to improve the modeling of components (structures) employed in component mode synthesis analyses. Deflection shapes of structures subjected to generalized loads of some specified distribution and of unit magnitude can also be considered to be attachment modes. Several papers which were written under this contract are summarized herein.

Differences in pain, function and coping in Multidimensional Pain Inventory subgroups of chronic back pain: a one-group pretest-posttest study.

PubMed

Verra, Martin L; Angst, Felix; Staal, J Bart; Brioschi, Roberto; Lehmann, Susanne; Aeschlimann, André; de Bie, Rob A

2011-06-30

Patients with non-specific back pain are not a homogeneous group but heterogeneous with regard to their bio-psycho-social impairments. This study examined a sample of 173 highly disabled patients with chronic back pain to find out how the three subgroups based on the Multidimensional Pain Inventory (MPI) differed in their response to an inpatient pain management program. Subgroup classification was conducted by cluster analysis using MPI subscale scores at entry into the program. At program entry and at discharge after four weeks, participants completed the MPI, the MOS Short Form-36 (SF-36), the Hospital Anxiety and Depression Scale (HADS), and the Coping Strategies Questionnaire (CSQ). Pairwise analyses of the score changes of the mentioned outcomes of the three MPI subgroups were performed using the Mann-Whitney-U-test for significance. Cluster analysis identified three MPI subgroups in this highly disabled sample: a dysfunctional, interpersonally distressed and an adaptive copers subgroup. The dysfunctional subgroup (29% of the sample) showed the highest level of depression in SF-36 mental health (33.4 ± 13.9), the interpersonally distressed subgroup (35% of the sample) a modest level of depression (46.8 ± 20.4), and the adaptive copers subgroup (32% of the sample) the lowest level of depression (57.8 ± 19.1). Significant differences in pain reduction and improvement of mental health and coping were observed across the three MPI subgroups, i.e. the effect sizes for MPI pain reduction were: 0.84 (0.44-1.24) for the dysfunctional subgroup, 1.22 (0.86-1.58) for the adaptive copers subgroup, and 0.53 (0.24-0.81) for the interpersonally distressed subgroup (p = 0.006 for pairwise comparison). Significant score changes between subgroups concerning activities and physical functioning could not be identified. MPI subgroup classification showed significant differences in score changes for pain, mental health and coping. These findings underscore the importance of assessing individual differences to understand how patients adjust to chronic back pain.

Going flat: examining heterogeneity in the soda–obesity relationship by subgroup and place of birth among Asian Americans

PubMed Central

Alcalá, Héctor E; Sharif, Mienah Z

2018-01-01

Objective To determine if the association between soda consumption and obesity is uniform among Asian-American population subgroups. Design We conducted multivariate logistic regression analyses on odds of being obese among seven Asian subgroups and by place of birth using data from the 2009 California Health Interview Survey. Setting An omnibus population-based health survey. Subjects Non-institutionalized adults, aged 18 years or over, residing in California (n 36 271). Results Despite low levels of soda consumption in several Asian-American ethnic groups, soda consumption increased the odds of being obese among Chinese, Koreans and Other Asians but not for Whites. Obesity risk varied across Asian subgroups and by place of birth within these subgroups. Conclusions More public health efforts addressing soda consumption in Asian-American communities are needed as a strategy for not only preventing chronic diseases but also disparities, considering the varying levels of soda intake across subgroups. Results support the growing body of literature critiquing acculturation theory in immigrant health research by documenting inconsistent findings by place of birth. Future research should take into account the heterogeneity among Asian Americans to advance our understanding of health outcomes and disparities. PMID:28233506

Going flat: examining heterogeneity in the soda-obesity relationship by subgroup and place of birth among Asian Americans.

PubMed

Alcalá, Héctor E; Sharif, Mienah Z

2017-06-01

To determine if the association between soda consumption and obesity is uniform among Asian-American population subgroups. We conducted multivariate logistic regression analyses on odds of being obese among seven Asian subgroups and by place of birth using data from the 2009 California Health Interview Survey. An omnibus population-based health survey. Non-institutionalized adults, aged 18 years or over, residing in California (n 36 271). Despite low levels of soda consumption in several Asian-American ethnic groups, soda consumption increased the odds of being obese among Chinese, Koreans and Other Asians but not for Whites. Obesity risk varied across Asian subgroups and by place of birth within these subgroups. More public health efforts addressing soda consumption in Asian-American communities are needed as a strategy for not only preventing chronic diseases but also disparities, considering the varying levels of soda intake across subgroups. Results support the growing body of literature critiquing acculturation theory in immigrant health research by documenting inconsistent findings by place of birth. Future research should take into account the heterogeneity among Asian Americans to advance our understanding of health outcomes and disparities.

Improved implementation of the risk-adjusted Bernoulli CUSUM chart to monitor surgical outcome quality.

PubMed

Keefe, Matthew J; Loda, Justin B; Elhabashy, Ahmad E; Woodall, William H

2017-06-01

The traditional implementation of the risk-adjusted Bernoulli cumulative sum (CUSUM) chart for monitoring surgical outcome quality requires waiting a pre-specified period of time after surgery before incorporating patient outcome information. We propose a simple but powerful implementation of the risk-adjusted Bernoulli CUSUM chart that incorporates outcome information as soon as it is available, rather than waiting a pre-specified period of time after surgery. A simulation study is presented that compares the performance of the traditional implementation of the risk-adjusted Bernoulli CUSUM chart to our improved implementation. We show that incorporating patient outcome information as soon as it is available leads to quicker detection of process deterioration. Deterioration of surgical performance could be detected much sooner using our proposed implementation, which could lead to the earlier identification of problems. © The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Symptoms and signs possibly indicating segmental, discogenic pain. A fusion study with 18 years of follow-up.

PubMed

Nyström, Bo; Weber, Henrik; Schillberg, Birgitta; Taube, Adam

2017-07-01

Only two out of the five existing randomized studies have reported better results from fusion surgery for chronic low back pain (CLBP) compared to conservative treatment. In these studies the back symptoms of the patients were described simply as "chronic low back pain". One possible reason for the modest results of surgery is the lack of a description of specified symptoms that might be related to a painful segment/disc, and patient selection may therefore be more or less a matter of chance. Previous prospective studies including facet joint injections and discography and eventually MRI have failed to identify patients with a painful segment/disc that will benefit from fusion surgery. Our purpose was to analyse in detail the pre-operative symptoms and signs presented by patients who showed substantial relief from their back pain following spinal fusion surgery with the aim of possibly finding a pain pattern indicating segmental, discogenic pain. We analysed 40 consecutive patients, mean age 41 years, with a history of disabling low back pain for a mean of 7.7 years. Before surgery the patients completed a detailed questionnaire concerning various aspects of their back pain, and findings at clinical examination were thoroughly noted. Monosegmental posterior lumbar interbody fusion without internal fixation was performed using microsurgical technique. Outcome was assessed at 1, 2 and 4 years after surgery and finally at 18 years, using self-reporting measures and assessment by an independent examiner. Assessment at 18 years applied the Balanced Inventory for Spinal Disorders Questionnaire and the Roland-Morris Disability Questionnaire. According to the independent observer's assessment at two years 27 of the 40 patients were much improved. Analysis of the pre-operative depiction of the back symptoms of this group revealed a rather uniform pattern, the most important being: dominating back pain originating in the midline of the spine, with a dull, aching character and stabbing pain in the same area provoked by sudden movements. Most patients in this group also had diffuse pain radiation of various extension down one or both legs and often bladder dysfunction with frequency. At clinical examination, localized interspinal tenderness was observed within the spinal area in question and the patient's back pain was provoked by pressure in that area and by tapping a neighbouring spinous process. At 18 years after surgery 19 patients assessed themselves as much improved. At that time 5 of them had pension due to age, 7 early pension, one worked full time and six patients part time. Eleven patients were re-operated due to defect bony healing. The results may suggest that the use of a detailed symptom analysis and clinical examination may make it possible to select a subgroup of patients within the CLBP group likely to have better outcome following fusion surgery. The next step would be to execute prospective studies and if our findings concerning back pain details and signs among CLPB patients can be confirmed this can provide for more accurate selection of patients suitable for fusion surgery. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

The influence of baseline severity on efficacy of escitalopram and citalopram in the treatment of major depressive disorder: an extended analysis.

PubMed

Lam, R W; Andersen, H F

2006-09-01

To determine the differences between escitalopram and citalopram in the treatment of patients with major depressive disorder across a range of baseline severity of depression using trend analysis. Data from the three placebo-controlled studies comparing escitalopram to citalopram were analyzed. The pre-specified primary outcome variable was MADRS total score; secondary outcomes included Clinical Global Impression-Severity (CGI-S) and -Improvement (CGI-I) scores. All analyses were based on an intent-to-treat (ITT) population and all direct comparisons were done by ANCOVA adjusting for baseline value and centre. Analyses of the pooled data (N=1203) show that, while the difference between citalopram and placebo was approximately constant across the range of baseline severity, the difference between escitalopram and placebo (p=0.0010 for no trend) and between escitalopram and citalopram (p=0.0012 for no trend) became greater, the more severely depressed the patients were at baseline. A similar pattern was apparent with the CGI-S and CGI-I results. There was a significant superiority of escitalopram over citalopram in response rate (defined as > or = 50% decrease in MADRS total score), and this difference increased with increasing baseline severity. These trend analyses thus indicate that the superiority of escitalopram over citalopram is more apparent as the baseline severity of depression increases.

A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases: A Danish Multidisciplinary Collaboration on Prognostic Factors and Personalised Medicine.

PubMed

Andersen, Vibeke; Holmskov, Uffe; Sørensen, Signe Bek; Jawhara, Mohamad; Andersen, Karina W; Bygum, Anette; Hvid, Lone; Grauslund, Jakob; Wied, Jimmi; Glerup, Henning; Fredberg, Ulrich; Villadsen, Jan Alexander; Kjær, Søren Geill; Fallingborg, Jan; Moghadd, Seyed A G R; Knudsen, Torben; Brodersen, Jacob; Frøjk, Jesper; Dahlerup, Jens F; Nielsen, Ole Haagen; Christensen, Robin; Bojesen, Anders Bo; Sorensen, Grith Lykke; Thiel, Steffen; Færgeman, Nils J; Brandslund, Ivan; Stensballe, Allan; Schmidt, Erik Berg; Franke, Andre; Ellinghaus, David; Rosenstiel, Philip; Raes, Jeroen; Heitmann, Berit; Boye, Mette; Nielsen, Charlotte Lindgaard; Werner, Lars; Kjeldsen, Jens; Ellingsen, Torkell

2017-05-15

Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including lifestyle and treatment response and biological specimens (blood, faeces, urine, and, in IBD patients, intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy. Both hypothesis-driven and data-driven analyses will be performed according to pre-specified protocols including pathway analyses resulting from candidate gene expression analyses and global approaches (e.g., metabolomics, metagenomics, proteomics). The final purpose is to improve the lives of patients suffering from CIDs, by providing tools facilitating treatment selection and dietary recommendations likely to improve the clinical outcome.

A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases: A Danish Multidisciplinary Collaboration on Prognostic Factors and Personalised Medicine

PubMed Central

Andersen, Vibeke; Holmskov, Uffe; Sørensen, Signe Bek; Jawhara, Mohamad; Andersen, Karina W.; Bygum, Anette; Hvid, Lone; Grauslund, Jakob; Wied, Jimmi; Glerup, Henning; Fredberg, Ulrich; Villadsen, Jan Alexander; Kjær, Søren Geill; Fallingborg, Jan; Moghadd, Seyed A. G. R.; Knudsen, Torben; Brodersen, Jacob; Frøjk, Jesper; Dahlerup, Jens F.; Nielsen, Ole Haagen; Christensen, Robin; Bojesen, Anders Bo; Sorensen, Grith Lykke; Thiel, Steffen; Færgeman, Nils J.; Brandslund, Ivan; Stensballe, Allan; Schmidt, Erik Berg; Franke, Andre; Ellinghaus, David; Rosenstiel, Philip; Raes, Jeroen; Heitmann, Berit; Boye, Mette; Nielsen, Charlotte Lindgaard; Werner, Lars; Kjeldsen, Jens; Ellingsen, Torkell

2017-01-01

Chronic inflammatory diseases (CIDs), including Crohn’s disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including lifestyle and treatment response and biological specimens (blood, faeces, urine, and, in IBD patients, intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy. Both hypothesis-driven and data-driven analyses will be performed according to pre-specified protocols including pathway analyses resulting from candidate gene expression analyses and global approaches (e.g., metabolomics, metagenomics, proteomics). The final purpose is to improve the lives of patients suffering from CIDs, by providing tools facilitating treatment selection and dietary recommendations likely to improve the clinical outcome. PMID:28505128

Effectiveness and safety of vedolizumab for treatment of Crohn's disease: a systematic review and meta-analysis.

PubMed

Moćko, Paweł; Kawalec, Paweł; Smela-Lipińska, Beata; Pilc, Andrzej

2016-10-01

The aim of this systematic review (SR) and meta-analysis was to assess the efficacy and safety of vedolizumab in the treatment of Crohn's disease (CD). A systematic literature search was conducted in Medline/PubMed, Embase and Cochrane Library until 25 January, 2015. Included studies were critically appraised according to the PRISMA protocol. Assessment in specified subgroups of CD patients and meta-analysis with Revman software were performed. Two randomized controlled trial (RCTs) were included in a meta-analysis for the induction phase of therapy: GEMINI II and GEMINI III. The clinical response was significantly higher for patients who received vedolizumab compared to placebo in the general population (risk benefit (RB) = 1.48; p = 0.0006) and in both analyzed subgroups: patients with previous failure of anti-TNFs treatment (RB = 1.51; p = 0.006) and patients naive to earlier anti-TNFs (RB = 1.41; p = 0.001). The clinical remission in the general population and subpopulation of TNF-antagonist naive patients was significantly higher for patients who received vedolizumab compared to placebo (RB = 1.77; p = 0.003; RB = 2.29; p = 0.0004; respectively). Meta-analysis for adverse events, serious adverse events (SAEs) and serious infections, revealed that vedolizumab was as safe as placebo in the induction phase of therapy. The clinical response was significantly higher for patients who received vedolizumab in the general population and in both analyzed subgroups of patients. The clinical remission in the general population and subpopulation of TNF-antagonist naive patients was significantly higher for vedolizumab, but no significant differences were revealed in the subgroup of patients with previous TNF antagonist failure.

Methane-metabolizing microbial communities in sediments of the Haima cold seep area, northwest slope of the South China Sea.

PubMed

Niu, Mingyang; Fan, Xibei; Zhuang, Guangchao; Liang, Qianyong; Wang, Fengping

2017-09-01

Cold seeps are widespread chemosynthetic ecosystems in the deep-sea environment, and cold seep microbial communities of the South China Sea are poorly constrained. Here we report on the archaeal communities, particularly those involved in methane metabolization, in sediments of a newly discovered cold seep (named 'Haima') on the northwest slope of the South China Sea. Archaeal diversity, abundance and distribution were investigated in two piston cores collected from a seep area (QDN-14B) and a non-seep control site (QDN-31B). Geochemical investigation of the QDN-14B core identified an estimated sulfate-methane transition zone (Estimated SMTZ) at 300-400 cm below sea floor (cmbsf), where a high abundance of anaerobic methane-oxidizing archaea (ANME) occurred, as revealed by analysis of the 16S rRNA gene and the gene (mcrA) encoding the α-subunit of the key enzyme methyl-coenzyme M reductase. ANME-2a/b was predominant in the upper and middle layers of the estimated SMTZ, whereas ANME-1b outcompeted ANME-2 in the sulfate-depleted bottom layers of the estimated SMTZ and the methanogenic zone. Fine-scale phylogenetic analysis further divided the ANME-1b group into three subgroups with different distribution patterns: ANME-1bI, ANME-1bII and ANME-1bIII. Multivariate analyses indicated that dissolved inorganic carbon and sulfate may be important factors controlling the composition of the methane-metabolizing community. Our study on ANME niche separation and interactions with other archaeal groups improves our understanding of the metabolic diversity and flexibility of ANME, and the findings further suggest that ANME subgroups may have evolved diversified/specified metabolic capabilities other than syntrophic anaerobic oxidation of methane coupled with sulfate reduction in marine sediments. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: A report from the Marfan Treatment Trialists' Collaboration

PubMed Central

Pitcher, Alex; Emberson, Jonathan; Lacro, Ronald V.; Sleeper, Lynn A.; Stylianou, Mario; Mahony, Lynn; Pearson, Gail D.; Groenink, Maarten; Mulder, Barbara J.; Zwinderman, Aeilko H.; De Backer, Julie; De Paepe, Anne M.; Arbustini, Eloisa; Erdem, Guliz; Jin, Xu Yu; Flather, Marcus D.; Mullen, Michael J.; Child, Anne H.; Forteza, Alberto; Evangelista, Arturo; Chiu, Hsin-Hui; Wu, Mei-Hwan; Sandor, George; Bhatt, Ami B.; Creager, Mark A.; Devereux, Richard B.; Loeys, Bart; Forfar, J. Colin; Neubauer, Stefan; Watkins, Hugh; Boileau, Catherine; Jondeau, Guillaume; Dietz, Harry C.; Baigent, Colin

2015-01-01

Rationale A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients with Marfan syndrome. If individual participant data from these trials were to be combined, a meta-analysis of the resulting data, totaling approximately 2,300 patients, would allow estimation across a number of trials of the treatment effects both of ARB therapy and of β-blockade. Such an analysis would also allow estimation of treatment effects in particular subgroups of patients on a range of end points of interest and would allow a more powerful estimate of the effects of these treatments on a composite end point of several clinical outcomes than would be available from any individual trial. Design A prospective, collaborative meta-analysis based on individual patient data from all randomized trials in Marfan syndrome of (i) ARBs versus placebo (or open-label control) and (ii) ARBs versus β-blockers will be performed. A prospective study design, in which the principal hypotheses, trial eligibility criteria, analyses, and methods are specified in advance of the unblinding of the component trials, will help to limit bias owing to data-dependent emphasis on the results of particular trials. The use of individual patient data will allow for analysis of the effects of ARBs in particular patient subgroups and for time-to-event analysis for clinical outcomes. The meta-analysis protocol summarized in this report was written on behalf of the Marfan Treatment Trialists' Collaboration and finalized in late 2012, without foreknowledge of the results of any component trial, and will be made available online (http://www.ctsu.ox.ac.uk/research/meta-trials). PMID:25965707

Sensitivity of cognitive tests in four cognitive domains in discriminating MDD patients from healthy controls: a meta-analysis.

PubMed

Lim, JaeHyoung; Oh, In Kyung; Han, Changsu; Huh, Yu Jeong; Jung, In-Kwa; Patkar, Ashwin A; Steffens, David C; Jang, Bo-Hyoung

2013-09-01

We performed a meta-analysis in order to determine which neuropsychological domains and tasks would be most sensitive for discriminating between patients with major depressive disorder (MDD) and healthy controls. Relevant articles were identified through a literature search of the PubMed and Cochrane Library databases for the period between January 1997 and May 2011. A meta-analysis was conducted using the standardized means of individual cognitive tests in each domain. The heterogeneity was assessed, and subgroup analyses according to age and medication status were performed to explore the sources of heterogeneity. A total of 22 trials involving 955 MDD patients and 7,664 healthy participants were selected for our meta-analysis. MDD patients showed significantly impaired results compared with healthy participants on the Digit Span and Continuous Performance Test in the attention domain; the Trail Making Test A (TMT-A) and the Digit Symbol Test in the processing speed domain; the Stroop Test, the Wisconsin Card Sorting Test, and Verbal Fluency in the executive function domain; and immediate verbal memory in the memory domain. The Finger Tapping Task, TMT-B, delayed verbal memory, and immediate and delayed visual memory failed to separate MDD patients from healthy controls. The results of subgroup analysis showed that performance of Verbal Fluency was significantly impaired in younger depressed patients (<60 years), and immediate visual memory was significantly reduced in depressed patients using antidepressants. Our findings have inevitable limitations arising from methodological issues inherent in the meta-analysis and we could not explain high heterogeneity between studies. Despite such limitations, current study has the strength of being the first meta-analysis which tried to specify cognitive function of depressed patients compared with healthy participants. And our findings may provide clinicians with further evidences that some cognitive tests in specific cognitive domains have sensitivity to discriminate MDD patients from healthy controls.

Subtyping attention-deficit/hyperactivity disorder using temperament dimensions: toward biologically based nosologic criteria

PubMed Central

Karalunas, Sarah L.; Fair, Damien; Musser, Erica D.; Aykes, Kamari; Iyer, Swathi P.; Nigg, Joel T.

2014-01-01

Importance Psychiatric nosology is limited by behavioral and biological heterogeneity within existing disorder categories. The imprecise nature of current nosological distinctions limits both mechanistic understanding and clinical prediction. Here, we demonstrate an approach consistent with the NIMH Research Domain Criteria (RDoC) initiative to identifying superior, neurobiologically-valid subgroups with better predictive capacity than existing psychiatric categories for childhood Attention-Deficit Hyperactivity Disorder (ADHD). Objective Refine subtyping of childhood ADHD by using biologically-based behavioral dimensions (i.e. temperament), novel classification algorithms, and multiple external validators. In doing so, we demonstrate how refined nosology is capable of improving on current predictive capacity of long-term outcomes relative to current DSM-based nosology. Design, Setting, Participants 437 clinically well-characterized, community-recruited children with and without ADHD participated in an on-going longitudinal study. Baseline data were used to classify children into subgroups based on temperament dimensions and to examine external validators including physiological and MRI measures. One-year longitudinal follow-up data are reported for a subgroup of the ADHD sample to address stability and clinical prediction. Main Outcome Measures Parent/guardian ratings of children on a measure of temperament were used as input features in novel community detection analyses to identify subgroups within the sample. Groups were validated using three widely-accepted external validators: peripheral physiology (cardiac measures of respiratory sinus arrhythmia and pre-ejection period), central nervous system functioning (via resting-state functional connectivity MRI), and clinical outcomes (at one-year longitudinal follow-up). Results The community detection algorithm suggested three novel types of ADHD, labeled as “Mild” (normative emotion regulation); “Surgent” (extreme levels of positive approach-motivation); and “Irritable” (extreme levels of negative emotionality, anger, and poor soothability). Types were independent of existing clinical demarcations, including DSM-5 presentations or symptom severity. These types showed stability over time and were distinguished by unique patterns of cardiac physiological response, resting-state functional brain connectivity, and clinical outcome one year later. Conclusions and Relevance Results suggest that a biologically-informed temperament-based typology, developed with a discovery-based community detection algorithm, provided a superior description of heterogeneity in the ADHD population than any current clinical nosology. This demonstration sets the stage for more aggressive attempts at a tractable, biologically-based nosology. PMID:25006969

Association analyses of vitamin D-binding protein gene with compression strength index variation in Caucasian nuclear families

PubMed Central

Xu, X.-H.; Xiong, D.-H.; Liu, X.-G.; Guo, Y.; Chen, Y.; Zhao, J.; Recker, R. R.; Deng, H.-W.

2010-01-01

Summary This study was conducted to test whether there exists an association between vitamin D-binding protein (DBP) gene and compression strength index (CSI) phenotype. Candidate gene association analyses were conducted in total sample, male subgroup, and female subgroup, respectively. Two single-nucleotide polymorphisms (SNPs) with significant association results were found in males, suggesting the importance of DBP gene polymorphisms on the variation in CSI especially in Caucasian males. Introduction CSI of the femoral neck (FN) is a newly developed phenotype integrating information about bone size, body size, and bone mineral density. It is considered to have the potential to improve the performance of risk assessment for hip fractures because it is based on a combination of phenotypic traits influencing hip fractures rather than a single trait. CSI is under moderate genetic determination (with a heritability of ~44% found in this study), but the relevant genetic study is still rather scarce. Methods Based on the known physiological role of DBP in bone biology and the relatively high heritability of CSI, we tested 12 SNPs of the DBP gene for association with CSI variation in 405 Caucasian nuclear families comprising 1,873 subjects from the Midwestern US. Association analyses were performed in the total sample, male and female subgroups, respectively. Results Significant associations with CSI were found with two SNPs (rs222029, P=0.0019; rs222020, P=0.0042) for the male subgroup. Haplotype-based association tests corroborated the single-SNP results. Conclusions Our findings suggest that the DBP gene might be one of the genetic factors influencing CSI phenotype in Caucasians, especially in males. PMID:19543766

Cluster Analysis to Identify Possible Subgroups in Tinnitus Patients.

PubMed

van den Berge, Minke J C; Free, Rolien H; Arnold, Rosemarie; de Kleine, Emile; Hofman, Rutger; van Dijk, J Marc C; van Dijk, Pim

2017-01-01

In tinnitus treatment, there is a tendency to shift from a "one size fits all" to a more individual, patient-tailored approach. Insight in the heterogeneity of the tinnitus spectrum might improve the management of tinnitus patients in terms of choice of treatment and identification of patients with severe mental distress. The goal of this study was to identify subgroups in a large group of tinnitus patients. Data were collected from patients with severe tinnitus complaints visiting our tertiary referral tinnitus care group at the University Medical Center Groningen. Patient-reported and physician-reported variables were collected during their visit to our clinic. Cluster analyses were used to characterize subgroups. For the selection of the right variables to enter in the cluster analysis, two approaches were used: (1) variable reduction with principle component analysis and (2) variable selection based on expert opinion. Various variables of 1,783 tinnitus patients were included in the analyses. Cluster analysis (1) included 976 patients and resulted in a four-cluster solution. The effect of external influences was the most discriminative between the groups, or clusters, of patients. The "silhouette measure" of the cluster outcome was low (0.2), indicating a "no substantial" cluster structure. Cluster analysis (2) included 761 patients and resulted in a three-cluster solution, comparable to the first analysis. Again, a "no substantial" cluster structure was found (0.2). Two cluster analyses on a large database of tinnitus patients revealed that clusters of patients are mostly formed by a different response of external influences on their disease. However, both cluster outcomes based on this dataset showed a poor stability, suggesting that our tinnitus population comprises a continuum rather than a number of clearly defined subgroups.

Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients: Subgroup Meta-analysis

PubMed Central

Chen, Xiao-Han; Kim, Sehee; Zeng, Xiao-Xi; Chen, Zhi-Bing; Cui, Tian-Lei; Hu, Zhang-Xue; Li, Yi; Fu, Ping

2017-01-01

Background: Catheter-based renal denervation (RDN) is a novel treatment for resistant hypertension (RH). A recent meta-analysis reported that RDN did not significantly reduce blood pressure (BP) based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. Methods: This was a meta-analysis of 9 randomized clinical trials (RCTs) among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure (SBP) level, antihypertensive medication change rates, and coronary heart disease (CHD). Results: In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-h SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP ≥155 mmHg (1 mmHg = 0.133 kPa) and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months (P = 0.100 and P = 0.009, respectively). Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months (P < 0.001). Conclusions: In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP. PMID:28639575

Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients: Subgroup Meta-analysis.

PubMed

Chen, Xiao-Han; Kim, Sehee; Zeng, Xiao-Xi; Chen, Zhi-Bing; Cui, Tian-Lei; Hu, Zhang-Xue; Li, Yi; Fu, Ping

2017-07-05

Catheter-based renal denervation (RDN) is a novel treatment for resistant hypertension (RH). A recent meta-analysis reported that RDN did not significantly reduce blood pressure (BP) based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. This was a meta-analysis of 9 randomized clinical trials (RCTs) among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure (SBP) level, antihypertensive medication change rates, and coronary heart disease (CHD). In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-h SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP ≥155 mmHg (1 mmHg = 0.133 kPa) and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months (P = 0.100 and P= 0.009, respectively). Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months (P < 0.001). In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP.

Metabolic differences between short children with GH peak levels in the lower normal range and healthy children of normal height.

PubMed

Tidblad, Anders; Gustafsson, Jan; Marcus, Claude; Ritzén, Martin; Ekström, Klas

2017-06-01

Severe growth hormone deficiency (GHD) leads to several metabolic effects in the body ranging from abnormal body composition to biochemical disturbances. However, less is known regarding these parameters in short children with GH peak levels in the lower normal range during provocation tests. Our aim was to study the metabolic profile of this group and compare it with that of healthy children of normal height. Thirty-five pre-pubertal short children (<-2.5 SDS) aged between 7 and 10years, with peak levels of GH between 7 and 14μg/L in an arginine insulin tolerance test (AITT), were compared with twelve age- and sex-matched children of normal height. The metabolic profile of the subjects was analysed by blood samples, DEXA, frequently sampled intravenous glucose tolerance test, microdialysis and stable isotope examinations of rates of glucose production and lipolysis. There were no overall significant metabolic differences between the groups. However, in the subgroup analysis, the short children with GH peaks <10μg/L had significantly lower fasting insulin levels which also correlated to other metabolic parameters. The short pre-pubertal children with GH peak levels between 7 and 14μg/L did not differ significantly from healthy children of normal height but subpopulations within this group show significant metabolic differences. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results.

PubMed

Motzer, Robert J; Ravaud, Alain; Patard, Jean-Jacques; Pandha, Hardev S; George, Daniel J; Patel, Anup; Chang, Yen-Hwa; Escudier, Bernard; Donskov, Frede; Magheli, Ahmed; Carteni, Giacomo; Laguerre, Brigitte; Tomczak, Piotr; Breza, Jan; Gerletti, Paola; Lechuga, Mariajose; Lin, Xun; Casey, Michelle; Serfass, Lucile; Pantuck, Allan J; Staehler, Michael

2018-01-01

Adjuvant sunitinib significantly improved disease-free survival (DFS) versus placebo in patients with locoregional renal cell carcinoma (RCC) at high risk of recurrence after nephrectomy (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.98; p=0.03). To report the relationship between baseline factors and DFS, pattern of recurrence, and updated overall survival (OS). Data for 615 patients randomized to sunitinib (n=309) or placebo (n=306) in the S-TRAC trial. Subgroup DFS analyses by baseline risk factors were conducted using a Cox proportional hazards model. Baseline risk factors included: modified University of California Los Angeles integrated staging system criteria, age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), weight, neutrophil-to-lymphocyte ratio (NLR), and Fuhrman grade. Of 615 patients, 97 and 122 in the sunitinib and placebo arms developed metastatic disease, with the most common sites of distant recurrence being lung (40 and 49), lymph node (21 and 26), and liver (11 and 14), respectively. A benefit of adjuvant sunitinib over placebo was observed across subgroups, including: higher risk (T3, no or undetermined nodal involvement, Fuhrman grade ≥2, ECOG PS ≥1, T4 and/or nodal involvement; hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.55-0.99; p=0.04), NLR ≤3 (HR 0.72, 95% CI 0.54-0.95; p=0.02), and Fuhrman grade 3/4 (HR 0.73, 95% CI 0.55-0.98; p=0.04). All subgroup analyses were exploratory, and no adjustments for multiplicity were made. Median OS was not reached in either arm (HR 0.92, 95% CI 0.66-1.28; p=0.6); 67 and 74 patients died in the sunitinib and placebo arms, respectively. A benefit of adjuvant sunitinib over placebo was observed across subgroups. The results are consistent with the primary analysis, which showed a benefit for adjuvant sunitinib in patients at high risk of recurrent RCC after nephrectomy. Most subgroups of patients at high risk of recurrent renal cell carcinoma after nephrectomy experienced a clinical benefit with adjuvant sunitinib. ClinicalTrials.gov NCT00375674. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Signal Processing Methods for Liquid Rocket Engine Combustion Stability Assessments

NASA Technical Reports Server (NTRS)

Kenny, R. Jeremy; Lee, Erik; Hulka, James R.; Casiano, Matthew

2011-01-01

The J2X Gas Generator engine design specifications include dynamic, spontaneous, and broadband combustion stability requirements. These requirements are verified empirically based high frequency chamber pressure measurements and analyses. Dynamic stability is determined with the dynamic pressure response due to an artificial perturbation of the combustion chamber pressure (bomb testing), and spontaneous and broadband stability are determined from the dynamic pressure responses during steady operation starting at specified power levels. J2X Workhorse Gas Generator testing included bomb tests with multiple hardware configurations and operating conditions, including a configuration used explicitly for engine verification test series. This work covers signal processing techniques developed at Marshall Space Flight Center (MSFC) to help assess engine design stability requirements. Dynamic stability assessments were performed following both the CPIA 655 guidelines and a MSFC in-house developed statistical-based approach. The statistical approach was developed to better verify when the dynamic pressure amplitudes corresponding to a particular frequency returned back to pre-bomb characteristics. This was accomplished by first determining the statistical characteristics of the pre-bomb dynamic levels. The pre-bomb statistical characterization provided 95% coverage bounds; these bounds were used as a quantitative measure to determine when the post-bomb signal returned to pre-bomb conditions. The time for post-bomb levels to acceptably return to pre-bomb levels was compared to the dominant frequency-dependent time recommended by CPIA 655. Results for multiple test configurations, including stable and unstable configurations, were reviewed. Spontaneous stability was assessed using two processes: 1) characterization of the ratio of the peak response amplitudes to the excited chamber acoustic mode amplitudes and 2) characterization of the variability of the peak response's frequency over the test duration. This characterization process assists in evaluating the discreteness of a signal as well as the stability of the chamber response. Broadband stability was assessed using a running root-mean-square evaluation. These techniques were also employed, in a comparative analysis, on available Fastrac data, and these results are presented here.

Validity of a scale of neighbourhood informal social control relevant to pre-schoolers' physical activity: A cross-sectional study.

PubMed

Cerin, Ester; Suen, Yi Nam; Barnett, Anthony; Huang, Wendy Y J; Mellecker, Robin R

2017-12-01

Childhood physical activity (PA) is important for health across the lifespan. Time pre-schoolers spend outdoors, which has been associated with more PA, is likely influenced by parents' perception of neighbourhood informal social control relevant to pre-schoolers' PA, defined as the willingness of neighbours to intervene to ensure social order and a safe community environment for young children's active play. To advance measurement of this construct, we assessed factorial and construct validities of the PA-related neighbourhood informal social control scale for parents of pre-schoolers (PANISC-PP). In 2013-2014, Hong Kong primary caregivers (n=394) of 3-5 year-old children completed a socio-demographic questionnaire, the preliminary version of the PANISC-PP, and self-report measures of theoretical neighbourhood correlates of PA-related neighbourhood informal social control (perceived signs of physical and social disorder, community cohesion, perceived stranger danger, risk of unintentional injury and traffic safety). The fit of the data to an a priori measurement model of the PANISC-PP was examined using confirmatory factor analyses. As the a priori model showed inadequate fit to the data, the factor structure was re-specified based on theoretical considerations. The final measurement models of the PANISC-PP showed acceptable fit to the data and consisted of three correlated latent factors: "General informal supervision", "Civic engagement for the creation of a better neighbourhood environment" and "Educating and assisting neighbourhood children". The internal reliability of the subscales was good (Cronbach's α values 0.82-0.89). Generalised additive mixed models indicated that all subscales were positively associated with community cohesion and scores on the subscale "Educating and assisting neighbourhood children" were related in the expected direction to all indicators of traffic and personal safety, supporting construct validity of the PANISC-PP. This study suggests that the PANISC-PP is a reliable and valid instrument for assessing parents' perceived neighbourhood informal social control related to pre-schoolers' PA.

Cluster analysis and subgrouping to investigate inter-individual variability to non-invasive brain stimulation: a systematic review.

PubMed

Pellegrini, Michael; Zoghi, Maryam; Jaberzadeh, Shapour

2018-01-12

Cluster analysis and other subgrouping techniques have risen in popularity in recent years in non-invasive brain stimulation research in the attempt to investigate the issue of inter-individual variability - the issue of why some individuals respond, as traditionally expected, to non-invasive brain stimulation protocols and others do not. Cluster analysis and subgrouping techniques have been used to categorise individuals, based on their response patterns, as responder or non-responders. There is, however, a lack of consensus and consistency on the most appropriate technique to use. This systematic review aimed to provide a systematic summary of the cluster analysis and subgrouping techniques used to date and suggest recommendations moving forward. Twenty studies were included that utilised subgrouping techniques, while seven of these additionally utilised cluster analysis techniques. The results of this systematic review appear to indicate that statistical cluster analysis techniques are effective in identifying subgroups of individuals based on response patterns to non-invasive brain stimulation. This systematic review also reports a lack of consensus amongst researchers on the most effective subgrouping technique and the criteria used to determine whether an individual is categorised as a responder or a non-responder. This systematic review provides a step-by-step guide to carrying out statistical cluster analyses and subgrouping techniques to provide a framework for analysis when developing further insights into the contributing factors of inter-individual variability in response to non-invasive brain stimulation.

Identifying and predicting subgroups of information needs among cancer patients: an initial study using latent class analysis.

PubMed

Neumann, Melanie; Wirtz, Markus; Ernstmann, Nicole; Ommen, Oliver; Längler, Alfred; Edelhäuser, Friedrich; Scheffer, Christian; Tauschel, Diethard; Pfaff, Holger

2011-08-01

Understanding how the information needs of cancer patients (CaPts) vary is important because met information needs affect health outcomes and CaPts' satisfaction. The goals of the study were to identify subgroups of CaPts based on self-reported cancer- and treatment-related information needs and to determine whether subgroups could be predicted on the basis of selected sociodemographic, clinical and clinician-patient relationship variables. Three hundred twenty-three CaPts participated in a survey using the "Cancer Patients Information Needs" scale, which is a new tool for measuring cancer-related information needs. The number of information need subgroups and need profiles within each subgroup was identified using latent class analysis (LCA). Multinomial logistic regression was applied to predict class membership. LCA identified a model of five subgroups exhibiting differences in type and extent of CaPts' unmet information needs: a subgroup with "no unmet needs" (31.4% of the sample), two subgroups with "high level of psychosocial unmet information needs" (27.0% and 12.0%), a subgroup with "high level of purely medical unmet information needs" (16.0%) and a subgroup with "high level of medical and psychosocial unmet information needs" (13.6%). An assessment of sociodemographic and clinical characteristics revealed that younger CaPts and CaPts' requiring psychological support seem to belong to subgroups with a higher level of unmet information needs. However, the most significant predictor for the subgroups with unmet information needs is a good clinician-patient relationship, i.e. subjective perception of high level of trust in and caring attention from nurses together with high degree of physician empathy seems to be predictive for inclusion in the subgroup with no unmet information needs. The results of our study can be used by oncology nurses and physicians to increase their awareness of the complexity and heterogeneity of information needs among CaPts and of clinically significant subgroups of CaPts. Moreover, regression analyses indicate the following association: Nurses and physicians seem to be able to reduce CaPts' unmet information needs by establishing a relationship with the patient, which is trusting, caring and empathic.

Safety and efficacy of canagliflozin in Japanese patients with type 2 diabetes mellitus: post hoc subgroup analyses according to body mass index in a 52-week open-label study.

PubMed

Inagaki, Nobuya; Goda, Maki; Yokota, Shoko; Maruyama, Nobuko; Iijima, Hiroaki

2015-01-01

The safety and efficacy of sodium glucose co-transporter 2 inhibitors in non-obese compared with obese patients with type 2 diabetes mellitus is unknown. We conducted post hoc analyses of the results of a 52-week open-label study of Japanese type 2 diabetes mellitus patients treated with 100 or 200 mg canagliflozin. Patients were divided into four subgroups according to their baseline body mass index (BMI): group I, BMI < 22 kg/m(2); group II, BMI ≥ 22 to < 25 kg/m(2); group III, BMI ≥ 25 to < 30 kg/m(2) and group IV, BMI ≥ 30 kg/m(2). The overall safety was similar among the four BMI subgroups, although there were slight differences in terms of the incidences of hypoglycemia, asymptomatic hypoglycemia, female genital infections and proportions of patients with total ketone body levels exceeding 1000 μmol/l at any time for both canagliflozin doses. Hemoglobin A1c, fasting plasma glucose and body weight decreased significantly from baseline to week 52 at both canagliflozin doses. The changes in hemoglobin A1c, and fasting plasma glucose were not significantly different among the four BMI subgroups for either dose. Canagliflozin was tolerated in patients irrespective of their BMI at the start of treatment, although some caution may be needed.

Raltegravir versus Efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses.

PubMed

Lennox, Jeffrey L; Dejesus, Edwin; Berger, Daniel S; Lazzarin, Adriano; Pollard, Richard B; Ramalho Madruga, Jose Valdez; Zhao, Jing; Wan, Hong; Gilbert, Christopher L; Teppler, Hedy; Rodgers, Anthony J; Barnard, Richard J O; Miller, Michael D; Dinubile, Mark J; Nguyen, Bach-Yen; Leavitt, Randi; Sklar, Peter

2010-09-01

We analyzed the 96-week results in the overall population and in prespecified subgroups from the ongoing STARTMRK study of treatment-naive HIV-infected patients. Eligible patients with HIV-1 RNA (vRNA) levels >5000 copies per milliliter and without baseline resistance to efavirenz, tenofovir, or emtricitabine were randomized in a double-blind noninferiority study to receive raltegravir or efavirenz, each combined with tenofovir/emtricitabine. At week 96 counting noncompleters as failures, 81% versus 79% achieved vRNA levels <50 copies per milliliter in the raltegravir and efavirenz groups, respectively [Delta (95% confidence interval) = 2% (-4 to 9), noninferiority P < 0.001]. Mean change in baseline CD4 count was 240 and 225 cells per cubic millimeter in the raltegravir and efavirenz groups, respectively [Delta (95% confidence interval) = 15 (-13 to 42)]. Treatment effects were consistent across prespecified baseline demographic and prognostic subgroups. Fewer drug-related clinical adverse events (47% versus 78%; P < 0.001) occurred in raltegravir than efavirenz recipients. Both regimens had modest effects on serum lipids and glucose levels and on body fat composition. When combined with tenofovir/emtricitabine in treatment-naive patients, raltegravir exhibited durable antiretroviral activity that was noninferior to the efficacy of efavirenz through 96 weeks of therapy. Subgroup analyses were generally consistent with the overall findings. Both regimens were well tolerated.

A new "American" subgroup of African-lineage Chikungunya virus detected in and isolated from mosquitoes collected in Haiti, 2016.

PubMed

White, Sarah Keller; Mavian, Carla; Salemi, Marco; Morris, John Glenn; Elbadry, Maha A; Okech, Bernard A; Lednicky, John A; Dunford, James C

2018-01-01

As part of on-going arboviral surveillance activity in a semi-rural region in Haiti, Chikungunya virus (CHIKV)-positive mosquito pools were identified in 2014 (the peak of the Caribbean Asian-clade epidemic), and again in 2016 by RT-PCR. In 2014, CHIKV was only identified in Aedes aegypti (11 positive pools/124 screened). In contrast, in sampling in 2016, CHIKV was not identified in Ae. aegypti, but, rather, in (a) a female Aedes albopictus pool, and (b) a female Culex quinquefasciatus pool. Genomic sequence analyses indicated that the CHIKV viruses in the 2016 mosquito pools were from the East-Central-South African (ECSA) lineage, rather than the Asian lineage. In phylogenetic studies, these ECSA lineage strains form a new ECSA subgroup (subgroup IIa) together with Brazilian ECSA lineage strains from an isolated human outbreak in 2014, and a mosquito pool in 2016. Additional analyses date the most recent common ancestor of the ECSA IIa subgroup around May 2007, and the 2016 Haitian CHIKV genomes around December 2015. Known CHIKV mutations associated with improved Ae. albopictus vector competence were not identified. Isolation of this newly identified lineage from Ae. albopictus is of concern, as this vector has a broader geographic range than Ae. aegypti, especially in temperate areas of North America, and stresses the importance for continued vector surveillance.

20 CFR 655.1302 - Required pre-filing activity.

Code of Federal Regulations, 2010 CFR

2010-04-01

... as specified in this section. (c) Retention of documentation. An employer filing an Application for... the certification. There is no record retention requirement for any application (and supporting... steps. An employer filing an application must: (1) Submit a job order to the SWA serving the area of...

42 CFR 410.152 - Amounts of payment.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., fair compensation, a pre-treatment prospective payment rate, or a standard overhead amount, or any... formula. (iv) Expenses in excess of the outpatient mental health treatment limitation described in § 410... section.) (b) Basic rules for payment. Except as specified in paragraphs (c) through (h) of this section...

42 CFR 410.152 - Amounts of payment.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., fair compensation, a pre-treatment prospective payment rate, or a standard overhead amount, or any... formula. (iv) Expenses in excess of the outpatient mental health treatment limitation described in § 410... section.) (b) Basic rules for payment. Except as specified in paragraphs (c) through (h) of this section...

42 CFR 410.152 - Amounts of payment.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., fair compensation, a pre-treatment prospective payment rate, or a standard overhead amount, or any... formula. (iv) Expenses in excess of the outpatient mental health treatment limitation described in § 410... section.) (b) Basic rules for payment. Except as specified in paragraphs (c) through (h) of this section...

State-of-Science Approaches to Determine Sensitive Taxa for Water Quality Criteria Derivation

EPA Science Inventory

Current Ambient Water Quality Criteria (AWQC) guidelines specify pre-defined taxa diversity requirements, which has limited chemical-specific criteria development in the U.S. to less than 100 chemicals. A priori knowledge of sensitive taxa to toxicologically similar groups of che...

The acute effects of grape polyphenols supplementation on endothelial function in adults: meta-analyses of controlled trials.

PubMed

Li, Shao-Hua; Tian, Hong-Bo; Zhao, Hong-Jin; Chen, Liang-Hua; Cui, Lian-Qun

2013-01-01

The acute effects of grape polyphenols on endothelial function in adults are inconsistent. Here, we performed meta-analyses to determine these acute effects as measured by flow-mediated dilation (FMD). Trials were searched in PubMed, Embase and the Cochrane Library database. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the PROSPERO register and our registration number is CRD42013004157. Nine studies were included in the present meta-analyses. The results showed that the FMD level was significantly increased in the initial 120 min after intake of grape polyphenols as compared with controls. Meta-regression and subgroup analyses were performed and showed that a health status was the main effect modifier of the significant heterogeneity. Subgroups indicated that intake of grape polyphenols could significantly increase FMD in healthy subjects, and the increased FMD appeared to be more obviously in subjects with high cardiovascular risk factors. Moreover, the peak effect of grape polyphenols on FMD in healthy subjects was found 30 min after ingestion, which was different from the effect in subjects with high cardiovascular risk factors, in whom the peak effect was found 60 min after ingestion. Endothelial function can be significantly improved in healthy adults in the initial 2 h after intake of grape polyphenols. The acute effect of grape polyphenols on endothelial function may be more significant but the peak effect is delayed in subjects with a smoking history or coronary heart disease as compared with the healthy subjects.

The Acute Effects of Grape Polyphenols Supplementation on Endothelial Function in Adults: Meta-Analyses of Controlled Trials

PubMed Central

Li, Shao-Hua; Tian, Hong-Bo; Zhao, Hong-Jin; Chen, Liang-Hua; Cui, Lian-Qun

2013-01-01

Background The acute effects of grape polyphenols on endothelial function in adults are inconsistent. Here, we performed meta-analyses to determine these acute effects as measured by flow-mediated dilation (FMD). Methods Trials were searched in PubMed, Embase and the Cochrane Library database. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the PROSPERO register and our registration number is CRD42013004157. Results Nine studies were included in the present meta-analyses. The results showed that the FMD level was significantly increased in the initial 120 min after intake of grape polyphenols as compared with controls. Meta-regression and subgroup analyses were performed and showed that a health status was the main effect modifier of the significant heterogeneity. Subgroups indicated that intake of grape polyphenols could significantly increase FMD in healthy subjects, and the increased FMD appeared to be more obviously in subjects with high cardiovascular risk factors. Moreover, the peak effect of grape polyphenols on FMD in healthy subjects was found 30 min after ingestion, which was different from the effect in subjects with high cardiovascular risk factors, in whom the peak effect was found 60 min after ingestion. Conclusions Endothelial function can be significantly improved in healthy adults in the initial 2 h after intake of grape polyphenols. The acute effect of grape polyphenols on endothelial function may be more significant but the peak effect is delayed in subjects with a smoking history or coronary heart disease as compared with the healthy subjects. PMID:23894543

SMS text pre-notification and delivery of reminder e-mails to increase response rates to postal questionnaires in the SUSPEND trial: a factorial design, randomised controlled trial.

PubMed

Starr, Kathryn; McPherson, Gladys; Forrest, Mark; Cotton, Seonaidh C

2015-07-08

Patient-reported outcomes are vital in informing randomised controlled trials (RCTs) and health-care interventions and policies from the patient's perspective. However, participant non-response may introduce bias and can affect the generalisability of the trial. This study evaluates two interventions aimed at increasing response rates to postal questionnaires within a large, UK-wide RCT: pre-notification via short messenger service (SMS) text prior to sending the initial mailing of trial questionnaires versus no pre-notification; for non-responders to the initial mailing of the questionnaires, an e-mail reminder (containing a hyperlink to complete the questionnaire online) versus a postal reminder. This study is a 2 × 2 partial factorial design RCT nested within an RCT of medical expulsive therapy for ureteric stone disease. Participants who supplied a mobile telephone number were randomly assigned to receive an SMS text pre-notification of questionnaire delivery or no pre-notification. Those who supplied an e-mail address were randomly assigned to receive a questionnaire reminder by e-mail or post. Participants could be randomly assigned to the pre-notification comparison or the reminder comparison or both. The primary outcome measure was response rate at each questionnaire time point. Four hundred eighteen participants were randomly assigned to the SMS pre-notification comparison (80% were male, and the mean age was 41 years with a standard deviation (SD) of 11.1). The intervention had no effect on response rate at either questionnaire time point. In subgroup analyses, SMS pre-notification increased response rates in women but only at the first questionnaire time point. One hundred nineteen participants were randomly assigned to the reminder comparison (80% were male, and the mean age was 42 years with an SD of 12.1). There was no difference in response rate in those who received an e-mail reminder compared with those who received a postal reminder. SMS text pre-notification of questionnaire delivery and email delivery of questionnaire reminders did not improve response rates. There was some evidence to suggest that SMS text pre-notification may be effective in women, and further studies to investigate this may be warranted. E-mail reminders for participants to return their postal questionnaire could be advantageous given that response rates were similar following either type of reminder and the low cost of delivering an e-mail compared with a postal reminder. This is a substudy of the SUSPEND trial (ISCTRN69423238) (18 Nov. 2010).

Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study

PubMed Central

Miliku, Kozeta; Bauer, Anna; Engel, Stephanie M; Felix, Janine F; Jaddoe, Vincent W V; Lawlor, Debbie A; London, Stephanie J; McGinnis, Ralph; Nystad, Wenche; Page, Christian M; Rivadeneira, Fernando; Stene, Lars C; Tapia, German; Williams, Nicholas; Bonilla, Carolina; Fraser, Abigail

2018-01-01

Abstract Objective To use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia. Design One and two sample mendelian randomisation analyses. Setting Two European pregnancy cohorts (Avon Longitudinal Study of Parents and Children, and Generation R Study), and two case-control studies (subgroup nested within the Norwegian Mother and Child Cohort Study, and the UK Genetics of Pre-eclampsia Study). Participants 7389 women in a one sample mendelian randomisation analysis (751 with gestational hypertension and 135 with pre-eclampsia), and 3388 pre-eclampsia cases and 6059 controls in a two sample mendelian randomisation analysis. Exposures Single nucleotide polymorphisms in genes associated with vitamin D synthesis (rs10741657 and rs12785878) and metabolism (rs6013897 and rs2282679) were used as instrumental variables. Main outcome measures Gestational hypertension and pre-eclampsia defined according to the International Society for the Study of Hypertension in Pregnancy. Results In the conventional multivariable analysis, the relative risk for pre-eclampsia was 1.03 (95% confidence interval 1.00 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, and 2.04 (1.02 to 4.07) for 25-hydroxyvitamin D levels <25 nmol/L compared with ≥75 nmol/L. No association was found for gestational hypertension. The one sample mendelian randomisation analysis using the total genetic risk score as an instrument did not provide strong evidence of a linear effect of 25-hydroxyvitamin D on the risk of gestational hypertension or pre-eclampsia: odds ratio 0.90 (95% confidence interval 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. The two sample mendelian randomisation estimate gave an odds ratio for pre-eclampsia of 0.98 (0.89 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, an odds ratio of 0.96 (0.80 to 1.15) per unit increase in the log(odds) of 25-hydroxyvitamin D level <75 nmol/L, and an odds ratio of 0.93 (0.73 to 1.19) per unit increase in the log(odds) of 25-hydroxyvitamin D levels <50 nmol/L. Conclusions No strong evidence was found to support a causal effect of vitamin D status on gestational hypertension or pre-eclampsia. Future mendelian randomisation studies with a larger number of women with pre-eclampsia or more genetic instruments that would increase the proportion of 25-hydroxyvitamin D levels explained by the instrument are needed. PMID:29925546

Accounting for Subgroup Structure in Line-Transect Abundance Estimates of False Killer Whales (Pseudorca crassidens) in Hawaiian Waters

PubMed Central

Bradford, Amanda L.; Forney, Karin A.; Oleson, Erin M.; Barlow, Jay

2014-01-01

For biological populations that form aggregations (or clusters) of individuals, cluster size is an important parameter in line-transect abundance estimation and should be accurately measured. Cluster size in cetaceans has traditionally been represented as the total number of individuals in a group, but group size may be underestimated if group members are spatially diffuse. Groups of false killer whales (Pseudorca crassidens) can comprise numerous subgroups that are dispersed over tens of kilometers, leading to a spatial mismatch between a detected group and the theoretical framework of line-transect analysis. Three stocks of false killer whales are found within the U.S. Exclusive Economic Zone of the Hawaiian Islands (Hawaiian EEZ): an insular main Hawaiian Islands stock, a pelagic stock, and a Northwestern Hawaiian Islands (NWHI) stock. A ship-based line-transect survey of the Hawaiian EEZ was conducted in the summer and fall of 2010, resulting in six systematic-effort visual sightings of pelagic (n = 5) and NWHI (n = 1) false killer whale groups. The maximum number and spatial extent of subgroups per sighting was 18 subgroups and 35 km, respectively. These sightings were combined with data from similar previous surveys and analyzed within the conventional line-transect estimation framework. The detection function, mean cluster size, and encounter rate were estimated separately to appropriately incorporate data collected using different methods. Unlike previous line-transect analyses of cetaceans, subgroups were treated as the analytical cluster instead of groups because subgroups better conform to the specifications of line-transect theory. Bootstrap values (n = 5,000) of the line-transect parameters were randomly combined to estimate the variance of stock-specific abundance estimates. Hawai’i pelagic and NWHI false killer whales were estimated to number 1,552 (CV = 0.66; 95% CI = 479–5,030) and 552 (CV = 1.09; 95% CI = 97–3,123) individuals, respectively. Subgroup structure is an important factor to consider in line-transect analyses of false killer whales and other species with complex grouping patterns. PMID:24587372

Accounting for subgroup structure in line-transect abundance estimates of false killer whales (Pseudorca crassidens) in Hawaiian waters.

PubMed

Bradford, Amanda L; Forney, Karin A; Oleson, Erin M; Barlow, Jay

2014-01-01

For biological populations that form aggregations (or clusters) of individuals, cluster size is an important parameter in line-transect abundance estimation and should be accurately measured. Cluster size in cetaceans has traditionally been represented as the total number of individuals in a group, but group size may be underestimated if group members are spatially diffuse. Groups of false killer whales (Pseudorca crassidens) can comprise numerous subgroups that are dispersed over tens of kilometers, leading to a spatial mismatch between a detected group and the theoretical framework of line-transect analysis. Three stocks of false killer whales are found within the U.S. Exclusive Economic Zone of the Hawaiian Islands (Hawaiian EEZ): an insular main Hawaiian Islands stock, a pelagic stock, and a Northwestern Hawaiian Islands (NWHI) stock. A ship-based line-transect survey of the Hawaiian EEZ was conducted in the summer and fall of 2010, resulting in six systematic-effort visual sightings of pelagic (n = 5) and NWHI (n = 1) false killer whale groups. The maximum number and spatial extent of subgroups per sighting was 18 subgroups and 35 km, respectively. These sightings were combined with data from similar previous surveys and analyzed within the conventional line-transect estimation framework. The detection function, mean cluster size, and encounter rate were estimated separately to appropriately incorporate data collected using different methods. Unlike previous line-transect analyses of cetaceans, subgroups were treated as the analytical cluster instead of groups because subgroups better conform to the specifications of line-transect theory. Bootstrap values (n = 5,000) of the line-transect parameters were randomly combined to estimate the variance of stock-specific abundance estimates. Hawai'i pelagic and NWHI false killer whales were estimated to number 1,552 (CV = 0.66; 95% CI = 479-5,030) and 552 (CV = 1.09; 95% CI = 97-3,123) individuals, respectively. Subgroup structure is an important factor to consider in line-transect analyses of false killer whales and other species with complex grouping patterns.

Adaptive pre-specification in randomized trials with and without pair-matching.

PubMed

Balzer, Laura B; van der Laan, Mark J; Petersen, Maya L

2016-11-10

In randomized trials, adjustment for measured covariates during the analysis can reduce variance and increase power. To avoid misleading inference, the analysis plan must be pre-specified. However, it is often unclear a priori which baseline covariates (if any) should be adjusted for in the analysis. Consider, for example, the Sustainable East Africa Research in Community Health (SEARCH) trial for HIV prevention and treatment. There are 16 matched pairs of communities and many potential adjustment variables, including region, HIV prevalence, male circumcision coverage, and measures of community-level viral load. In this paper, we propose a rigorous procedure to data-adaptively select the adjustment set, which maximizes the efficiency of the analysis. Specifically, we use cross-validation to select from a pre-specified library the candidate targeted maximum likelihood estimator (TMLE) that minimizes the estimated variance. For further gains in precision, we also propose a collaborative procedure for estimating the known exposure mechanism. Our small sample simulations demonstrate the promise of the methodology to maximize study power, while maintaining nominal confidence interval coverage. We show how our procedure can be tailored to the scientific question (intervention effect for the study sample vs. for the target population) and study design (pair-matched or not). Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in the treatment of advanced pancreatic cancer

PubMed Central

Deplanque, G.; Demarchi, M.; Hebbar, M.; Flynn, P.; Melichar, B.; Atkins, J.; Nowara, E.; Moyé, L.; Piquemal, D.; Ritter, D.; Dubreuil, P.; Mansfield, C. D.; Acin, Y.; Moussy, A.; Hermine, O.; Hammel, P.

2015-01-01

Background Masitinib is a selective oral tyrosine–kinase inhibitor. The efficacy and safety of masitinib combined with gemcitabine was compared against single-agent gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDAC). Patients and methods Patients with inoperable, chemotherapy-naïve, PDAC were randomized (1 : 1) to receive gemcitabine (1000 mg/m2) in combination with either masitinib (9 mg/kg/day) or a placebo. The primary endpoint was overall survival (OS) in the modified intent-to-treat population. Secondary OS analyses aimed to characterize subgroups with poor survival while receiving single-agent gemcitabine with subsequent evaluation of masitinib therapeutic benefit. These prospectively declared subgroups were based on pharmacogenomic data or a baseline characteristic. Results Three hundred and fifty-three patients were randomly assigned to receive either masitinib plus gemcitabine (N = 175) or placebo plus gemcitabine (N = 178). Median OS was similar between treatment-arms for the overall population, at respectively, 7.7 and 7.1 months, with a hazard ratio (HR) of 0.89 (95% CI [0.70; 1.13]. Secondary analyses identified two subgroups having a significantly poor survival rate when receiving single-agent gemcitabine; one defined by an overexpression of acyl–CoA oxidase-1 (ACOX1) in blood, and another via a baseline pain intensity threshold (VAS > 20 mm). These subgroups represent a critical unmet medical need as evidenced from median OS of 5.5 months in patients receiving single-agent gemcitabine, and comprise an estimated 63% of patients. A significant treatment effect was observed in these subgroups for masitinib with median OS of 11.7 months in the ‘ACOX1’ subgroup [HR = 0.23 (0.10; 0.51), P = 0.001], and 8.0 months in the ‘pain’ subgroup [HR = 0.62 (0.43; 0.89), P = 0.012]. Despite an increased toxicity of the combination as compared with single-agent gemcitabine, side-effects remained manageable. Conclusions The present data warrant initiation of a confirmatory study that may support the use of masitinib plus gemcitabine for treatment of PDAC patients with overexpression of ACOX1 or baseline pain (VAS > 20mm). Masitinib's effect in these subgroups is also supported by biological plausibility and evidence of internal clinical validation. Trial Registration ClinicalTrials.gov:NCT00789633. PMID:25858497

Influenza and pneumococcal vaccination rates among Vietnamese, Asian, and non-Hispanic white Americans.

PubMed

Daniels, Nicholas A; Gildengorin, Ginny; Nguyen, Tung T; Liao, Youlian; Luong, Thien-Nhien; McPhee, Stephen J

2010-06-01

Vaccination data for Asian Americans are comparable to those for whites, possibly because they are reported in aggregate rather than for subgroups. We compared influenza and pneumococcal vaccination rates among eligible Asian Americans and white Americans, and for Vietnamese Americans as a subgroup, and assessed factors associated with these vaccinations. Cross-sectional study of data collected from three ethnic groups over 4 years by telephone survey. Data were weighted for selection probability and population estimates and analyzed by multivariate logistic regression. Vietnamese Americans had a higher rate of influenza vaccination (61%) than Asian Americans (45%) and white Americans (52%), and lower rate of pneumococcal vaccination (41%) than Asian Americans (56%), both lower than white Americans (67%). When analyzed as a subgroup, Vietnamese Americans had a higher influenza vaccination rate, but a lower pneumococcal vaccination rate, compared to Asian Americans and white Americans, which may indicate that health behaviors and outcomes can differ widely among Asian subgroups. Analyses of preventive care measures in Asian Americans should focus on subgroups to ensure accuracy and quality of assessments.

Pre-linguistic communication skill development in an infant with a diagnosis of galactosaemia.

PubMed

Lewis, Fiona M; Coman, David J; Kilcoyne, Sarah; Murdoch, Bruce E; Syrmis, Maryanne

2014-10-01

Neonatal screening for galactosaemia (GAL) identifies the condition early, but subsequent biomedical and genetic testing fails to identify which subgroup of infants with GAL are at most risk of the language disorders associated with the condition. This study aims to present preliminary data on an infant with GAL based on assessment of pre-linguistic communication behaviours known to underpin language development. This single case-control study profiles the pre-linguistic skills of a 13-month-old infant with GAL. The Index Infant's performance was descriptively compared to that of a typically developing, suitably matched control infant. The Index Infant was identified as presenting with clinically significant delays on 9 of the 11 pre-linguistic skills assessed. The early identification of risk of developmental language difficulties in the Index Infant allows for the implementation of early intervention using the infant's parents as facilitators of language stimulation. Monitoring of the infant's progress is warranted.

Pre-Travel Medical Preparation of Business and Occupational Travelers

PubMed Central

Khan, Nomana M.; Jentes, Emily S.; Brown, Clive; Han, Pauline; Rao, Sowmya R.; Kozarsky, Phyllis; Hagmann, Stefan H.F.; LaRocque, Regina C.; Ryan, Edward T.

2016-01-01

Objectives: The aim of the study was to understand more about pre-travel preparations and itineraries of business and occupational travelers. Methods: De-identified data from 18 Global TravEpiNet clinics from January 2009 to December 2012 were analyzed. Results: Of 23,534 travelers, 61% were non-occupational and 39% occupational. Business travelers were more likely to be men, had short times to departure and shorter trip durations, and commonly refused influenza, meningococcal, and hepatitis B vaccines. Most business travelers indicated that employers suggested the pre-travel health consultation, whereas non-occupational travelers sought consultations because of travel health concerns. Conclusions: Sub-groups of occupational travelers have characteristic profiles, with business travelers being particularly distinct. Employers play a role in encouraging business travelers to seek pre-travel consultations. Such consultations, even if scheduled immediately before travel, can identify vaccination gaps and increase coverage. PMID:26479857

Pre-Travel Medical Preparation of Business and Occupational Travelers: An Analysis of the Global TravEpiNet Consortium, 2009 to 2012.

PubMed

Khan, Nomana M; Jentes, Emily S; Brown, Clive; Han, Pauline; Rao, Sowmya R; Kozarsky, Phyllis; Hagmann, Stefan H F; LaRocque, Regina C; Ryan, Edward T

2016-01-01

The aim of the study was to understand more about pre-travel preparations and itineraries of business and occupational travelers. De-identified data from 18 Global TravEpiNet clinics from January 2009 to December 2012 were analyzed. Of 23,534 travelers, 61% were non-occupational and 39% occupational. Business travelers were more likely to be men, had short times to departure and shorter trip durations, and commonly refused influenza, meningococcal, and hepatitis B vaccines. Most business travelers indicated that employers suggested the pre-travel health consultation, whereas non-occupational travelers sought consultations because of travel health concerns. Sub-groups of occupational travelers have characteristic profiles, with business travelers being particularly distinct. Employers play a role in encouraging business travelers to seek pre-travel consultations. Such consultations, even if scheduled immediately before travel, can identify vaccination gaps and increase coverage.

40 CFR 91.512 - Request for public hearing.

Code of Federal Regulations, 2010 CFR

2010-07-01

... plans and statistical analyses have been properly applied (specifically, whether sampling procedures and statistical analyses specified in this subpart were followed and whether there exists a basis for... will be made available to the public during Agency business hours. ...

Risk of bias and methodological issues in randomised controlled trials of acupuncture for knee osteoarthritis: a cross-sectional study

PubMed Central

Lee, Andy H; Zhou, Xu; Kang, Deying; Luo, Yanan; Liu, Jiali; Sun, Xin

2018-01-01

Objective To assess risk of bias and to investigate methodological issues concerning the design, conduct and analysis of randomised controlled trials (RCTs) testing acupuncture for knee osteoarthritis (KOA). Methods PubMed, EMBASE, Cochrane Central Register of Controlled Trials and four major Chinese databases were searched for RCTs that investigated the effect of acupuncture for KOA. The Cochrane tool was used to examine the risk of bias of eligible RCTs. Their methodological details were examined using a standardised and pilot-tested questionnaire of 48 items, together with the association between four predefined factors and important methodological quality indicators. Results A total of 248 RCTs were eligible, of which 39 (15.7%) used computer-generated randomisation sequence. Of the 31 (12.5%) trials that stated the allocation concealment, only one used central randomisation. Twenty-five (10.1%) trials mentioned that their acupuncture procedures were standardised, but only 18 (7.3%) specified how the standardisation was achieved. The great majority of trials (n=233, 94%) stated that blinding was in place, but 204 (87.6%) did not clarify who was blinded. Only 27 (10.9%) trials specified the primary outcome, for which 7 used intention-to-treat analysis. Only 17 (6.9%) trials included details on sample size calculation; none preplanned an interim analysis and associated stopping rule. In total, 46 (18.5%) trials explicitly stated that loss to follow-up occurred, but only 6 (2.4%) provided some information to deal with the issue. No trials prespecified, conducted or reported any subgroup or adjusted analysis for the primary outcome. Conclusion The overall risk of bias was high among published RCTs testing acupuncture for KOA. Methodological limitations were present in many important aspects of design, conduct and analyses. These findings inform the development of evidence-based methodological guidance for future trials assessing the effect of acupuncture for KOA. PMID:29511016

Artificial Stroke Clots: How Wide is the Gap to the Real World?

PubMed

Berndt, Maria; Prothmann, Sascha; Maegerlein, Christian; Oberdieck, Paul; Zimmer, Claus; Hegge, Barbara; Pelisek, Jaroslav; Schirmer, Lucas; Poppert, Holger; Boeckh-Behrens, Tobias

2018-02-01

Especially since the establishment of mechanical thrombectomy as part of standard stroke therapy, artificial thrombi have become important in the training of interventionalists as well as for the development and testing of devices. So far, these in vitro clots have lacked direct comparisons with ex vivo thrombi. We therefore compared the histologic appearance of dynamically produced clots with that of stroke thrombi acquired during mechanical recanalization. Thrombi of 145 consecutive patients with stroke with large-vessel occlusions were histologically compared with 10 artificial clots, dynamically created from human blood and pig's blood using a Chandler loop system. Quantified FP/RBC ratios (fibrin/platelets divided by red blood cell fraction) and white blood cell (WBC) fractions were identified and compared between artificial (human and pig) and ex vivo thrombi obtained from patients with various stroke causes. There were no significant differences in the analysis of FP/RBC ratios between artificial thrombi and ex vivo thrombi (P = 0.42) or in the more precise analyses considering etiologic subgroups. Distinct differences were observed for the WBC fraction, with lower values in artificial thrombi (median, 1.34%) than in ex vivo thrombi (median, 5%) (P < 0.001). The main clot components, FP and RBC, are presumably the most influential factors for clot stability and mechanical resistance. Similarities between artificially generated and ex vivo stroke clots (and when considering different stroke subgroups) support the usefulness of these artificial thrombi in the pre-evaluation of thrombus extraction devices and as appropriate training material. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization of skin reactions and pain reported by patients receiving radiation therapy for cancer at different sites.

PubMed

Gewandter, Jennifer S; Walker, Joanna; Heckler, Charles E; Morrow, Gary R; Ryan, Julie L

2013-12-01

Skin reactions and pain are commonly reported side effects of radiation therapy (RT). To characterize RT-induced symptoms according to treatment site subgroups and identify skin symptoms that correlate with pain. A self-report survey-adapted from the MD Anderson Symptom Inventory and the McGill Pain Questionnaire--assessed RT-induced skin problems, pain, and specific skin symptoms. Wilcoxon Sign Ranked tests compared mean severity or pre- and post-RT pain and skin problems within each RT-site subgroup. Multiple linear regression (MLR) investigated associations between skin symptoms and pain. Survey respondents (N = 106) were 58% female and on average 64 years old. RT sites included lung, breast, lower abdomen, head/neck/brain, and upper abdomen. Only patients receiving breast RT reported significant increases in treatment site pain and skin problems (P < or = .007). Patients receiving head/neck/brain RT reported increased skin problems (P < .0009). MLR showed that post-RT skin tenderness and tightness were most strongly associated with post-RT pain (P = .066 and P = .122, respectively). Small sample size, exploratory analyses, and nonvalidated measure. Only patients receiving breast RT reported significant increases in pain and skin problems at the RT site while patients receiving head/neck/brain RT had increased skin problems but not pain. These findings suggest that the severity of skin problems is not the only factor that contributes to pain and that interventions should be tailored to specifically target pain at the RT site, possibly by targeting tenderness and tightness. These findings should be confirmed in a larger sampling of RT patients.

RNA sequencing enables systematic identification of platelet transcriptomic alterations in NSCLC patients.

PubMed

Zhang, Qun; Hu, Huan; Liu, Hongda; Jin, Jiajia; Zhu, Peiyuan; Wang, Shujun; Shen, Kaikai; Hu, Yangbo; Li, Zhou; Zhan, Ping; Zhu, Suhua; Fan, Hang; Zhang, Jianya; Lv, Tangfeng; Song, Yong

2018-05-29

Platelets are implicated as key players in the metastatic dissemination of tumor cells. Previous evidence demonstrated platelets retained cytoplasmic RNAs with physiologically activity, splicing pre-mRNA to mRNA and translating into functional proteins in response to external stimulation. Recently, platelets gene profile of healthy or diseased individuals were characterized with the help of RNA sequencing (RNA-Seq) in some studies, leading to new insights into the mechanisms underlying disease pathogenesis. In this study, we performed RNA-seq in platelets from 7 healthy individuals and 15 non-small cell lung cancer (NSCLC) patients. Our data revealed a subset of near universal differently expressed gene (DEG) profiles in platelets of metastatic NSCLC compared to healthy individuals, including 626 up-regulated RNAs (mRNAs and ncRNAs) and 1497 down-regulated genes. The significant over-expressed genes showed enrichment in focal adhesion, platelets activation, gap junction and adherens junction pathways. The DEGs also included previously reported tumor-related genes such as PDGFR, VEGF, EGF, etc., verifying the consistence and significance of platelet RNA-Seq in oncology study. We also validated several up-regulated DEGs involved in tumor cell-induced platelet aggregation (TCIPA) and tumorigenesis. Additionally, transcriptomic comparison analyses of NSCLC subgroups were conducted. Between non-metastatic and metastatic NSCLC patients, 526 platelet DEGs were identified with the most altered expression. The outcomes from subgroup analysis between lung adenocarcinoma and lung squamous cell carcinoma demonstrated the diagnostic potential of platelet RNA-Seq on distinguishing tumor histological types. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Patch test results with patients' own perfumes, deodorants and shaving lotions: results of the IVDK 1998-2002.

PubMed

Uter, W; Geier, J; Schnuch, A; Frosch, P J

2007-03-01

Assessment of the value of patch testing patients' own perfumes, eau de toilette, deodorants and shaving lotions with regard to diagnosing contact allergy to fragrances, and an analysis of the spectrum of concurrent patch test reactions to single fragrance allergens. Data of the Information Network of Departments of Dermatology (IVDK; http://www.ivdk.org) regarding patch test results with above products brought in by the patient, considered as possible cause of contact dermatitis, were retrospectively analysed. Between 1998 and 2002, 1468 patients were patch tested with 2557 single products (deodorants, n = 1094; eau de toilette, n = 598; perfume, n = 530; and pre- or after-shave, n = 325; remainder not classifiable), mostly 'as is'. Positive reactions were observed in 129 patients (to 191 products). In 58 of these patients, no further patch test reactions to the fragrance mix (FM-I), Myroxylon pereirae resin (balsam of Peru) or 4-(4-hydroxy-4-methyl-pentyl)-3-cyclohexencarboxaldehyde (e.g. Lyral(R)) were found. A strong association between contact sensitivity to the above commercial allergens and positive reactions to products was observed. Some single compounds such as ylang-ylang oil, propolis and especially oak moss absolute are important allergens in the 'perfume-positive' subgroup, but less in a subgroup positive to own deodorants. Patch testing this scope of products, brought in by the patient, can be regarded as a simple, safe and effective method to diagnose clinically relevant contact sensitization - the more so, as the composition of such products is ever-changing, and the sensitivity of established 'screening allergens' is thus insufficient.

An advanced approach to traditional round robin CPU scheduling algorithm to prioritize processes with residual burst time nearest to the specified time quantum

NASA Astrophysics Data System (ADS)

Swaraj Pati, Mythili N.; Korde, Pranav; Dey, Pallav

2017-11-01

The purpose of this paper is to introduce an optimised variant to the round robin scheduling algorithm. Every algorithm works in its own way and has its own merits and demerits. The proposed algorithm overcomes the shortfalls of the existing scheduling algorithms in terms of waiting time, turnaround time, throughput and number of context switches. The algorithm is pre-emptive and works based on the priority of the associated processes. The priority is decided on the basis of the remaining burst time of a particular process, that is; lower the burst time, higher the priority and higher the burst time, lower the priority. To complete the execution, a time quantum is initially specified. In case if the burst time of a particular process is less than 2X of the specified time quantum but more than 1X of the specified time quantum; the process is given high priority and is allowed to execute until it completes entirely and finishes. Such processes do not have to wait for their next burst cycle.

Synthesis of Globulins in Maize Embryos 1

PubMed Central

Kriz, Alan L.; Schwartz, Drew

1986-01-01

The two major components of the globulin fraction in Zea mays embryos are specified by the Prot gene. Pulse-chase analysis of protein synthesis in cultured, immature embryos indicates that the smaller Prot-specific polypeptide, PROT, is derived from the larger polypeptide, PROT'. These experiments also demonstrate that PROT' is derived from a short-lived precursor polypeptide, prePROT'. The primary Prot-specific translation product, as detected by in vitro translation of immature embryo RNA, is of a lower apparent molecular weight than pre-PROT', suggesting the involvement of co- and/or post-translational modification in the production of prePROT'. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:16665136

50 CFR 217.144 - Mitigation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... the entire 30-minute pre-activity monitoring time period in order for the activity to begin. (v) BP... SPECIFIED ACTIVITIES Taking of Marine Mammals Incidental to Operation of Offshore Oil and Gas Facilities in the U.S. Beaufort Sea § 217.144 Mitigation. (a) When conducting the activities identified in § 217.140...

47 CFR 5.313 - Innovation zones.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 1 2014-10-01 2014-10-01 false Innovation zones. 5.313 Section 5.313... Licenses § 5.313 Innovation zones. (a) An innovation zone is a specified geographic location with pre... own motion or in response to a request from the public. Innovation zones will be announced via public...

47 CFR 5.313 - Innovation zones.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 1 2013-10-01 2013-10-01 false Innovation zones. 5.313 Section 5.313... Licenses § 5.313 Innovation zones. (a) An innovation zone is a specified geographic location with pre... own motion or in response to a request from the public. Innovation zones will be announced via public...

29 CFR 4044.12 - Priority category 2 benefits.

Code of Federal Regulations, 2013 CFR

2013-07-01

...-retirement death benefit that returns mandatory employee contributions or, if a participant so elects under... sum of the values of the annuity benefit and the pre-retirement death benefit determined under the... shall be made using the interest rates and factors specified in paragraph (b)(2) of this section. The...

29 CFR 4044.12 - Priority category 2 benefits.

Code of Federal Regulations, 2010 CFR

2010-07-01

...-retirement death benefit that returns mandatory employee contributions or, if a participant so elects under... sum of the values of the annuity benefit and the pre-retirement death benefit determined under the... shall be made using the interest rates and factors specified in paragraph (b)(2) of this section. The...

29 CFR 4044.12 - Priority category 2 benefits.

Code of Federal Regulations, 2014 CFR

2014-07-01

...-retirement death benefit that returns mandatory employee contributions or, if a participant so elects under... sum of the values of the annuity benefit and the pre-retirement death benefit determined under the... shall be made using the interest rates and factors specified in paragraph (b)(2) of this section. The...