Enabling Comprehension of Patient Subgroups and Characteristics in Large Bipartite Networks: Implications for Precision Medicine

PubMed Central

Bhavnani, Suresh K.; Chen, Tianlong; Ayyaswamy, Archana; Visweswaran, Shyam; Bellala, Gowtham; Rohit, Divekar; Kevin E., Bassler

2017-01-01

A primary goal of precision medicine is to identify patient subgroups based on their characteristics (e.g., comorbidities or genes) with the goal of designing more targeted interventions. While network visualization methods such as Fruchterman-Reingold have been used to successfully identify such patient subgroups in small to medium sized data sets, they often fail to reveal comprehensible visual patterns in large and dense networks despite having significant clustering. We therefore developed an algorithm called ExplodeLayout, which exploits the existence of significant clusters in bipartite networks to automatically “explode” a traditional network layout with the goal of separating overlapping clusters, while at the same time preserving key network topological properties that are critical for the comprehension of patient subgroups. We demonstrate the utility of ExplodeLayout by visualizing a large dataset extracted from Medicare consisting of readmitted hip-fracture patients and their comorbidities, demonstrate its statistically significant improvement over a traditional layout algorithm, and discuss how the resulting network visualization enabled clinicians to infer mechanisms precipitating hospital readmission in specific patient subgroups. PMID:28815099

Loss of GPER identifies new targets for therapy among a subgroup of ERα-positive endometrial cancer patients with poor outcome

PubMed Central

Krakstad, C; Trovik, J; Wik, E; Engelsen, I B; Werner, H M J; Birkeland, E; Raeder, M B; Øyan, A M; Stefansson, I M; Kalland, K H; Akslen, L A; Salvesen, H B

2012-01-01

Background: The G protein-coupled oestrogen receptor, GPER, has been suggested as an alternative oestrogen receptor. Our purpose was to investigate the potential of GPER as a prognostic and predictive marker in endometrial carcinoma and to search for new drug candidates to improve treatment of aggressive disease. Materials and method: A total of 767 primary endometrial carcinomas derived from three patient series, including an external dataset, were studied for protein and mRNA expression levels to investigate and validate if GPER loss identifies poor prognosis and new targets for therapy in endometrial carcinoma. Gene expression levels, according to ERα/GPER status, were used to search the connectivity map database for small molecular inhibitors with potential for treatment of metastatic disease for receptor status subgroups. Results: Loss of GPER protein is significantly correlated with low GPER mRNA, high FIGO stage, non-endometrioid histology, high grade, aneuploidy and ERα loss (all P-values ⩽0.05). Loss of GPER among ERα-positive patients identifies a subgroup with poor prognosis that until now has been unrecognised, with reduced 5-year survival from 93% to 76% (P=0.003). Additional loss of GPER from primary to metastatic lesion counterparts further supports that loss of GPER is associated with disease progression. Conclusion: These results support that GPER status adds clinically relevant information to ERα status in endometrial carcinoma and suggest a potential for new inhibitors in the treatment of metastatic endometrial cancers with ERα expression and GPER loss. PMID:22415229

Mining geriatric assessment data for in-patient fall prediction models and high-risk subgroups

PubMed Central

2012-01-01

Background Hospital in-patient falls constitute a prominent problem in terms of costs and consequences. Geriatric institutions are most often affected, and common screening tools cannot predict in-patient falls consistently. Our objectives are to derive comprehensible fall risk classification models from a large data set of geriatric in-patients' assessment data and to evaluate their predictive performance (aim#1), and to identify high-risk subgroups from the data (aim#2). Methods A data set of n = 5,176 single in-patient episodes covering 1.5 years of admissions to a geriatric hospital were extracted from the hospital's data base and matched with fall incident reports (n = 493). A classification tree model was induced using the C4.5 algorithm as well as a logistic regression model, and their predictive performance was evaluated. Furthermore, high-risk subgroups were identified from extracted classification rules with a support of more than 100 instances. Results The classification tree model showed an overall classification accuracy of 66%, with a sensitivity of 55.4%, a specificity of 67.1%, positive and negative predictive values of 15% resp. 93.5%. Five high-risk groups were identified, defined by high age, low Barthel index, cognitive impairment, multi-medication and co-morbidity. Conclusions Our results show that a little more than half of the fallers may be identified correctly by our model, but the positive predictive value is too low to be applicable. Non-fallers, on the other hand, may be sorted out with the model quite well. The high-risk subgroups and the risk factors identified (age, low ADL score, cognitive impairment, institutionalization, polypharmacy and co-morbidity) reflect domain knowledge and may be used to screen certain subgroups of patients with a high risk of falling. Classification models derived from a large data set using data mining methods can compete with current dedicated fall risk screening tools, yet lack diagnostic precision. High

Mining geriatric assessment data for in-patient fall prediction models and high-risk subgroups.

PubMed

Marschollek, Michael; Gövercin, Mehmet; Rust, Stefan; Gietzelt, Matthias; Schulze, Mareike; Wolf, Klaus-Hendrik; Steinhagen-Thiessen, Elisabeth

2012-03-14

Hospital in-patient falls constitute a prominent problem in terms of costs and consequences. Geriatric institutions are most often affected, and common screening tools cannot predict in-patient falls consistently. Our objectives are to derive comprehensible fall risk classification models from a large data set of geriatric in-patients' assessment data and to evaluate their predictive performance (aim#1), and to identify high-risk subgroups from the data (aim#2). A data set of n = 5,176 single in-patient episodes covering 1.5 years of admissions to a geriatric hospital were extracted from the hospital's data base and matched with fall incident reports (n = 493). A classification tree model was induced using the C4.5 algorithm as well as a logistic regression model, and their predictive performance was evaluated. Furthermore, high-risk subgroups were identified from extracted classification rules with a support of more than 100 instances. The classification tree model showed an overall classification accuracy of 66%, with a sensitivity of 55.4%, a specificity of 67.1%, positive and negative predictive values of 15% resp. 93.5%. Five high-risk groups were identified, defined by high age, low Barthel index, cognitive impairment, multi-medication and co-morbidity. Our results show that a little more than half of the fallers may be identified correctly by our model, but the positive predictive value is too low to be applicable. Non-fallers, on the other hand, may be sorted out with the model quite well. The high-risk subgroups and the risk factors identified (age, low ADL score, cognitive impairment, institutionalization, polypharmacy and co-morbidity) reflect domain knowledge and may be used to screen certain subgroups of patients with a high risk of falling. Classification models derived from a large data set using data mining methods can compete with current dedicated fall risk screening tools, yet lack diagnostic precision. High-risk subgroups may be identified

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.

Single-cell quantitative HER2 measurement identifies heterogeneity and distinct subgroups within traditionally defined HER2-positive patients.

PubMed

Onsum, Matthew D; Geretti, Elena; Paragas, Violette; Kudla, Arthur J; Moulis, Sharon P; Luus, Lia; Wickham, Thomas J; McDonagh, Charlotte F; MacBeath, Gavin; Hendriks, Bart S

2013-11-01

Human epidermal growth factor receptor 2 (HER2) is an important biomarker for breast and gastric cancer prognosis and patient treatment decisions. HER2 positivity, as defined by IHC or fluorescent in situ hybridization testing, remains an imprecise predictor of patient response to HER2-targeted therapies. Challenges to correct HER2 assessment and patient stratification include intratumoral heterogeneity, lack of quantitative and/or objective assays, and differences between measuring HER2 amplification at the protein versus gene level. We developed a novel immunofluorescence method for quantitation of HER2 protein expression at the single-cell level on FFPE patient samples. Our assay uses automated image analysis to identify and classify tumor versus non-tumor cells, as well as quantitate the HER2 staining for each tumor cell. The HER2 staining level is converted to HER2 protein expression using a standard cell pellet array stained in parallel with the tissue sample. This approach allows assessment of HER2 expression and heterogeneity within a tissue section at the single-cell level. By using this assay, we identified distinct subgroups of HER2 heterogeneity within traditional definitions of HER2 positivity in both breast and gastric cancers. Quantitative assessment of intratumoral HER2 heterogeneity may offer an opportunity to improve the identification of patients likely to respond to HER2-targeted therapies. The broad applicability of the assay was demonstrated by measuring HER2 expression profiles on multiple tumor types, and on normal and diseased heart tissues. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Subgroups of advanced cancer patients clustered by their symptom profiles: quality-of-life outcomes.

PubMed

Husain, Amna; Myers, Jeff; Selby, Debbie; Thomson, Barbara; Chow, Edward

2011-11-01

Symptom cluster analysis is a new frontier of research in symptom management. This study clustered patients by their symptom profiles to identify subgroups that may be at higher risk for poor quality of life (QOL) and that may, therefore, benefit most from targeted interventions. Longitudinal study of metastatic cancer patients using the Edmonton Symptom Assessment Scale (ESAS). We generated two-, three-, and four-cluster subgroups and examined the relationship of cluster membership with patient outcomes. To address the problem of missing longitudinal data, we developed a novel outcome variable (QualTime) that measures both QOL and time in study. Two hundred and twenty-one patients with a mean Palliative Performance Scale (PPS) of 59.1 were enrolled. The three-cluster model was chosen for further analysis. The low-burden subgroup had all low severity symptom scores. The intermediate subgroup separates from the low-burden group on the "debility" profile of fatigue, drowsiness, appetite, and well-being. The high-burden group separates from the intermediate-burden group on pain, depression, and anxiety. At baseline, PPS (p=0.0003) and cluster membership (p<0.0001) contributed significantly to global QOL. In univariate analysis, cluster membership was related to the longitudinal outcome, QualTime. In a multivariate model, the relationship of PPS to QualTime was still significant (p=0.0002), but subgroup membership was no longer significant (p=0.1009). PPS is a stronger predictor of the longitudinal variable than cluster subgroups; however, cluster subgroups provide a target for clinical interventions that may improve QOL.

Subgroups of haemodialysis patients in relation to fluid intake restrictions: a cluster analytical approach.

PubMed

Lindberg, Magnus; Wikström, Björn; Lindberg, Per

2010-11-01

To determine whether definable subgroups exist in a sample of haemodialysis patients with regard to self-efficacy, attentional style and depressive symptomatology and to compare whether interdialytic weight gain varies between patients in groups with different cognitive profiles. Theory-based research suggests that cognitive factors (e.g. self-efficacy and attentional style) and depressive symptomatology undermine adherence to health protective regimens. Preventing negative outcomes of fluid overload is essential for haemodialysis patients but many patients cannot achieve fluid control, and nursing interventions aimed to help the patients reduce fluid intake are ineffective. Understanding the interaction between cognitive factors and how this is related to adherence outcomes might therefore lead to the development of helpful nursing interventions. Explorative cross-sectional multicentre survey. The sample consisted of 133 haemodialysis patients. Data were collected using structured questionnaires. A brief self-report form and data on interdialytic weight gain was also used. Two-step cluster analysis was used to identify subgroups. One-way analysis of variance (anova) or Pearson's chi-square test was used for comparing subgroups. Three distinct subgroups were found and subsequently labelled: (1) low self-efficacy, (2) distraction and depressive symptoms and (3) high self-efficacy. The subgroups differed in fluid intake, but not in age, dialysis vintage, gender, residual urine output or in receiving any fluid intake advice. Clinically relevant subgroups of haemodialysis patients could be defined by their profiles regarding self-efficacy, attentional style and depressive symptoms. Based on this study, we would encourage clinical practitioners to take into account cognitive profiles while performing their work. This is especially important when a targeted nursing intervention, which aims to encourage and maintain the patient's fluid control, is introduced. © 2010

A Longitudinal Comparison of Systems Used to Identify Subgroups of Learning Disabled Children.

ERIC Educational Resources Information Center

Goldstein, David; Dundon, William D.

This paper addresses the problem of heterogeneity of samples of learning disabled (LD) children by comparing five different systems for identifying homogeneous subgroups in terms of their ability to predict longitudinal reading and mathematics scores. One hundred and sixty LD children served as subjects. Three of the five subgrouping systems were…

Identifying Subgroups of Tinnitus Using Novel Resting State fMRI Biomarkers and Cluster Analysis

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-2-0032 TITLE: Identifying Subgroups of Tinnitus Using Novel Resting State fMRI Biomarkers and Cluster Analysis PRINCIPAL...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Identifying Subgroups of Tinnitus Using Novel Resting State fMRI Biomarkers and Cluster Analysis 5b...Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The subject of the project is FY14 PRMRP Topic Area – Tinnitus . The broad

Identifying Subgroups of Tinnitus Using Novel Resting State fMRI Biomarkers and Cluster Analysis

DTIC Science & Technology

2017-10-13

AWARD NUMBER: W81XWH-15-2-0032 TITLE: Identifying Subgroups of Tinnitus Using Novel Resting State fMRI Biomarkers and Cluster Analysis...TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-15-2-0032 5b. GRANT NUMBER Identifying Subgroups of Tinnitus Using Novel Resting State fMRI...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The subject of the project is FY14 PRMRP Topic Area – Tinnitus . The broad goal is

Serum TK levels in CLL identify Binet stage A patients within biologically defined prognostic subgroups most likely to undergo disease progression.

PubMed

Matthews, Christine; Catherwood, Mark A; Morris, T C M; Kettle, Paul J; Drake, Mary B; Gilmore, William S; Alexander, H Denis

2006-10-01

Serum thymidine kinase (TK) levels have been shown to be correlated with survival in many malignancies, including chronic lymphocytic leukaemia (CLL). This study was designed to investigate associations between TK levels and other prognostic markers, in newly and previously diagnosed Binet stage A patients. Furthermore, the use of serum TK measurement to identify subcategories of disease within those defined by IgV(H) mutational status, gene usage and chromosomal aberrations was investigated. Ninety-one CLL patients were enrolled. Serum TK levels were measured using a radioenzyme assay. IgV(H) mutational status and V(H) gene usage were determined using BIOMED-2 primers and protocol. Recurring chromosomal abnormalities were detected by interphase fluorescent in situ hybridisation (FISH). Flow cytometry and reverse transcriptase polymerase chain reaction (RT-PCR) determined CD38 and Zap-70 expression, respectively. Significantly higher serum TK levels were found in IgV(H) unmutated, compared with IgV(H) mutated, patients (P < 0.001). Elevated TK levels were also found in patients with CD38 and Zap-70 positivity (P = 0.004, P < 0.001, respectively), short lymphocyte doubling time (LDT) (P = 0.044) and poor or intermediate prognosis chromosomal aberrations (P < 0.001). A TK level of >8.5 U/L best identified patients with progressive disease. Elevated TK levels could identify patients categorised, at diagnosis, into good prognosis subgroups by the various biological markers (mutated IgV(H), good prognosis chromosomal aberrations, Zap-70(-) and CD38(-)) who subsequently showed disease progression. Additionally, patients with V(H)3-21 gene usage showed high TK levels, irrespective of mutational status, and serum TK measurement retained predictive power as disease progressed in all subcategories studied.

Manual therapy in osteoarthritis of the hip: outcome in subgroups of patients.

PubMed

Hoeksma, H L; Dekker, J; Ronday, H K; Breedveld, F C; Van den Ende, C H M

2005-04-01

To investigate whether manual therapy has particular benefit in subgroups of patients defined on the basis of hip function, range of joint motion, pain and radiological deterioration. The study was performed in the out-patient clinic of physical therapy of a large hospital. Data on 109 patients with OA of the hip (clinical ACR criteria) participating in a randomized clinical trial on the effects of manual therapy were used. The outcomes for hip function (Harris hip score), range of joint motion (ROM) and pain (VAS) were compared for specific subgroups. Subgroups were assigned by the median split method. The interaction effect between subgroup and treatment was tested using multiple regression analysis. No differences were observed in the effect of manual therapy in specific subgroups of patients defined on the basis of baseline levels of hip function, pain and ROM. On the basis of radiological grading of osteoarthritis (OA), we found that patients with severe radiological grading of OA had significantly worse outcome on ROM as a result of manual therapy than patients with mild or moderate radiological grading of OA. A significant interaction effect was found for only 1 out of 12 hypotheses investigated. Therefore, we conclude that there is no evidence for the particular benefit of manual therapy in subgroups of patients.

Somatosensory profiles in subgroups of patients with myogenic temporomandibular disorders and Fibromyalgia Syndrome.

PubMed

Pfau, Doreen B; Rolke, Roman; Nickel, Ralf; Treede, Rolf-Detlef; Daublaender, Monika

2009-12-15

Some patients with myofascial pain from temporomandibular disorders (TMD) report pain in extra-trigeminal body regions. Our aim was to distinguish TMD as regional musculoskeletal pain syndrome (n=23) from a widespread pain syndrome (FMS; n=18) based on patients' tender point scores, pain drawings and quantitative sensory testing (QST) profiles. Referenced to 18 age- and gender-matched healthy subjects significant group differences for cold, pressure and pinprick pain thresholds, suprathreshold pinprick sensitivity and mechanical detection thresholds were found. Pain sensitivity in TMD patients ranged between those of FMS patients and healthy controls. The group of TMD patients was inhomogeneous with respect to their tender point count with an insensitive group (n=12) resembling healthy controls and a sensitive TMD group (n=9) resembling FMS patients. Nevertheless sensitive TMD patients did not fulfil diagnostic criteria for FMS in regard to widespread pain as shown by their pain drawings. TMD subgroups did not differ with respect to psychological parameters. The sensitive subgroup was more sensitive compared to healthy controls and to insensitive TMD patients in regard to their QST profile over all test areas as well as to their tenderness over orofacial muscles and trigeminal foramina. However, sensitive TMD patients had a short pain duration arguing against a transition from TMD to FMS over time. Data rather suggest an overlap in pathophysiology with FMS, e.g. a disturbance of central pain processing, in this subgroup of TMD patients. Those patients could be identified on the basis of their tender point count as an easy practicable screening tool.

Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

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

Jakobi, Annika, E-mail: Annika.Jakobi@OncoRay.de; Bandurska-Luque, Anna; Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden

Purpose: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. Methods and Materials: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based onmore » primary tumor location. Results: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. Conclusions: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons.« less

Sub-grouping patients with non-specific low back pain based on cluster analysis of discriminatory clinical items.

PubMed

Billis, Evdokia; McCarthy, Christopher J; Roberts, Chris; Gliatis, John; Papandreou, Maria; Gioftsos, George; Oldham, Jacqueline A

2013-02-01

To identify potential subgroups amongst patients with non-specific low back pain based on a consensus list of potentially discriminatory examination items. Exploratory study. A convenience sample of 106 patients with non-specific low back pain (43 males, 63 females, mean age 36 years, standard deviation 15.9 years) and 7 physiotherapists. Based on 3 focus groups and a two-round Delphi involving 23 health professionals and a random stratified sample of 150 physiotherapists, respectively, a comprehensive examination list comprising the most "discriminatory" items was compiled. Following reliability analysis, the most reliable clinical items were assessed with a sample of patients with non-specific low back pain. K-means cluster analysis was conducted for 2-, 3- and 4-cluster options to explore for meaningful homogenous subgroups. The most clinically meaningful cluster was a two-subgroup option, comprising a small group (n = 24) with more severe clinical presentation (i.e. more widespread pain, functional and sleeping problems, other symptoms, increased investigations undertaken, more severe clinical signs, etc.) and a larger less dysfunctional group (n = 80). A number of potentially discriminatory clinical items were identified by health professionals and sub-classified, based on a sample of patients with non-specific low back pain, into two subgroups. However, further work is needed to validate this classification process.

Subgrouping Automata: automatic sequence subgrouping using phylogenetic tree-based optimum subgrouping algorithm.

PubMed

Seo, Joo-Hyun; Park, Jihyang; Kim, Eun-Mi; Kim, Juhan; Joo, Keehyoung; Lee, Jooyoung; Kim, Byung-Gee

2014-02-01

Sequence subgrouping for a given sequence set can enable various informative tasks such as the functional discrimination of sequence subsets and the functional inference of unknown sequences. Because an identity threshold for sequence subgrouping may vary according to the given sequence set, it is highly desirable to construct a robust subgrouping algorithm which automatically identifies an optimal identity threshold and generates subgroups for a given sequence set. To meet this end, an automatic sequence subgrouping method, named 'Subgrouping Automata' was constructed. Firstly, tree analysis module analyzes the structure of tree and calculates the all possible subgroups in each node. Sequence similarity analysis module calculates average sequence similarity for all subgroups in each node. Representative sequence generation module finds a representative sequence using profile analysis and self-scoring for each subgroup. For all nodes, average sequence similarities are calculated and 'Subgrouping Automata' searches a node showing statistically maximum sequence similarity increase using Student's t-value. A node showing the maximum t-value, which gives the most significant differences in average sequence similarity between two adjacent nodes, is determined as an optimum subgrouping node in the phylogenetic tree. Further analysis showed that the optimum subgrouping node from SA prevents under-subgrouping and over-subgrouping. Copyright © 2013. Published by Elsevier Ltd.

The medical genetics workforce: an analysis of clinical geneticist subgroups.

PubMed

Cooksey, Judith A; Forte, Gaetano; Flanagan, Patricia A; Benkendorf, Judith; Blitzer, Miriam G

2006-10-01

Clinical geneticists with a Doctor of Medicine degree face challenges to meet the growing population demand for genetic services. This study was designed to assist the profession with workforce planning by identifying clinically relevant subgroups of geneticists and describing their professional characteristics and clinical practices. Geneticists' patient care productivity is compared across subgroups and other medical specialists. Part of a comprehensive national study of genetic services and the health workforce, this study uses data from a 2003 survey of geneticists certified by the American Board of Medical Genetics. This study includes 610 clinical geneticists who spend at least 5% of their time in direct patient-care services. An iterative approach was used to identify five subgroups based on the types of new patients seen. We conducted a descriptive analysis of subgroups by demographic, training, professional, and practice characteristics. The subgroups include general (36%), pediatric (28%), reproductive (15%), metabolic (14%), and adult (7%) geneticists. Clinically relevant variations across subgroups were noted in training, professional, and practice parameters. Subgroups vary across patient care hours (median, 15-33 hours/week) and total weekly work hours (52-60 hours). New patient visits (mean, 222-900/year) are higher than follow-up patient visits (mean, 155-405) for all subgroups except metabolic geneticists. Although many geneticists practice as generalist geneticists, this study provides an evidence base for distinguishing clinically relevant subgroups of geneticists. Geneticists provide similar numbers of new patient visits and far fewer follow-up visits than other medical specialists. These findings are relevant to geneticist workforce planning.

Patterns of Warfarin Use in Subgroups of Patients with Atrial Fibrillation: A Cross-Sectional Analysis of 430 General Practices in the United Kingdom

PubMed Central

Mohammed, Mohammed A.; Marshall, Tom; Nirantharakumar, Krishnarajah; Stevens, Andrew; Fitzmaurice, David

2013-01-01

Background Despite the proven efficacy of warfarin, its use in patients with Atrial Fibrillation (AF) is reportedly low. We investigated the underuse and overuse of warfarin in the management of AF in general practices in the United Kingdom (UK) against the National Institute of Clinical Excellence (NICE, UK) guidelines whilst seeking to identify subgroups of AF patients to inform efforts to optimise warfarin use. Methodology A retrospective database analysis to determine warfarin prescribing using tree models based on 50361 patients with AF (classified as low, moderate and high risk of stroke using CHADS2) from 430 general practices in the UK. Results Over one-third (37.0%, 4573/12351) of low risk AF patients were on warfarin, compared with 47.1% (8349/17709) moderate risk AF patients and 54.9% (11142/20301) high risk AF patients. Clinical subgroups (n = 15 low risk subgroups, n = 15 medium risk subgroups, n = 22 high risk subgroups) were identified. Several factors not supported by current guidelines (age, BMI, dementia, gender) were associated with the use of warfarin. Gender and BMI were associated with warfarin use in low and medium risk AF patients but not in high risk AF patients. Conclusion Whilst NICE guidelines suggest that all high risk AF patients should be on warfarin, half of those at moderate risk should be on warfarin and none of those at low risk should be on warfarin, we found evidence of over and under use of warfarin. Interventions to optimise warfarin therapy tailored to and targeting specific subgroups of AF patients identified by the tree models are required. PMID:23658703

Identification of subgroups of patients with tension type headache with higher widespread pressure pain hyperalgesia.

PubMed

Fernández-de-Las-Peñas, César; Benito-González, Elena; Palacios-Ceña, María; Wang, Kelun; Castaldo, Matteo; Arendt-Nielsen, Lars

2017-12-01

Identification of subgroups of patients with different levels of sensitization and clinical features can help to identify groups at risk and the development of better therapeutic strategies. The aim of this study was to identify subgroups of patients with tension type headache (TTH) with different levels of sensitization, clinical pain features, and psychological outcomes. A total of 197 individuals with TTH participated. Headache intensity, frequency, and duration and medication intake were collected with a 4-weeks diary. Pressure pain thresholds were assessed bilaterally over the temporalis muscle, C5-C6 joint, second metacarpal and tibialis anterior muscle to determine widespread pressure pain hyperalgesia. The Hospital Anxiety and Depression Scale assessed anxiety and depression. The State-Trait Anxiety Inventory evaluated the state and trait levels of anxiety. The Headache Disability Inventory evaluated the burden of headache. Health-related quality of life was determined with the SF-36 questionnaire. Groups were considered as positive (three or more criteria) or negative (less than three criteria) on a clinical prediction rule: headache duration <8.5 h/day; headache frequency <5.5 days/week; bodily pain <47 and vitality <47.5. The ANCOVA revealed that subjects in group 1 (positive rule, n = 89) exhibited longer headache history, shorter headache duration, lower headache frequency, higher widespread pressure hyperalgesia, higher anxiety trait levels, and lower quality of life (all, P < 0.01) than those subjects within group 2 (negative rule, n = 108). Differences were similar between men and women. This study identified a subgroup of patients with TTH with higher sensitization, higher chronicity of headaches and worse quality of life but lower frequency and duration of headache episodes. This subgroup of individuals with TTH may need particular attention and specific therapeutic programs for avoiding potential chronification.

Type 2 Diabetes: Identifying High Risk Asian American Subgroups in a Clinical Population

PubMed Central

Wang, Elsie J.; Wong, Eric C.; Dixit, Anjali A.; Fortmann, Stephen P.; Linde, Randolph B.; Palaniappan, Latha P.

2011-01-01

Aims We compared the prevalence and treatment of type 2 diabetes across Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and Non-Hispanic Whites (NHWs) in a Northern California healthcare system. Methods A three-year, cross-sectional sample of patient electronic health records was accessed to compare diabetes prevalence in 21,816 Asian and 73,728 NHWs aged 35+ years. Diabetes was classified through ICD-9 codes, abnormal laboratory values, or use of oral anti-diabetic medication. Multivariate adjusted prevalence rates for each Asian subgroup, and adjusted odds ratios (OR) relative to NHWs, were compared. Results Age-adjusted prevalence ranged from 5.8%-18.2% (women) and 8.1%-25.3% (men). Age-adjusted ORs of Asian subgroups ranged 1.11-3.94 (women) and 1.14-4.56 (men). The odds of diabetes were significantly higher in Asian Indians (women OR 3.44, men OR 3.54) and Filipinos (women OR 3.94, men OR 4.56), compared to NHWs. Results for Asian Indians and Filipinos were similar with age-and-BMI adjustment. Treatment rates across subgroups were 59.7-82.0% (women) and 62.9-79.4% (men). Conclusions Heterogeneity exists in the prevalence of diabetes across Asian subgroups, independent of obesity prevalence. Asian Indian and Filipino subgroups had particularly high prevalence of diabetes when compared to NHWs. Future studies should explore these clinically important differences among Asian subgroups. PMID:21665315

Type 2 diabetes: identifying high risk Asian American subgroups in a clinical population.

PubMed

Wang, Elsie J; Wong, Eric C; Dixit, Anjali A; Fortmann, Stephen P; Linde, Randolph B; Palaniappan, Latha P

2011-08-01

We compared the prevalence and treatment of type 2 diabetes across Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and Non-Hispanic Whites (NHWs) in a Northern California healthcare system. A three-year, cross-sectional sample of patient electronic health records was accessed to compare diabetes prevalence in 21,816 Asian and 73,728 NHWs aged 35+ years. Diabetes was classified through ICD-9 codes, abnormal laboratory values, or use of oral anti-diabetic medication. Multivariate adjusted prevalence rates for each Asian subgroup, and adjusted odds ratios (OR) relative to NHWs, were compared. Age-adjusted prevalence ranged from 5.8% to 18.2% (women) and 8.1 to 25.3% (men). Age-adjusted ORs of Asian subgroups ranged 1.11-3.94 (women) and 1.14-4.56 (men). The odds of diabetes were significantly higher in Asian Indians (women OR 3.44, men OR 3.54) and Filipinos (women OR 3.94, men OR 4.56), compared to NHWs. Results for Asian Indians and Filipinos were similar with age-and-BMI adjustment. Treatment rates across subgroups were 59.7-82.0% (women) and 62.9-79.4% (men). Heterogeneity exists in the prevalence of diabetes across Asian subgroups, independent of obesity prevalence. Asian Indian and Filipino subgroups had particularly high prevalence of diabetes when compared to NHWs. Future studies should explore these clinically important differences among Asian subgroups. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Subgroups of musculoskeletal pain patients and their psychobiological patterns - the LOGIN study protocol.

PubMed

Gerhardt, Andreas; Hartmann, Mechthild; Tesarz, Jonas; Janke, Susanne; Leisner, Sabine; Seidler, Günter; Eich, Wolfgang

2012-08-03

Pain conditions of the musculoskeletal system are very common and have tremendous socioeconomic impact. Despite its high prevalence, musculoskeletal pain remains poorly understood and predominantly non-specifically and insufficiently treated.The group of chronic musculoskeletal pain patients is supposed to be heterogeneous, due to a multitude of mechanisms involved in chronic pain. Psychological variables, psychophysiological processes, and neuroendocrine alterations are expected to be involved. Thus far, studies on musculoskeletal pain have predominantly focused on the general aspects of pain processing, thus neglecting the heterogeneity of patients with musculoskeletal pain. Consequently, there is a need for studies that comprise a multitude of mechanisms that are potentially involved in the chronicity and spread of pain. This need might foster research and facilitate a better pathophysiological understanding of the condition, thereby promoting the development of specific mechanism-based treatments for chronic pain. Therefore, the objectives of this study are as follows: 1) identify and describe subgroups of patients with musculoskeletal pain with regard to clinical manifestations (including mental co-morbidity) and 2) investigate whether distinct sensory profiles or 3) distinct plasma levels of pain-related parameters due to different underlying mechanisms can be distinguished in various subgroups of pain patients. We will examine a population-based chronic pain sample (n = 100), a clinical tertiary care sample (n = 100) and pain-free patients with depression or post-traumatic stress disorder and pain-free healthy controls (each n = 30, respectively). The samples will be pain localisation matched by sex and age to the population-based sample. Patients will undergo physical examination and thorough assessments of mental co-morbidity (including psychological trauma), perceptual and central sensitisation (quantitative sensory testing), descending

A 6-gene signature identifies four molecular subgroups of neuroblastoma

PubMed Central

2011-01-01

Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p < 0.05, one-way ANOVA test). PCA clusters p1, p2, and p3 were found to correspond well to the postulated subtypes 1, 2A, and 2B, respectively. Remarkably, a fourth novel cluster was detected in all three independent data sets. This cluster comprised mainly 11q-deleted MNA-negative tumours with low expression of ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and/or dead of disease, p < 0.05, Fisher's exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group's specific characteristics. PMID:21492432

Intertumoral Heterogeneity within Medulloblastoma Subgroups.

PubMed

Cavalli, Florence M G; Remke, Marc; Rampasek, Ladislav; Peacock, John; Shih, David J H; Luu, Betty; Garzia, Livia; Torchia, Jonathon; Nor, Carolina; Morrissy, A Sorana; Agnihotri, Sameer; Thompson, Yuan Yao; Kuzan-Fischer, Claudia M; Farooq, Hamza; Isaev, Keren; Daniels, Craig; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Lee, Ji Yeoun; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Vasiljevic, Alexandre; Faure-Conter, Cecile; Jouvet, Anne; Giannini, Caterina; Nageswara Rao, Amulya A; Li, Kay Ka Wai; Ng, Ho-Keung; Eberhart, Charles G; Pollack, Ian F; Hamilton, Ronald L; Gillespie, G Yancey; Olson, James M; Leary, Sarah; Weiss, William A; Lach, Boleslaw; Chambless, Lola B; Thompson, Reid C; Cooper, Michael K; Vibhakar, Rajeev; Hauser, Peter; van Veelen, Marie-Lise C; Kros, Johan M; French, Pim J; Ra, Young Shin; Kumabe, Toshihiro; López-Aguilar, Enrique; Zitterbart, Karel; Sterba, Jaroslav; Finocchiaro, Gaetano; Massimino, Maura; Van Meir, Erwin G; Osuka, Satoru; Shofuda, Tomoko; Klekner, Almos; Zollo, Massimo; Leonard, Jeffrey R; Rubin, Joshua B; Jabado, Nada; Albrecht, Steffen; Mora, Jaume; Van Meter, Timothy E; Jung, Shin; Moore, Andrew S; Hallahan, Andrew R; Chan, Jennifer A; Tirapelli, Daniela P C; Carlotti, Carlos G; Fouladi, Maryam; Pimentel, José; Faria, Claudia C; Saad, Ali G; Massimi, Luca; Liau, Linda M; Wheeler, Helen; Nakamura, Hideo; Elbabaa, Samer K; Perezpeña-Diazconti, Mario; Chico Ponce de León, Fernando; Robinson, Shenandoah; Zapotocky, Michal; Lassaletta, Alvaro; Huang, Annie; Hawkins, Cynthia E; Tabori, Uri; Bouffet, Eric; Bartels, Ute; Dirks, Peter B; Rutka, James T; Bader, Gary D; Reimand, Jüri; Goldenberg, Anna; Ramaswamy, Vijay; Taylor, Michael D

2017-06-12

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular Classification of Grade 3 Endometrioid Endometrial Cancers Identifies Distinct Prognostic Subgroups.

PubMed

Bosse, Tjalling; Nout, Remi A; McAlpine, Jessica N; McConechy, Melissa K; Britton, Heidi; Hussein, Yaser R; Gonzalez, Carlene; Ganesan, Raji; Steele, Jane C; Harrison, Beth T; Oliva, Esther; Vidal, August; Matias-Guiu, Xavier; Abu-Rustum, Nadeem R; Levine, Douglas A; Gilks, C Blake; Soslow, Robert A

2018-05-01

Our aim was to investigate whether molecular classification can be used to refine prognosis in grade 3 endometrial endometrioid carcinomas (EECs). Grade 3 EECs were classified into 4 subgroups: p53 abnormal, based on mutant-like immunostaining (p53abn); MMR deficient, based on loss of mismatch repair protein expression (MMRd); presence of POLE exonuclease domain hotspot mutation (POLE); no specific molecular profile (NSMP), in which none of these aberrations were present. Overall survival (OS) and recurrence-free survival (RFS) rates were compared using the Kaplan-Meier method (Log-rank test) and univariable and multivariable Cox proportional hazard models. In total, 381 patients were included. The median age was 66 years (range, 33 to 96 y). Federation Internationale de Gynecologie et d'Obstetrique stages (2009) were as follows: IA, 171 (44.9%); IB, 120 (31.5%); II, 24 (6.3%); III, 50 (13.1%); IV, 11 (2.9%). There were 49 (12.9%) POLE, 79 (20.7%) p53abn, 115 (30.2%) NSMP, and 138 (36.2%) MMRd tumors. Median follow-up of patients was 6.1 years (range, 0.2 to 17.0 y). Compared to patients with NSMP, patients with POLE mutant grade 3 EEC (OS: hazard ratio [HR], 0.36 [95% confidence interval, 0.18-0.70]; P=0.003; RFS: HR, 0.17 [0.05-0.54]; P=0.003) had a significantly better prognosis; patients with p53abn tumors had a significantly worse RFS (HR, 1.73 [1.09-2.74]; P=0.021); patients with MMRd tumors showed a trend toward better RFS. Estimated 5-year OS rates were as follows: POLE 89%, MMRd 75%, NSMP 69%, p53abn 55% (Log rank P=0.001). Five-year RFS rates were as follows: POLE 96%, MMRd 77%, NSMP 64%, p53abn 47% (P=0.000001), respectively. In a multivariable Cox model that included age and Federation Internationale de Gynecologie et d'Obstetrique stage, POLE and MMRd status remained independent prognostic factors for better RFS; p53 status was an independent prognostic factor for worse RFS. Molecular classification of grade 3 EECs reveals that these tumors are a

Identifying and Assessing Interesting Subgroups in a Heterogeneous Population.

PubMed

Lee, Woojoo; Alexeyenko, Andrey; Pernemalm, Maria; Guegan, Justine; Dessen, Philippe; Lazar, Vladimir; Lehtiö, Janne; Pawitan, Yudi

2015-01-01

Biological heterogeneity is common in many diseases and it is often the reason for therapeutic failures. Thus, there is great interest in classifying a disease into subtypes that have clinical significance in terms of prognosis or therapy response. One of the most popular methods to uncover unrecognized subtypes is cluster analysis. However, classical clustering methods such as k-means clustering or hierarchical clustering are not guaranteed to produce clinically interesting subtypes. This could be because the main statistical variability--the basis of cluster generation--is dominated by genes not associated with the clinical phenotype of interest. Furthermore, a strong prognostic factor might be relevant for a certain subgroup but not for the whole population; thus an analysis of the whole sample may not reveal this prognostic factor. To address these problems we investigate methods to identify and assess clinically interesting subgroups in a heterogeneous population. The identification step uses a clustering algorithm and to assess significance we use a false discovery rate- (FDR-) based measure. Under the heterogeneity condition the standard FDR estimate is shown to overestimate the true FDR value, but this is remedied by an improved FDR estimation procedure. As illustrations, two real data examples from gene expression studies of lung cancer are provided.

Identifying and Assessing Interesting Subgroups in a Heterogeneous Population

PubMed Central

Lee, Woojoo; Alexeyenko, Andrey; Pernemalm, Maria; Guegan, Justine; Dessen, Philippe; Lazar, Vladimir; Lehtiö, Janne; Pawitan, Yudi

2015-01-01

Biological heterogeneity is common in many diseases and it is often the reason for therapeutic failures. Thus, there is great interest in classifying a disease into subtypes that have clinical significance in terms of prognosis or therapy response. One of the most popular methods to uncover unrecognized subtypes is cluster analysis. However, classical clustering methods such as k-means clustering or hierarchical clustering are not guaranteed to produce clinically interesting subtypes. This could be because the main statistical variability—the basis of cluster generation—is dominated by genes not associated with the clinical phenotype of interest. Furthermore, a strong prognostic factor might be relevant for a certain subgroup but not for the whole population; thus an analysis of the whole sample may not reveal this prognostic factor. To address these problems we investigate methods to identify and assess clinically interesting subgroups in a heterogeneous population. The identification step uses a clustering algorithm and to assess significance we use a false discovery rate- (FDR-) based measure. Under the heterogeneity condition the standard FDR estimate is shown to overestimate the true FDR value, but this is remedied by an improved FDR estimation procedure. As illustrations, two real data examples from gene expression studies of lung cancer are provided. PMID:26339613

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…

Molecular subgroups of adult medulloblastoma: a long-term single-institution study.

PubMed

Zhao, Fu; Ohgaki, Hiroko; Xu, Lei; Giangaspero, Felice; Li, Chunde; Li, Peng; Yang, Zhijun; Wang, Bo; Wang, Xingchao; Wang, Zhenmin; Ai, Lin; Zhang, Jing; Luo, Lin; Liu, Pinan

2016-07-01

Recent transcriptomic approaches have demonstrated that there are at least 4 distinct subgroups in medulloblastoma (MB); however, survival studies of molecular subgroups in adult MB have been inconclusive because of small sample sizes. The aim of this study is to investigate the molecular subgroups in adult MB and identify their clinical and prognostic implications in a large, single-institution cohort. We determined gene expression profiles for 13 primary adult MBs. Bioinformatics tools were used to establish distinct molecular subgroups based on the most informative genes in the dataset. Immunohistochemistry with subgroup-specific antibodies was then used for validation within an independent cohort of 201 formalin-fixed MB tumors, in conjunction with a systematic analysis of clinical and histological characteristics. Three distinct molecular variants of adult MB were identified: the SHH, WNT, and group 4 subgroups. Validation of these subgroups in the 201-tumor cohort by immunohistochemistry identified significant differences in subgroup-specific demographics, histology, and metastatic status. The SHH subgroup accounted for the majority of the tumors (62%), followed by the group 4 subgroup (28%) and the WNT subgroup (10%). Group 4 tumors had significantly worse progression-free and overall survival compared with tumors of the other molecular subtypes. We have identified 3 subgroups of adult MB, characterized by distinct expression profiles, clinical features, pathological features, and prognosis. Clinical variables incorporated with molecular subgroup are more significantly informative for predicting adult patient outcome. © 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.

Empirically derived pain-patient MMPI subgroups: prediction of treatment outcome.

PubMed

Moore, J E; Armentrout, D P; Parker, J C; Kivlahan, D R

1986-02-01

Fifty-seven male chronic pain patients admitted to an inpatient multimodal pain treatment program at a Midwestern Veterans Administration hospital completed the MMPI, Profile of Mood States (POMS), Tennessee Self-Concept Scale (TSCS), Rathus Assertiveness Schedule (RAS), activity diaries, and an extensive pain questionnaire. All patients were assessed both before and after treatment, and most also were assessed 2-5 months prior to treatment. No significant changes occurred during the baseline period, but significant improvements were evident at posttreatment on most variables: MMPI, POMS, TSCS, RAS, pain severity, sexual functioning, and activity diaries. MMPI subgroup membership, based on a hierarchical cluster analysis in a larger sample, was not predictive of differential treatment outcome. Possible reasons for comparable treatment gains among these subgroups, which previously have been shown to differ on many psychological and behavioral factors, are discussed.

Three subgroups of pain profiles identified in 227 women with arthritis: a latent class analysis.

PubMed

de Luca, Katie; Parkinson, Lynne; Downie, Aron; Blyth, Fiona; Byles, Julie

2017-03-01

The objectives were to identify subgroups of women with arthritis based upon the multi-dimensional nature of their pain experience and to compare health and socio-demographic variables between subgroups. A latent class analysis of 227 women with self-reported arthritis was used to identify clusters of women based upon the sensory, affective, and cognitive dimensions of the pain experience. Multivariate multinomial logistic regression analysis was used to determine the relationship between cluster membership and health and sociodemographic characteristics. A three-class cluster model was most parsimonious. 39.5 % of women had a unidimensional pain profile; 38.6 % of women had moderate multidimensional pain profile that included additional pain symptomatology such as sensory qualities and pain catastrophizing; and 21.9 % of women had severe multidimensional pain profile that included prominent pain symptomatology such as sensory and affective qualities of pain, pain catastrophizing, and neuropathic pain. Women with severe multidimensional pain profile have a 30.5 % higher risk of poorer quality of life and a 7.3 % higher risk of suffering depression, and women with moderate multidimensional pain profile have a 6.4 % higher risk of poorer quality of life when compared to women with unidimensional pain. This study identified three distinct subgroups of pain profiles in older women with arthritis. Women had very different experiences of pain, and cluster membership impacted significantly on health-related quality of life. These preliminary findings provide a stronger understanding of profiles of pain and may contribute to the development of tailored treatment options in arthritis.

Challenges and solutions to pre- and post-randomization subgroup analyses.

PubMed

Desai, Manisha; Pieper, Karen S; Mahaffey, Ken

2014-01-01

Subgroup analyses are commonly performed in the clinical trial setting with the purpose of illustrating that the treatment effect was consistent across different patient characteristics or identifying characteristics that should be targeted for treatment. There are statistical issues involved in performing subgroup analyses, however. These have been given considerable attention in the literature for analyses where subgroups are defined by a pre-randomization feature. Although subgroup analyses are often performed with subgroups defined by a post-randomization feature--including analyses that estimate the treatment effect among compliers--discussion of these analyses has been neglected in the clinical literature. Such analyses pose a high risk of presenting biased descriptions of treatment effects. We summarize the challenges of doing all types of subgroup analyses described in the literature. In particular, we emphasize issues with post-randomization subgroup analyses. Finally, we provide guidelines on how to proceed across the spectrum of subgroup analyses.

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.

Differences in feedforward trunk muscle activity in subgroups of patients with mechanical low back pain.

PubMed

Silfies, Sheri P; Mehta, Rupal; Smith, Sue S; Karduna, Andrew R

2009-07-01

To investigate alterations in trunk muscle timing patterns in subgroups of patients with mechanical low back pain (MLBP). Our hypothesis was that subjects with MLBP would demonstrate delayed muscle onset and have fewer muscles functioning in a feedforward manner than the control group. We further hypothesized that we would find differences between subgroups of our patients with MLBP, grouped according to diagnosis (segmental instability and noninstability). Case-control. Laboratory. Forty-three patients with chronic MLBP (25 instability, 18 noninstability) and 39 asymptomatic controls. Not applicable. Surface electromyography was used to measure onset time of 10 trunk muscles during a self-perturbation task. Trunk muscle onset latency relative to the anterior deltoid was calculated and the number of muscles functioning in feedforward determined. Activation timing patterns (P<.01; eta=.50; 1-beta=.99) and number of muscles functioning in feedforward (P=.02; eta=.30; 1-beta=.83) were statistically different between patients with MLBP and controls. The control group activated the external oblique, lumbar multifidus, and erector spinae muscles in a feedforward manner. The heterogeneous MLBP group did not activate the trunk musculature in feedforward, but responded with significantly delayed activations. MLBP subgroups demonstrated significantly different timing patterns. The noninstability MLBP subgroup activated trunk extensors in a feedforward manner, similar to the control group, but significantly earlier than the instability subgroup. Lack of feedforward activation of selected trunk musculature in patients with MLBP may result in a period of inefficient muscular stabilization. Activation timing was more impaired in the instability than the noninstability MLBP subgroup. Training specifically for recruitment timing may be an important component of the rehabilitation program.

Patient characteristics in low back pain subgroups based on an existing classification system. A descriptive cohort study in chiropractic practice.

PubMed

Eirikstoft, Heidi; Kongsted, Alice

2014-02-01

Sub-grouping of low back pain (LBP) is believed to improve prediction of prognosis and treatment effects. The objectives of this study were: (1) to examine whether chiropractic patients could be sub-grouped according to an existing pathoanatomically-based classification system, (2) to describe patient characteristics within each subgroup, and (3) to determine the proportion of patients in whom clinicians considered the classification to be unchanged after approximately 10 days. A cohort of 923 LBP patients was included during their first consultation. Patients completed an extensive questionnaire and were examined according to a standardised protocol. Based on the clinical examination, patients were classified into diagnostic subgroups. After approximately 10 days, chiropractors reported whether they considered the subgroup had changed. The most frequent subgroups were reducible and partly reducible disc syndromes followed by facet joint pain, dysfunction and sacroiliac (SI)-joint pain. Classification was inconclusive in 5% of the patients. Differences in pain, activity limitation, and psychological factors were small across subgroups. Within 10 days, 82% were reported to belong to the same subgroup as at the first visit. In conclusion, LBP patients could be classified according to a standardised protocol, and chiropractors considered most patient classifications to be unchanged within 10 days. Differences in patient characteristics between subgroups were very small, and the clinical relevance of the classification system should be investigated by testing its value as a prognostic factor or a treatment effect modifier. It is recommended that this classification system be combined with psychological and social factors if it is to be useful. Copyright © 2013 Elsevier Ltd. All rights reserved.

Genetic and molecular alterations across medulloblastoma subgroups.

PubMed

Skowron, Patryk; Ramaswamy, Vijay; Taylor, Michael D

2015-10-01

Medulloblastoma is the most common malignant brain tumour diagnosed in children. Over the last few decades, advances in radiation and chemotherapy have significantly improved the odds of survival. Nevertheless, one third of all patients still succumb to their disease, and many long-term survivors are afflicted with neurocognitive sequelae. Large-scale multi-institutional efforts have provided insight into the transcriptional and genetic landscape of medulloblastoma. Four distinct subgroups of medulloblastoma have been identified, defined by distinct transcriptomes, genetics, demographics and outcomes. Integrated genomic profiling of each of these subgroups has revealed distinct genetic alterations, driving pathways and in some instances cells of origin. In this review, we highlight, in a subgroup-specific manner, our current knowledge of the genetic and molecular alterations in medulloblastoma and underscore the possible avenues for future therapeutic intervention.

Phenome-Wide Association Study of Rheumatoid Arthritis Subgroups Identifies Association Between Seronegative Disease and Fibromyalgia.

PubMed

Doss, Jayanth; Mo, Huan; Carroll, Robert J; Crofford, Leslie J; Denny, Joshua C

2017-02-01

The differences between seronegative and seropositive rheumatoid arthritis (RA) have not been widely reported. We performed electronic health record (EHR)-based phenome-wide association studies (PheWAS) to identify disease associations in seropositive and seronegative RA. A validated algorithm identified RA subjects from the de-identified version of the Vanderbilt University Medical Center EHR. Serotypes were determined by rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) values. We tested EHR-derived phenotypes using PheWAS comparing seropositive RA and seronegative RA, yielding disease associations. PheWAS was also performed in RF-positive versus RF-negative subjects and ACPA-positive versus ACPA-negative subjects. Following PheWAS, select phenotypes were then manually reviewed, and fibromyalgia was specifically evaluated using a validated algorithm. A total of 2,199 RA individuals with either RF or ACPA testing were identified. Of these, 1,382 patients (63%) were classified as seropositive. Seronegative RA was associated with myalgia and myositis (odds ratio [OR] 2.1, P = 3.7 × 10 -10 ) and back pain. A manual review of the health record showed that among subjects coded for Myalgia and Myositis, ∼80% had fibromyalgia. Follow-up with a specific EHR algorithm for fibromyalgia confirmed that seronegative RA was associated with fibromyalgia (OR 1.8, P = 4.0 × 10 -6 ). Seropositive RA was associated with chronic airway obstruction (OR 2.2, P = 1.4 × 10 -4 ) and tobacco use (OR 2.2, P = 7.0 × 10 -4 ). This PheWAS of RA patients identifies a strong association between seronegativity and fibromyalgia. It also affirms relationships between seropositivity and chronic airway obstruction and between seropositivity and tobacco use. These findings demonstrate the utility of the PheWAS approach to discover novel phenotype associations within different subgroups of a disease. © 2016, American College of Rheumatology.

An observational study identifying obese subgroups among older adults at increased risk of mobility disability: do perceptions of the neighborhood environment matter?

PubMed

King, Abby C; Salvo, Deborah; Banda, Jorge A; Ahn, David K; Gill, Thomas M; Miller, Michael; Newman, Anne B; Fielding, Roger A; Siordia, Carlos; Moore, Spencer; Folta, Sara; Spring, Bonnie; Manini, Todd; Pahor, Marco

2015-12-18

Obesity is an increasingly prevalent condition among older adults, yet relatively little is known about how built environment variables may be associated with obesity in older age groups. This is particularly the case for more vulnerable older adults already showing functional limitations associated with subsequent disability. The Lifestyle Interventions and Independence for Elders (LIFE) trial dataset (n = 1600) was used to explore the associations between perceived built environment variables and baseline obesity levels. Age-stratified recursive partitioning methods were applied to identify distinct subgroups with varying obesity prevalence. Among participants aged 70-78 years, four distinct subgroups, defined by combinations of perceived environment and race-ethnicity variables, were identified. The subgroups with the lowest obesity prevalence (45.5-59.4%) consisted of participants who reported living in neighborhoods with higher residential density. Among participants aged 79-89 years, the subgroup (of three distinct subgroups identified) with the lowest obesity prevalence (19.4%) consisted of non-African American/Black participants who reported living in neighborhoods with friends or acquaintances similar in demographic characteristics to themselves. Overall support for the partitioned subgroupings was obtained using mixed model regression analysis. The results suggest that, in combination with race/ethnicity, features of the perceived neighborhood built and social environments differentiated distinct groups of vulnerable older adults from different age strata that differed in obesity prevalence. Pending further verification, the results may help to inform subsequent targeting of such subgroups for further investigation. Clinicaltrials.gov Identifier =  NCT01072500.

Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology.

PubMed

Walker, Steven M; Knight, Laura A; McCavigan, Andrena M; Logan, Gemma E; Berge, Viktor; Sherif, Amir; Pandha, Hardev; Warren, Anne Y; Davidson, Catherine; Uprichard, Adam; Blayney, Jaine K; Price, Bethanie; Jellema, Gera L; Steele, Christopher J; Svindland, Aud; McDade, Simon S; Eden, Christopher G; Foster, Chris; Mills, Ian G; Neal, David E; Mason, Malcolm D; Kay, Elaine W; Waugh, David J; Harkin, D Paul; Watson, R William; Clarke, Noel W; Kennedy, Richard D

2017-10-01

Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy. To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy. Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months. Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis. A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation. The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential. The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in

Subgroup Analysis in Burnout: Relations Between Fatigue, Anxiety, and Depression

PubMed Central

van Dam, Arno

2016-01-01

Several authors have suggested that burned out patients do not form a homogeneous group and that subgroups should be considered. The identification of these subgroups may contribute to a better understanding of the burnout construct and lead to more specific therapeutic interventions. Subgroup analysis may also help clarify whether burnout is a distinct entity and whether subgroups of burnout overlap with other disorders such as depression and chronic fatigue syndrome. In a group of 113 clinically diagnosed burned out patients, levels of fatigue, depression, and anxiety were assessed. In order to identify possible subgroups, we performed a two-step cluster analysis. The analysis revealed two clusters that differed from one another in terms of symptom severity on the three aforementioned measures. Depression appeared to be the strongest predictor of group membership. These results are considered in the light of the scientific debate on whether burnout can be distinguished from depression and whether burnout subtyping is useful. Finally, implications for clinical practice and future research are discussed. PMID:26869983

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

Novel subgroups of attention-deficit/hyperactivity disorder identified by topological data analysis and their functional network modular organizations

PubMed Central

Kyeong, Sunghyon; Kim, Jae-Jin; Kim, Eunjoo

2017-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a clinically heterogeneous condition and identification of clinically meaningful subgroups would open up a new window for personalized medicine. Thus, we aimed to identify new clinical phenotypes in children and adolescents with ADHD and to investigate whether neuroimaging findings validate the identified phenotypes. Neuroimaging and clinical data from 67 children with ADHD and 62 typically developing controls (TDCs) from the ADHD-200 database were selected. Clinical measures of ADHD symptoms and intelligence quotient (IQ) were used as input features into a topological data analysis (TDA) to identify ADHD subgroups within our sample. As external validators, graph theoretical measures obtained from the functional connectome were compared to address the biological meaningfulness of the identified subtypes. The TDA identified two unique subgroups of ADHD, labelled as mild symptom ADHD (mADHD) and severe symptom ADHD (sADHD). The output topology shape was repeatedly observed in the independent validation dataset. The graph theoretical analysis showed a decrease in the degree centrality and PageRank in the bilateral posterior cingulate cortex in the sADHD group compared with the TDC group. The mADHD group showed similar patterns of intra- and inter-module connectivity to the sADHD group. Relative to the TDC group, the inter-module connectivity between the default mode network and executive control network were significantly increased in the sADHD group but not in the mADHD group. Taken together, our results show that the data-driven TDA is potentially useful in identifying objective and biologically relevant disease phenotypes in children and adolescents with ADHD. PMID:28829775

Subgroup analysis of Asian patients in the INPULSIS® trials of nintedanib in idiopathic pulmonary fibrosis.

PubMed

Taniguchi, Hiroyuki; Xu, Zuojun; Azuma, Arata; Inoue, Yoshikazu; Li, Huiping; Fujimoto, Tsuyoshi; Bailes, Zelie; Schlenker-Herceg, Rozsa; Kim, Dong S

2016-11-01

In the two-replicate randomized Phase III INPULSIS® trials in patients with idiopathic pulmonary fibrosis (IPF), nintedanib 150 mg bd significantly reduced the annual rate of decline in forced vital capacity (FVC) compared with placebo. The key secondary endpoints were time to first investigator-reported acute exacerbation and change from baseline in St George's Respiratory Questionnaire total score, both over 52 weeks. Here, we assessed the effect of nintedanib in Asian patients. Pre-specified subgroup analyses of the effect of nintedanib on the primary and key secondary endpoints in Asian versus White patients were undertaken based on pooled data from the two INPULSIS® trials. Safety data were analyzed descriptively. Of the treated patients, 322 were Asian (nintedanib n = 194; placebo n = 128) and 608 were White (nintedanib n = 360; placebo n = 248). In Asian patients, the nintedanib versus placebo difference in the adjusted annual rate of decline in FVC was 94.1 mL/year (95% CI: 33.7, 154.6). The treatment effect of nintedanib on the annual rate of decline in FVC in Asian and White patients was similar (treatment-by-subgroup interaction P = 0.72) and consistent with the overall population. No significant treatment-by-subgroup interaction was observed for the key secondary endpoints between Asian and White patients. In Asian patients, the most common adverse event in the nintedanib group was diarrhoea (56.2% of patients vs 15.6% for placebo). In pre-specified subgroup analyses of Asian versus White patients with IPF in the INPULSIS® trials, race did not influence the effect of nintedanib on disease progression. © 2016 Asian Pacific Society of Respirology.

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.

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

Identifying patients with AAA with the highest risk following endovascular repair.

PubMed

Cadili, Ali; Turnbull, Robert; Hervas-Malo, Marilou; Ghosh, Sunita; Chyczij, Harold

2012-08-01

It has been demonstrated that endovascular repair of arterial disease results in reduced perioperative morbidity and mortality compared to open surgical repair. The rates of complications and need for reinterventions, however, have been found to be higher than that in open repair. The purpose of this study was to identify the predictors of endograft complications and mortality in patients undergoing endovascular abdominal aortic aneurysm (AAA) repair; specifically, our aim was to identify a subset of patients with AAA whose risk of periprocedure mortality was so high that they should not be offered endovascular repair. We undertook a prospective review of patients with AAA receiving endovascular therapy at a single institution. Collected variables included age, gender, date of procedure, indication for procedure, size of aneurysm (where applicable), type of endograft used, presence of rupture, American Society of Anesthesiologists (ASA) class, major medical comorbidities, type of anesthesia (general, epidural, or local), length of intensive care unit (ICU) stay, and length of hospital stay. These factors were correlated with the study outcomes (overall mortality, graft complications, morbidity, and reintervention) using univariate and multivariate logistic regression. A total of 199 patients underwent endovascular AAA repair during the study period. The ICU stay, again, was significantly correlated with the primary outcomes (death and graft complications). In addition, length of hospital stay greater than 3 days, also emerged as a statistically significant predictor of graft complications in this subgroup (P = .024). Survival analysis for patients with AAA revealed that age over 85 years and ICU stay were predictive of decreased survival. Statistical analysis for other subgroups of patients (inflammatory AAA or dissection) was not performed due to the small numbers in these subgroups. Patients with AAA greater than 85 years of age are at a greater risk of mortality

Using Learning Analytics to Identify Medical Student Misconceptions in an Online Virtual Patient Environment

ERIC Educational Resources Information Center

Poitras, Eric G.; Naismith, Laura M.; Doleck, Tenzin; Lajoie, Susanne P.

2016-01-01

This study aimed to identify misconceptions in medical student knowledge by mining user interactions in the MedU online learning environment. Data from 13000 attempts at a single virtual patient case were extracted from the MedU MySQL database. A subgroup discovery method was applied to identify patterns in learner-generated annotations and…

A multi-marker molecular signature approach for treatment-specific subgroup identification with survival outcomes.

PubMed

Li, L; Guennel, T; Marshall, S; Cheung, L W-K

2014-10-01

Delivering on the promise of personalized medicine has become a focus of the pharmaceutical industry as the era of the blockbuster drug is fading. Central to realizing this promise is the need for improved analytical strategies for effectively integrating information across various biological assays (for example, copy number variation and targeted protein expression) toward identification of a treatment-specific subgroup-identifying the right patients. We propose a novel combination of elastic net followed by a maximal χ(2) and semiparametric bootstrap. The combined approaches are presented in a two-stage strategy that estimates patient-specific multi-marker molecular signatures (MMMS) to identify and directly test for a biomarker-driven subgroup with enhanced treatment effect. This flexible strategy provides for incorporation of business-specific needs, such as confining the search space to a subgroup size that is commercially viable, ultimately resulting in actionable information for use in empirically based decision making.

Identification and Characterization of Unique Subgroups of Chronic Pain Individuals with Dispositional Personality Traits.

PubMed

Mehta, S; Rice, D; McIntyre, A; Getty, H; Speechley, M; Sequeira, K; Shapiro, A P; Morley-Forster, P; Teasell, R W

2016-01-01

Objective. The current study attempted to identify and characterize distinct CP subgroups based on their level of dispositional personality traits. The secondary objective was to compare the difference among the subgroups in mood, coping, and disability. Methods. Individuals with chronic pain were assessed for demographic, psychosocial, and personality measures. A two-step cluster analysis was conducted in order to identify distinct subgroups of patients based on their level of personality traits. Differences in clinical outcomes were compared using the multivariate analysis of variance based on cluster membership. Results. In 229 participants, three clusters were formed. No significant difference was seen among the clusters on patient demographic factors including age, sex, relationship status, duration of pain, and pain intensity. Those with high levels of dispositional personality traits had greater levels of mood impairment compared to the other two groups (p < 0.05). Significant difference in disability was seen between the subgroups. Conclusions. The study identified a high risk group of CP individuals whose level of personality traits significantly correlated with impaired mood and coping. Use of pharmacological treatment alone may not be successful in improving clinical outcomes among these individuals. Instead, a more comprehensive treatment involving psychological treatments may be important in managing the personality traits that interfere with recovery.

Phenome-Wide Association Study of Rheumatoid Arthritis Subgroups Identifies Association between Seronegative Disease and Fibromyalgia

PubMed Central

Doss, Jayanth; Mo, Huan; Carroll, Robert J.; Crofford, Leslie J.; Denny, Joshua C.

2016-01-01

Objective The differences between seronegative and seropositive rheumatoid arthritis (RA) have not been widely reported. We performed electronic health record (EHR)-based phenome-wide association studies (PheWAS) to identify disease associations in seropositive and seronegative RA. Methods A validated algorithm identified RA subjects from the de-identified EHR. Serotypes were determined by values of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA). We tested EHR-derived phenotypes using PheWAS comparing seropositive RA against seronegative RA, yielding disease associations. PheWAS was also performed on RF-positive versus RF-negative subjects and ACPA-positive versus ACPA-negative subjects. Following PheWAS, select phenotypes were then manually reviewed and fibromyalgia was specifically evaluated using a validated algorithm. Results There were 2199 individuals identified with RA and either RF or ACPA testing. Of these, 1382 (63%) were seropositive. Seronegative RA was associated with “Myalgia and Myositis” (odds ratio [OR] 2.1, P=3.7×10−10) and back pain. A manual record review showed 80% of Myalgia and Myositis codes were used for fibromyalgia, and follow-up with a specific EHR algorithm for fibromyalgia confirmed that seronegative RA was associated with fibromyalgia (OR=1.8, P=4.0×10−6). Seropositive RA was associated with Chronic Airway Obstruction (OR=2.2, P=1.4×10−4) and tobacco use (OR=2.2, P=7.0×10−4). Conclusion This PheWAS in RA patients identifies a strong association between seronegativity and fibromyalgia. It also affirms relationships between seropositivity with chronic airway obstruction and seropositivity with tobacco use. These findings demonstrate the utility of the PheWAS approach to discover novel phenotype associations within different subgroups of a disease. PMID:27589350

Detection of Patient Subgroups with Differential Expression in Omics Data: A Comprehensive Comparison of Univariate Measures

PubMed Central

Ahrens, Maike; Turewicz, Michael; Casjens, Swaantje; May, Caroline; Pesch, Beate; Stephan, Christian; Woitalla, Dirk; Gold, Ralf; Brüning, Thomas; Meyer, Helmut E.

2013-01-01

Detection of yet unknown subgroups showing differential gene or protein expression is a frequent goal in the analysis of modern molecular data. Applications range from cancer biology over developmental biology to toxicology. Often a control and an experimental group are compared, and subgroups can be characterized by differential expression for only a subgroup-specific set of genes or proteins. Finding such genes and corresponding patient subgroups can help in understanding pathological pathways, diagnosis and defining drug targets. The size of the subgroup and the type of differential expression determine the optimal strategy for subgroup identification. To date, commonly used software packages hardly provide statistical tests and methods for the detection of such subgroups. Different univariate methods for subgroup detection are characterized and compared, both on simulated and on real data. We present an advanced design for simulation studies: Data is simulated under different distributional assumptions for the expression of the subgroup, and performance results are compared against theoretical upper bounds. For each distribution, different degrees of deviation from the majority of observations are considered for the subgroup. We evaluate classical approaches as well as various new suggestions in the context of omics data, including outlier sum, PADGE, and kurtosis. We also propose the new FisherSum score. ROC curve analysis and AUC values are used to quantify the ability of the methods to distinguish between genes or proteins with and without certain subgroup patterns. In general, FisherSum for small subgroups and -test for large subgroups achieve best results. We apply each method to a case-control study on Parkinson's disease and underline the biological benefit of the new method. PMID:24278130

Three-dimensional Cervical Movement Characteristics in Healthy Subjects and Subgroups of Chronic Neck Pain Patients Based on Their Pain Location.

PubMed

Waeyaert, Patirck; Jansen, Daniel; Bastiaansen, Marco; Scafoglieri, Aldo; Buyl, Ronald; Schmitt, Maarten; Cattrysse, Erik

2016-08-01

A cross-sectional observational study of three-dimensional (3D) cervical kinematics in 41 chronic neck pain (CNPs) patients and 156 asymptomatic controls. The objective was to investigate 3D cervical kinematics by analyzing and comparing quantitative and qualitative parameters in healthy subjects and CNPs. Furthermore, subgroups were formed to explore the influence of pain-location on cervical kinematics. The possible correlation of kinematic parameters with the degree of functional disability was examined as well. In patients with chronic neck pain, a clear pathological cause is frequently not identifiable. Therefore, the need to assess neck pain with a broader view than structure or anatomical-based divergences is desirable. Movements of the cervical spine were registered using an electromagnetic tracking system. Quantitative and qualitative kinematics were analyzed for active axial rotation, lateral bending, and flexion-extension motion components. During lateral bending, the range of the main motion demonstrated significant higher values (P = 0.001) in the controls (mean: 68.67° ± 15.17°) than patients (mean: 59.28° ± 15.41°). Significant differences were demonstrated between subgroups for several kinematic parameters (P < 0.05). Although differences were predominantly recorded between the "symmetrical" and "asymmetrical" pain group, some parameters also distinguished subgroups from controls. On average, the symmetrical group showed significant less harmonic movement patterns, expressed by qualitative parameters, in comparison with the "asymmetrical" group and controls. Furthermore, the "asymmetrical" group showed significant lower scores on quantitative parameters than the "symmetrical" group and controls. The degree of functional disability correlated moderately with changes in qualitative parameters. In this study, chronic neck pain patients with a symmetrical pain pattern showed significant poorer quality of movement, while those with

Subgroup-Elimination Transcriptomics Identifies Signaling Proteins that Define Subclasses of TRPV1-Positive Neurons and a Novel Paracrine Circuit

PubMed Central

Isensee, Jörg; Wenzel, Carsten; Buschow, Rene; Weissmann, Robert; Kuss, Andreas W.; Hucho, Tim

2014-01-01

Normal and painful stimuli are detected by specialized subgroups of peripheral sensory neurons. The understanding of the functional differences of each neuronal subgroup would be strongly enhanced by knowledge of the respective subgroup transcriptome. The separation of the subgroup of interest, however, has proven challenging as they can hardly be enriched. Instead of enriching, we now rapidly eliminated the subgroup of neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia. Elimination was accomplished by brief treatment with TRPV1 agonists followed by the removal of compromised TRPV1(+) neurons using density centrifugation. By differential microarray and sequencing (RNA-Seq) based expression profiling we compared the transcriptome of all cells within sensory ganglia versus the same cells lacking TRPV1 expressing neurons, which revealed 240 differentially expressed genes (adj. p<0.05, fold-change>1.5). Corroborating the specificity of the approach, many of these genes have been reported to be involved in noxious heat or pain sensitization. Beyond the expected enrichment of ion channels, we found the TRPV1 transcriptome to be enriched for GPCRs and other signaling proteins involved in adenosine, calcium, and phosphatidylinositol signaling. Quantitative population analysis using a recent High Content Screening (HCS) microscopy approach identified substantial heterogeneity of expressed target proteins even within TRPV1-positive neurons. Signaling components defined distinct further subgroups within the population of TRPV1-positive neurons. Analysis of one such signaling system showed that the pain sensitizing prostaglandin PGD2 activates DP1 receptors expressed predominantly on TRPV1(+) neurons. In contrast, we found the PGD2 producing prostaglandin D synthase to be expressed exclusively in myelinated large-diameter neurons lacking TRPV1, which suggests a novel paracrine neuron-neuron communication. Thus, subgroup analysis based

Premorbid IQ subgroups in first episode non affective psychosis patients: Long-term sex differences in function and neurocognition.

PubMed

Ayesa-Arriola, Rosa; Setién-Suero, Esther; Neergaard, Karl David; Belzunces, Àuria Albacete; Contreras, Fernando; van Haren, Neeltje E M; Crespo-Facorro, Benedicto

2017-12-21

Low IQ has been associated with schizophrenia, even to the point of being posited as a possible causal factor for psychosis. However, individuals with normal and high IQ also develop psychotic illnesses. The aim of this study was to characterize premorbid IQ subgroups at first episode of psychosis (FEP). The study sample comes from a large epidemiological, 3-year longitudinal, intervention program on psychosis containing individuals living in a catchment area in Spain. Estimated premorbid IQ (epIQ) scores were used to build low (<90), normal (90-110) and high (>110) epIQ subgroups in samples of FEP patients (N=292) and healthy controls (N=199). The epIQ subgroups were compared in sociodemographic, neuropsychological, clinical and premorbid characteristics. Long-term functional and cognitive outcome, with a focus on sex differences, were also explored. Low-epIQ was more frequently found in FEP patients (28.8%) than in healthy controls (14.6%). Low-epIQ patients were more likely to have worse premorbid adjustment, belong to low socioeconomic status families, have less years of education, and to be single, unemployed, and younger. They presented more severe impairments in processing speed, executive and global cognitive function. Female patients with low-epIQ showed better baseline function and more stable outcome than males. Our results indicate that low premorbid IQ is a morbid manifestation, easily detected in a subgroup of FEP patients that predicts poorer outcome particularly in males. This perspective provides important information for the tailoring of subgroup-specific early intervention programs for psychosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Uncovering multiple pathways to substance use: a comparison of methods for identifying population subgroups.

PubMed

Dierker, Lisa; Rose, Jennifer; Tan, Xianming; Li, Runze

2010-12-01

This paper describes and compares a selection of available modeling techniques for identifying homogeneous population subgroups in the interest of informing targeted substance use intervention. We present a nontechnical review of the common and unique features of three methods: (a) trajectory analysis, (b) functional hierarchical linear modeling (FHLM), and (c) decision tree methods. Differences among the techniques are described, including required data features, strengths and limitations in terms of the flexibility with which outcomes and predictors can be modeled, and the potential of each technique for helping to inform the selection of targets and timing of substance intervention programs.

Diffusion-weighted MRI derived apparent diffusion coefficient identifies prognostically distinct subgroups of pediatric diffuse intrinsic pontine glioma.

PubMed

Lober, Robert M; Cho, Yoon-Jae; Tang, Yujie; Barnes, Patrick D; Edwards, Michael S; Vogel, Hannes; Fisher, Paul G; Monje, Michelle; Yeom, Kristen W

2014-03-01

While pediatric diffuse intrinsic pontine gliomas (DIPG) remain fatal, recent data have shown subgroups with distinct molecular biology and clinical behavior. We hypothesized that diffusion-weighted MRI can be used as a prognostic marker to stratify DIPG subsets with distinct clinical behavior. Apparent diffusion coefficient (ADC) values derived from diffusion-weighted MRI were computed in 20 consecutive children with treatment-naïve DIPG tumors. The median ADC for the cohort was used to stratify the tumors into low and high ADC groups. Survival, gender, therapy, and potential steroid effects were compared between the ADC groups. Median age at diagnosis was 6.6 (range 2.3-13.2) years, with median follow-up seven (range 1-36) months. There were 14 boys and six girls. Seventeen patients received radiotherapy, five received chemotherapy, and six underwent cerebrospinal fluid diversion. The median ADC of 1,295 × 10(-6) mm(2)/s for the cohort partitioned tumors into low or high diffusion groups, which had distinct median survivals of 3 and 13 months, respectively (log-rank p < 0.001). Low ADC tumors were found only in boys, whereas high ADC tumors were found in both boys and girls. Available tissue specimens in three low ADC tumors demonstrated high-grade histology, whereas one high ADC tumor demonstrated low-grade histology with a histone H3.1 K27M mutation and high-grade metastatic lesion at autopsy. ADC derived from diffusion-weighted MRI may identify prognostically distinct subgroups of pediatric DIPG.

Novel mutations target distinct subgroups of medulloblastoma

PubMed Central

Robinson, Giles; Parker, Matthew; Kranenburg, Tanya A.; Lu, Charles; Chen, Xiang; Ding, Li; Phoenix, Timothy N.; Hedlund, Erin; Wei, Lei; Zhu, Xiaoyan; Chalhoub, Nader; Baker, Suzanne J.; Huether, Robert; Kriwacki, Richard; Curley, Natasha; Thiruvenkatam, Radhika; Wang, Jianmin; Wu, Gang; Rusch, Michael; Hong, Xin; Beckford, Jared; Gupta, Pankaj; Ma, Jing; Easton, John; Vadodaria, Bhavin; Onar-Thomas, Arzu; Lin, Tong; Li, Shaoyi; Pounds, Stanley; Paugh, Steven; Zhao, David; Kawauchi, Daisuke; Roussel, Martine F.; Finkelstein, David; Ellison, David W.; Lau, Ching C.; Bouffet, Eric; Hassall, Tim; Gururangan, Sridharan; Cohn, Richard; Fulton, Robert S.; Fulton, Lucinda L.; Dooling, David J.; Ochoa, Kerri; Gajjar, Amar; Mardis, Elaine R.; Wilson, Richard K.; Downing, James R.; Zhang, Jinghui; Gilbertson, Richard J.

2012-01-01

Summary Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. To identify mutations that drive medulloblastoma we sequenced the entire genomes of 37 tumours and matched normal blood. One hundred and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet implicated in medulloblastoma: several target distinct components of the epigenetic machinery in different disease subgroups, e.g., regulators of H3K27 and H3K4 trimethylation in subgroup-3 and 4 (e.g., KDM6A and ZMYM3), and CTNNB1-associated chromatin remodellers in WNT-subgroup tumours (e.g., SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours, identified genes that maintain this cell lineage (DDX3X) as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumourigenesis. These data provide important new insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic development. PMID:22722829

Topology based data analysis identifies a subgroup of breast cancers with a unique mutational profile and excellent survival.

PubMed

Nicolau, Monica; Levine, Arnold J; Carlsson, Gunnar

2011-04-26

High-throughput biological data, whether generated as sequencing, transcriptional microarrays, proteomic, or other means, continues to require analytic methods that address its high dimensional aspects. Because the computational part of data analysis ultimately identifies shape characteristics in the organization of data sets, the mathematics of shape recognition in high dimensions continues to be a crucial part of data analysis. This article introduces a method that extracts information from high-throughput microarray data and, by using topology, provides greater depth of information than current analytic techniques. The method, termed Progression Analysis of Disease (PAD), first identifies robust aspects of cluster analysis, then goes deeper to find a multitude of biologically meaningful shape characteristics in these data. Additionally, because PAD incorporates a visualization tool, it provides a simple picture or graph that can be used to further explore these data. Although PAD can be applied to a wide range of high-throughput data types, it is used here as an example to analyze breast cancer transcriptional data. This identified a unique subgroup of Estrogen Receptor-positive (ER(+)) breast cancers that express high levels of c-MYB and low levels of innate inflammatory genes. These patients exhibit 100% survival and no metastasis. No supervised step beyond distinction between tumor and healthy patients was used to identify this subtype. The group has a clear and distinct, statistically significant molecular signature, it highlights coherent biology but is invisible to cluster methods, and does not fit into the accepted classification of Luminal A/B, Normal-like subtypes of ER(+) breast cancers. We denote the group as c-MYB(+) breast cancer.

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…

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

Subgrouping low back pain: A comparison of the STarT Back Tool with the Örebro Musculoskeletal Pain Screening Questionnaire

PubMed Central

Hill, Jonathan C.; Dunn, Kate M.; Main, Chris J.; Hay, Elaine M.

2010-01-01

Introduction Clinicians require brief, practical tools to help identify low back pain (LBP) subgroups requiring early, targeted secondary prevention. The STarT Back Tool (SBT) was recently validated to subgroup LBP patients into early treatment pathways. Aim To test the SBT’s concurrent validity against an existing, popular LBP subgrouping tool, the Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ), and to compare the clinical characteristics of subgroups identified by each tool. Methods Two hundred and forty-four consecutive ‘non-specific’ LBP consulters at 8 UK GP practices aged 18–59 years were invited to complete a questionnaire. Measures included the ÖMPSQ and SBT, disability, fear, catastrophising, pain intensity, episode duration and demographics. Instruments were compared using Spearman’s correlations, tests for subgroup agreement and discriminant analysis of subgroup characteristics according to reference standards. Results Completed SBT (9-items) and ÖMPSQ (24-items) data was available for 130/244 patients (53%). The correlation of SBT and ÖMPSQ scores was ‘excellent (rs = 0.80). Subgroup characteristics were similar across the low, medium and high subgroups, but, the proportions allocated to ‘low’, ‘medium’ and ‘high’ risk groups were different, with fewer patients in the SBT’s high risk group. Both instruments similarly discriminated for reference standards such as disability, catastrophising, fear, comorbid pain and time off work. The ÖMPSQ was better at discriminating pain intensity, while the SBT was better for discriminating bothersomeness of back pain and referred leg pain. Conclusions The SBT baseline psychometrics performed similarly to the ÖMPSQ, but the SBT is shorter and easier to score and is an appropriate alternative for identifying high risk LBP patients in primary care. PMID:19223271

Score distribution of the scoliosis research society-22 questionnaire in subgroups of patients of all ages with idiopathic scoliosis.

PubMed

Parent, Eric C; Dang, Rohan; Hill, Doug; Mahood, Jim; Moreau, Marc; Raso, Jim; Lou, Edmond

2010-03-01

Cross-sectional measurement study. To analyze the score distribution of the Scoliosis Research Society (SRS)-22 questionnaire domains and items for patients with idiopathic scoliosis (IS) of all ages. Scoliosis-related quality-of-life questionnaires have demonstrated high ceiling effects in younger patients. However, the score distribution has not been examined thoroughly in other clinically relevant IS subgroups. The SRS-22 was completed by 173 females with IS. The proportions of ceiling effects, floor effects, of patients scoring greater than or equal to 4 out of 5 and the box plots of the score distribution for each domain and item were compared between subgroups. Subgroups were formed based on age (k = 4), management (k = 6), curve severity (k = 3), and curve type (k = 4). Domain ceiling effects varied between 0% and 23.1%. Domain floor effects were observed only for Self-image (<7%) and Satisfaction (<12%). Only Pain and Satisfaction showed moderate (>20%) ceiling effects. Ceiling effects for Pain and Mental Health decreased with increasing age (P < 0.05). Pain ceiling effects decreased and Satisfaction ceiling effects increased from least to most invasive management (P < 0.05), but no differences were found among Cobb severity or curve types subgroups. Of the 22 items, 9 had major (>or=50%) ceiling effects and 11 had moderate ceiling effects. Most subgroups (14/16) had 4 to 6 items with major ceiling effects. The following items had major ceiling effects in the majority of subgroups: Function, 9 and 15; Pain, 11 and 17; and Self-image, 14. Most SRS-22 domains had acceptable levels of ceiling effects (<20%) in the majority of the subgroups examined. However, more sensitive measurements may be needed to supplement the SRS-22 in assessing Pain in patients below 18 years or Satisfaction after surgery.

Analysis of efficacy and safety of treatment with collagenase Clostridium histolyticum among subgroups of patients with Dupuytren contracture.

PubMed

Raven, Raymond B; Kushner, Harvey; Nguyen, Dat; Naam, Nash; Curtin, Catherine

2014-09-01

Collagenase Clostridium histolyticum (CCH) injection is a nonoperative treatment of hand contractures from Dupuytren disease. This study assessed the efficacy and safety of CCH in several subgroups of patients with increased surgical risk.Data were pooled from 3 randomized, placebo-controlled, double-blind trials. This analysis included 271 patients with metacarpophalangeal (n = 167) or proximal interphalangeal (n = 104) joint contractures greater than or equal to 20 degrees treated with CCH (0.58 mg collagenase per injection). Subgroups included age, sex, and diabetes status. End points included rate of clinical success (reduction in contracture to 0-5 degrees of normal) and percentage of adverse events.There was no significant difference in clinical success by age, diabetes status, or sex with 63% reaching the end point. There was no difference in adverse events among the subgroups, with peripheral edema, contusion, and injection-site hemorrhage being most common.High-risk subgroups do not demonstrate differences in efficacy or safety with CCH treatment of Dupuytren-related contractures.

Subgroup Specific Alternative Splicing in Medulloblastoma

PubMed Central

Kloosterhof, Nanne K; Northcott, Paul A; Yu, Emily PY; Shih, David; Peacock, John; Grajkowska, Wieslawa; van Meter, Timothy; Eberhart, Charles G; Pfister, Stefan; Marra, Marco A; Weiss, William A; Scherer, Stephen W; Rutka, James T; French, Pim J; Taylor, Michael D

2014-01-01

Medulloblastoma is comprised of four distinct molecular variants: WNT, SHH, Group 3, and Group 4. We analyzed alternative splicing usage in 14 normal cerebellar samples and 103 medulloblastomas of known subgroup. Medulloblastoma samples have a statistically significant increase in alternative splicing as compared to normal fetal cerebella (2.3-times; P<6.47E-8). Splicing patterns are distinct and specific between molecular subgroups. Unsupervised hierarchical clustering of alternative splicing events accurately assigns medulloblastomas to their correct subgroup. Subgroup-specific splicing and alternative promoter usage was most prevalent in Group 3 (19.4%) and SHH (16.2%) medulloblastomas, while observed less frequently in WNT (3.2%), and Group 4 (9.3%) tumors. Functional annotation of alternatively spliced genes reveals over-representation of genes important for neuronal development. Alternative splicing events in medulloblastoma may be regulated in part by the correlative expression of antisense transcripts, suggesting a possible mechanism affecting subgroup specific alternative splicing. Our results identify additional candidate markers for medulloblastoma subgroup affiliation, further support the existence of distinct subgroups of the disease, and demonstrate an additional level of transcriptional heterogeneity between medulloblastoma subgroups. PMID:22358458

The Immunohistochemical Analysis of SOCS3 Protein Identifies a Subgroup of Prostatic Cancer Biopsies With Aggressive Behavior.

PubMed

Pierconti, Francesco; Martini, Maurizio; Cenci, Tonia; Larocca, Luigi M

Recently, we demonstrated that hypermethylation of SOCS3 determines a significant reduction of its mRNA and protein expression and identifies a subgroup of prostate cancer with aggressive behavior. In this paper, our objective was to investigate whether the immunohistochemical expression of the SOCS3 protein could represent an alternative method to molecular analysis for the individualization of aggressive prostate carcinoma. We analyzed the SOCS3 immunohistochemical expression in 65 patients undergoing biopsies at the Institute of Urology of our hospital between September 2011 and October 2011 (median age, 66.4 y; range, 50 to 73 y), and in 35 cases, a subset of 65 cases originally used for the immunohistochemical study, we studied the methylation status of the SOCS3 promoter. We found that the percentage of cases with SOCS3 negativity (-) or with SOCS3 weak staining in <50% of the neoplastic glands (+/-) correlated to the worst prognosis in terms of the Gleason score (P=0.0001; Fisher's exact test), the pT stage (P=0.012; Fisher's exact test), and progression-free survival (P=0.0334; hazard ratio, 0.34; and 95% confidence interval, from 0.1261 to 0.9188). Moreover, some cases with an SOCS3 unmethylated pattern showed SOCS3-negative immunostaining (-) or SOCS3-negative glands with weak cytoplasmatic staining in <50% of the neoplastic glands (+/-). Our data suggest that in prostatic cancer biopsies, the immunohistochemical analysis of SOCS3 protein expression may provide a method that is less expensive and easier to apply than SOCS3 methylation analysis for the distinction of a subgroup of prostate cancer with a more aggressive behavior.

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.

Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome.

PubMed

Nagy-Szakal, Dorottya; Williams, Brent L; Mishra, Nischay; Che, Xiaoyu; Lee, Bohyun; Bateman, Lucinda; Klimas, Nancy G; Komaroff, Anthony L; Levine, Susan; Montoya, Jose G; Peterson, Daniel L; Ramanan, Devi; Jain, Komal; Eddy, Meredith L; Hornig, Mady; Lipkin, W Ian

2017-04-26

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the

Predictive factors for bleeding during treatment with rivaroxaban and warfarin in Japanese patients with atrial fibrillation - Subgroup analysis of J-ROCKET AF.

PubMed

Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-Ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Cavaliere, Mary; Iekushi, Kazuma; Yamanaka, Satoshi

2016-12-01

Results from the J-ROCKET AF study revealed that rivaroxaban was non-inferior to warfarin with respect to the principal safety outcomes in patients with non-valvular atrial fibrillation. This subgroup analysis evaluated whether non-major clinically relevant bleeding (NMCRB) could be a predictive factor for major bleeding (MB). Other predictive factors for MB were also obtained in both rivaroxaban and warfarin treatment groups. The temporal incidence of MB was compared between the rivaroxaban and warfarin treatment groups. Assessment was made whether MB events were often preceded by NMCRB. Univariate and multivariate analyses were carried out to identify any independent predictive factors for MB in both treatment groups. The incidences of MB and NMCRB were 18.04% (138/639 patients) in the rivaroxaban arm, and 16.42% in the warfarin arm (124/639 patients). NMCRB preceded MB in only four patients in each treatment group (rivaroxaban: 4/117 and warfarin: 4/98). Multivariate analysis identified predictive factors for bleeding events: anemia with warfarin treatment and concomitant use of antiplatelet agents with rivaroxaban treatment. Results from this subgroup analysis, particularly the fact that there was no repeated or sequential pattern between NMCRB and MB occurrences in both treatment groups, suggests that NMCRB might not be a predictive factor for MB. On the contrary, anemia and concomitant use of antiplatelet therapy were likely predictive factors for bleeding with warfarin and rivaroxaban treatment, respectively. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

G-protein coupled receptor expression patterns delineate medulloblastoma subgroups

PubMed Central

2013-01-01

Background Medulloblastoma is the most common malignant brain tumor in children. Genetic profiling has identified four principle tumor subgroups; each subgroup is characterized by different initiating mutations, genetic and clinical profiles, and prognoses. The two most well-defined subgroups are caused by overactive signaling in the WNT and SHH mitogenic pathways; less is understood about Groups 3 and 4 medulloblastoma. Identification of tumor subgroup using molecular classification is set to become an important component of medulloblastoma diagnosis and staging, and will likely guide therapeutic options. However, thus far, few druggable targets have emerged. G-protein coupled receptors (GPCRs) possess characteristics that make them ideal targets for molecular imaging and therapeutics; drugs targeting GPCRs account for 30-40% of all current pharmaceuticals. While expression patterns of many proteins in human medulloblastoma subgroups have been discerned, the expression pattern of GPCRs in medulloblastoma has not been investigated. We hypothesized that analysis of GPCR expression would identify clear subsets of medulloblastoma and suggest distinct GPCRs that might serve as molecular targets for both imaging and therapy. Results Our study found that medulloblastoma tumors fall into distinct clusters based solely on GPCR expression patterns. Normal cerebellum clustered separately from the tumor samples. Further, two of the tumor clusters correspond with high fidelity to the WNT and SHH subgroups of medulloblastoma. Distinct over-expressed GPCRs emerge; for example, LGR5 and GPR64 are significantly and uniquely over-expressed in the WNT subgroup of tumors, while PTGER4 is over-expressed in the SHH subgroup. Uniquely under-expressed GPCRs were also observed. Our key findings were independently validated using a large international dataset. Conclusions Our results identify GPCRs with potential to act as imaging and therapeutic targets. Elucidating tumorigenic pathways

T-cell subsets in lymph nodes identify a subgroup of follicular lymphoma patients with favorable outcome.

PubMed

Magnano, Laura; Martínez, Antonio; Carreras, Joaquim; Martínez-Trillos, Alejandra; Giné, Eva; Rovira, Jordina; Dlouhy, Ivan; Baumann, Tycho; Balagué, Olga; Campo, Elías; López-Guillermo, Armando; Villamor, Neus

2017-04-01

We have analyzed in lymph nodes at diagnosis of 75 patients with follicular lymphoma (FL) the relationship between different T-cell subpopulations, assessed by immunohistochemistry (IHC) and flow cytometry (FC), with the outcome. CD4 + cells were the most abundant T-cells in tumor tissue sections, whilst CD57 + cells were the less frequent. In addition to nonambulatory performance status, advanced stage and FLIPI, low CD4 + CD57 + /CD4 + ratio (p = .041), and low CD4 + /CD8 + ratio (p = .008) predicted poor overall survival (OS). Multivariate analysis showed that CD4 + CD57 + /CD4 + ratio was the most important variable for OS. In conclusion, T-cell subpopulations, including CD4 + CD57 + /CD4 + ratio analyzed by FC, could identify FL patients with favorable outcome.

Could the clinical interpretability of subgroups detected using clustering methods be improved by using a novel two-stage approach?

PubMed

Kent, Peter; Stochkendahl, Mette Jensen; Christensen, Henrik Wulff; Kongsted, Alice

2015-01-01

Recognition of homogeneous subgroups of patients can usefully improve prediction of their outcomes and the targeting of treatment. There are a number of research approaches that have been used to recognise homogeneity in such subgroups and to test their implications. One approach is to use statistical clustering techniques, such as Cluster Analysis or Latent Class Analysis, to detect latent relationships between patient characteristics. Influential patient characteristics can come from diverse domains of health, such as pain, activity limitation, physical impairment, social role participation, psychological factors, biomarkers and imaging. However, such 'whole person' research may result in data-driven subgroups that are complex, difficult to interpret and challenging to recognise clinically. This paper describes a novel approach to applying statistical clustering techniques that may improve the clinical interpretability of derived subgroups and reduce sample size requirements. This approach involves clustering in two sequential stages. The first stage involves clustering within health domains and therefore requires creating as many clustering models as there are health domains in the available data. This first stage produces scoring patterns within each domain. The second stage involves clustering using the scoring patterns from each health domain (from the first stage) to identify subgroups across all domains. We illustrate this using chest pain data from the baseline presentation of 580 patients. The new two-stage clustering resulted in two subgroups that approximated the classic textbook descriptions of musculoskeletal chest pain and atypical angina chest pain. The traditional single-stage clustering resulted in five clusters that were also clinically recognisable but displayed less distinct differences. In this paper, a new approach to using clustering techniques to identify clinically useful subgroups of patients is suggested. Research designs, statistical

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

Aliskiren/amlodipine as a single-pill combination in hypertensive patients: subgroup analysis of elderly patients, with metabolic risk factors or high body mass index

PubMed Central

Axthelm, Christoph; Sieder, Christian; Meister, Franziska; Pittrow, David; Kaiser, Edelgard

2013-01-01

Aims Blood pressure (BP) reduction in hypertensive patients is more difficult to achieve in the elderly or in the presence of comorbidities. We aimed to investigate the efficacy of the single-pill combination (SPC) aliskiren/amlodipine in hypertensive elderly patients, patients with high body mass index (BMI), with at least one metabolic risk factor, and/or type 2 diabetes mellitus (DM). Methods In an open-label non-randomized study, patients not adequately controlled by previous treatment with the SPC olmesarten 40/amlodipine 10 (phase 1) were switched to the SPC aliskiren 300/amlodipine 10 (phase 2). The present post-hoc analysis investigated BP reduction in phase 2 in the named subgroups. The EudraCT identifier was 2009-016693-33, ClinicalTrials.gov identifier NCT01113047. Results Of the 187 patients not adequately controlled in phase 1 and thus treated with the SPC aliskiren 300/amlodipine 10 in phase 2, 69 were of advanced age (≥65 years), 74 or 89 were overweight or obese (BMI 25.0–29.9 kg/m2 or ≥30 kg/m2, respectively), 91 had metabolic risk factors (without DM) and 41 had DM. At the beginning of phase 2, depending on the subgroup, baseline SBP was 168–169 mmHg and DBP 103–104 mmHg. After 4 weeks of treatment with aliskiren 300/amlodipine 10, SBP/DBP was lowered by −5.1/−4.8 mmHg in the total cohort, by −5.5/−5.1 mmHg in elderly patients, by −6.7/−5.5 in overweight and by −4.2/−4.5 mmHg in obese patients, by −6.4/−4.7 mmHg in patients with metabolic risk factors without DM, and by −3.3/−5.0 mmHg in DM patients. Limitations include low sample size, limited treatment duration and the fact that the post-hoc defined groups were not mutually exclusive. Conclusions In this study reflecting clinical practice, the aliskiren/amlodipine combination achieved effective BP reduction in elderly patients or with metabolic comorbidities, including DM that might be more difficult to treat. This consistent BP lowering

Detection of high-sensitivity troponin in outpatients with stable pulmonary hypertension identifies a subgroup at higher risk of adverse outcomes.

PubMed

Roy, Andrew K; McCullagh, Brian N; Segurado, Ricardo; McGorrian, Catherine; Keane, Elizabeth; Keaney, John; Fitzgibbon, Maria N; Mahon, Niall G; Murray, Patrick T; Gaine, Sean P

2014-01-01

The detection of elevations in cardiorenal biomarkers, such as troponins, B-type natriuretic peptides (BNPs), and neutrophil gelatinase-associated lipocalins, are associated with poor outcomes in patients hospitalized with acute heart failure. Less is known about the association of these markers with adverse events in chronic right ventricular dysfunction due to pulmonary hypertension, or whether their measurement may improve risk assessment in the outpatient setting. We performed a cohort study of 108 patients attending the National Pulmonary Hypertension Unit in Dublin, Ireland, from 2007 to 2009. Cox proportional hazards analysis and receiver operating characteristic curves were used to determine predictors of mortality and hospitalization. Death or hospitalization occurred in 50 patients (46.3%) during the median study period of 4.1 years. Independent predictors of mortality were: 1) decreasing 6-minute walk test (6MWT; hazard ratio [HR] 12.8; P < .001); 2) BNP (HR 6.68; P < .001); and 3) highly sensitive troponin (hsTnT; HR 5.48; P < .001). Adjusted hazard analyses remained significant when hsTnT was added to a model with BNP and 6MWT (HR 9.26, 95% CI 3.61-23.79), as did the predictive ability of the model for death and rehospitalization (area under the receiver operating characteristic curve 0.81, 95% CI 0.73-0.90). Detection of troponin using a highly sensitive assay identifies a pulmonary hypertension subgroup with a poorer prognosis. hsTnT may also be used in a risk prediction model to identify patients at higher risk who may require escalation of targeted pulmonary vasodilator therapies and closer clinical surveillance. Copyright © 2014 Elsevier Inc. All rights reserved.

Analysis of chronic lymphotic leukemia transcriptomic profile: differences between molecular subgroups.

PubMed

Jantus Lewintre, Eloisa; Reinoso Martín, Cristina; Montaner, David; Marín, Miguel; José Terol, María; Farrás, Rosa; Benet, Isabel; Calvete, Juan J; Dopazo, Joaquín; García-Conde, Javier

2009-01-01

B cell chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder with a variable clinical course. Patients with unmutated IgV(H) gene show a shorter progression-free and overall survival than patients with immunoglobulin heavy chain variable regions (IgV(H)) gene mutated. In addition, BCL6 mutations identify a subgroup of patients with high risk of progression. Gene expression was analysed in 36 early-stage patients using high-density microarrays. Around 150 genes differentially expressed were found according to IgV(H) mutations, whereas no difference was found according to BCL6 mutations. Functional profiling methods allowed us to distinguish KEGG and gene ontology terms showing coordinated gene expression changes across subgroups of CLL. We validated a set of differentially expressed genes according to IgV(H) status, scoring them as putative prognostic markers in CLL. Among them, CRY1, LPL, CD82 and DUSP22 are the ones with at least equal or superior performance to ZAP70 which is actually the most used surrogate marker of IgV(H) status.

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.

A distinct subgroup of cardiomyopathy patients characterized by transcriptionally active cardiotropic erythrovirus and altered cardiac gene expression.

PubMed

Kuhl, U; Lassner, D; Dorner, A; Rohde, M; Escher, F; Seeberg, B; Hertel, E; Tschope, C; Skurk, C; Gross, U M; Schultheiss, H-P; Poller, W

2013-09-01

Recent studies have detected erythrovirus genomes in the hearts of cardiomyopathy and cardiac transplant patients. Assessment of the functional status of viruses may provide clinically important information beyond detection of the viral genomes. Here, we report transcriptional activation of cardiotropic erythrovirus to be associated with strongly altered myocardial gene expression in a distinct subgroup of cardiomyopathy patients. Endomyocardial biopsies (EMBs) from 415 consecutive cardiac erythrovirus (B19V)-positive patients with clinically suspected cardiomyopathy were screened for virus-encoded VP1/VP2 mRNA indicating transcriptional activation of the virus, and correlated with cardiac host gene expression patterns in transcriptionally active versus latent infections, and in virus-free control hearts. Transcriptional activity was detected in baseline biopsies of only 66/415 patients (15.9 %) harbouring erythrovirus. At the molecular level, significant differences between cardiac B19V-positive patients with transcriptionally active versus latent virus were revealed by expression profiling of EMBs. Importantly, latent B19V infection was indistinguishable from controls. Genes involved encode proteins of antiviral immune response, B19V receptor complex, and mitochondrial energy metabolism. Thus, functional mapping of erythrovirus allows definition of a subgroup of B19V-infected cardiomyopathy patients characterized by virus-encoded VP1/VP2 transcripts and anomalous host myocardial transcriptomes. Cardiac B19V reactivation from latency, as reported here for the first time, is a key factor required for erythrovirus to induce altered cardiac gene expression in a subgroup of cardiomyopathy patients. Virus genome detection is insufficient to assess pathogenic potential, but additional transcriptional mapping should be incorporated into future pathogenetic and therapeutic studies both in cardiology and transplantation medicine.

The Role of Anger in Psychosocial Subgrouping for Patients with Low Back Pain

PubMed Central

Nisenzon, Anne N.; George, Steven Z.; Beneciuk, Jason M.; Wandner, Laura D.; Torres, Calia; Robinson, Michael E.

2014-01-01

Low back pain (LBP) is a common and costly condition that often becomes chronic if not properly addressed. Recent research has shown that psychosocial symptoms can complicate LBP, necessitating more comprehensive screening measures. The present study investigated the role of psychosocial factors, including anger regulation, in pain and disability using a screening measure designed for LBP treated with physical therapy. One-hundred and three LBP patients initiating physical therapy completed an established screening measure to assess risk for developing chronic pain, as well as psychosocial measures assessing anger, depression, anxiety, fear-avoidance, and pain-catastrophizing before and after four weeks of treatment. Dependent variables were pain intensity, physical impairment, and patient-reported disability. Risk subgrouping based on anger and other psychosocial measures was examined using established screening methods and through employing an empirical statistical approach. Analyses revealed that risk subgroups differed according to corresponding levels of negative affect, as opposed to anger alone. General psychosocial distress also predicted disability post-treatment, but, interestingly, did not have a strong relationship to pain. Subsequent hierarchical agglomerative clustering procedures divided patients into overall High and Low Distress groups, with follow-up analyses revealing that the High Distress group had higher baseline measures of pain, disability, and impairment. Findings suggest that anger may be part of generalized negative affect rather than a unique predictor when assessing risk for pain and disability in LBP treatment. Continued research in the area of screening for psychosocial prognostic indicators in LBP may ultimately guide treatment protocols in physical therapy for more comprehensive patient care. PMID:24281272

The impact of subgroup type and subgroup configurational properties on work team performance.

PubMed

Carton, Andrew M; Cummings, Jonathon N

2013-09-01

Scholars have invoked subgroups in a number of theories related to teams, yet certain tensions in the literature remain unresolved. In this article, we address 2 of these tensions, both relating to how subgroups are configured in work teams: (a) whether teams perform better with a greater number of subgroups and (b) whether teams perform better when they have imbalanced subgroups (majorities and minorities are present) or balanced subgroups (subgroups are of equal size). We predict that the impact of the number and balance of subgroups depends on the type of subgroup-whether subgroups are formed according to social identity (i.e., identity-based subgroups) or information processing (i.e., knowledge-based subgroups). We first propose that teams are more adversely affected by 2 identity-based subgroups than by any other number, yet the uniquely negative impact of a 2-subgroup configuration is not apparent for knowledge-based subgroups. Instead, a larger number of knowledge-based subgroups is beneficial for performance, such that 2 subgroups is worse for performance when compared with 3 or more subgroups but better for performance when compared with no subgroups or 1 subgroup. Second, we argue that teams perform better when identity-based subgroups are imbalanced yet knowledge-based subgroups are balanced. We also suggest that there are interactive effects between the number and balance of subgroups-however, the nature of this interaction depends on the type of subgroup. To test these predictions, we developed and validated an algorithm that measures the configurational properties of subgroups in organizational work teams. Results of a field study of 326 work teams from a multinational organization support our predictions. PsycINFO Database Record (c) 2013 APA, all rights reserved

Symptom dimensions and subgroups in childhood-onset schizophrenia.

PubMed

Craddock, Kirsten E S; Zhou, Xueping; Liu, Siyuan; Gochman, Peter; Dickinson, Dwight; Rapoport, Judith L

2017-11-13

This study investigated symptom dimensions and subgroups in the National Institute of Mental Health (NIMH) childhood-onset schizophrenia (COS) cohort and their similarities to adult-onset schizophrenia (AOS) literature. Scores from the Scales for the Assessment of Positive and Negative Symptoms (SAPS & SANS) from 125 COS patients were assessed for fit with previously established symptom dimensions from AOS literature using confirmatory factor analysis (CFA). K-means cluster analysis of each individual's scores on the best fitting set of dimensions was used to form patient clusters, which were then compared using demographic and clinical data. CFA showed the SAPS & SANS data was well suited to a 2-dimension solution, including positive and negative dimensions, out of five well established models. Cluster analysis identified three patient groups characterized by different dimension scores: (1) low scores on both dimensions, (2) high negative, low positive scores, and (3) high scores on both dimensions. These groups had different Full scale IQ, Children's Global Assessment Scale (CGAS) scores, ages of onset, and prevalence of some co-morbid behavior disorders (all p<3.57E-03). Our analysis found distinct symptom-based subgroups within the NIMH COS cohort using an established AOS symptom structure. These findings confirm the heterogeneity of COS and were generally consistent with AOS literature. Published by Elsevier B.V.

Subgrouping For Patients With Low Back Pain: A Multidimensional Approach Incorporating Cluster Analysis & The STarT Back Screening Tool

PubMed Central

Beneciuk, Jason M.; Robinson, Michael E.; George, Steven Z.

2014-01-01

Early screening for psychological distress has been suggested to improve patient management for individuals experiencing low back pain. This study compared two approaches to psychological screening (i.e., multidimensional and unidimensional) so that preliminary recommendations on which approach may be appropriate for use in clinical settings other than primary care could be provided. Specifically, this study investigated STarT Back Screening Tool (SBT): 1) discriminant validity by evaluating its relationship with unidimensional psychological measures and 2) construct validity by evaluating how SBT risk categories compared to empirically derived subgroups using unidimensional psychological and disability measures. Patients (n = 146) receiving physical therapy for LBP were administered the SBT and a battery of unidimensional psychological measures at initial evaluation. Clinical measures consisted of pain intensity and self-reported disability. Several SBT risk dependent relationships (i.e., SBT low < medium < high risk) were identified for unidimensional psychological measure scores with depressive symptom scores associated with the strongest influence on SBT risk categorization. Empirically derived subgroups indicated that there was no evidence of distinctive patterns amongst psychological or disability measures other than high or low profiles, therefore two groups may provide a more clear representation of the level of pain associated psychological distress, maladaptive coping and disability in this setting, as compared to three groups which have been suggested when using the SBT in primary care settings. PMID:25451622

Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications.

PubMed

Kasenda, Benjamin; Schandelmaier, Stefan; Sun, Xin; von Elm, Erik; You, John; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J; Stegert, Mihaela; Olu, Kelechi K; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M; Mertz, Dominik; Akl, Elie A; Bassler, Dirk; Busse, Jason W; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Rosenthal, Rachel; Ebrahim, Shanil; Vandvik, Per O; Johnston, Bradley C; Walter, Martin A; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G; Bucher, Heiner C; Guyatt, Gordon H; Briel, Matthias

2014-07-16

To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. Cohort of protocols of randomised controlled trial and subsequent full journal publications. Six research ethics committees in Switzerland, Germany, and Canada. 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials. © The DISCO study group 2014.

Cost-Effectiveness of Endovascular Stroke Therapy: A Patient Subgroup Analysis From a US Healthcare Perspective.

PubMed

Kunz, Wolfgang G; Hunink, M G Myriam; Sommer, Wieland H; Beyer, Sebastian E; Meinel, Felix G; Dorn, Franziska; Wirth, Stefan; Reiser, Maximilian F; Ertl-Wagner, Birgit; Thierfelder, Kolja M

2016-11-01

Endovascular therapy in addition to standard care (EVT+SC) has been demonstrated to be more effective than SC in acute ischemic large vessel occlusion stroke. Our aim was to determine the cost-effectiveness of EVT+SC depending on patients' initial National Institutes of Health Stroke Scale (NIHSS) score, time from symptom onset, Alberta Stroke Program Early CT Score (ASPECTS), and occlusion location. A decision model based on Markov simulations estimated lifetime costs and quality-adjusted life years (QALYs) associated with both strategies applied in a US setting. Model input parameters were obtained from the literature, including recently pooled outcome data of 5 randomized controlled trials (ESCAPE [Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke], EXTEND-IA [Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial], MR CLEAN [Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands], REVASCAT [Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within 8 Hours of Symptom Onset], and SWIFT PRIME [Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment]). Probabilistic sensitivity analysis was performed to estimate uncertainty of the model results. Net monetary benefits, incremental costs, incremental effectiveness, and incremental cost-effectiveness ratios were derived from the probabilistic sensitivity analysis. The willingness-to-pay was set to $50 000/QALY. Overall, EVT+SC was cost-effective compared with SC (incremental cost: $4938, incremental effectiveness: 1.59 QALYs, and incremental cost-effectiveness ratio: $3110/QALY) in 100% of simulations. In all patient subgroups, EVT+SC led to gained QALYs (range: 0.47-2.12), and mean incremental cost-effectiveness ratios were considered cost

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

Clustering Multiple Sclerosis Subgroups with Multifractal Methods and Self-Organizing Map Algorithm

NASA Astrophysics Data System (ADS)

Karaca, Yeliz; Cattani, Carlo

Magnetic resonance imaging (MRI) is the most sensitive method to detect chronic nervous system diseases such as multiple sclerosis (MS). In this paper, Brownian motion Hölder regularity functions (polynomial, periodic (sine), exponential) for 2D image, such as multifractal methods were applied to MR brain images, aiming to easily identify distressed regions, in MS patients. With these regions, we have proposed an MS classification based on the multifractal method by using the Self-Organizing Map (SOM) algorithm. Thus, we obtained a cluster analysis by identifying pixels from distressed regions in MR images through multifractal methods and by diagnosing subgroups of MS patients through artificial neural networks.

Can patients at risk for persistent negative symptoms be identified during their first episode of psychosis?

PubMed

Malla, Ashok K; Norman, Ross M G; Takhar, Jatinder; Manchanda, Rahul; Townsend, Laurel; Scholten, Derek; Haricharan, Raj

2004-07-01

Patients with schizophrenia who show persistent negative symptoms are an important subgroup, but they are difficult to identify early in the course of illness. The objective of this study was to examine characteristics that discriminate between first-episode psychosis (FEP) patients in whom primary negative symptoms did or did not persist after 1 year of treatment. Patients with a DSM-IV diagnosis of FEP whose primary negative symptoms did (N = 36) or did not (N = 35) persist at 1 year were contrasted on their baseline and 1-year characteristics. Results showed that patients with persistent primary negative symptoms (N = 36) had a significantly longer duration of untreated psychosis (p < .005), worse premorbid adjustment during early (p < .001) and late adolescence (p < .01), and a higher level of affective flattening (p < .01) at initial presentation compared with patients with transitory primary negative symptoms. The former group also showed significantly lower remission rates at 1 year (p < .001). Multiple regression analysis confirmed the independent contribution of duration of untreated psychosis, premorbid adjustment, and affective flattening at baseline to the patients' likelihood of developing persistent negative symptoms. It may therefore be possible to distinguish a subgroup of FEP patients whose primary negative symptoms are likely to persist on the basis of characteristics shown at initial presentation for treatment.

Subgroup analysis of telehealthcare for patients with chronic obstructive pulmonary disease: the cluster-randomized Danish Telecare North Trial

PubMed Central

Witt Udsen, Flemming; Lilholt, Pernille H; Hejlesen, Ole K; Ehlers, Lars H

2017-01-01

Purpose Results from the Danish cluster-randomized trial of telehealthcare to 1,225 patients with chronic obstructive pulmonary disease (COPD), the Danish Telecare North Trial, concluded that the telehealthcare solution was unlikely to be cost-effective, by applying international willingness-to-pay threshold values. The purpose of this article was to assess potential sources of variation across subgroups, which could explain overall cost-effectiveness results or be utilized in future economic studies in telehealthcare research. Methods First, the cost-structures and cost-effectiveness across COPD severities were analyzed. Second, five additional subgroup analyses were conducted, focusing on differences in cost-effectiveness across a set of comorbidities, age-groups, genders, resource patterns (resource use in the social care sector prior to randomization), and delivery sites. All subgroups were investigated post hoc. In analyzing cost-effectiveness, two separate linear mixed-effects models with treatment-by-covariate interactions were applied: one for quality-adjusted life-year (QALY) gain and one for total healthcare and social sector costs. Probabilistic sensitivity analysis was used for each subgroup result in order to quantify the uncertainty around the cost-effectiveness results. Results The study concludes that, across the COPD severities, patients with severe COPD (GOLD 3 classification) are likely to be the most cost-effective group. This is primarily due to lower hospital-admission and primary-care costs. Telehealthcare for patients younger than 60 years is also more likely to be cost-effective than for older COPD patients. Overall, results indicate that existing resource patterns of patients and variations in delivery-site practices might have a strong influence on cost-effectiveness, possibly stronger than the included health or sociodemographic sources of heterogeneity. Conclusion Future research should focus more on sources of heterogeneity found in

A Systematic Approach to Subgroup Classification in Intellectual Disability

ERIC Educational Resources Information Center

Schalock, Robert L.; Luckasson, Ruth

2015-01-01

This article describes a systematic approach to subgroup classification based on a classification framework and sequential steps involved in the subgrouping process. The sequential steps are stating the purpose of the classification, identifying the classification elements, using relevant information, and using clearly stated and purposeful…

Efficacy of Tofacitinib for the Treatment of Moderate-to-Severe Chronic Plaque Psoriasis in Patient Subgroups from Two Randomised Phase 3 Trials.

PubMed

Menter, M Alan; Papp, Kim A; Cather, Jennifer; Leonardi, Craig; Pariser, David M; Krueger, James G; Wohlrab, Johannes; Amaya-Guerra, Mario; Kaszuba, Andrzej; Nadashkevich, Oleg; Tsai, Tsen-Fang; Gupta, Pankaj; Tan, Huaming; Valdez, Hernan; Mallbris, Lotus; Tatulych, Svitlana

2016-05-01

Tofacitinib is a Janus kinase inhibitor being investigated for the treatment of moderate-to-severe plaque psoriasis. We report efficacy of tofacitinib in patient subgroups based on pooled data from two Phase 3 trials (NCT01276639, NCT01309737).
To assess consistency of treatment effects of tofacitinib versus placebo in subgroups defined by baseline characteristics, and to ascertain whether baseline characteristics are of value in optimizing tofacitinib use.
Pooled data from the two trials were used to evaluate ≥75% reduction in PASI from baseline (PASI75 response) in subgroups defined by age, age at psoriasis onset, gender, race, geographical region, weight, body mass index, diabetes, metabolic syndrome, tobacco/alcohol use, psoriatic arthritis, disease activity, and prior therapy.
Week 16 PASI75 response rates (N=1843) were 43%, 59% and 9% with tofacitinib 5 and 10mg twice daily (BID) and placebo, respectively (each P<0.0001 versus placebo). Tofacitinib 5 and 10mg BID were effective regardless of baseline characteristics. Across subgroups, tofacitinib generally produced greater response rates with the 10 versus 5mg BID dosage. Lower absolute response rates were seen in heavier patients and patients with prior biologic experience.
Both tofacitinib dosages demonstrated consistent efficacy versus placebo across subgroups. Lower response rates were seen in heavier patients and those with prior biologic experience. Tofacitinib 10mg BID resulted in a substantial proportion of responders regardless of baseline characteristics.

J Drugs Dermatol. 2016;15(5):568-580.

The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups.

PubMed

Curtis, Christina; Shah, Sohrab P; Chin, Suet-Feung; Turashvili, Gulisa; Rueda, Oscar M; Dunning, Mark J; Speed, Doug; Lynch, Andy G; Samarajiwa, Shamith; Yuan, Yinyin; Gräf, Stefan; Ha, Gavin; Haffari, Gholamreza; Bashashati, Ali; Russell, Roslin; McKinney, Steven; Langerød, Anita; Green, Andrew; Provenzano, Elena; Wishart, Gordon; Pinder, Sarah; Watson, Peter; Markowetz, Florian; Murphy, Leigh; Ellis, Ian; Purushotham, Arnie; Børresen-Dale, Anne-Lise; Brenton, James D; Tavaré, Simon; Caldas, Carlos; Aparicio, Samuel

2012-04-18

The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in ~40% of genes, with the landscape dominated by cis- and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP and MAP2K4. Unsupervised analysis of paired DNA–RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, oestrogen-receptor-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the ‘CNA-devoid’ subgroup and a basal-specific chromosome 5 deletion-associated mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic CNAs on the transcriptome.

The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups

PubMed Central

Curtis, Christina; Shah, Sohrab P.; Chin, Suet-Feung; Turashvili, Gulisa; Rueda, Oscar M.; Dunning, Mark J.; Speed, Doug; Lynch, Andy G.; Samarajiwa, Shamith; Yuan, Yinyin; Gräf, Stefan; Ha, Gavin; Haffari, Gholamreza; Bashashati, Ali; Russell, Roslin; McKinney, Steven; Langerød, Anita; Green, Andrew; Provenzano, Elena; Wishart, Gordon; Pinder, Sarah; Watson, Peter; Markowetz, Florian; Murphy, Leigh; Ellis, Ian; Purushotham, Arnie; Børresen-Dale, Anne-Lise; Brenton, James D.; Tavaré, Simon; Caldas, Carlos; Aparicio, Samuel

2012-01-01

The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in ~40% of genes, with the landscape dominated by cis- and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP and MAP2K4. Unsupervised analysis of paired DNA–RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, oestrogen-receptor-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the ‘CNA-devoid’ subgroup and a basal-specific chromosome 5 deletion-associated mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic CNAs on the transcriptome. PMID:22522925

High utilizers of medical care: a crucial subgroup among somatizing patients.

PubMed

Hiller, Wolfgang; Fichter, Manfred M

2004-04-01

Patients with somatoform disorders (SFD) are likely to overutilize healthcare services. This study investigates (a) whether extraordinarily high medical costs can be predicted from patient characteristics or psychopathology, and (b) whether high-utilizing patients respond differently to cognitive-behavioral treatment. We compared 42 SFD high utilizers with 53 SFD average utilizers and 29 patients suffering from other than SFD mental disorders. High utilization was defined by healthcare expenditures of > or = 2500 euros during the past 2 years. Costs were computed from medical and billing records of health insurance companies. Somatization distress, hypochondriasis, depression, dysfunctional cognitions related to bodily symptoms, general psychopathology, personality profiles, and psychosocial disabilities were assessed before treatment. High utilizers had higher levels of self- and observer-rated illness behavior, self-perceived bodily weakness, and psychosocial disabilities. Although they did not report more somatization symptoms, their subjective symptom distress was higher. There were no differences between high and average utilizers concerning general psychopathology, DSM-IV comorbidity, and personality profiles. Treatment improvements were similar. High- and average-utilizing somatizers represent distinguishable subgroups. The results emphasize the importance of mechanisms specifically related to SFD and may enhance the early detection of patients who are likely to develop overutilization. Copyright 2004 Elsevier Inc.

Application of implantable hemodynamic monitoring in the management of patients with diastolic heart failure: a subgroup analysis of the COMPASS-HF trial.

PubMed

Zile, Michael R; Bourge, Robert C; Bennett, Tom D; Stevenson, Lynne Warner; Cho, Yong K; Adamson, Philip B; Aaron, Mark F; Aranda, Juan M; Abraham, William T; Smart, Frank W; Kueffer, Fred J

2008-12-01

Nearly half of all patients with chronic heart failure (HF) have a normal ejection fraction (EF), and abnormal diastolic function (ie, diastolic heart failure [DHF]). However, appropriate management of DHF patients remains a difficult and uncertain challenge. The Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial was designed to evaluate whether an implantable hemodynamic monitor (IHM) was safe and effective in reducing the number of heart failure-related events (HFRE) in patients with chronic HF. The current study presents data on a prespecified and planned subgroup analysis from the COMPASS-HF trial: 70 patients with an EF > or =50% (ie, DHF). As such, this represents a subgroup analysis of the COMPASS-HF Trial. DHF patients were randomized to IHM-guided care (treatment) vs. standard care (control) for 6 months. All 70 patients received optimal medical therapy, but the hemodynamic information from the IHM was used to guide patient management only in the treatment group. The HFRE rate in DHF patients randomized to treatment was 0.58 events/6 months compared with DHF patients randomized to control, which was 0.73 events/6 months; this represented a 20% nonsignificant reduction in the overall HFRE rate in the treatment group (95% CI = -46, 56, P = .66). There was a 29% nonsignificant reduction in the relative risk of a HF hospitalization in the DHF patients randomized to treatment compared with DHF patients randomized to control (95% CI = -69, 70, P = .43). The IHM was shown to be safe and was associated with a very low system-related and procedure-related complication rate in DHF patients. However, in this subgroup analysis limited to 70 DHF patients, the addition IHM-guided care did not significantly lower the rate of HFR events. The results of this subgroup analysis in DHF patients, for whom there are currently no proven, effective management strategies, will be used to design future studies defining the

Low Back Pain Subgroups using Fear-Avoidance Model Measures: Results of a Cluster Analysis

PubMed Central

Beneciuk, Jason M.; Robinson, Michael E.; George, Steven Z.

2012-01-01

Objectives The purpose of this secondary analysis was to test the hypothesis that an empirically derived psychological subgrouping scheme based on multiple Fear-Avoidance Model (FAM) constructs would provide additional capabilities for clinical outcomes in comparison to a single FAM construct. Methods Patients (n = 108) with acute or sub-acute low back pain (LBP) enrolled in a clinical trial comparing behavioral physical therapy interventions to classification based physical therapy completed baseline questionnaires for pain catastrophizing (PCS), fear-avoidance beliefs (FABQ-PA, FABQ-W), and patient-specific fear (FDAQ). Clinical outcomes were pain intensity and disability measured at baseline, 4-weeks, and 6-months. A hierarchical agglomerative cluster analysis was used to create distinct cluster profiles among FAM measures and discriminant analysis was used to interpret clusters. Changes in clinical outcomes were investigated with repeated measures ANOVA and differences in results based on cluster membership were compared to FABQ-PA subgrouping used in the original trial. Results Three distinct FAM subgroups (Low Risk, High Specific Fear, and High Fear & Catastrophizing) emerged from cluster analysis. Subgroups differed on baseline pain and disability (p’s<.01) with the High Fear & Catastrophizing subgroup associated with greater pain than the Low Risk subgroup (p<.01) and the greatest disability (p’s<.05). Subgroup × time interactions were detected for both pain and disability (p’s<.05) with the High Fear & Catastrophizing subgroup reporting greater changes in pain and disability than other subgroups (p’s<.05). In contrast, FABQ-PA subgroups used in the original trial were not associated with interactions for clinical outcomes. Discussion These data suggest that subgrouping based on multiple FAM measures may provide additional information on clinical outcomes in comparison to determining subgroup status by FABQ-PA alone. Subgrouping methods for

Latent profiles of problem behavior within learning, peer, and teacher contexts: identifying subgroups of children at academic risk across the preschool year.

PubMed

Bulotsky-Shearer, Rebecca J; Bell, Elizabeth R; Domínguez, Ximena

2012-12-01

Employing a developmental and ecological model, the study identified initial levels and rates of change in academic skills for subgroups of preschool children exhibiting problem behavior within routine classroom situations. Six distinct latent profile types of emotional and behavioral adjustment were identified for a cohort of low-income children early in the preschool year (N=4417). Profile types provided a descriptive picture of patterns of classroom externalizing, internalizing, and situational adjustment problems common to subgroups of children early in the preschool year. The largest profile type included children who exhibited low problem behavior and were characterized as well-adjusted to the preschool classroom early in the year. The other profile types were characterized by distinct combinations of elevated internalizing, externalizing, and situational problem behavior. Multinomial logistic regression identified younger children and boys at increased risk for classification in problem types, relative to the well-adjusted type. Latent growth models indicated that children classified within the extremely socially and academically disengaged profile type, started and ended the year with the lowest academic skills, relative to all other types. Implications for future research, policy, and practice are discussed. Copyright © 2012 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Identification of five chronic obstructive pulmonary disease subgroups with different prognoses in the ECLIPSE cohort using cluster analysis.

PubMed

Rennard, Stephen I; Locantore, Nicholas; Delafont, Bruno; Tal-Singer, Ruth; Silverman, Edwin K; Vestbo, Jørgen; Miller, Bruce E; Bakke, Per; Celli, Bartolomé; Calverley, Peter M A; Coxson, Harvey; Crim, Courtney; Edwards, Lisa D; Lomas, David A; MacNee, William; Wouters, Emiel F M; Yates, Julie C; Coca, Ignacio; Agustí, Alvar

2015-03-01

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that likely includes clinically relevant subgroups. To identify subgroups of COPD in ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) subjects using cluster analysis and to assess clinically meaningful outcomes of the clusters during 3 years of longitudinal follow-up. Factor analysis was used to reduce 41 variables determined at recruitment in 2,164 patients with COPD to 13 main factors, and the variables with the highest loading were used for cluster analysis. Clusters were evaluated for their relationship with clinically meaningful outcomes during 3 years of follow-up. The relationships among clinical parameters were evaluated within clusters. Five subgroups were distinguished using cross-sectional clinical features. These groups differed regarding outcomes. Cluster A included patients with milder disease and had fewer deaths and hospitalizations. Cluster B had less systemic inflammation at baseline but had notable changes in health status and emphysema extent. Cluster C had many comorbidities, evidence of systemic inflammation, and the highest mortality. Cluster D had low FEV1, severe emphysema, and the highest exacerbation and COPD hospitalization rate. Cluster E was intermediate for most variables and may represent a mixed group that includes further clusters. The relationships among clinical variables within clusters differed from that in the entire COPD population. Cluster analysis using baseline data in ECLIPSE identified five COPD subgroups that differ in outcomes and inflammatory biomarkers and show different relationships between clinical parameters, suggesting the clusters represent clinically and biologically different subtypes of COPD.

A utility-based design for randomized comparative trials with ordinal outcomes and prognostic subgroups.

PubMed

Murray, Thomas A; Yuan, Ying; Thall, Peter F; Elizondo, Joan H; Hofstetter, Wayne L

2018-01-22

A design is proposed for randomized comparative trials with ordinal outcomes and prognostic subgroups. The design accounts for patient heterogeneity by allowing possibly different comparative conclusions within subgroups. The comparative testing criterion is based on utilities for the levels of the ordinal outcome and a Bayesian probability model. Designs based on two alternative models that include treatment-subgroup interactions are considered, the proportional odds model and a non-proportional odds model with a hierarchical prior that shrinks toward the proportional odds model. A third design that assumes homogeneity and ignores possible treatment-subgroup interactions also is considered. The three approaches are applied to construct group sequential designs for a trial of nutritional prehabilitation versus standard of care for esophageal cancer patients undergoing chemoradiation and surgery, including both untreated patients and salvage patients whose disease has recurred following previous therapy. A simulation study is presented that compares the three designs, including evaluation of within-subgroup type I and II error probabilities under a variety of scenarios including different combinations of treatment-subgroup interactions. © 2018, The International Biometric Society.

Differences in Psychosocial Predictors of Obesity Among LGBT Subgroups.

PubMed

Warren, Jacob C; Smalley, K Bryant; Barefoot, K Nikki

2016-08-01

The purpose of the current study was to examine the overall presence of and differences in rates of overweight/obesity among a large, nationally diverse sample of lesbian, gay, bisexual, transgender (LGBT)-identified individuals (i.e., cisgender lesbians, cisgender gay men, cisgender bisexual women, cisgender bisexual men, transgender women, and transgender men) and to identify specific psychosocial predictors of obesity within each of the six LGBT subgroups. A total of 2702 LGBT-identified participants participated in the online study. Participants completed a series of demographic questions (including weight and height) and the Depression Anxiety Stress Scale 21. The percentage of participants who were overweight/obese did not differ significantly across LGBT subgroups, with 61.1% of the total sample being overweight/obese. However, the percentage of participants who self-reported body mass indexes in the obese range differed significantly across the six LGBT subgroups, with the highest prevalence in transgender men (46.0%). In addition, the predictors of obesity varied by subgroup, with age a significant predictor for cisgender lesbians, cisgender gay men, and cisgender bisexual women, relationship status for cisgender bisexual women, employment status for both cisgender gay men and cisgender bisexual women, education level for cisgender lesbians, and depression, anxiety, and stress for cisgender gay men. None of the examined psychosocial factors emerged as predictors of obesity for cisgender bisexual men, transgender women, or transgender men. These findings suggest that there are substantial variations in the presence and predictors of obesity across LGBT subgroups that support the need for culturally tailored healthy weight promotion efforts within the LGBT community.

Prevalence of Psychiatric Comorbidity in Symptomatic Gastroesophageal Reflux Subgroups.

PubMed

Bilgi, Mustafa Melih; Vardar, Rukiye; Yıldırım, Esra; Veznedaroğlu, Baybars; Bor, Serhat

2017-04-01

Limited data exist regarding the psychosocial aspects of gastroesophageal reflux disease (GERD). Some GERD subgroups, such as functional heartburn and hypersensitive esophagus, might show different psychiatric comorbidities than others. We aimed to evaluate the psychiatric comorbidities of GERD subgroups using a cross-sectional design. A group of GERD patients at a tertiary outpatient clinic were evaluated via upper GIS (gastrointestinal system) endoscopy, esophageal manometry, and 24-h impedance-pH monitoring. Thirty-nine patients diagnosed with erosive reflux disease, 44 with non-erosive reflux disease, 20 with functional heartburn, 11 with hypersensitive esophagus, and 44 healthy controls participated. Psychiatric diagnoses were made using the Structured Clinical Interview for Diagnostics and Statistical Manual of Mental Disorders IV. Psychometric measurements of the patients were performed using the Somatosensory Amplification Scale, Beck Depression Inventory, State-Trait Anxiety Inventory, and Short-Form 36. Healthy controls were evaluated with the same psychometric scales except for the Short-Form 36. All of the GERD subgroups were significantly more depressed than the control group. Depressive disorders were significantly more prevalent in the functional heartburn group than in the non-erosive reflux disease and erosive reflux disease groups. The trait anxiety level of the functional heartburn group was significantly higher than those of the control and non-erosive reflux disease groups. The quality of life scores of the GERD subgroups were significantly lower than the population standards. Depressive disorders were frequently comorbid in the GERD subgroups studied (30-65 %). It is essential to consider the high prevalence rates of comorbid depression when managing GERD.

Subgroups at high risk for ischaemic heart disease:identification and validation in 67 000 individuals from the general population

PubMed Central

Frikke-Schmidt, Ruth; Tybjærg-Hansen, Anne; Dyson, Greg; Haase, Christiane L; Benn, Marianne; Nordestgaard, Børge G; Sing, Charles F

2015-01-01

Background The aetiology of ischaemic heart disease (IHD) is complex and is influenced by a spectrum of environmental factors and susceptibility genes. Traditional statistical modelling considers such factors to act independently in an additive manner. The Patient Rule-Induction Method (PRIM) is a multi-model building strategy for evaluating risk attributable to context-dependent gene and environmental effects. Methods PRIM was applied to 9073 participants from the prospective Copenhagen City Heart Study (CCHS). Gender-specific cumulative incidences were estimated for subgroups defined by categories of age, smoking, hypertension, diabetes, body mass index, total cholesterol, high-density lipoprotein cholesterol and triglycerides and by 94 single nucleotide variants (SNVs).Cumulative incidences for subgroups were validated using an independently ascertained sample of 58 240 participants from the Copenhagen General Population Study (CGPS). Results In the CCHS the overall cumulative incidences were 0.17 in women and 0.21 in men. PRIM identified six and four mutually exclusive subgroups in women and men, respectively, with cumulative incidences of IHD ranging from 0.02 to 0.34. Cumulative incidences of IHD generated by PRIM in the CCHS were validated in four of the six subgroups of women and two of the four subgroups of men in the CGPS. Conclusions PRIM identified high-risk subgroups characterized by specific contexts of selected values of traditional risk factors and genetic variants. These subgroups were validated in an independently ascertained cohort study. Thus, a multi-model strategy may identify groups of individuals with substantially higher risk of IHD than the overall risk for the general population. PMID:25361584

IDENTIFYING A SUSCEPTIBLE SUBGROUP: EFFECTS OF THE PITTSBURGH AIR POLLUTION EPISODE UPON SCHOOL CHILDREN

EPA Science Inventory

Pulmonary function test results on 224 parochial schoolchildren collected during and after the Pittsburgh air pollution episode of November 1975 were reanalyzed to determine whether a small subgroup of susceptible children could be defined. Individual regressions of three-quarter...

A single test for rejecting the null hypothesis in subgroups and in the overall sample.

PubMed

Lin, Yunzhi; Zhou, Kefei; Ganju, Jitendra

2017-01-01

In clinical trials, some patient subgroups are likely to demonstrate larger effect sizes than other subgroups. For example, the effect size, or informally the benefit with treatment, is often greater in patients with a moderate condition of a disease than in those with a mild condition. A limitation of the usual method of analysis is that it does not incorporate this ordering of effect size by patient subgroup. We propose a test statistic which supplements the conventional test by including this information and simultaneously tests the null hypothesis in pre-specified subgroups and in the overall sample. It results in more power than the conventional test when the differences in effect sizes across subgroups are at least moderately large; otherwise it loses power. The method involves combining p-values from models fit to pre-specified subgroups and the overall sample in a manner that assigns greater weight to subgroups in which a larger effect size is expected. Results are presented for randomized trials with two and three subgroups.

Efficacy and safety of golimumab in Indian patients with rheumatoid arthritis: Subgroup data from GO-MORE study.

PubMed

Pal, Sarvajeet; Veeravalli, Sarath Chandra Mouli; Das, Siddharth Kumar; Shobha, Vineeta; Uppuluri, Ramakrishna Rao; Dharmanand, B G; Nadkar, Milind; Hsia, Elizabeth; Fei, Kaiyin; Yao, Ruji; Khalifa, Ahmed

2016-11-01

To conduct a subgroup analysis of GO-MORE trial Part 1, comparing efficacy and safety of add-on subcutaneous golimumab therapy in rheumatoid arthritis (RA) patients enrolled from and outside India. GO-MORE was an open-label, multicenter, prospective trial of add-on golimumab in biologic-naïve RA patients, having active disease despite being on conventional DMARD regimen(s). Part 1 of the study was chosen as the focus of this subgroup analysis because a substantial number of Indian patients (106) were enrolled compared to no Indian patients in Part 2. The primary efficacy outcome was proportion of patients achieving good to moderate DAS28-ESR (Disease Activity Score of 28 joints calculated using erythrocyte sedimentation rate) European League Against Rheumatism (EULAR) response at month 6. Efficacy evaluable population comprised of 105 and 3175 patients from India and outside India, respectively. Safety analysis included 106 patients enrolled from India and 3251 from outside India. A higher proportion of Indian patients had a high disease activity as measured by DAS28 ESR than outside India patients. At month 6, the proportion of Indian and non-Indian patients achieving DAS28-ESR, DAS28 - C-reactive protein, simplified disease activity index (SDAI) remission, and EuroQoL Quality-of-Life Questionnaire (EQ-5D) scores were comparable. Incidence of all adverse events was lower in Indian patients. There were no deaths, cases of tuberculosis or malignancy reported in the patients from India at month 6. The efficacy and safety results with add-on golimumab were consistent between RA patients from India and outside India, despite high baseline disease activity in the Indian patients. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis.

PubMed

Geersing, G J; Zuithoff, N P A; Kearon, C; Anderson, D R; Ten Cate-Hoek, A J; Elf, J L; Bates, S M; Hoes, A W; Kraaijenhagen, R A; Oudega, R; Schutgens, R E G; Stevens, S M; Woller, S C; Wells, P S; Moons, K G M

2014-03-10

To assess the accuracy of the Wells rule for excluding deep vein thrombosis and whether this accuracy applies to different subgroups of patients. Meta-analysis of individual patient data. Authors of 13 studies (n = 10,002) provided their datasets, and these individual patient data were merged into one dataset. Studies were eligible if they enrolled consecutive outpatients with suspected deep vein thrombosis, scored all variables of the Wells rule, and performed an appropriate reference standard. Multilevel logistic regression models, including an interaction term for each subgroup, were used to estimate differences in predicted probabilities of deep vein thrombosis by the Wells rule. In addition, D-dimer testing was added to assess differences in the ability to exclude deep vein thrombosis using an unlikely score on the Wells rule combined with a negative D-dimer test result. Overall, increasing scores on the Wells rule were associated with an increasing probability of having deep vein thrombosis. Estimated probabilities were almost twofold higher in patients with cancer, in patients with suspected recurrent events, and (to a lesser extent) in males. An unlikely score on the Wells rule (≤ 1) combined with a negative D-dimer test result was associated with an extremely low probability of deep vein thrombosis (1.2%, 95% confidence interval 0.7% to 1.8%). This combination occurred in 29% (95% confidence interval 20% to 40%) of patients. These findings were consistent in subgroups defined by type of D-dimer assay (quantitative or qualitative), sex, and care setting (primary or hospital care). For patients with cancer, the combination of an unlikely score on the Wells rule and a negative D-dimer test result occurred in only 9% of patients and was associated with a 2.2% probability of deep vein thrombosis being present. In patients with suspected recurrent events, only the modified Wells rule (adding one point for the previous event) is safe. Combined with a negative D

Tracking cohesive subgroups over time in inferred social networks

NASA Astrophysics Data System (ADS)

Chin, Alvin; Chignell, Mark; Wang, Hao

2010-04-01

As a first step in the development of community trackers for large-scale online interaction, this paper shows how cohesive subgroup analysis using the Social Cohesion Analysis of Networks (SCAN; Chin and Chignell 2008) and Data-Intensive Socially Similar Evolving Community Tracker (DISSECT; Chin and Chignell 2010) methods can be applied to the problem of identifying cohesive subgroups and tracking them over time. Three case studies are reported, and the findings are used to evaluate how well the SCAN and DISSECT methods work for different types of data. In the largest of the case studies, variations in temporal cohesiveness are identified across a set of subgroups extracted from the inferred social network. Further modifications to the DISSECT methodology are suggested based on the results obtained. The paper concludes with recommendations concerning further research that would be beneficial in addressing the community tracking problem for online data.

The value of maximum jaw motion measurements for distinguishing between common temporomandibular disorder subgroups.

PubMed

Masumi, S; Kim, Y J; Clark, G T

2002-05-01

The purpose of this study was to determine if mandibular motion measurements could be used to distinguish between common temporomandibular disorder (TMD) subgroups that were established on the basis of only clinical signs and symptoms. Patients were 41 consecutive TMD clinic patients (31 women and 10 men). These patients were divided into 6 typical TMD subgroups. The subgroups were patients with (1) arthromyalgia, (2) arthromyalgia with disk condyle incoordination, (3) disk condyle incoordination only, (4) osteoarthritis, (5) suspected disk displacement without reduction, or (6) other diagnoses. There were no subjects in the other-diagnosis subgroup and only 1 subject with suspected disk displacement without reduction who was dropped without further consideration. The data for mean age showed that the osteoarthritis subgroup (n = 12) was statistically older (17 years) than the disk-condyle-incoordination-only subgroup (n = 11). The mean age of the other 2 groups, arthromyalgia (n = 11) and arthromyalgia with disk condyle incoordination (n = 6), was between the osteoarthritis and the disk-condyle-incoordination-only subgroups. For the 4 TMD subgroups whose data were analyzed, the mean differences between similar jaw opening measurements ranged from 6 to 8 mm with a standard deviation of approximately 8 to 10 mm. The mean left lateral motions were 0.5 to 1.3 mm larger than observed on the right. The widest mean jaw opening (56 mm) occurred in the disk-condyle-incoordination-only group. These differences were not found to be statistically significant. Analysis of opening, lateral and protrusive jaw motion data showed these measurements could not reliably differentiate between patients with osteoarthritis, arthromyalgia, arthromyalgia with disk condyle incoordination and disk condyle incoordination only.

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

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

A brain-derived neurotrophic factor polymorphism Val66Met identifies fibromyalgia syndrome subgroup with higher body mass index and C-reactive protein.

PubMed

Xiao, Yangming; Russell, I Jon; Liu, Ya-Guang

2012-08-01

A common single nucleotide polymorphism (SNP) in the gene of brain-derived neurotrophic factor (BDNF) results from a substitution at position 66 from valine (Val) to methionine (Met) and may predispose to human neuropsychiatric disorders. We proposed to determine whether these BDNF gene SNPs were associated with fibromyalgia syndrome (FMS) and/or any of its typical phenotypes. Patients with FMS (N = 95) and healthy normal controls (HNC, N = 58) were studied. Serum high-sensitivity C-reactive protein (hsCRP) levels were measured using an enzyme-linked immunosorbent assay (ELISA). The BDNF SNPs were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).The BDNF SNP distribution was 65 (68%) Val/Val, 28 (30%) Val/Met, and 2 (2%) Met/Met for FMS and 40 (69%), 17(29%), and 1 (2%) for HNC, respectively. The serum high-sensitivity C-reactive protein (hsCRP)and body mass index (BMI) in FMS were higher than in HNC. The FMS with BDNF Val66Val had significantly higher mean BMI (P = 0.0001) and hsCRP (P = 0.02) than did FMS carrying the Val66Met genotype. This pattern was not found in HNC. Phenotypic measures of subjective pain, pain threshold, depression, or insomnia did not relate to either of the BDNF SNPs in FMS. The relative distribution BDNF SNPs did not differ between FMS and HNC. The BDNF Val66Met polymorphism is not selective for FMS. The BDNF Val66Val SNP identifies a subgroup of FMS with elevated hsCRP and higher BMI. This is the first study to associate a BDNF polymorphism with a FMS subgroup phenotype.

Identifying differences in early literacy skills across subgroups of language-minority children: A latent profile analysis.

PubMed

Lonigan, Christopher J; Goodrich, J Marc; Farver, JoAnn M

2018-04-01

Despite acknowledgment that language-minority children come from a wide variety of home language backgrounds and have a wide range of proficiency in their first (L1) and second (L2) languages, it is unknown whether differences across language-minority children in relative and absolute levels of proficiency in L1 and L2 predict subsequent development of literacy-related skills. The purpose of this study was to identify subgroups of language-minority children and evaluate whether differences in level and rate of growth of early literacy skills differed across subgroups. Five-hundred and twenty-six children completed measures of Spanish and English language and early literacy skills at the beginning, middle, and end of the preschool year. Latent growth models indicated that children's early literacy skills were increasing over the course of the preschool year. Latent profile analysis indicated that language-minority children could be classified into nine distinct groups, each with unique patterns of absolute and relative levels of proficiency in L1 and L2. Results of three-step mixture models indicated that profiles were closely associated with level of early literacy skills at the beginning of the preschool year. Initial level of early literacy skills was positively associated with growth in code-related skills (i.e., print knowledge, phonological awareness) and inversely associated with growth in language skills. These findings suggest that language-minority children are a diverse group with regard to their L1 and L2 proficiencies and that growth in early literacy skills is most associated with level of proficiency in the same language. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Effects of canagliflozin, an SGLT2 inhibitor, on hepatic function in Japanese patients with type 2 diabetes mellitus: pooled and subgroup analyses of clinical trials.

PubMed

Seko, Yuya; Sumida, Yoshio; Sasaki, Kazuyo; Itoh, Yoshito; Iijima, Hiroaki; Hashimoto, Toshio; Ishii, Shinichi; Inagaki, Nobuya

2018-01-01

We aimed to investigate the efficacy of canagliflozin (based on its effect on liver function and blood glucose levels) and its safety in high alanine aminotransferase (ALT) patients (ALT >30 U/L). This post hoc analysis of canagliflozin in type 2 diabetes mellitus (T2DM) patients was divided into Study 1 (pooled analysis of 12- and 24-week placebo-controlled, monotherapy studies) and Study 2 (52-week monotherapy/combination therapy study). The canagliflozin 100 mg group data were compared with placebo or baseline ALT subgroup (baseline ALT >30 or ≤30 U/L) data. The primary endpoint was change in ALT level from baseline. Secondary endpoints were changes in efficacy-related parameters. Adverse events (AEs) were evaluated. The mean ALT change at 12 weeks was -10.3 ± 11.7 and -3.2 ± 17.6 U/L in the canagliflozin vs. placebo group in the high ALT subgroup (P = 0.0206); no significant difference was shown in the low ALT subgroup (Study 1). In both ALT subgroups, glycosylated hemoglobin (HbA1c) and body weight were significantly reduced in the canagliflozin vs. placebo group (all P < 0.0001). The mean change in ALT at 52 weeks was -16.0 ± 18.8 U/L in the high ALT subgroup (P < 0.0001, Study 2). The incidence of AEs or serious AEs in the high ALT subgroup in the canagliflozin group was similar to that in the placebo group (Study 1) or low ALT subgroup (Studies 1 and 2). In T2DM patients with impaired liver function, canagliflozin may improve liver function, reduce HbA1c and body weight, and be well tolerated.

Interpersonal differentiation within depression diagnosis: relating interpersonal subgroups to symptom load and the quality of the early therapeutic alliance.

PubMed

Grosse Holtforth, Martin; Altenstein, David; Krieger, Tobias; Flückiger, Christoph; Wright, Aidan G C; Caspar, Franz

2014-01-01

We examined interpersonal problems in psychotherapy outpatients with a principal diagnosis of a depressive disorder in routine care (n=361). These patients were compared to a normative non-clinical sample and to outpatients with other principal diagnoses (n=959). Furthermore, these patients were statistically assigned to interpersonally defined subgroups that were compared regarding symptoms and the quality of the early alliance. The sample of depressive patients reported higher levels of interpersonal problems than the normative sample and the sample of outpatients without a principal diagnosis of depression. Latent Class Analysis identified eight distinct interpersonal subgroups, which differed regarding self-reported symptom load and the quality of the early alliance. However, therapists' alliance ratings did not differentiate between the groups. This interpersonal differentiation within the group of patients with a principal diagnosis of depression may add to a personalized psychotherapy based on interpersonal profiles.

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.

Conditions for Effective Application of Analysis of Symmetrically-Predicted Endogenous Subgroups

ERIC Educational Resources Information Center

Peck, Laura R.

2015-01-01

Several analytic strategies exist for opening up the "black box" to reveal more about what drives policy and program impacts. This article focuses on one of these strategies: the Analysis of Symmetrically-Predicted Endogenous Subgroups (ASPES). ASPES uses exogenous baseline data to identify endogenously-defined subgroups, keeping the…

Active medulloblastoma enhancers reveal subgroup-specific cellular origins

PubMed Central

Lin, Charles Y.; Erkek, Serap; Tong, Yiai; Yin, Linlin; Federation, Alexander J.; Zapatka, Marc; Haldipur, Parthiv; Kawauchi, Daisuke; Risch, Thomas; Warnatz, Hans-Jörg; Worst, Barbara C.; Ju, Bensheng; Orr, Brent A.; Zeid, Rhamy; Polaski, Donald R.; Segura-Wang, Maia; Waszak, Sebastian M.; Jones, David T.W.; Kool, Marcel; Hovestadt, Volker; Buchhalter, Ivo; Sieber, Laura; Johann, Pascal; Chavez, Lukas; Gröschel, Stefan; Ryzhova, Marina; Korshunov, Andrey; Chen, Wenbiao; Chizhikov, Victor V.; Millen, Kathleen J.; Amstislavskiy, Vyacheslav; Lehrach, Hans; Yaspo, Marie-Laure; Eils, Roland; Lichter, Peter; Korbel, Jan O.; Pfister, Stefan M.; Bradner, James E.; Northcott, Paul A.

2016-01-01

Summary Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is lacking. Using H3K27ac and BRD4 ChIP-Seq, coupled with tissue-matched DNA methylation and transcriptome data, we describe the active cis-regulatory landscape across 28 primary medulloblastoma specimens. Analysis of differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity and revealed novel, clinically relevant insights into medulloblastoma biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors, validated by ChIP-Seq, that are responsible for subgroup divergence and implicate candidate cells-of-origin for Group 4. Our integrated analysis of enhancer elements in a large series of primary tumour samples reveals insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins. PMID:26814967

Myasthenia gravis: subgroup classification and therapeutic strategies.

PubMed

Gilhus, Nils Erik; Verschuuren, Jan J

2015-10-01

Myasthenia gravis is an autoimmune disease that is characterised by muscle weakness and fatigue, is B-cell mediated, and is associated with antibodies directed against the acetylcholine receptor, muscle-specific kinase (MUSK), lipoprotein-related protein 4 (LRP4), or agrin in the postsynaptic membrane at the neuromuscular junction. Patients with myasthenia gravis should be classified into subgroups to help with therapeutic decisions and prognosis. Subgroups based on serum antibodies and clinical features include early-onset, late-onset, thymoma, MUSK, LRP4, antibody-negative, and ocular forms of myasthenia gravis. Agrin-associated myasthenia gravis might emerge as a new entity. The prognosis is good with optimum symptomatic, immunosuppressive, and supportive treatment. Pyridostigmine is the preferred symptomatic treatment, and for patients who do not adequately respond to symptomatic therapy, corticosteroids, azathioprine, and thymectomy are first-line immunosuppressive treatments. Additional immunomodulatory drugs are emerging, but therapeutic decisions are hampered by the scarcity of controlled studies. Long-term drug treatment is essential for most patients and must be tailored to the particular form of myasthenia gravis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinico-Epidemiological Comparison of Delusion-Prominent and Hallucination-Prominent Clinical Subgroups of Paranoid Schizophrenia.

PubMed

Kreinin, Anatoly; Krishtul, Vladimir; Kirsh, Zvi; Menuchin, Michael

2015-01-01

Though hallucinations and delusions are prominent basic impairments in schizophrenia, reports of the relationship between hallucinatory and delusional symptoms among schizophrenia patients are scant. To examine the epidemiological and clinical differences between mainly hallucinatory and mainly delusional subgroups of paranoid schizophrenia patients. One hundred schizophrenia patients, paranoid type, were recruited. In a cross-sectional study, participants were divided into Mainly Hallucinatory (H) and Mainly Delusional (D) subgroups. Demographic variables were compared and clinical characteristics were evaluated using the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Clinical Global Impression Scale. The Quality-of-Life Enjoyment and Satisfaction Questionnaire-18 was used to assess quality of life. Clinically, the H group was more heterogeneous as expressed by the broader range of scores that described the clinical picture of patients in that subgroup (in 43 of 78 variables, 55.13%) and similar ranges of scores (31 of 78 variables, 39.74%) for patients in the D group. Duration of hospitalization was significantly longer in group H than in group D (p=0.047). There was no statistically significant difference between the H and D subgroups in demographic characteristics. There are distinct epidemiological and clinical differences between the H and D subgroups, with more severe positive and negative symptoms and greater functional impairment in the H group. Paranoid schizophrenia patients with prominent hallucinations have poorer prognosis and need intensive therapeutic rehabilitation beginning with onset-of-illness. Further genetic studies and comparisons of fMRI and/or PET findings are warranted to investigate additional distinctive characteristics of these subgroups.

Identifying a susceptible subgroup: effects of the Pittsburgh air pollution episode upon schoolchildren.

PubMed

Stebbings, J H; Fogleman, D G

1979-07-01

Pulmonary function test results on 224 parochial schoolchildren collected during and after the Pittsburgh air pollution episode of November 1975 were reanalyzed to determine whether a small subgroup of susceptible children could be defined. Individual regressions of three-quarter second forced expiratory volumes (FEV.75) and forced vital capacities (FVC) on time over the six-day study period were calculated, and the distributions of individual slopes for the four exposed and two control schools were compared. Excesses of strong upward trends in the exposed areas would suggest effects of suspended particulate air pollution by indicating significant improvement following the episode. A highly statistically significant excess of strong upward trends in the FVC among exposed students was observed, and was consistent by sex and by school within sex. Approximately 10--15% of the students appear susceptible to an average impairment of about 20% of the FVC. The findings are limited by the small number of subjects with strong post-episode upward trends in the FVC, and by lack of validation by replication of the study design, but do suggest that episode levels of suspended particulates induce lung damage, and that this may occur only in a small susceptible subgroup. Children with low baseline pulmonary function values, histories of asthma, or with acute respiratory symptoms immediately following the episode were not found to be especially susceptible to these effects of suspended particulates.

SUBGR: A Program to Generate Subgroup Data for the Subgroup Resonance Self-Shielding Calculation

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

Kim, Kang Seog

2016-06-06

The Subgroup Data Generation (SUBGR) program generates subgroup data, including levels and weights from the resonance self-shielded cross section table as a function of background cross section. Depending on the nuclide and the energy range, these subgroup data can be generated by (a) narrow resonance approximation, (b) pointwise flux calculations for homogeneous media; and (c) pointwise flux calculations for heterogeneous lattice cells. The latter two options are performed by the AMPX module IRFFACTOR. These subgroup data are to be used in the Consortium for Advanced Simulation of Light Water Reactors (CASL) neutronic simulator MPACT, for which the primary resonance self-shieldingmore » method is the subgroup method.« less

Real-world Clinical Outcomes Among Patients With Type 2 Diabetes Receiving Canagliflozin at a Specialty Diabetes Clinic: Subgroup Analysis by Baseline HbA1c and Age.

PubMed

Johnson, June Felice; Parsa, Rahul; Bailey, Robert A

2017-06-01

Canagliflozin, a sodium glucose co-transporter 2 inhibitor developed for the treatment of type 2 diabetes mellitus (T2DM), has demonstrated effectiveness in patients with T2DM receiving care at a specialty diabetes clinic. We report the outcomes in these patients in subgroups classified by baseline hemoglobin A 1c (HbA 1c ) and age. This subgroup analysis was based on a review of data from the electronic health records of adults with T2DM who were prescribed canagliflozin at a specialty diabetes clinic and who returned for ≥1 follow-up office visit. Mean changes from baseline to the first and second follow-up office visits in HbA 1c , body weight, and systolic and diastolic blood pressure (BP) were calculated in each subgroup classified by baseline HbA 1c (≥7.0%, ≥8.0%, and >9.0%) and age (<65 and ≥65 years). Of the 462 patients included in the study, 430, 305, and 169 patients had baseline HbA 1c ≥7.0%, ≥8.0%, and >9.0%, respectively; 396 and 66 patients were aged <65 and ≥65 years, respectively. With canagliflozin use, patients across subgroups classified by baseline HbA 1c and age experienced clinically and statistically significant reductions from baseline in HbA 1c , body weight, and systolic BP that were sustained over 2 office visits; diastolic BP was also reduced across baseline HbA 1c and age subgroups. Greater reductions in HbA 1c were seen among the canagliflozin-treated patients with higher baseline HbA 1c and among younger versus older patients. These findings from clinical practice demonstrate real-world effectiveness of canagliflozin in lowering HbA 1c , body weight, and systolic BP among patients with T2DM, regardless of baseline HbA 1c levels or age. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Is the performance of MRI in preoperative staging of breast cancer independent of clinical and histological factors? A subgroup analysis.

PubMed

Carreira Gómez, C; Zamora Romero, J; Gil de Miguel, A; Chiva de Agustín, M; Plana Farrás, M N; Martínez González, J

2015-01-01

To determine whether preoperative breast MRI is more useful in patients according to their breast density, age, menopausal status, and biopsy findings of carcinoma in situ. We retrospectively studied 264 patients treated for breast cancer who had undergone mammography, ultrasonography, and MRI. We compared the size of the tumor on the three techniques and the sensitivity of the techniques for detecting additional lesions both in the overall group and in subgroups of patients classified according to their breast density, age, menopausal status, and histological findings of intraductal carcinoma. The definitive histological diagnosis was used as the gold standard. MRI was the technique that was most concordant with the histological findings for the size of the lesion, and it was also the technique that detected the most additional lesions. With MRI, we observed no differences in lesion size between the overall group and the subgroups in which MRI provided added value. Likewise, we observed no differences in the number of additional lesions detected in the overall group except for multicentric lesions, which was larger in older patients (P=.02). In the subgroup of patients in which MRI provided added value, the sensitivity for bilateral lesions was higher in patients with fatty breasts (P=.04). Multifocal lesions were detected significantly better in premenopausal patients (P=.03). MRI is better than mammography and better than ultrasonography for establishing the size of the tumor and for detecting additional lesions. Our results did not identify any subgroups in which the technique was more useful. Copyright © 2013 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

The Value of Heterogeneity for Cost-Effectiveness Subgroup Analysis

PubMed Central

Manca, Andrea; Claxton, Karl; Sculpher, Mark J.

2014-01-01

This article develops a general framework to guide the use of subgroup cost-effectiveness analysis for decision making in a collectively funded health system. In doing so, it addresses 2 key policy questions, namely, the identification and selection of subgroups, while distinguishing 2 sources of potential value associated with heterogeneity. These are 1) the value of revealing the factors associated with heterogeneity in costs and outcomes using existing evidence (static value) and 2) the value of acquiring further subgroup-related evidence to resolve the uncertainty given the current understanding of heterogeneity (dynamic value). Consideration of these 2 sources of value can guide subgroup-specific treatment decisions and inform whether further research should be conducted to resolve uncertainty to explain variability in costs and outcomes. We apply the proposed methods to a cost-effectiveness analysis for the management of patients with acute coronary syndrome. This study presents the expected net benefits under current and perfect information when subgroups are defined based on the use and combination of 6 binary covariates. The results of the case study confirm the theoretical expectations. As more subgroups are considered, the marginal net benefit gains obtained under the current information show diminishing marginal returns, and the expected value of perfect information shows a decreasing trend. We present a suggested algorithm that synthesizes the results to guide policy. PMID:24944196

Oesophageal intraluminal impedance can identify subtle bolus transit abnormalities in patients with mild oesophagitis.

PubMed

Sifrim, Daniel; Tutuian, Radu

2005-03-01

In a subgroup of patients with non-erosive gastroesophageal reflux disease (GORD) or mild oesophagitis, acid clearance is prolonged in spite of favourable gravity and normal or minimally impaired oesophageal peristalsis. Dysphagia is rare in this group but might also be present or develop after anti-reflux surgery. The causal relationship between prolonged clearance or dysphagia and oesophageal body dysmotility in these patients is not completely clear. New techniques are now available to assess oesophageal motility and transit and might help to detect more subtle defects underlying functional impairment in patients with GORD. Combined video-fluoroscopy and intraluminal impedance indicate an excellent correlation between both methods in detecting oesophageal bolus transit. Combined intraluminal impedance and manometry has the capability to evaluate oesophageal contractions and bolus transit without the use of radiation. Subtle bolus transit abnormalities were identified in a small proportion of patients with mild oesophagits and normal oesophageal peristalsis. Outcome data are needed to evaluate the prognostic value of combined manometry-impedance in patients with GORD undergoing anti-reflux surgery.

Predicting the Risk of Clostridium difficile Infection upon Admission: A Score to Identify Patients for Antimicrobial Stewardship Efforts.

PubMed

Kuntz, Jennifer L; Smith, David H; Petrik, Amanda F; Yang, Xiuhai; Thorp, Micah L; Barton, Tracy; Barton, Karen; Labreche, Matthew; Spindel, Steven J; Johnson, Eric S

2016-01-01

Increasing morbidity and health care costs related to Clostridium difficile infection (CDI) have heightened interest in methods to identify patients who would most benefit from interventions to mitigate the likelihood of CDI. To develop a risk score that can be calculated upon hospital admission and used by antimicrobial stewards, including pharmacists and clinicians, to identify patients at risk for CDI who would benefit from enhanced antibiotic review and patient education. We assembled a cohort of Kaiser Permanente Northwest patients with a hospital admission from July 1, 2005, through December 30, 2012, and identified CDI in the six months following hospital admission. Using Cox regression, we constructed a score to identify patients at high risk for CDI on the basis of preadmission characteristics. We calculated and plotted the observed six-month CDI risk for each decile of predicted risk. We identified 721 CDIs following 54,186 hospital admissions-a 6-month incidence of 13.3 CDIs/1000 patient admissions. Patients with the highest predicted risk of CDI had an observed incidence of 53 CDIs/1000 patient admissions. The score differentiated between patients who do and do not develop CDI, with values for the extended C-statistic of 0.75. Predicted risk for CDI agreed closely with observed risk. Our risk score accurately predicted six-month risk for CDI using preadmission characteristics. Accurate predictions among the highest-risk patient subgroups allow for the identification of patients who could be targeted for and who would likely benefit from review of inpatient antibiotic use or enhanced educational efforts at the time of discharge planning.

Forum Guide to Collecting and Using Disaggregated Data on Racial/Ethnic Subgroups. NFES 2017-017

ERIC Educational Resources Information Center

National Forum on Education Statistics, 2016

2016-01-01

The National Forum on Education Statistics convened the Data Disaggregation of Racial/Ethnic Subgroups Working Group to identify best practices for disaggregating data on racial/ethnic subgroups. This guide is intended to identify some of the overarching benefits and challenges involved in data disaggregation; recommend appropriate practices for…

A Simple and Reliable Strategy for BK Virus Subtyping and Subgrouping

PubMed Central

Morel, Virginie; Martin, Elodie; François, Catherine; Helle, François; Faucher, Justine; Mourez, Thomas; Choukroun, Gabriel; Duverlie, Gilles; Castelain, Sandrine

2017-01-01

ABSTRACT BK virus (BKV)-associated diseases in transplant recipients are an emerging issue. However, identification of the various BK virus subtypes/subgroups is a long and delicate process on the basis of currently available data. Therefore, we wanted to define a simple and effective one-step strategy for characterizing all BK virus strains from the VP1 gene sequence. Based on the analysis of 199 available complete DNA VP1 sequences, phylogenetic trees, alignments, and isolated polymorphisms were used to define an effective strategy for distinguishing the 12 different BK virus subtypes/subgroups. Based on the 12 subtypes identified from the 199 complete BKV VP1 sequences (1,089 bp), 60 mutations that can be used to differentiate these various subtypes/subgroups were identified. Some genomic areas were more variable and comprised mutational hot spots. From a subregion of only 100 bp in the VP1 region (1977 through 2076), we therefore constructed an algorithm that enabled rapid determination of all BKV subtypes/subgroups with 99% agreement (197/199) relative to the complete VP1 sequence. We called this domain of the BK viral genome the BK typing and grouping region (BKTGR). Finally, we validated our viral subtype identification process in a population of 100 transplant recipients with 100% efficiency. The new simpler method of BKV subtyping/subgrouping reported here constitutes a useful tool for future studies that will help us to more clearly understand the impact of BKV subtypes/subgroups on diagnosis, infection, and BK virus-associated diseases. PMID:28151406

[Does the Youth Psychopathic Traits Inventory (YPI) identify a clinically relevant subgroup among young offenders?].

PubMed

Mingers, Daniel; Köhler, Denis; Huchzermeier, Christian; Hinrichs, Günter

2017-01-01

Does the Youth Psychopathic Traits Inventory identify one or more high-risk subgroups among young offenders? Which recommendations for possible courses of action can be derived for individual clinical or forensic cases? Method: Model-based cluster analysis (Raftery, 1995) was conducted on a sample of young offenders (N = 445, age 14–22 years, M = 18.5, SD = 1.65). The resulting model was then tested for differences between clusters with relevant context variables of psychopathy. The variables included measures of intelligence, social competence, drug use, and antisocial behavior. Results: Three clusters were found (Low Trait, Impulsive/Irresponsible, Psychopathy) that differ highly significantly concerning YPI scores and the variables mentioned above. The YPI Scores Δ Low = 4.28 (Low Trait – Impulsive/Irresponsible) and Δ High = 6.86 (Impulsive/Irresponsible – Psychopathy) were determined to be thresholds between the clusters. The allocation of a person to be assessed within the calculated clusters allows for an orientation of consequent tests beyond the diagnosis of psychopathy. We conclude that the YPI is a valuable instrument for the assessment of young offenders, as it yields clinically and forensically relevant information concerning the cause and expected development of psychopathological behavior.

Cluster analysis reveals subclinical subgroups with shared autistic and schizotypal traits.

PubMed

Ford, Talitha C; Apputhurai, Pragalathan; Meyer, Denny; Crewther, David P

2018-07-01

Autism and schizophrenia spectrum research is typically based on coarse diagnostic classification, which overlooks individual variation within clinical groups. This method limits the identification of underlying cognitive, genetic and neural correlates of specific symptom dimensions. This study, therefore, aimed to identify homogenous subclinical subgroups of specific autistic and schizotypal traits dimensions, that may be utilised to establish more effective diagnostic and treatment practices. Latent profile analysis of subscale scores derived from an autism-schizotypy questionnaire, completed by 1678 subclinical adults aged 18-40 years (1250 females), identified a local optimum of eight population clusters: High, Moderate and Low Psychosocial Difficulties; High, Moderate and Low Autism-Schizotypy; High Psychosis-Proneness; and Moderate Schizotypy. These subgroups represent the convergent and discriminant dimensions of autism and schizotypy in the subclinical population, and highlight the importance of examining subgroups of specific symptom characteristics across these spectra in order to identify the underlying genetic and neural correlates that can be utilised to advance diagnostic and treatment practices. Copyright © 2018 Elsevier B.V. All rights reserved.

Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials.

PubMed

Sun, Xin; Briel, Matthias; Busse, Jason W; Akl, Elie A; You, John J; Mejza, Filip; Bala, Malgorzata; Diaz-Granados, Natalia; Bassler, Dirk; Mertz, Dominik; Srinathan, Sadeesh K; Vandvik, Per Olav; Malaga, German; Alshurafa, Mohamed; Dahm, Philipp; Alonso-Coello, Pablo; Heels-Ansdell, Diane M; Bhatnagar, Neera; Johnston, Bradley C; Wang, Li; Walter, Stephen D; Altman, Douglas G; Guyatt, Gordon H

2009-11-09

Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome. We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes. A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim

Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials

PubMed Central

Sun, Xin; Briel, Matthias; Busse, Jason W; Akl, Elie A; You, John J; Mejza, Filip; Bala, Malgorzata; Diaz-Granados, Natalia; Bassler, Dirk; Mertz, Dominik; Srinathan, Sadeesh K; Vandvik, Per Olav; Malaga, German; Alshurafa, Mohamed; Dahm, Philipp; Alonso-Coello, Pablo; Heels-Ansdell, Diane M; Bhatnagar, Neera; Johnston, Bradley C; Wang, Li; Walter, Stephen D; Altman, Douglas G; Guyatt, Gordon H

2009-01-01

Background Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome. Methods We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes. Discussion A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of

Distinguishing 6 Population Subgroups by Timing and Characteristics of the Menopausal Transition

PubMed Central

Huang, Xiaobi; Harlow, Siobán D.; Elliott, Michael R.

2012-01-01

Changes in women’s menstrual bleeding patterns precede the onset of menopause. In this paper, the authors identify population subgroups based on menstrual characteristics of the menopausal transition experience. Using the TREMIN data set (1943–1979), the authors apply a Bayesian change-point model with 8 parameters for each woman that summarize change in menstrual bleeding patterns during the menopausal transition. The authors then use estimates from this model to classify menstrual patterns into subgroups using a K-medoids algorithm. They identify 6 subgroups of women whose transition experience can be distinguished by age at onset, variability of the menstrual cycle, and duration of the early transition. These results suggest that for most women, mean and variance change points are well aligned with proposed bleeding markers of the menopausal transition, but for some women they are not clearly associated. Increasing understanding of population differences in the transition experience may lead to new insights into ovarian aging. Because of age inclusion criteria, most longitudinal studies of the menopausal transition probably include only a subset of the 6 subgroups of women identified in this paper, suggesting a potential bias in the understanding of both the menopausal transition and the linkage between the transition and chronic disease. PMID:22138039

Does classification of persons with fibromyalgia into Multidimensional Pain Inventory subgroups detect differences in outcome after a standard chronic pain management program?

PubMed Central

Verra, Martin L; Angst, Felix; Brioschi, Roberto; Lehmann, Susanne; Keefe, Francis J; Staal, J Bart; de Bie, Rob A; Aeschlimann, André

2009-01-01

INTRODUCTION: The present study aimed to replicate and validate the empirically derived subgroup classification based on the Multidimensional Pain Inventory (MPI) in a sample of highly disabled fibromyalgia (FM) patients. Second, it examined how the identified subgroups differed in their response to an intensive, interdisciplinary inpatient pain management program. METHODS: Participants were 118 persons with FM who experienced persistent pain and were disabled. Subgroup classification was conducted by cluster analysis using MPI subscale scores at entry to the program. At program entry and discharge, participants completed the MPI, Medical Outcomes Study Short Form-36, Hospital Anxiety and Depression Scale and Coping Strategies Questionnaire. RESULTS: Cluster analysis identified three subgroups in the highly disabled sample that were similar to those described by other studies using less disabled samples of FM. The dysfunctional subgroup (DYS; 36% of the sample) showed the highest level of depression, the interpersonally distressed subgroup (ID; 24%) showed a modest level of depression and the adaptive copers subgroup (AC; 38%) showed the lowest depression scores in the MPI (negative mood), Medical Outcomes Study Short Form-36 (mental health), Hospital Anxiety and Depression Scale (depression) and Coping Strategies Questionnaire (catastrophizing). Significant differences in treatment outcome were observed among the three subgroups in terms of reduction of pain severity (as assessed using the MPI). The effect sizes were 1.42 for DYS, 1.32 for AC and 0.62 for ID (P=0.004 for pairwise comparison of ID-AC and P=0.018 for ID-DYS). DISCUSSION: These findings underscore the importance of assessing individuals’ differences in how they adjust to FM. PMID:20011715

Everolimus for Advanced Pancreatic Neuroendocrine Tumours: A Subgroup Analysis Evaluating Japanese Patients in the RADIANT-3 Trial

PubMed Central

Ito, Tetsuhide; Okusaka, Takuji; Ikeda, Masafumi; Igarashi, Hisato; Morizane, Chigusa; Nakachi, Kohei; Tajima, Takeshi; Kasuga, Akio; Fujita, Yoshie; Furuse, Junji

2012-01-01

Objective Everolimus, an inhibitor of the mammalian target of rapamycin, has recently demonstrated efficacy and safety in a Phase III, double-blind, randomized trial (RADIANT-3) in 410 patients with low- or intermediate-grade advanced pancreatic neuroendocrine tumours. Everolimus 10 mg/day provided a 2.4-fold improvement compared with placebo in progression-free survival, representing a 65% risk reduction for progression. The purpose of this analysis was to investigate the efficacy and safety of everolimus in the Japanese subgroup enrolled in the RADIANT-3 study. Methods Subgroup analysis of the Japanese patients was performed comparing efficacy and safety between everolimus 10 mg/day orally (n = 23) and matching placebo (n = 17). The primary endpoint was progression-free survival. Safety was evaluated on the basis of the incidence of adverse drug reactions. Results Progression-free survival was significantly prolonged with everolimus compared with placebo. The median progression-free survival was 19.45 months (95% confidence interval, 8.31–not available) with everolimus vs 2.83 months (95% confidence interval, 2.46–8.34) with placebo, resulting in an 81% risk reduction in progression (hazard ratio, 0.19; 95% confidence interval, 0.08–0.48; P< 0.001). Adverse drug reactions occurred in all 23 (100%) Japanese patients receiving everolimus and in 13 (77%) patients receiving placebo; most were grade 1/2 in severity. The most common adverse drug reactions in the everolimus group were rash (n = 20; 87%), stomatitis (n = 17; 74%), infections (n = 15; 65%), nail disorders (n = 12; 52%), epistaxis (n = 10; 44%) and pneumonitis (n = 10; 44%). Conclusions These results support the use of everolimus as a valuable treatment option for Japanese patients with advanced pancreatic neuroendocrine tumours. PMID:22859827

Functional Status, Quality of Life, and Costs Associated With Fibromyalgia Subgroups: A Latent Profile Analysis.

PubMed

Luciano, Juan V; Forero, Carlos G; Cerdà-Lafont, Marta; Peñarrubia-María, María Teresa; Fernández-Vergel, Rita; Cuesta-Vargas, Antonio I; Ruíz, José M; Rozadilla-Sacanell, Antoni; Sirvent-Alierta, Elena; Santo-Panero, Pilar; García-Campayo, Javier; Serrano-Blanco, Antoni; Pérez-Aranda, Adrián; Rubio-Valera, María

2016-10-01

Although fibromyalgia syndrome (FM) is considered a heterogeneous condition, there is no generally accepted subgroup typology. We used hierarchical cluster analysis and latent profile analysis to replicate Giesecke's classification in Spanish FM patients. The second aim was to examine whether the subgroups differed in sociodemographic characteristics, functional status, quality of life, and in direct and indirect costs. A total of 160 FM patients completed the following measures for cluster derivation: the Center for Epidemiological Studies-Depression Scale, the Trait Anxiety Inventory, the Pain Catastrophizing Scale, and the Control over Pain subscale. Pain threshold was measured with a sphygmomanometer. In addition, the Fibromyalgia Impact Questionnaire-Revised, the EuroQoL-5D-3L, and the Client Service Receipt Inventory were administered for cluster validation. Two distinct clusters were identified using hierarchical cluster analysis ("hypersensitive" group, 69.8% and "functional" group, 30.2%). In contrast, the latent profile analysis goodness-of-fit indices supported the existence of 3 FM patient profiles: (1) a "functional" profile (28.1%) defined as moderate tenderness, distress, and pain catastrophizing; (2) a "dysfunctional" profile (45.6%) defined by elevated tenderness, distress, and pain catastrophizing; and (3) a "highly dysfunctional and distressed" profile (26.3%) characterized by elevated tenderness and extremely high distress and catastrophizing. We did not find significant differences in sociodemographic characteristics between the 2 clusters or among the 3 profiles. The functional profile was associated with less impairment, greater quality of life, and lower health care costs. We identified 3 distinct profiles which accounted for the heterogeneity of FM patients. Our findings might help to design tailored interventions for FM patients.

Comparison of clinicopathological findings among patients whose mammography results were classified as category 4 subgroups of the BI-RADS.

PubMed

Leblebici, Ihsan Metin; Bozkurt, Suleyman; Eren, Turgut Tunc; Ozemir, Ibrahim Ali; Sagiroglu, Julide; Alimoglu, Orhan

2014-01-01

Our aim is to compare mammographic, demographic and clinicopathological characteristics of patients whose mammographies were classified as subgroups of BI-RADS 4 category (Breast Imaging - Reporting and Data System). In total, 103 patients with mammography (Senographe 600t Senix HF; General Electric, Moulineaux, France) results classified as BI-RADS 4 were included in the study. Demographic data (age, menopause, and family history) were recorded. All data were compared among BI-RADS 4 subgroups. In all, 68.9% (71/103), 7.8% (8/103) and 23.3% (24/103) the patients were in groups BI-RADS 4A, 4B and 4C, respectively. The incidence of malignancy was higher in Groups 4B and 4C than in Group 4A (p<0.05), but similar in Groups 4B and 4C (p>0.05). Mean age was lower in Group 4B than in Groups 4A and 4C (p<0.05). A positive family history was more common in Group 4A than in Group 4B (p=0.025). The frequency of menopausal patients was greater in Groups 4A and 4C than in Group 4B (p=0.021, and 0.003, respectively). The rate of malignancy was higher in Groups 4B, and 4C than in Group 4A. A positive family history was more common in Group 4A than in Group 4C. Groups 4A, and 4C patients tended to be older and were more likely to be menopausal than Group 4B patients.

Early antihypertensive treatment and clinical outcomes in acute ischemic stroke: subgroup analysis by baseline blood pressure.

PubMed

He, William J; Zhong, Chongke; Xu, Tan; Wang, Dali; Sun, Yingxian; Bu, Xiaoqing; Chen, Chung-Shiuan; Wang, Jinchao; Ju, Zhong; Li, Qunwei; Zhang, Jintao; Geng, Deqin; Zhang, Jianhui; Li, Dong; Li, Yongqiu; Yuan, Xiaodong; Zhang, Yonghong; Kelly, Tanika N

2018-06-01

We studied the effect of early antihypertensive treatment on death, major disability, and vascular events among patients with acute ischemic stroke according to their baseline SBP. We randomly assigned 4071 acute ischemic stroke patients with SBP between 140 and less than 220 mmHg to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. A composite primary outcome of death and major disability and secondary outcomes were compared between treatment and control stratified by baseline SBP levels of less than 160, 160-179, and at least 180 mmHg. At 24 h after randomization, differences in SBP reductions were 8.8, 8.6 and 7.8 mmHg between the antihypertensive treatment and control groups among patients with baseline SBP less than 160, 160-179, and at least 180 mmHg, respectively (P < 0.001 among subgroups). At day 14 or hospital discharge, the primary and secondary outcomes were not significantly different between the treatment and control groups among subgroups. However, there was a significant interaction between antihypertensive treatment and baseline SBP subgroups on death (P = 0.02): odds ratio (95% CI) of 2.42 (0.74-7.89) in patients with baseline SBP less than 60 mmHg and 0.34 (0.11-1.09) in those with baseline SBP at least 180 mmHg. At the 3-month follow-up, the primary and secondary clinical outcomes were not significantly different between the treatment and control groups by baseline SBP levels. Early antihypertensive treatment had a neutral effect on clinical outcomes among acute ischemic stroke patients with various baseline SBP levels. Future clinical trials are warranted to test BP-lowering effects in acute ischemic stroke patients by baseline SBP levels. ClinicalTrials.gov Identifier: NCT01840072.

Different demographic, genetic, and longitudinal traits in language versus memory Alzheimer's subgroups.

PubMed

Mez, Jesse; Cosentino, Stephanie; Brickman, Adam M; Huey, Edward D; Mayeux, Richard

2013-01-01

The study's objective was to compare demographics, APOE genotypes, and rate of rise over time in functional impairment in neuropsychologically defined language, typical, and memory subgroups of clinical Alzheimer's disease (AD). 1,368 participants from the National Alzheimer's Coordinating Center database with a diagnosis of probable AD (CDR 0.5-1.0) were included. A language subgroup (n = 229) was defined as having language performance >1 SD worse than memory performance. A memory subgroup (n = 213) was defined as having memory performance >1 SD worse than language performance. A typical subgroup (n = 926) was defined as having a difference in language and memory performance of <1 SD. Compared with the memory subgroup, the language subgroup was 3.7 years older and more frequently self-identified as African American (OR = 3.69). Under a dominant genetic model, the language subgroup had smaller odds of carrying at least one APOEε4 allele relative to the memory subgroup. While this difference was present for all ages, it was more striking at a younger age (OR = 0.19 for youngest tertile; OR = 0.52 for oldest tertile). Compared with the memory subgroup, the language subgroup rose 35% faster on the Functional Assessment Questionnaire and 44% faster on CDR sum of boxes over time. Among a subset of participants who underwent autopsy (n = 98), the language, memory, and typical subgroups were equally likely to have an AD pathologic diagnosis, suggesting that variation in non-AD pathologies across subtypes did not lead to the observed differences. The study demonstrates that a language subgroup of AD has different demographics, genetic profile, and disease course in addition to cognitive phenotype.

Trace gluten contamination may play a role in mucosal and clinical recovery in a subgroup of diet-adherent non-responsive celiac disease patients

PubMed Central

2013-01-01

Background Patients with persistent symptoms and/or villous atrophy despite strict adherence to a gluten-free diet (GFD) have non-responsive celiac disease (NRCD). A subset of these patients has refractory celiac disease (RCD), yet some NRCD patients may simply be reacting to gluten cross-contamination. Here we describe the effects of a 3-6 month diet of whole, unprocessed foods, termed the Gluten Contamination Elimination Diet (GCED), on NRCD. We aim to demonstrate that this diet reclassifies the majority of patients thought to have RCD type 1 (RCD1). Methods We reviewed the records of all GFD-adherent NRCD patients cared for in our celiac center from 2005-2011 who were documented to have started the GCED. Response to the GCED was defined as being asymptomatic after the diet, with normal villous architecture on repeat biopsy, if performed. Results Prior to the GCED, all patients were interviewed by an experienced dietitian and no sources of hidden gluten ingestion were identified. 17 patients completed the GCED; 15 were female (88%). Median age at start of the GCED was 42 years (range 6-73). Fourteen patients (82%) responded to the GCED. Six patients met criteria for RCD prior to the GCED; 5 (83%) were asymptomatic after the GCED and no longer meet RCD criteria. Of the 14 patients who responded to the GCED, 11 (79%) successfully returned to a traditional GFD without resurgence of symptoms. Conclusions The GCED may be an effective therapeutic option for GFD-adherent NRCD patients. Response to this diet identifies a subgroup of patients, previously classified as RCD1, that is not truly refractory to dietary treatment. Preventing an inaccurate diagnosis of RCD1 avoids immunotherapy. Most patients are able to return to a traditional GFD without return of symptoms. PMID:23448408

Trace gluten contamination may play a role in mucosal and clinical recovery in a subgroup of diet-adherent non-responsive celiac disease patients.

PubMed

Hollon, Justin R; Cureton, Pamela A; Martin, Margaret L; Puppa, Elaine L Leonard; Fasano, Alessio

2013-02-28

Patients with persistent symptoms and/or villous atrophy despite strict adherence to a gluten-free diet (GFD) have non-responsive celiac disease (NRCD). A subset of these patients has refractory celiac disease (RCD), yet some NRCD patients may simply be reacting to gluten cross-contamination. Here we describe the effects of a 3-6 month diet of whole, unprocessed foods, termed the Gluten Contamination Elimination Diet (GCED), on NRCD. We aim to demonstrate that this diet reclassifies the majority of patients thought to have RCD type 1 (RCD1). We reviewed the records of all GFD-adherent NRCD patients cared for in our celiac center from 2005-2011 who were documented to have started the GCED. Response to the GCED was defined as being asymptomatic after the diet, with normal villous architecture on repeat biopsy, if performed. Prior to the GCED, all patients were interviewed by an experienced dietitian and no sources of hidden gluten ingestion were identified. 17 patients completed the GCED; 15 were female (88%). Median age at start of the GCED was 42 years (range 6-73). Fourteen patients (82%) responded to the GCED. Six patients met criteria for RCD prior to the GCED; 5 (83%) were asymptomatic after the GCED and no longer meet RCD criteria. Of the 14 patients who responded to the GCED, 11 (79%) successfully returned to a traditional GFD without resurgence of symptoms. The GCED may be an effective therapeutic option for GFD-adherent NRCD patients. Response to this diet identifies a subgroup of patients, previously classified as RCD1, that is not truly refractory to dietary treatment. Preventing an inaccurate diagnosis of RCD1 avoids immunotherapy. Most patients are able to return to a traditional GFD without return of symptoms.

Gene Expression Profiling in BRAF-Mutated Melanoma Reveals Patient Subgroups with Poor Outcomes to Vemurafenib That May Be Overcome by Cobimetinib Plus Vemurafenib.

PubMed

Wongchenko, Matthew J; McArthur, Grant A; Dréno, Brigitte; Larkin, James; Ascierto, Paolo A; Sosman, Jeffrey; Andries, Luc; Kockx, Mark; Hurst, Stephen D; Caro, Ivor; Rooney, Isabelle; Hegde, Priti S; Molinero, Luciana; Yue, Huibin; Chang, Ilsung; Amler, Lukas; Yan, Yibing; Ribas, Antoni

2017-09-01

Purpose: The association of tumor gene expression profiles with progression-free survival (PFS) outcomes in patients with BRAF V600 -mutated melanoma treated with vemurafenib or cobimetinib combined with vemurafenib was evaluated. Experimental Design: Gene expression of archival tumor samples from patients in four trials (BRIM-2, BRIM-3, BRIM-7, and coBRIM) was evaluated. Genes significantly associated with PFS ( P < 0.05) were identified by univariate Cox proportional hazards modeling, then subjected to unsupervised hierarchical clustering, principal component analysis, and recursive partitioning to develop optimized gene signatures. Results: Forty-six genes were identified as significantly associated with PFS in both BRIM-2 ( n = 63) and the vemurafenib arm of BRIM-3 ( n = 160). Two distinct signatures were identified: cell cycle and immune. Among vemurafenib-treated patients, the cell-cycle signature was associated with shortened PFS compared with the immune signature in the BRIM-2/BRIM-3 training set [hazard ratio (HR) 1.8; 95% confidence interval (CI), 1.3-2.6, P = 0.0001] and in the coBRIM validation set ( n = 101; HR, 1.6; 95% CI, 1.0-2.5; P = 0.08). The adverse impact of the cell-cycle signature on PFS was not observed in patients treated with cobimetinib combined with vemurafenib ( n = 99; HR, 1.1; 95% CI, 0.7-1.8; P = 0.66). Conclusions: In vemurafenib-treated patients, the cell-cycle gene signature was associated with shorter PFS. However, in cobimetinib combined with vemurafenib-treated patients, both cell cycle and immune signature subgroups had comparable PFS. Cobimetinib combined with vemurafenib may abrogate the adverse impact of the cell-cycle signature. Clin Cancer Res; 23(17); 5238-45. ©2017 AACR . ©2017 American Association for Cancer Research.

Use of the radial approach in primary angioplasty: results in 1029 consecutive patients and analyses in unfavorable subgroups.

PubMed

Hernández-Pérez, Francisco J; Blasco-Lobo, Ana; Goicolea, Leire; Muñiz-Lozano, Ana; Fernandez-Díaz, José A; Domínguez, José R; Goicolea-Ruigómez, Javier

2014-01-01

The transradial approach is associated with a reduction in vascular access-related complications after primary percutaneous coronary interventions. The purpose of this study was to examine the feasibility of the routine use of transradial access in primary angioplasty and to evaluate how it affects subgroups with less favorable characteristics. We analyzed 1029 consecutive patients with an ST-segment elevation acute coronary syndrome treated with primary angioplasty. Transradial access was the primary approach in 93.1% of the patients. The success rate of primary angioplasty was 95.9%, and 87.6% of the patients were event-free 30 days after the procedure. Crossover was required in 3.0% of the patients with primary transradial access, and this rate remained stable over the years. Predictors of the need for crossover were age older than 75 years (odds ratio=2.50, 95% confidence interval, 1.09-5.71; P=.03) and a history of ischemic heart disease (odds ratio=2.65; 95% confidence interval, 1.12-6.24; P=.02). Primary transfemoral access use was higher in women older than 75 years. Use of the transradial approach in this subgroup did not affect reperfusion time or the success of angioplasty, although there was a greater need for crossover (10.9% vs 2.6%; P=.006). Among patients in cardiogenic shock, the transradial approach was used in 51.5%; reperfusion times and angioplasty success rates were similar to those obtained with transfemoral access, but there was a greater need for crossover. Transradial access can be used safely and effectively in most primary angioplasty procedures. In older women and in patients in cardiogenic shock, there is a higher crossover requirement, with no detriment to reperfusion time. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Do self-management interventions in COPD patients work and which patients benefit most? An individual patient data meta-analysis.

PubMed

Jonkman, Nini H; Westland, Heleen; Trappenburg, Jaap Ca; Groenwold, Rolf Hh; Bischoff, Erik Wma; Bourbeau, Jean; Bucknall, Christine E; Coultas, David; Effing, Tanja W; Epton, Michael J; Gallefoss, Frode; Garcia-Aymerich, Judith; Lloyd, Suzanne M; Monninkhof, Evelyn M; Nguyen, Huong Q; van der Palen, Job; Rice, Kathryn L; Sedeno, Maria; Taylor, Stephanie Jc; Troosters, Thierry; Zwar, Nicholas A; Hoes, Arno W; Schuurmans, Marieke J

2016-01-01

Self-management interventions are considered effective in patients with COPD, but trials have shown inconsistent results and it is unknown which patients benefit most. This study aimed to summarize the evidence on effectiveness of self-management interventions and identify subgroups of COPD patients who benefit most. Randomized trials of self-management interventions between 1985 and 2013 were identified through a systematic literature search. Individual patient data of selected studies were requested from principal investigators and analyzed in an individual patient data meta-analysis using generalized mixed effects models. Fourteen trials representing 3,282 patients were included. Self-management interventions improved health-related quality of life at 12 months (standardized mean difference 0.08, 95% confidence interval [CI] 0.00-0.16) and time to first respiratory-related hospitalization (hazard ratio 0.79, 95% CI 0.66-0.94) and all-cause hospitalization (hazard ratio 0.80, 95% CI 0.69-0.90), but had no effect on mortality. Prespecified subgroup analyses showed that interventions were more effective in males (6-month COPD-related hospitalization: interaction P=0.006), patients with severe lung function (6-month all-cause hospitalization: interaction P=0.016), moderate self-efficacy (12-month COPD-related hospitalization: interaction P=0.036), and high body mass index (6-month COPD-related hospitalization: interaction P=0.028 and 6-month mortality: interaction P=0.026). In none of these subgroups, a consistent effect was shown on all relevant outcomes. Self-management interventions exert positive effects in patients with COPD on respiratory-related and all-cause hospitalizations and modest effects on 12-month health-related quality of life, supporting the implementation of self-management strategies in clinical practice. Benefits seem similar across the subgroups studied and limiting self-management interventions to specific patient subgroups cannot be

Detection of Problem Gambler Subgroups Using Recursive Partitioning

ERIC Educational Resources Information Center

Markham, Francis; Young, Martin; Doran, Bruce

2013-01-01

The multivariate socio-demographic risk factors for problem gambling have been well documented. While this body of research is valuable in determining risk factors aggregated across various populations, the majority of studies tend not to specifically identify particular subgroups of problem gamblers based on the interaction between variables. The…

Structure and content of Native American stereotypic subgroups: Not just (ig)noble.

PubMed

Burkley, Edward; Durante, Federica; Fiske, Susan T; Burkley, Melissa; Andrade, Angela

2017-04-01

Prejudice against Native Americans as an overall group generally polarizes into positive and negative stereotypic extremes, but distinct subgroups may explain this variability. Using college student samples (Study 1), a preliminary study identified common Native American subgroups and then a main study (N = 153, 74% women, 73% White, mean age = 19 years) had participants rate these subgroups on basic dimensions of stereotype content (i.e., warmth and competence), elicited emotions (e.g., admiration, contempt), and elicited behaviors (e.g., facilitation, harm). In Study 2, these preliminary study and main study procedures were replicated using nationwide samples (main study: N = 139, 51% women, 78% White, mean age = 35 years). For the most part, similar Native American subgroups emerged in both samples. Using the stereotype content model (SCM; Fiske, Cuddy, Glick, & Xu, 2002), the subgroups were found to vary along a competence-by-warmth space. The majority of subgroups (e.g., alcoholics, lazy) were judged low in both competence and warmth. Additional subgroups (e.g., casino operators, warriors) were ambivalently judged as high on competence but low on warmth. Subgroups perceived as high in both competence and warmth elicited more admiration, those low in both competence and warmth elicited more contempt, those high in competence elicited more passive facilitation and less passive harm, and those high in warmth elicited more active facilitation and less active harm. Native American stereotypes are apparently characterized by both noble and ignoble subgroups, highlighting the importance of studying stereotypes at the subgroup level. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Prognostic subgroups for remission and response in the Coordinated Anxiety Learning and Management (CALM) trial.

PubMed

Kelly, J MacLaren; Jakubovski, Ewgeni; Bloch, Michael H

2015-03-01

Most patients with anxiety disorders receive treatment in primary care settings. Limited moderator data are available to inform clinicians of likely prognostic outcomes for individual patients. We identify baseline characteristics associated with outcome in adults seeking treatment for anxiety disorders. We conducted an exploratory moderator analysis from the Coordinated Anxiety Learning and Management (CALM) trial. In the CALM trial, 1,004 adults who met DSM-IV criteria for generalized anxiety disorder (GAD), panic disorder, social anxiety disorder, and/or posttraumatic stress disorder (PTSD) were randomized to usual care (UC) or a collaborative care intervention (ITV) of cognitive-behavioral therapy and/or pharmacotherapy between June 2006 and April 2008. Logistic regression was used to examine baseline characteristics associated with remission and response overall and by treatment condition. Receiver operating curve (ROC) analyses identified subgroups associated with similar likelihood of response and remission of global anxiety symptoms. Remission was defined as score < 6 on the 12-item Brief Symptom Inventory (BSI-12) anxiety and somatization subscales. Response was defined as at least 50% reduction on BSI-12, or meeting remission criteria. Randomization to ITV over UC was often the strongest predictor of outcome. Several baseline patient characteristics were associated with poor treatment outcome including comorbid depression, increased severity of underlying anxiety disorder(s) (P < .001), low socioeconomic status (perceived [P < .001] and actual [P < .05]), and limited social support (P < .001). Patient characteristics associated with particular benefit from ITV were being female (P < .05), increased depression (P < .01)/GAD severity (P < .05), and low socioeconomic status (P < .05). ROC analysis demonstrated prognostic subgroups with large differences in response likelihood. Further research should focus on the effectiveness of implementing the ITV

Activity of Eribulin in Patients With Advanced Liposarcoma Demonstrated in a Subgroup Analysis From a Randomized Phase III Study of Eribulin Versus Dacarbazine.

PubMed

Demetri, George D; Schöffski, Patrick; Grignani, Giovanni; Blay, Jean-Yves; Maki, Robert G; Van Tine, Brian A; Alcindor, Thierry; Jones, Robin L; D'Adamo, David R; Guo, Matthew; Chawla, Sant

2017-10-20

Purpose A phase III study comparing eribulin with dacarbazine in patients with advanced liposarcoma (LPS) or leiomyosarcoma showed a significant improvement in overall survival (OS) for the eribulin arm, with a manageable toxicity profile. We now report the histology-specific subgroup analysis of the efficacy and safety of eribulin compared with dacarbazine in patients with LPS, an independently randomized stratified subgroup of this phase III trial. Methods Patients ≥ 18 years with advanced or metastatic dedifferentiated, myxoid/round cell, or pleomorphic LPS incurable by surgery or radiotherapy were included. Patients with Eastern Cooperative Oncology Group performance status ≤ 2 and two or more prior systemic treatment regimens, including one with anthracycline, were randomly assigned 1:1 to receive eribulin mesylate (1.4 mg/m 2 intravenously on days 1 and 8) or dacarbazine (850, 1,000, or 1,200 mg/m 2 intravenously on day 1) every 21 days. OS, progression-free survival (PFS), and safety were analyzed. Results In the LPS subgroup, OS was significantly improved: 15.6 versus 8.4 months (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P < .001) with eribulin versus dacarbazine, respectively. Longer OS with eribulin was observed in all LPS histologic subtypes and in all geographic regions evaluated. PFS was also improved with eribulin versus dacarbazine (2.9 v 1.7 months, respectively; hazard ratio, 0.52; 95% CI, 0.35 to 0.78; P = .0015). Adverse events were similar between arms. Conclusion In patients with previously treated LPS, eribulin was associated with significantly superior OS and PFS compared with dacarbazine. Eribulin represents an important treatment option for patients with LPS, a sarcoma subtype for which limited effective systemic treatments are available. Further studies are justified to explore the role of eribulin in earlier lines of therapy as well as in combination with other agents.

A Simulation Study of Methods for Selecting Subgroup-Specific Doses in Phase I Trials

PubMed Central

Morita, Satoshi; Thall, Peter F.; Takeda, Kentaro

2016-01-01

Summary Patient heterogeneity may complicate dose-finding in phase I clinical trials if the dose-toxicity curves differ between subgroups. Conducting separate trials within subgroups may lead to infeasibly small sample sizes in subgroups having low prevalence. Alternatively, it is not obvious how to conduct a single trial while accounting for heterogeneity. To address this problem, we consider a generalization of the continual reassessment method (O’Quigley, et al., 1990) based on a hierarchical Bayesian dose-toxicity model that borrows strength between subgroups under the assumption that the subgroups are exchangeable. We evaluate a design using this model that includes subgroup-specific dose selection and safety rules. A simulation study is presented that includes comparison of this method to three alternative approaches, based on non-hierarchical models, that make different types of assumptions about within-subgroup dose-toxicity curves. The simulations show that the hierarchical model-based method is recommended in settings where the dose-toxicity curves are exchangeable between subgroups. We present practical guidelines for application, and provide computer programs for trial simulation and conduct. PMID:28111916

Customizing treatment for chronic pain patients: who, what, and why.

PubMed

Turk, D C

1990-12-01

Despite advances in the understanding of pain mechanisms and innovative strategies to assess pain patients, there continues to be a substantial proportion of patients who do not appear to benefit from treatment interventions available. One possible explanation for these results is the tendency to treat chronic pain patients as a homogeneous group with generic treatments--adherence to "patient and treatment uniformity myths." Following from the traditional medical model, several attempts have been made to identify specific subgroups of patients exclusively on the basis of physical factors. In addition, a number of studies have attempted to empirically identify subgroups of pain patients using standard psychiatric assessment instruments (e.g., MMPI, SCL-90) and, recently, cognitive measures and measures of pain behaviors. These different approaches and the assessment instruments used are reviewed, and the limitations are described. Alternative strategies to classify subgroups of pain patients based on combinations of physical, psychosocial, and behavioral measures (i.e., multiaxial strategies) are presented. The efforts to classify homogeneous subgroups of chronic pain patients are reviewed, and the potential utility of customizing therapeutic interventions to patient characteristics is discussed.

Identification of clinically relevant phenotypes in patients with Ebstein anomaly.

PubMed

Cabrera, Rodrigo; Miranda-Fernández, Marta Catalina; Huertas-Quiñones, Victor Manuel; Carreño, Marisol; Pineda, Ivonne; Restrepo, Carlos M; Silva, Claudia Tamar; Quero, Rossi; Cano, Juan David; Manrique, Diana Carolina; Camacho, Camila; Tabares, Sebastián; García, Alberto; Sandoval, Néstor; Moreno Medina, Karen Julieth; Dennis Verano, Rodolfo José

2018-03-01

Ebstein anomaly (EA) is a heterogeneous congenital heart defect (CHD), frequently accompanied by diverse cardiac and extracardiac comorbidities, resulting in a wide range of clinical outcomes. Phenotypic characterization of EA patients has the potential to identify variables that influence prognosis and subgroups with distinct contributing factors. A comprehensive cross-sectional phenotypic characterization of 147 EA patients from one of the main referral institutions for CHD in Colombia was carried out. The most prevalent comorbidities and distinct subgroups within the patient cohort were identified through cluster analysis. The most prevalent cardiac comorbidities identified were atrial septal defect (61%), Wolff-Parkinson-White syndrome (WPW; 27%), and right ventricular outflow tract obstruction (25%). Cluster analysis showed that patients can be classified into 2 distinct subgroups with defined phenotypes that determine disease severity and survival. Patients in cluster 1 represented a particularly homogeneous subgroup with a milder spectrum of disease, including only patients with WPW and/or supraventricular tachycardia (SVT). Cluster 2 included patients with more diverse cardiovascular comorbidities. This study represents one of the largest phenotypic characterizations of EA patients reported. The data show that EA is a heterogeneous disease, very frequently associated with cardiovascular and noncardiovascular comorbidities. Patients with WPW and SVT represent a homogeneous subgroup that presents with a less severe spectrum of disease and better survival when adequately managed. This should be considered when searching for genetic causes of EA and in the clinical setting. © 2018 Wiley Periodicals, Inc.

Discrete subgroups of adolescents diagnosed with borderline personality disorder: a latent class analysis of personality features.

PubMed

Ramos, Vera; Canta, Guilherme; de Castro, Filipa; Leal, Isabel

2014-08-01

Research suggests that borderline personality disorder (BPD) can be diagnosed in adolescents and is marked by considerable heterogeneity. This study aimed to identify personality features characterizing adolescents with BPD and possible meaningful patterns of heterogeneity that could lead to personality subgroups. The authors analyzed data on 60 adolescents, ages 15 to 18 years, who met DSM criteria for a BPD diagnosis. The authors used latent class analysis (LCA) to identify subgroups based on the personality pattern scales from the Millon Adolescent Clinical Inventory (MACI). LCA indicated that the best-fitting solution was a two-class model, identifying two discrete subgroups of BPD adolescents that were described as internalizing and externalizing. The subgroups were then compared on clinical and sociodemographic variables, measures of personality dimensions, DSM BPD criteria, and perception of attachment styles. Adolescents with a BPD diagnosis constitute a heterogeneous group and vary meaningfully on personality features that can have clinical implications for treatment.

Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial.

PubMed

Easton, J Donald; Lopes, Renato D; Bahit, M Cecilia; Wojdyla, Daniel M; Granger, Christopher B; Wallentin, Lars; Alings, Marco; Goto, Shinya; Lewis, Basil S; Rosenqvist, Mårten; Hanna, Michael; Mohan, Puneet; Alexander, John H; Diener, Hans-Christoph

2012-06-01

In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18,201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0-3·0). The median duration of follow-up was 1·8 years (IQR 1·4-2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984. Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI -0·08 to 1·63) in patients with

Prevalence and Profile of Phonological and Surface Subgroups in College Students with a History of Reading Disability

ERIC Educational Resources Information Center

Birch, Stacy L.

2016-01-01

The purpose of the present study was to identify and characterize surface and phonological subgroups of readers among college students with a prior diagnosis of developmental reading disability (RD). Using a speeded naming task derived from Castles and Coltheart's subtyping study, we identified subgroups of readers from among college students with…

Predictors of Renal Function Decline in Chinese Patients with Type 2 Diabetes Mellitus and in a Subgroup of Normoalbuminuria: A Retrospective Cohort Study.

PubMed

Hu, Ping; Zhou, Xiang-Hai; Wen, Xin; Ji, Linong

2016-10-01

Risk factors related to renal function decline in type 2 diabetes mellitus (T2DM) remain uncertain. This study aimed to investigate risk factors in relation to renal function decline in patients with T2DM and in a subgroup of patients with normoalbuminuria. This study was a retrospective cohort study, which included 451 patients with T2DM aged 63 ± 14 years admitted to a tertiary hospital in Beijing, China, between April and December 2010 and followed up for 6-60 months. Endpoint was renal function decline, defined as estimated glomerular filtration rate less than 60 mL/min 1.73 m 2 or at least twofold increase of serum creatinine. Cox proportional hazards analysis was used to estimate hazard ratios (HRs) for candidate risk factors of renal function decline. After a median follow-up of 3.3 years, 94 (20.8%) patients developed renal function decline. Increased age (HR, 1.045; 95% CI, 1.020-1.070), albuminuria (HR, 1.956; 95%CI, 1.271-3.011), mild renal dysfunction (HR, 4.521; 95%CI, 2.734-7.476), hyperfiltration (HR, 3.897; 95%CI, 1.572-9.663), and increased hemoglobin A1c (HR, 1.128; 95%CI, 1.020-1.249) were identified as major risk factors. Among a subgroup of 344 patients with normoalbuminuria at baseline, 53 (15.4%) patients developed renal function decline. Increased age (HR, 1.089; 95%CI, 1.050-1.129), mild renal dysfunction (HR, 4.667; 95%CI, 2.391-9.107), hyperfiltration (HR, 5.677; 95%CI, 1.544-20.872), smoking (HR, 2.886; 95%CI, 1.370-6.082), higher pulse pressure (HR, 1.022; 95%CI, 1.004-1.040), and increased fasting glucose (HR, 1.104; 95%CI, 1.020-1.194) were major risk factors. Risk factors of diabetic renal impairment in T2DM should be screened and evaluated at an early stage of diabetes. Albuminuria, mild renal dysfunction, hyperfiltration, increased blood glucose, increased pulse pressure, and smoking were all predictors for diabetic renal impairment and interventions that focus on these risk factors may reduce further decline in renal

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.

The Effect of IV Amino Acid Supplementation on Mortality in ICU Patients May Be Dependent on Kidney Function: Post Hoc Subgroup Analyses of a Multicenter Randomized Trial.

PubMed

Zhu, Ran; Allingstrup, Matilde J; Perner, Anders; Doig, Gordon S

2018-05-15

We investigated whether preexisting kidney function determines if ICU patients may benefit from increased (2.0 g/kg/d) protein intake. Post hoc, hypothesis-generating, subgroup analysis of a multicenter, phase 2, randomized clinical trial. All analyses were conducted by intention to treat and maintained group allocation. Ninety-day mortality was the primary outcome. ICUs of 16 hospitals throughout Australia and New Zealand. Adult critically ill patients expected to remain in the study ICU for longer than 2 days. Random allocation to receive a daily supplement of up to 100 g of IV amino acids to achieve a total protein intake of 2.0 g/kg/d or standard nutrition care. A total of 474 patients were randomized: 235 to standard care and 239 to IV amino acid supplementation. There was a statistically significant interaction between baseline kidney function and supplementation with study amino acids (p value for interaction = 0.026). Within the subgroup of patients with normal kidney function at randomization, patients who were allocated to receive the study amino acid supplement were less likely to die before study day 90 (covariate-adjusted risk difference, -7.9%; 95% CI, -15.1 to -0.7; p = 0.034). Furthermore, amino acid supplementation significantly increased estimated glomerular filtration rate in these patients (repeated-measures treatment × time interaction p = 0.009). Within the subgroup of patients with baseline kidney dysfunction and/or risk of progression of acute kidney injury, a significant effect of the study intervention on mortality was not found (covariate-adjusted risk difference, -0.6%; 95% CI, -16.2 to 15.2; p = 0.95). In this post hoc, hypothesis-generating, subgroup analysis, we observed reduced mortality and improved estimated glomerular filtration rate in ICU patients with normal kidney function who were randomly allocated to receive increased protein intake (up to 2.0 g/kg/d). We strongly recommend confirmation of these results in trials

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

Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis.

PubMed

Frejo, L; Martin-Sanz, E; Teggi, R; Trinidad, G; Soto-Varela, A; Santos-Perez, S; Manrique, R; Perez, N; Aran, I; Almeida-Branco, M S; Batuecas-Caletrio, A; Fraile, J; Espinosa-Sanchez, J M; Perez-Guillen, V; Perez-Garrigues, H; Oliva-Dominguez, M; Aleman, O; Benitez, J; Perez, P; Lopez-Escamez, J A

2017-12-01

To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD. A cross-sectional study with a two-step cluster analysis. A tertiary referral multicenter study. Nine hundred and eighty-eight adult patients with unilateral MD. best predictors to define clinical subgroups with potential different aetiologies. We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials. © 2017 John Wiley & Sons Ltd.

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.

Patterns of Alcohol Use and Consequences Among Empirically Derived Sexual Minority Subgroups

PubMed Central

Talley, Amelia E.; Sher, Kenneth J.; Steinley, Douglas; Wood, Phillip K.; Littlefield, Andrew K.

2012-01-01

Objective: The current study develops an empirically determined classification of sexual orientation developmental patterns based on participants’ annual reports of self-identifications, sexual attractions, and sexual behaviors during the first 4 years of college. A secondary aim of the current work was to examine trajectories of alcohol involvement among identified subgroups. Method: Data were drawn from a subsample of a longitudinal study of incoming first-time college students at a large, public university (n = 2,068). Longitudinal latent class analysis was used to classify sexual minority participants into empirically derived subgroups based on three self-reported facets of sexual orientation. Multivariate repeated-measures analyses were conducted to examine how trajectories of alcohol involvement varied by sexual orientation class membership. Results: Four unique subclasses of sexual orientation developmental patterns were identified for males and females: one consistently exclusively heterosexual group and three sexual minority groups. Despite generally similar alcohol use patterns among subclasses, certain sexual minority subgroups reported elevated levels of alcohol-related negative consequences and maladaptive motivations for use throughout college compared with their exclusively heterosexual counterparts. Conclusions: Elevations in coping and conformity motivations for alcohol use were seen among those subgroups that also evidenced heightened negative alcohol-related consequences. Implications and limitations of the current work are discussed. PMID:22333337

Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial.

PubMed

Cortés, Javier; Rugo, Hope S; Awada, Ahmad; Twelves, Chris; Perez, Edith A; Im, Seock-Ah; Gómez-Pardo, Patricia; Schwartzberg, Lee S; Diéras, Veronique; Yardley, Denise A; Potter, David A; Mailliez, Audrey; Moreno-Aspitia, Alvaro; Ahn, Jin-Seok; Zhao, Carol; Hoch, Ute; Tagliaferri, Mary; Hannah, Alison L; O'Shaughnessy, Joyce

2017-09-01

Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician's choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conducted. In the trial, 67 BCBM patients were randomized (EP, n = 36; TPC, n = 31). Treatment subgroups were balanced for baseline characteristics and GPA indices. EP was associated with a significant reduction in the risk of death (HR 0.51; P < 0.01) versus TPC; median OS was 10.0 and 4.8 months, respectively. Improvement in OS was observed in both poorer and better GPA prognostic groups. Survival rates at 12 months were 44.4% for EP versus 19.4% for TPC. Consistent with the overall BEACON population, fewer patients on EP experienced grade ≥3 toxicity (50 vs. 70%). The significant improvement in survival in BCBM patients provides encouraging data for EP in this difficult-to-treat subgroup of patients. A phase three trial of EP in BCBM patients is underway (ClinicalTrials.gov NCT02915744).

Combined group ECC protection and subgroup parity protection

DOEpatents

Gara, Alan G.; Chen, Dong; Heidelberger, Philip; Ohmacht, Martin

2013-06-18

A method and system are disclosed for providing combined error code protection and subgroup parity protection for a given group of n bits. The method comprises the steps of identifying a number, m, of redundant bits for said error protection; and constructing a matrix P, wherein multiplying said given group of n bits with P produces m redundant error correction code (ECC) protection bits, and two columns of P provide parity protection for subgroups of said given group of n bits. In the preferred embodiment of the invention, the matrix P is constructed by generating permutations of m bit wide vectors with three or more, but an odd number of, elements with value one and the other elements with value zero; and assigning said vectors to rows of the matrix P.

A subgroup-specific evaluation of the efficacy of intraarticular triamcinolone hexacetonide in juvenile chronic arthritis.

PubMed

Breit, W; Frosch, M; Meyer, U; Heinecke, A; Ganser, G

2000-11-01

To determine the subgroup-specific differences of intraarticular triamcinolone hexacetonide (TH) in the treatment of joint inflammation in patients with juvenile chronic arthritis (JCA). A retrospective review of 194 children of all subgroups of JCA, treated by a single or repeated TH injection between 1989 to 1994. Efficacy and duration of benefit were evaluated after a mean duration of 3, 15, 30, and 64 weeks. In all, 1439 TH injections were given to 194 patients; 368 of these were reinjections. The median duration of improvement of all injections was 74 weeks. Responses were significantly different among subgroups (p = 0.0001): there were 121 weeks of efficacy in early-onset pauciarticular JCA type I (223 injections), 47 weeks in late-onset pauciarticular JCA type II (190 injections), 105 weeks in rheumatoid factor negative polyarticular JCA (445 injections), 63 weeks in rheumatoid factor positive polyarticular JCA (127 injections), and 36 weeks in systemic JCA (413 injections). Forty-one injections were done in other rheumatic diseases. In relation to this result there were also differences with regard to joint groups, antinuclear antibody (ANA) and HLA-B27 status, and sex. Side effects were rare: infections of skin or joints were not noted; skin and lipoatrophy were seen after 15 injections, necrosis of the hip in one case, luxation of 2 shoulders of one patient, and periarticular calcification in 3 patients. Intraarticular TH is an effective therapy for inflammatory joint disease in all subgroups of JCA. The risk of major complications is low. The median duration of improvement depends on the subgroup of the disease.

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.

A person-centered approach to examining heterogeneity and subgroups among survivors of sexual assault.

PubMed

Masters, N Tatiana; Stappenbeck, Cynthia A; Kaysen, Debra; Kajumulo, Kelly F; Davis, Kelly Cue; George, William H; Norris, Jeanette; Heiman, Julia R

2015-08-01

This study identified subgroups of female sexual assault survivors based on characteristics of their victimization experiences, validated the subgroup structure in a second cohort of women recruited identically to the first, and examined subgroups' differential associations with sexual risk/safety behavior, heavy episodic drinking (HED), psychological distress symptomatology, incarceration, transactional sex, and experiences with controlling and violent partners. The community sample consisted of 667 female survivors of adolescent or adult sexual assault who were 21 to 30 years old (M = 24.78, SD = 2.66). Eligibility criteria included having unprotected sex within the past year, other HIV/STI risk factors, and some experience with HED, but without alcohol problems or dependence. Latent class analyses (LCA) were used to identify subgroups of women with similar victimization experiences. Three groups were identified and validated across 2 cohorts of women using multiple-group LCA: contact or attempted assault (17% of the sample), incapacitated assault (52%), and forceful severe assault (31%). Groups did not differ in their sexual risk/safety behavior. Women in the forceful severe category had higher levels of anxiety, depression, and trauma symptoms; higher proportions of incarceration and transactional sex; and more experiences with controlling and violent partners than did women in the other 2 groups. Women in the forceful severe category also reported a higher frequency of HED than women in the incapacitated category. Different types of assault experiences appear to be differentially associated with negative outcomes. Understanding heterogeneity and subgroups among sexual assault survivors has implications for improving clinical care and contributing to recovery. (c) 2015 APA, all rights reserved).

A Person-Centered Approach to Examining Heterogeneity and Subgroups Among Survivors of Sexual Assault

PubMed Central

Masters, N. Tatiana; Stappenbeck, Cynthia A.; Kaysen, Debra; Kajumulo, Kelly F.; Davis, Kelly Cue; George, William H.; Norris, Jeanette; Heiman, Julia R.

2015-01-01

This study identified subgroups of female sexual assault survivors based on characteristics of their victimization experiences, validated the subgroup structure in a second cohort of women recruited identically to the first, and examined subgroups' differential associations with sexual risk/safety behavior, heavy episodic drinking (HED), psychological distress symptomatology, incarceration, transactional sex, and experiences with controlling and violent partners. The community sample consisted of 667 female survivors of adolescent or adult sexual assault who were 21 to 30 years old (M=24.78, SD=2.66). Eligibility criteria included having unprotected sex within the past year, other HIV/STI risk factors, and some experience with HED, but without alcohol problems or dependence. Latent class analyses (LCA) were used to identify subgroups of women with similar victimization experiences. Three groups were identified and validated across two cohorts of women using multiple-group LCA: Contact or Attempted assault (17% of the sample), Incapacitated assault (52%), and Forceful Severe assault (31%). Groups did not differ in their sexual risk/safety behavior. Women in the Forceful Severe category had higher levels of anxiety, depression, and trauma symptoms, higher proportions of incarceration and transactional sex, and more experiences with controlling and violent partners than did women in the other two groups. Women in the Forceful Severe category also reported a higher frequency of HED than women in the Incapacitated category. Different types of assault experiences appear to be differentially associated with negative outcomes. Understanding heterogeneity and subgroups among sexual assault survivors has implications for improving clinical care and contributing to recovery. PMID:26052619

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.

Does Kinesiophobia Modify the Effects of Physical Therapy on Outcomes in Patients With Sciatica in Primary Care? Subgroup Analysis From a Randomized Controlled Trial.

PubMed

Verwoerd, Annemieke J H; Luijsterburg, Pim A J; Koes, Bart W; el Barzouhi, Abdelilah; Verhagen, Arianne P

2015-09-01

A higher level of kinesiophobia appears to be associated with poor recovery in patients with sciatica. The aim of this study was to investigate whether kinesiophobia modifies the effect of physical therapy on outcomes in patients with sciatica. This was a subgroup analysis from a randomized controlled trial. The study was conducted in a primary care setting. A total of 135 patients with acute sciatica participated. Patients were randomly assigned to groups that received (1) physical therapy plus general practitioners' care (intervention group) or (2) general practitioners' care alone (control group). Kinesiophobia at baseline was measured with the Tampa Scale for Kinesiophobia (TSK) and a single substitute question for kinesiophobia (SQK). Pain and recovery were assessed at 3- and 12-month follow-ups. Regression analysis was used to test for interaction between the level of kinesiophobia at baseline and treatment allocation. Subgroup results were calculated for patients classified with high fear of movement and for those classified with low fear of movement. Kinesiophobia at baseline interacted with physical therapy in the analysis with leg pain intensity at 12-month follow-up. Kinesiophobia at baseline did not interact with physical therapy regarding any outcome at 3-month follow-up or recovery at 12-month follow-up. When comparing both treatment groups in the subgroup of patients with high fear of movement (n=73), the only significant result was found for leg pain intensity difference from baseline at 12-month follow-up (intervention group: X̅=-5.0, SD=2.6; control group: X̅=-3.6, SD=2.7). The post hoc study design and relatively small sample size were limitations of the study. In 135 patients with sciatica, evidence shows that patients with a higher level of kinesiophobia at baseline may particularly benefit from physical therapy with regard to decreasing leg pain intensity at 12-month follow-up. © 2015 American Physical Therapy Association.

Does the impact of case management vary in different subgroups of multimorbidity? Secondary analysis of a quasi-experiment.

PubMed

Stokes, Jonathan; Kristensen, Søren Rud; Checkland, Kath; Cheraghi-Sohi, Sudeh; Bower, Peter

2017-08-03

Health systems must transition from catering primarily to acute conditions, to meet the increasing burden of chronic disease and multimorbidity. Case management is a popular method of integrating care, seeking to accomplish this goal. However, the intervention has shown limited effectiveness. We explore whether the effects of case management vary in patients with different types of multimorbidity. We extended a previously published quasi-experiment (difference-in-differences analysis) with 2049 propensity matched case management intervention patients, adding an additional interaction term to determine subgroup effects (difference-in-difference-in-differences) by different conceptualisations of multimorbidity: 1) Mental-physical comorbidity versus others; 2) 3+ chronic conditions versus <3; 3) Discordant versus concordant conditions; 4) Cardiovascular/metabolic cluster conditions only versus others; 5) Mental health-associated cluster conditions only versus others; 6) Musculoskeletal disorder cluster conditions only versus others 7) Charlson index >5 versus others. Outcome measures included a variety of secondary care utilisation and cost measures. The majority of conceptualisations suggested little to no difference in effect between subgroups. Where results were significant, the vast majority of effect sizes identified in either direction were very small. The trend across the majority of the results appeared to show very slight increases of admissions with treatment for the most complex patients (highest risk). The exceptions to this, patients with a Charlson index >5 may benefit slightly more from case management with decreased ACSC admissions (effect size (ES): −0.06) and inpatient re-admissions (30 days, ES: −0.05), and patients with only cardiovascular/metabolic cluster conditions may benefit slightly more with decreased inpatient non-elective admissions (ES: −0.12). Only the three significant estimates for the musculoskeletal disorder cluster met the

Hierarchical Bayes approach for subgroup analysis.

PubMed

Hsu, Yu-Yi; Zalkikar, Jyoti; Tiwari, Ram C

2017-01-01

In clinical data analysis, both treatment effect estimation and consistency assessment are important for a better understanding of the drug efficacy for the benefit of subjects in individual subgroups. The linear mixed-effects model has been used for subgroup analysis to describe treatment differences among subgroups with great flexibility. The hierarchical Bayes approach has been applied to linear mixed-effects model to derive the posterior distributions of overall and subgroup treatment effects. In this article, we discuss the prior selection for variance components in hierarchical Bayes, estimation and decision making of the overall treatment effect, as well as consistency assessment of the treatment effects across the subgroups based on the posterior predictive p-value. Decision procedures are suggested using either the posterior probability or the Bayes factor. These decision procedures and their properties are illustrated using a simulated example with normally distributed response and repeated measurements.

Elevated peripheral cytokines characterize a subgroup of people with schizophrenia displaying poor verbal fluency and reduced Broca's area volume

PubMed Central

Fillman, S G; Weickert, T W; Lenroot, R K; Catts, S V; Bruggemann, J M; Catts, V S; Weickert, C S

2016-01-01

Previous studies on schizophrenia have detected elevated cytokines in both brain and blood, suggesting neuroinflammation may contribute to the pathophysiology in some cases. We aimed to determine the extent to which elevated peripheral cytokine messenger RNA (mRNA) expression: (1) characterizes a subgroup of people with schizophrenia and (2) shows a relationship to cognition, brain volume and/or symptoms. Forty-three outpatients with schizophrenia or schizoaffective disorder and matched healthy controls were assessed for peripheral cytokine mRNAs (interleukin (IL)-1β, IL-2, IL-6, IL-8 and IL-18), intelligence quotient, memory and verbal fluency, symptom severity and cortical brain volumes integral to language (that is, Broca's and Wernicke's areas). IL-1β mRNA levels were 28% increased in schizophrenia compared with controls (t(82)=2.64, P<0.01). Using a two-step clustering procedure, we identified a subgroup of people displaying relatively elevated cytokine mRNA levels (17/43 people with schizophrenia and 9/42 controls). Individuals with schizophrenia in the elevated cytokine subgroup performed significantly worse than the low-cytokine subgroup on verbal fluency (F(1,40)=15.7, P<0.001). There was a 17% volume reduction of the left pars opercularis (POp) (Broca's area) in patients with elevated cytokines compared with patients with lower cytokines (F(1,29)=9.41, P=0.005). Negative linear relationships between IL-1β mRNA levels and both verbal fluency and left POp volume were found in schizophrenia. This study is among the first to link blood biomarkers of inflammation with both cognitive deficits and brain volume reductions in people with schizophrenia, supporting that those with elevated cytokines represent a neurobiologically meaningful subgroup. These findings raise the possibility that targeted anti-inflammatory treatments may ameliorate cognitive and brain morphological abnormalities in some people with schizophrenia. PMID:26194183

Latent class-derived subgroups of depressive symptoms in a community sample of older adults: the Cache County Study.

PubMed

Lee, Chien-Ti; Leoutsakos, Jeannie-Marie; Lyketsos, Constantine G; Steffens, David C; Breitner, John C S; Norton, Maria C

2012-10-01

We sought to identify possible subgroups of elders that varied in depressive symptomatology and to examine symptom patterns and health status differences between subgroups. The Cache County memory study is a population-based epidemiological study of dementia with 5092 participants. Depressive symptoms were measured with a modified version of the diagnostic interview schedule-depression. There were 400 nondemented participants who endorsed currently (i.e., in the past 2 weeks) experiencing at least one of the three "gateway" depressive symptoms and then completed a full depression interview. Responses to all nine current depressive symptoms were modeled using the latent class analysis. Three depression subgroups were identified: a significantly depressed subgroup (62%), with the remainder split evenly between a subgroup with low probability of all symptoms (21%), and a subgroup with primarily psychomotor changes, sleep symptoms, and fatigue (17%). Latent class analysis derived subgroups of depressive symptoms and Diagnostic and statistical manual of mental disorders, fourth edition depression diagnostic group were nonredundant. Age, gender, education, marital status, early or late onset, number of episodes, current episode duration, and functional status were not significant predictors of depression subgroup. The first subgroup was more likely to be recently bereaved and had less physical health problems, whereas the third subgroup were less likely to be using antidepressants compared with the second subgroup. There are distinct subgroups of depressed elders, which are not redundant with the Diagnostic and statistical manual of mental disorders, fourth edition classification scheme, offering an alternative diagnostic approach to clinicians and researchers. Future work will examine whether these depressive symptom profiles are predictive of incident dementia and earlier mortality. Copyright © 2011 John Wiley & Sons, Ltd.

Comparative Persistence of Subgroups of F-Specific RNA Phages in River Water

PubMed Central

Yang, Yongheng

2013-01-01

F-specific (F+) RNA phages are widely used as indicators for the presence of fecal contamination and/or enteric viruses in water, and identifying subgroups of F+ RNA phages provides an approach for microbial source tracking. Different survival characteristics of the F+ RNA phage subgroups result in a misinterpretation of their original proportion in water, thus giving misleading information when they are used for microbial source tracking. This study investigated the comparative persistence of subgroups of F+ RNA phages in river water under different conditions. Results suggested that temperature and pH are the major factors affecting the persistence of F+ RNA phages in river water, and organic substances promote phage survival. The comparative persistence patterns of subgroups of F+ RNA phages varied and may bias extrapolation of their initial proportions in surface water. Thus, the characteristics of water should be taken into consideration and the results should be carefully interpreted when F+ RNA phages are used for microbial source tracking. PMID:23686274

Medulloblastoma. The identification of prognostic subgroups and implications for multimodality management

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

Kopelson, G.; Linggood, R.M.; Kleinman, G.M.

1983-01-15

For 43 medulloblatoma patients who had five-and ten-year actuarial survival rates of 56%, prognostic factors of statistical significance included: T-stage, M-stage and histopathologic tumor score. Posterior fossa local control rates were also function of T-stage and TS. Combining TS with T-stage, patients fell into three prognostic and local control groups, which may have different future management implications: Small (T1,2) tumors of favorable (TS less than or equal to 5) histology had a 92% ten-year actuarial survival rate with 100% (8/8) local control; no change from current management is suggested. For the intermediate prognosis group, increasing the irradiation dose alone maymore » improve survival because these tumors exhibited an irradiation dose-response relationship. However, it is the poor prognosis group which might be suitable for future adjuvant chemotherapy or radiosensitizer trials since there is no evidence that higher irradiation doses improve local control. This article identifies prognostic subgroups based on histologic type and TM staging in medulloblastoma patients which potentially may be utilized to improve therapeutic results, and confirms the value of staging patients with central nervous system malignancies.« less

[Generalization of the results of clinical studies through the analysis of subgroups].

PubMed

Costa, João; Fareleira, Filipa; Ascensão, Raquel; Vaz Carneiro, António

2012-01-01

Subgroup analysis in clinical trials are usually performed to define the potential heterogeneity of treatment effect in relation with the baseline risk, physiopathology, practical application of therapy or the under-utilization in clinical practice of effective interventions due to uncertainties of its benefit/risk ratio. When appropriately planned, subgroup analysis are a valid methodology the define benefits in subgroups of patients, thus providing good quality evidence to support clinical decision making. However, in order to be correct, subgroup analysis should be defined a priori, done in small numbers, should be fully reported and, most important, must endure statistical tests for interaction. In this paper we present an example of the treatment of post-menopausal osteoporosis, in which the benefits of an intervention (the higher the fracture risk is, the better the benefit is) with a specific agent (bazedoxifene) was only disclosed after a post-hoc analysis of the initial global trial sample.

Combined group ECC protection and subgroup parity protection

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

Gara, Alan; Cheng, Dong; Heidelberger, Philip

A method and system are disclosed for providing combined error code protection and subgroup parity protection for a given group of n bits. The method comprises the steps of identifying a number, m, of redundant bits for said error protection; and constructing a matrix P, wherein multiplying said given group of n bits with P produces m redundant error correction code (ECC) protection bits, and two columns of P provide parity protection for subgroups of said given group of n bits. In the preferred embodiment of the invention, the matrix P is constructed by generating permutations of m bit widemore » vectors with three or more, but an odd number of, elements with value one and the other elements with value zero; and assigning said vectors to rows of the matrix P.« less

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

PRIM versus CART in subgroup discovery: when patience is harmful.

PubMed

Abu-Hanna, Ameen; Nannings, Barry; Dongelmans, Dave; Hasman, Arie

2010-10-01

We systematically compare the established algorithms CART (Classification and Regression Trees) and PRIM (Patient Rule Induction Method) in a subgroup discovery task on a large real-world high-dimensional clinical database. Contrary to current conjectures, PRIM's performance was generally inferior to CART's. PRIM often considered "peeling of" a large chunk of data at a value of a relevant discrete ordinal variable unattractive, ultimately missing an important subgroup. This finding has considerable significance in clinical medicine where ordinal scores are ubiquitous. PRIM's utility in clinical databases would increase when global information about (ordinal) variables is better put to use and when the search algorithm keeps track of alternative solutions.

Discriminative and predictive validity of the scoliosis research society-22 questionnaire in management and curve-severity subgroups of adolescents with idiopathic scoliosis.

PubMed

Parent, Eric C; Hill, Doug; Mahood, Jim; Moreau, Marc; Raso, Jim; Lou, Edmond

2009-10-15

Prospective cross-sectional measurement study. To determine the ability of the Scoliosis Research Society (SRS)-22 questionnaire to discriminate among management and scoliosis severity subgroups and to correlate with internal and external measures of curve severity. In earlier studies of the SRS-22 discriminative ability, age was not a controlled factor. The ability of the SRS-22 to predict curve severity has not been thoroughly examined. The SRS-22 was completed by 227 females with adolescent idiopathic scoliosis. Using Analysis of covariance analyses controlling for age, the SRS-22 scores were compared among management subgroups (observation, brace, presurgery, and postsurgery) and curve-severity subgroups (in nonoperated subjects: Cobb angles of <30 degrees, 30 degrees -50 degrees, and >50 degrees). A stepwise discriminant analysis was used to identify the SRS-22 domains most discriminative for curve-severity categories. Correlation between SRS-22 scores and radiographic or surface topography measurements was used to determine the predictive ability of the questionnaire. Pain was better for subjects treated with braces than for those planning surgery. Self-image was better for subjects under observation or postsurgery than for those planning surgery. Satisfaction was better for the brace and postsurgery subgroups than for the observation or presurgery subgroups. Statistically significant mean differences between subgroups were all larger than 0.5, which is within the range of minimal clinically important differences recommended for each of the 5-point SRS-22 domain scoring scales. Pain and mental health were worse for those with Cobb angles of >50 degrees than with Cobb angles of 30 degrees to 50 degrees. Self-image and total scores were worse for those with Cobb angles of >50 degrees than both other subgroups. Using discriminant analysis, self-image was the only SRS-22 domain score selected to classify subjects within curve severity subgroups. The percentage of

Phenotypic subgroups of polycystic ovary syndrome have different intra-renal resistance symptoms.

PubMed

Ciftci, Ceylan F; Uckuyu, Ayla; Karadeli, Elif; Turhan, Erdem; Toprak, Erzat; Ozcimen, Emel E

2012-12-01

The polycystic ovary syndrome (PCOS) is known to be related with increased metabolic and cardiovascular risks. Various phenotypic subgroups of PCOS have been proven to have metabolic and endocrine disorders with varying degrees of severity However, intra-renal vascular resistance, which is an indirect indication of atherosclerosis, remains unknown in PCOS subgroups. In this study we examined whether PCOS subgroups have different intra-renal resistance symptoms. 98 PCOS patients (diagnosed according to the Rotterdam criteria) 30 controls were included in the study The diagnosis of PCOS was established in the presence of at least two of the following criteria: 1-oligo and/or amenorrhea (OM); 2-clinic and/or biochemical signs of hyperandrogenism (HA); 3-polycystic ovarian morphology (PCO) detected by transvaginal ultrasonography 37 patients (Group 1) met all three criteria (HA+OM+PCO), 29 patients (Group 2) met two of the criteria including hyperandrogenism (HA+OM or HA+PCO) and the remaining 32 patients (Group 3) had no hyperandrogenism but fulfilled the other two criteria; PCO+OM. Renal Doppler ultrasonography and hormonal/biochemical analyses were carried out. The first outcome measure was designated as the differences in the renal resistive index (RRI) values of the groups, and the second outcome measure was designated as the relation of RRI with the insulin resistance and lipid profile. In Group 1, the RRI and the homeostasis model assessment of insulin resistance (HOMA-IR) values were significantly higher than in Group 3 and controls (P < 0.031, P < 0.001, respectively after adjusting for age and BMI). The RRI and HOMA-IR values in Group 3 were similar to those of the control group. It was determined that RRI has a positive correlation with HOMA-IR (r = 0.784, P < .0001) and BMI (r = 0.645, P < .0001). In this study we demonstrated that PCOS subgroups have metabolic and endocrine disorders and cardiovascular risks of varying degrees of severity Moreover, we

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

Subgroups of adolescents differing in physical and social environmental preferences towards cycling for transport: A latent class analysis.

PubMed

Verhoeven, Hannah; Ghekiere, Ariane; Van Cauwenberg, Jelle; Van Dyck, Delfien; De Bourdeaudhuij, Ilse; Clarys, Peter; Deforche, Benedicte

2018-07-01

In order to be able to tailor environmental interventions to adolescents at risk for low levels of physical activity, the aim of the present study is to identify subgroups of adolescents with different physical and social environmental preferences towards cycling for transport and to determine differences in individual characteristics between these subgroups. In this experimental study, 882 adolescents (12-16 years) completed 15 choice tasks with manipulated photographs. Participants chose between two possible routes to cycle to a friend's house which differed in seven physical micro-environmental factors, cycling distance and co-participation in cycling (i.e. cycling alone or with a friend). Latent class analysis was performed. Data were collected from March till October 2016 across Flanders (Belgium). Three subgroups could be identified. Subgroup 1 attached most importance to separation of the cycle path and safety-related aspects. Subgroup 2 attached most importance to being able to cycle together with a friend and had the highest percentage of regular cyclists. In subgroup 3, the importance of cycling distance clearly stood out. This subgroup included the lowest percentage of regular cyclists. Results showed that in order to stimulate the least regular cyclists, and thus also the subgroup most at risk for low levels of active transport, cycling distances should be as short as possible. In general, results showed that providing well-separated cycle paths which enable adolescents to cycle side by side and introducing shortcuts for cyclists may encourage different subgroups of adolescents to cycle for transport without discouraging other subgroups. Copyright © 2018 Elsevier Inc. All rights reserved.

An exploration of subgroups of mild cognitive impairment based on cognitive, neuropsychiatric and functional features: analysis of data from the National Alzheimer's Coordinating Center.

PubMed

Hanfelt, John J; Wuu, Joanne; Sollinger, Ann B; Greenaway, Melanie C; Lah, James J; Levey, Allan I; Goldstein, Felicia C

2011-11-01

To empirically expand the existing subtypes of mild cognitive impairment (MCI) by incorporating information on neuropsychiatric and functional features, and to assess whether cerebrovascular disease (CVD) risk factors are associated with any of these subgroups. Latent class analysis using 1,655 patients with MCI. Participants in the Uniform Data Set (UDS) from 29 National Institutes of Health-supported Alzheimer's Disease Centers. Patients with a consensus diagnosis of MCI from each center and with a Mini-Mental State Examination score of 22 or greater. UDS cognitive battery, Neuropsychiatric Inventory Questionnaire, and Functional Assessment Questionnaire administered at initial visit. Seven empirically based subgroups of MCI were identified: 1) minimally impaired (relative frequency, 12%); 2) amnestic only (16%); 3) amnestic with functional and neuropsychiatric features (16%); 4) amnestic multidomain (12%); 5) amnestic multidomain with functional and neuropsychiatric features (12%); 6) functional and neuropsychiatric features (15%); and 7) executive function and language impairments (18%). Two of these subgroups with functional and neuropsychiatric features were at least 3.8 times more likely than the minimally impaired subgroup to have a Rosen-Hachinski score of 4 or greater, an indicator of probable CVD. Findings suggest that there are several distinct phenotypes of MCI characterized by prominent cognitive features, prominent functional features, and neuropsychiatric features or a combination of all three. Subgroups with functional and neuropsychiatric features are significantly more likely to have CVD, which suggests that there may be distinct differences in disease etiology from the other phenotypes.

An Approach to Revealing Clinically Relevant Subgroups Across the Mood Spectrum

PubMed Central

Wallace, Meredith L.; Simsek, Burcin; Kupfer, David J.; Swartz, Holly A.; Fagiolini, Andrea; Frank, Ellen

2016-01-01

Background Individuals diagnosed with bipolar 1 disorder (BP1), bipolar 2 disorder (BP2), or major depressive disorder (MDD) experience varying levels of depressive and (hypo)manic symptoms. Clarifying symptom heterogeneity is meaningful, as even subthreshold symptoms may impact quality of life and treatment outcome. The MOODS Lifetime self-report instrument was designed to capture the full range of depressive and (hypo)manic characteristics. Methods This study applied clustering methods to 347 currently depressed adults with MDD, BP2, or BP1 to reveal naturally occurring MOODS subgroups. Subgroups were then compared on baseline clinical and demographic characteristics and as well as depressive and (hypo)manic symptoms over twenty weeks of treatment. Results Four subgroups were identified: (1) high depressive and (hypo)manic symptoms (N=77, 22%), (2) moderate depressive and (hypo)manic symptoms (N=115, 33%), (3) low depressive and moderate (hypo)manic symptoms (N=82, 24%), and (4) low depressive and (hypo)manic symptoms (N=73, 21%). Individuals in the low lifetime depressive/moderate lifetime (hypo)manic subgroup had poorer quality of life and greater depressive symptoms over the course of treatment. Individuals in the high and moderate severity subgroups had greater substance use, longer duration of illness, and greater (hypo)manic symptoms throughout treatment. Treatment outcomes were primarily driven by individuals diagnosed with MDD. Limitations The sample was drawn from three randomized clinical trials. Validation is required for this exploratory study. Conclusions After validation, these subgroups may inform classification and personalized treatment beyond categorical diagnosis. PMID:27314813

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

Psychological, behavioral, and family characteristics of pediatric patients with chronic pain: a 1-year retrospective study and cluster analysis.

PubMed

Scharff, Lisa; Langan, Nicole; Rotter, Nancy; Scott-Sutherland, Jennifer; Schenck, Clorinda; Tayor, Neil; McDonald-Nolan, Lori; Masek, Bruce

2005-01-01

There has been a longstanding recognition that adult patients with chronic pain are not a homogenous population and that there are subgroups of patients who report high levels of distress and interpersonal difficulties as well as subgroups of patients who report little distress and high functioning. The purpose of the present study was to attempt to identify similar subgroups in a pediatric chronic pain population. The sample consisted of 117 children with chronic pain and their parents who were assessed in a multidisciplinary pain clinic during 2001. Participants completed a set of psychologic self-report questionnaires, as well as demographic and pain characteristic information. A cluster analysis was conducted to identify 3 distinct subgroups of patients to replicate similar studies of adult chronic pain sufferers. Overall, mean scores were within population norms on measures of distress and family functioning, with somatic symptoms at a level of clinical significance. The cluster analysis identified the 3 subgroups that were strikingly similar to those identified in adult chronic pain populations: one with high levels of distress and disability, another with relatively low scores on distress and disability, and a third group that scored in between the other 2 on these measures but with marked low family cohesion. The similarity of these subgroups to the adult chronic pain population subgroups as well as implications for future studies are discussed.

Pain modulatory phenotypes differentiate subgroups with different clinical and experimental pain sensitivity.

PubMed

Vaegter, Henrik B; Graven-Nielsen, Thomas

2016-07-01

Pain biomarkers are warranted for individualized pain management. Based on different pain modulatory phenotypes, the objectives of this study were to explore the existence of subgroups within patients with nonmalignant chronic pain and to investigate differences in clinical pain and pain hypersensitivity between subgroups. Cuff algometry was performed on lower legs in 400 patients with chronic pain to assess pressure pain threshold, pressure pain tolerance, temporal summation of pain (TSP: increase in pain scores to 10 repeated stimulations), and conditioned pain modulation (CPM: increase in cuff pressure pain threshold during cuff pain conditioning on the contralateral leg). Heat detection and heat pain thresholds at clinical painful and nonpainful body areas were assessed. Based on TSP and CPM, 4 distinct groups were formed: group 1 (n = 85) had impaired CPM and facilitated TSP; group 2 (n = 148) had impaired CPM and normal TSP; group 3 (n = 45) had normal CPM and facilitated TSP; and group 4 (n = 122) had normal CPM and normal TSP. Group 1 showed more pain regions than the other 3 groups (P < 0.001), indicating that impaired CPM and facilitated TSP play an important role in widespread pain. Groups 1 and 2 compared with group 4 had lower heat pain threshold at nonpainful areas and lower cuff pressure pain tolerance (P < 0.02), indicating that CPM plays a role for widespread hyperalgesia. Moreover, group 1 demonstrated higher clinical pain scores than group 4 (P < 0.05). Although not different between subgroups, patients were profiled on demographics, disability, pain catastrophizing, and fear of movement. Future research should investigate interventions tailored towards these subgroups.

Latent Subgroup Analysis of a Randomized Clinical Trial Through a Semiparametric Accelerated Failure Time Mixture Model

PubMed Central

Altstein, L.; Li, G.

2012-01-01

Summary This paper studies a semiparametric accelerated failure time mixture model for estimation of a biological treatment effect on a latent subgroup of interest with a time-to-event outcome in randomized clinical trials. Latency is induced because membership is observable in one arm of the trial and unidentified in the other. This method is useful in randomized clinical trials with all-or-none noncompliance when patients in the control arm have no access to active treatment and in, for example, oncology trials when a biopsy used to identify the latent subgroup is performed only on subjects randomized to active treatment. We derive a computational method to estimate model parameters by iterating between an expectation step and a weighted Buckley-James optimization step. The bootstrap method is used for variance estimation, and the performance of our method is corroborated in simulation. We illustrate our method through an analysis of a multicenter selective lymphadenectomy trial for melanoma. PMID:23383608

Radiofrequency ablation for locally advanced pancreatic cancer: SMAD4 analysis segregates a responsive subgroup of patients.

PubMed

Paiella, Salvatore; Malleo, Giuseppe; Cataldo, Ivana; Gasparini, Clizia; De Pastena, Matteo; De Marchi, Giulia; Marchegiani, Giovanni; Rusev, Borislav; Scarpa, Aldo; Girelli, Roberto; Giardino, Alessandro; Frigerio, Isabella; D'Onofrio, Mirko; Secchettin, Erica; Bassi, Claudio; Salvia, Roberto

2018-03-01

SMAD4 mutational status correlates with pancreatic ductal adenocarcinoma (PDAC) failure pattern. We investigated in a subset of locally advanced patients submitted to radiofrequency ablation (RFA) whether the assessment of SMAD4 status is a useful way to select the patients. Clinical, radiological, and follow-up details of patients submitted to RFA for locally advanced pancreatic cancer (LAPC), in whom cytohistological material was available at our institution, were retrospectively retrieved. SMAD4 expression was evaluated by immunohistochemistry (IHC) and considered "negative" or "positive." The survival analysis was conducted using Kaplan-Meier and Cox proportional hazards models. The study population consisted of 30 patients. Thirteen patients (43.3%) received RFA upfront, whereas 17 (56.7%) after induction treatments. SMAD4 was mutant in 18 out of 30 patients (60%). The overall estimated post-RFA disease-specific survival (DSS) was 15 months (95% CI 11.64-18.35). The estimated post-RFA DSS of patients with wild-type and mutant SMAD4 was 22 and 12 months, respectively (log-rank p < 0.05). At the multivariate analysis, SMAD4 was the only independent predictor of survival (p = 0.05). The pattern of failure was not associated with SMAD4 status (p = 0.4). Within patients undergoing RFA for LAPC, SMAD4 analysis could segregate a subgroup of subjects with improved survival, who likely benefited from tumor ablation.

Molecular subgroups of medulloblastoma

PubMed Central

Northcott, Paul A; Dubuc, Adrian M; Pfister, Stefan; Taylor, Michael D

2014-01-01

Recent efforts at stratifying medulloblastomas based on their molecular features have revolutionized our understanding of this morbidity. Collective efforts by multiple independent groups have subdivided medulloblastoma from a single disease into four distinct molecular subgroups characterized by disparate transcriptional signatures, mutational spectra, copy number profiles and, most importantly, clinical features. We present a summary of recent studies that have contributed to our understanding of the core medulloblastoma subgroups, focusing largely on clinically relevant discoveries that have already, and will continue to, shape research. PMID:22853794

Variation in Patient Profiles and Outcomes in US and Non-US Subgroups of the Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION) PHOENIX Trial

PubMed Central

Vaduganathan, Muthiah; Harrington, Robert A.; Stone, Gregg W.; Steg, Ph. Gabriel; Gibson, C. Michael; Hamm, Christian W.; Price, Matthew J.; Prats, Jayne; Deliargyris, Efthymios N.; Mahaffey, Kenneth W.; White, Harvey D.

2016-01-01

Background— The Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION) PHOENIX trial demonstrated superiority of cangrelor in reducing ischemic events at 48 hours in patients undergoing percutaneous coronary intervention compared with clopidogrel. Methods and Results— We analyzed all patients included in the modified intention-to-treat analysis in US (n=4097; 37.4%) and non-US subgroups (n=6845; 62.6%). The US cohort was older, had a higher burden of cardiovascular risk factors, and had more frequently undergone prior cardiovascular procedures. US patients more frequently underwent percutaneous coronary intervention for stable angina (77.9% versus 46.2%). Almost all US patients (99.1%) received clopidogrel loading doses of 600 mg, whereas 40.5% of non-US patients received 300 mg. Bivalirudin was more frequently used in US patients (56.7% versus 2.9%). At 48 hours, rates of the primary composite end point were comparable in the US and non-US cohorts (5.5% versus 5.2%; P=0.53). Cangrelor reduced rates of the primary composite end point compared with clopidogrel in US (4.5% versus 6.4%; odds ratio 0.70 [95% confidence interval 0.53–0.92]) and in non-US patients (4.8% versus 5.6%; odds ratio 0.85 [95% confidence interval 0.69–1.05]; interaction P=0.26). Similarly, rates of the key secondary end point, stent thrombosis, were reduced by cangrelor in both regions. Rates of Global Use of Strategies to Open Occluded Arteries (GUSTO)–defined severe bleeding were low and not significantly increased by cangrelor in either region. Conclusions— Despite broad differences in clinical profiles and indications for percutaneous coronary intervention by region in a large global cardiovascular clinical trial, cangrelor consistently reduced rates of ischemic end points compared with clopidogrel without an excess in severe bleeding in both the US and non-US subgroups. Clinical Trial Registration— URL: http

Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis.

PubMed

Thompson, Eric M; Hielscher, Thomas; Bouffet, Eric; Remke, Marc; Luu, Betty; Gururangan, Sridharan; McLendon, Roger E; Bigner, Darell D; Lipp, Eric S; Perreault, Sebastien; Cho, Yoon-Jae; Grant, Gerald; Kim, Seung-Ki; Lee, Ji Yeoun; Rao, Amulya A Nageswara; Giannini, Caterina; Li, Kay Ka Wai; Ng, Ho-Keung; Yao, Yu; Kumabe, Toshihiro; Tominaga, Teiji; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Low, David C Y; Seow, Wan Tew; Chang, Kenneth T E; Mora, Jaume; Pollack, Ian F; Hamilton, Ronald L; Leary, Sarah; Moore, Andrew S; Ingram, Wendy J; Hallahan, Andrew R; Jouvet, Anne; Fèvre-Montange, Michelle; Vasiljevic, Alexandre; Faure-Conter, Cecile; Shofuda, Tomoko; Kagawa, Naoki; Hashimoto, Naoya; Jabado, Nada; Weil, Alexander G; Gayden, Tenzin; Wataya, Takafumi; Shalaby, Tarek; Grotzer, Michael; Zitterbart, Karel; Sterba, Jaroslav; Kren, Leos; Hortobágyi, Tibor; Klekner, Almos; László, Bognár; Pócza, Tímea; Hauser, Peter; Schüller, Ulrich; Jung, Shin; Jang, Woo-Youl; French, Pim J; Kros, Johan M; van Veelen, Marie-Lise C; Massimi, Luca; Leonard, Jeffrey R; Rubin, Joshua B; Vibhakar, Rajeev; Chambless, Lola B; Cooper, Michael K; Thompson, Reid C; Faria, Claudia C; Carvalho, Alice; Nunes, Sofia; Pimentel, José; Fan, Xing; Muraszko, Karin M; López-Aguilar, Enrique; Lyden, David; Garzia, Livia; Shih, David J H; Kijima, Noriyuki; Schneider, Christian; Adamski, Jennifer; Northcott, Paul A; Kool, Marcel; Jones, David T W; Chan, Jennifer A; Nikolic, Ana; Garre, Maria Luisa; Van Meir, Erwin G; Osuka, Satoru; Olson, Jeffrey J; Jahangiri, Arman; Castro, Brandyn A; Gupta, Nalin; Weiss, William A; Moxon-Emre, Iska; Mabbott, Donald J; Lassaletta, Alvaro; Hawkins, Cynthia E; Tabori, Uri; Drake, James; Kulkarni, Abhaya; Dirks, Peter; Rutka, James T; Korshunov, Andrey; Pfister, Stefan M; Packer, Roger J; Ramaswamy, Vijay; Taylor, Michael D

2016-04-01

Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (<1·5 cm(2) tumour remaining), or sub-total resection (≥1·5 cm(2) tumour remaining). We did multivariable analyses of overall survival and progression-free survival using the variables molecular subgroup (WNT, SHH, group 4, and group 3), age (<3 vs ≥3 years old), metastatic status (metastases vs no metastases), geographical location of therapy (North America/Australia vs rest of the world), receipt of chemotherapy (yes vs no) and receipt of craniospinal irradiation (<30 Gy or >30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression

Physiotherapy in Primary Care Triage - the effects on utilization of medical services at primary health care clinics by patients and sub-groups of patients with musculoskeletal disorders: a case-control study.

PubMed

Bornhöft, Lena; Larsson, Maria E H; Thorn, Jörgen

2015-01-01

Primary Care Triage is a patient sorting system used in some primary health care clinics (PHCCs) in Sweden where patients with musculoskeletal disorders (MSD) are triaged directly to physiotherapists. The purpose of this study was to investigate whether sorting/triaging patients seeking a PHCC for MSD directly to physiotherapists affects their utilization of medical services at the clinic for the MSD and to determine whether the effects of the triaging system vary for different sub-groups of patients. A retrospective case-control study design was used at two PHCCs. At the intervention clinic, 656 patients with MSD were initially triaged to physiotherapists. At the control clinic, 1673 patients were initially assessed by general practitioners (GPs). The main outcome measures were the number of patients continuing to visit GPs after the initial assessment, the number of patients receiving referrals to specialists/external examinations, doctors' notes for sick-leave or prescriptions for analgesics during one year, all for the original MSD. Significantly fewer patients triaged to physiotherapists required multiple GP visits for the MSD or received MSD-related referrals to specialists/external examinations, sick-leave recommendations or prescriptions during the following year compared to the GP-assessed group. This applies to all sub-groups except for the group with lower extremity disorders, which did not reach significance for either multiple GP visits or sick-leave recommendations. The reduced utilization of medical services by patients with MSD who were triaged to physiotherapists at a PHCC is likely due to altered management of MSD with initial assessment by physiotherapists.

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.

Impact of age on the efficacy and safety of extended-duration thromboprophylaxis in medical patients. Subgroup analysis from the EXCLAIM randomised trial.

PubMed

Yusen, Roger D; Hull, Russell D; Schellong, Sebastian M; Tapson, Victor F; Monreal, Manuel; Samama, Meyer-Michel; Chen, Min; Deslandes, Bruno; Turpie, Alexander G G

2013-12-01

The EXCLAIM study enrolled hospitalised acutely ill medical patients with age >40 years and recently-reduced mobility into a trial of extended-duration anticoagulant thromboprophylaxis. This post-hocanalysis evaluated the impact of age on patient outcomes. After completion of open-label therapy with enoxaparin 40 mg once-daily (10 ± 4 days), eligible patients underwent randomisation to receive double-blind therapy of enoxaparin (n=2,975) or placebo (n=2,988) for 28 ± 4 days. During follow-up, the venous thromboembolism (VTE) risk increased with age in both treatment groups. In patients with age >75 years, those who received extended-duration enoxaparin had lower incidence of VTE (2.5% vs 6.7%; absolute difference [AD] [95% confidence interval]: -4.2% [-6.5, -2.0]), proximal deep-vein thrombosis (2.5% vs 6.6%; AD -4.1% [-6.2, -2.0]), and symptomatic VTE (0.3% vs 1.5%; AD -1.2% [-2.2, -0.3]), in comparison to those who received placebo. In patients with age ≤75 years, those who received enoxaparin had reduced VTE (2.4% vs 2.8%; AD -0.4% [-1.5, 0.7]) and symptomatic VTE (0.2% vs 0.7%; AD -0.6% [-1.0, -0.1]) in comparison to those who received placebo. In both age subgroups, patients who received enoxaparin had increased rates of major bleeding versus those who received placebo: age >75 years (0.6% vs 0.2%; AD +0.3% [-0.2, 0.9], respectively); age ≤75 years (0.7% vs 0.2%; AD +0.5% [0.1, 0.9]). Patients in both age subgroups that received enoxaparin had similar low bleeding rates (0.6% and 0.7%, respectively). VTE risk increased with age, though the bleeding risk did not. Patients with age >75 years had a more favourable benefit-to-harm profile than younger patients.

A Subgroup Analysis of the Impact of Vortioxetine on Functional Capacity, as Measured by UPSA, in Patients with Major Depressive Disorder and Subjective Cognitive Dysfunction.

PubMed

Keefe, Richard S E; Nomikos, George; Zhong, Wei; Christensen, Michael Cronquist; Jacobson, William

2018-05-01

We evaluated vortioxetine's effects on functional capacity in demographic and clinical subgroups of patients with major depressive disorder. This was an exploratory analysis of the CONNECT study (NCT01564862) that evaluated changes in functional capacity using University of California San Diego Performance-based Skills Assessment data, categorized by sex, age, education, employment status, and baseline disease severity (Montgomery-Åsberg Depression Rating Scale, Clinical Global Impressions-Severity of Illness). Greater changes in University of California San Diego Performance-based Skills Assessment composite scores were observed with vortioxetine vs placebo in specific subgroups: males (∆+3.2), females (∆+2.9), 45-54 or ≥55 years (∆+5.6, ∆+3.4), working (∆+2.8), high school or greater education (∆+2.7, ∆+2.8), disease severity (Montgomery-Åsberg Depression Rating Scale, <30, ∆+3.5; ≥30, ∆+2.5; Clinical Global Impressions-Severity of Illness ≤4, ∆+2.8; >4, ∆+3.0), major depressive episodes (≤2, >2 [∆+2.7,+3.3]), and episode duration (≤22, >22 weeks [∆+3.7,+2.4]). Our findings support the need for additional studies to assess whether vortioxetine improves functional capacity within specific patient subgroups. clinicaltrials.gov: NCT01564862.

Subgroup Achievement and Gap Trends: Wyoming, 2010

ERIC Educational Resources Information Center

Center on Education Policy, 2010

2010-01-01

This paper profiles the student subgroup achievement and gap trends in Wyoming for 2010. Wyoming's demographic profile is such that achievement trends could only be determined for white, Latino, male and female, and low-income student subgroups. In grade 8 (the only grade in which subgroup trends were analyzed by achievement level), the white,…

Identification of Heterogeneous Cognitive Subgroups in Community-Dwelling Older Adults: A Latent Class Analysis of the Einstein Aging Study.

PubMed

Zammit, Andrea R; Hall, Charles B; Lipton, Richard B; Katz, Mindy J; Muniz-Terrera, Graciela

2018-05-01

The aim of this study was to identify natural subgroups of older adults based on cognitive performance, and to establish each subgroup's characteristics based on demographic factors, physical function, psychosocial well-being, and comorbidity. We applied latent class (LC) modeling to identify subgroups in baseline assessments of 1345 Einstein Aging Study (EAS) participants free of dementia. The EAS is a community-dwelling cohort study of 70+ year-old adults living in the Bronx, NY. We used 10 neurocognitive tests and 3 covariates (age, sex, education) to identify latent subgroups. We used goodness-of-fit statistics to identify the optimal class solution and assess model adequacy. We also validated our model using two-fold split-half cross-validation. The sample had a mean age of 78.0 (SD=5.4) and a mean of 13.6 years of education (SD=3.5). A 9-class solution based on cognitive performance at baseline was the best-fitting model. We characterized the 9 identified classes as (i) disadvantaged, (ii) poor language, (iii) poor episodic memory and fluency, (iv) poor processing speed and executive function, (v) low average, (vi) high average, (vii) average, (viii) poor executive and poor working memory, (ix) elite. The cross validation indicated stable class assignment with the exception of the average and high average classes. LC modeling in a community sample of older adults revealed 9 cognitive subgroups. Assignment of subgroups was reliable and associated with external validators. Future work will test the predictive validity of these groups for outcomes such as Alzheimer's disease, vascular dementia and death, as well as markers of biological pathways that contribute to cognitive decline. (JINS, 2018, 24, 511-523).

International collaboration including patients is essential to develop new therapies for patients with myositis.

PubMed

Lundberg, Ingrid E; Vencovsky, Jiri

2017-05-01

To discuss the needs for international collaborations between investigators in different disciplines working with myositis and with patients with myositis. Recent advances in detection of several myositis-specific autoantibodies that are associated with distinct clinical phenotypes, will enable studies in new well defined clinically homogenous subgroups of myositis This is likely to lead to development of new information on molecular pathogenesis that might be different in different myositis subgroups. Subgrouping patients according to autoantibody profile may also be important to assess outcome, to identify prognostic biomarkers and in clinical trials. As these are rare disorders international collaboration is essential to enrol large enough cohorts of the subgroups. To facilitate such collaboration we have developed a web-based international myositis register, www.euromyositis.eu, which includes validated outcome measures and patient reported outcome measures. This register is to support research but also to support decision-making in the clinic. We welcome investigators to join the Euromyositis register. Myositis is a heterogeneous disorder with varying treatment response and outcome. There is a high unmet need for new therapies which can only be achieved by increased knowledge on molecular disease mechanisms. Subgrouping patients according to autoantibody profile may be a new way forward to get a better understanding on disease mechanisms and to develop novel therapies.

Constipation incidence and impact in medical critical care patients: importance of the definition criterion.

PubMed

Prat, Dominique; Messika, Jonathan; Avenel, Alexandre; Jacobs, Frédéric; Fichet, Jérome; Lemeur, Matthieu; Ricard, Jean-Damien; Sztrymf, Benjamin

2016-03-01

Constipation incidence and impact remain controversial in the ICU. This may depend on the definition criterion used in the previous studies on the field. We aimed to determine the frequency and significance of constipation according to its definition criterion. This is a prospective observational study. Adult patients without a cause of transit time modification and laxative intake within the first 3 days were screened. Constipation was defined by a first stool passage occurring after 3 days of ICU stay. Thereafter, we identified two subgroups of patients: absence of stool passage more than 3 days but less than 6 days (3-day subgroup), and no stool passage for 6 days or more (6-day subgroup). Survival, length of stay and time spent under mechanical ventilation (MV) were compared according to constipation status. Among 189 included patients [age 60.8 (49.5-74.2) years, SAPS II 44 (34-53)], 98 (51.9%) exhibited constipation (3-day subgroup n=53, 6-day subgroup n=45). Constipated patients were more likely to receive MV, sedation, vasopressors, enteral nutrition and neuromuscular blocking agents. ICU length of stay and time spent under MV was longer in the 6-day subgroup but not in the 3-day subgroup of patients. With regard to outcomes, defining constipation by the absence of stool passage less than 6 days after ICU admission does not identify a specific subset of population. Further studies on the management of this condition should focus on these 'long-term' constipated patients.

Streptococcus pneumoniae PspC Subgroup Prevalence in Invasive Disease and Differences in Contribution to Complement Evasion.

PubMed

van der Maten, Erika; van den Broek, Bryan; de Jonge, Marien I; Rensen, Kim J W; Eleveld, Marc J; Zomer, Aldert L; Cremers, Amelieke J H; Ferwerda, Gerben; de Groot, Ronald; Langereis, Jeroen D; van der Flier, Michiel

2018-04-01

The pneumococcal capsular serotype is an important determinant of complement resistance and invasive disease potential, but other virulence factors have also been found to contribute. Pneumococcal surface protein C (PspC), a highly variable virulence protein that binds complement factor H to evade C3 opsonization, is divided into two subgroups: choline-bound subgroup I and LPxTG-anchored subgroup II. The prevalence of different PspC subgroups in invasive pneumococcal disease (IPD) and functional differences in complement evasion are unknown. The prevalence of PspC subgroups in IPD isolates was determined in a collection of 349 sequenced strains of Streptococcus pneumoniae isolated from adult patients. pspC deletion mutants and isogenic pspC switch mutants were constructed to study differences in factor H binding and complement evasion in relation to capsule thickness. Subgroup I pspC was far more prevalent in IPD isolates than subgroup II pspC The presence of capsule was associated with a greater ability of bound factor H to reduce complement opsonization. Pneumococcal subgroup I PspC bound significantly more factor H and showed more effective complement evasion than subgroup II PspC in isogenic encapsulated pneumococci. We conclude that variation in the PspC subgroups, independent of capsule serotypes, affects pneumococcal factor H binding and its ability to evade complement deposition. Copyright © 2018 American Society for Microbiology.

Efficacy and safety of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis homozygous for Phe508del CFTR by pulmonary function subgroup: a pooled analysis.

PubMed

Elborn, J Stuart; Ramsey, Bonnie W; Boyle, Michael P; Konstan, Michael W; Huang, Xiaohong; Marigowda, Gautham; Waltz, David; Wainwright, Claire E

2016-08-01

Lumacaftor/ivacaftor combination therapy has shown clinical benefits in patients with cystic fibrosis homozygous for the Phe508del CFTR mutation; however, pretreatment lung function is a confounding factor that potentially affects the efficacy and safety of this therapy. We aimed to assess the efficacy and safety of lumacaftor/ivacaftor therapy in these patients, defined by specific categories of lung function. Both trials (TRAFFIC and TRANSPORT) included in this pooled analysis were multinational, randomised, double-blind, placebo-controlled, parallel-group, phase 3 studies. Eligible patients from 187 participating centres in North America, Australia, and the European Union (both trials) were aged 12 years or older with a confirmed diagnosis of cystic fibrosis, homozygous for the Phe508del CFTR mutation, and with a percent predicted FEV1 (ppFEV1) of 40-90 at the time of screening. Patients were randomly assigned with an interactive web response system (1:1:1) to receive placebo, lumacaftor (600 mg once daily) plus ivacaftor (250 mg every 12 h), or lumacaftor (400 mg every 12 h) plus ivacaftor (250 mg every 12 h) for 24 weeks. Prespecified subgroup analyses of pooled efficacy and safety data by lung function, as measured by ppFEV1, were done for patients with baseline ppFEV1 (<40 and ≥40) and screening ppFEV1 (<70 and ≥70). The primary endpoint was the absolute change from baseline in ppFEV1 at week 24 analysed in all randomised patients who received at least one dose of study drug. Both trials are registered with ClinicalTrials.gov (TRAFFIC: NCT01807923; TRANSPORT: NCT01807949). Both trials were done between April, 2013, and April, 2014. Of the 1108 patients included in the efficacy analysis, 81 patients had a ppFEV1 that decreased to lower than 40 between screening and baseline and 1016 had a ppFEV1 of 40 or higher at baseline. At screening, 730 had a ppFEV1 of less than 70, and 342 had a ppFEV1 of 70 or higher. Improvements in the absolute change from

Nutritional habits in functional dyspepsia and its subgroups: a comparative study.

PubMed

Göktaş, Zeynep; Köklü, Seyfettin; Dikmen, Derya; Öztürk, Ömer; Yılmaz, Bülent; Asıl, Mehmet; Korkmaz, Hüseyin; Tuna, Yaşar; Kekilli, Murat; Karamanoğlu Aksoy, Evrim; Köklü, Hayretdin; Demir, Aslıhan; Köklü, Gülşah; Arslan, Serab

2016-08-01

Research data demonstrating nutritional habits of functional dyspepsia (FD) patients are very limited. This is the first study to evaluate nutritional habits in FD subgroups according to Rome III criteria. Our aim was to evaluate nutritional habits of FD patients and determine the food items that may provoke a dyspepsia symptom. A total of 168 adults with FD and 135 healthy control subjects participated in the study. FD subjects were divided into epigastric pain syndrome (EP-FD), postprandial distress syndrome (PS-FD), mixed (MX-FD) subgroups according to Rome Criteria III. Subjects completed a questionnaire that included a short-form food frequency questionnaire. Furthermore, subjects were asked to list the food items that were causing a dyspepsia symptom. Functional dyspepsia subjects had a slightly higher BMI (26.1 ± 4.97 kg/m(2)) than control subjects (24.6 ± 4.08 kg/m(2)). The most common symptom triggering foods among all the FD groups were fried and fatty foods (27.1%), hot spices (26.4%), and carbonated drinks (21.8%). In FD subgroups, carbonated drinks were more likely to cause a symptom in PS-FD group (37.3%) than MX-FD (25.7%) and EP-FD (22.1%) groups. There was no difference in frequency of main meals and snacks among any of the groups. Fatty and spicy foods and carbonated drinks were the most common symptom triggering food items in FD group. In subgroups, carbonated drinks and legumes were more likely to cause a symptom in PS-FD. Removing these food items during the course of treatment might help alleviate the symptoms.

Net clinical benefit of rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation: a subgroup analysis of J-ROCKET AF.

PubMed

Uchiyama, Shinichiro; Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-Ichi; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iekushi, Kazuma; Yamanaka, Satoshi; Tajiri, Masahiro

2014-01-01

The risk factors that have been identified for bleeding events with rivaroxaban are predominantly the same as those predicting thromboembolic ones in patients with atrial fibrillation (AF). Our aim was to determine the net clinical benefit (NCB) from the results of the J-ROCKET AF trial, in which rivaroxaban was compared with warfarin in Japanese patients with AF. Two strategies were adopted to quantify the NCB. First, the NCB was calculated as the number of ischemic strokes avoided with anticoagulation minus the number of excess intracranial hemorrhage (ICH) with a weight of 1.5. Second, the composite end point of major bleeding events and secondary efficacy end points (stroke, noncentral nervous system systemic embolism, myocardial infarction and death) to ascertain the NCB were established. Subgroup analysis by CHADS2 score or creatinine clearance was also performed. The adjusted NCB, which was given a weight of 1.5 for ICH, was nominally significant in favor of rivaroxaban therapy (difference in incidence rate -2.13; 95% confidence interval [CI]: -.26 to -3.99). Furthermore, the event rate of the composite end point tended to be lower in patients treated with rivaroxaban than in those treated with warfarin (rivaroxaban: 4.97% per year, warfarin: 6.11% per year; difference in incidence rate: -1.14; 95% CI: -3.40 to 1.12). The event rate of the composite end point tended to be consistently low in patients treated with rivaroxaban in the subanalysis by CHADS2 score and renal function. Analysis of the NCB supports that rivaroxaban therapy provides clinical benefit for Japanese patients with AF. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

The value of heterogeneity for cost-effectiveness subgroup analysis: conceptual framework and application.

PubMed

Espinoza, Manuel A; Manca, Andrea; Claxton, Karl; Sculpher, Mark J

2014-11-01

This article develops a general framework to guide the use of subgroup cost-effectiveness analysis for decision making in a collectively funded health system. In doing so, it addresses 2 key policy questions, namely, the identification and selection of subgroups, while distinguishing 2 sources of potential value associated with heterogeneity. These are 1) the value of revealing the factors associated with heterogeneity in costs and outcomes using existing evidence (static value) and 2) the value of acquiring further subgroup-related evidence to resolve the uncertainty given the current understanding of heterogeneity (dynamic value). Consideration of these 2 sources of value can guide subgroup-specific treatment decisions and inform whether further research should be conducted to resolve uncertainty to explain variability in costs and outcomes. We apply the proposed methods to a cost-effectiveness analysis for the management of patients with acute coronary syndrome. This study presents the expected net benefits under current and perfect information when subgroups are defined based on the use and combination of 6 binary covariates. The results of the case study confirm the theoretical expectations. As more subgroups are considered, the marginal net benefit gains obtained under the current information show diminishing marginal returns, and the expected value of perfect information shows a decreasing trend. We present a suggested algorithm that synthesizes the results to guide policy. © The Author(s) 2014.

Identifying groups of nonparticipants in type 2 diabetes mellitus education.

PubMed

Schäfer, Ingmar; Küver, Claudia; Wiese, Birgitt; Pawels, Marc; van den Bussche, Hendrik; Kaduszkiewicz, Hannah

2013-06-01

Patient education is a compulsory element of the nationwide disease management program (DMP) for type 2 diabetes mellitus in Germany. However, a considerable proportion of patients do not attend diabetes self-management education courses. Therefore, the purpose of this study was to describe patient-reported reasons for nonparticipation and to identify typical subgroups of nonparticipants in order to improve recruitment strategies. The authors performed a cross-sectional observational study on 165 participants and 132 nonparticipants in diabetes education using a postal survey and chart review. Participants and nonparticipants were compared using 2-sided t tests and χ2 tests. Nonparticipants were grouped by cluster analysis based on the reasons for nonparticipation. A total of 95% of participants and 36% of nonparticipants reported to have received a recommendation for diabetes education from their physician. The authors identified 4 typical subgroups of nonparticipants: the "informed and responsible," the "unconcerned without desire for more information," the "uninformed but responsible," and the "anxious and burdened with psychosocial problems and functional limitations." The physician's recommendation seems to influence participation in diabetes education and should be used intentionally to increase participation rates. Also, differentiating barriers of nonparticipants can be determined by the degree of feeling informed and responsible for diabetes management. Physicians should more clearly explore patients' perception of their knowledge of diabetes and their attribution of responsibility for diabetes management. Starting from this patient perspective might help physicians motivate patients to participate in diabetes education.

Real-world assessment of diquafosol in dry eye patients with risk factors such as contact lens, meibomian gland dysfunction, and conjunctivochalasis: subgroup analysis from a prospective observational study

PubMed Central

Yamaguchi, Masahiko; Nishijima, Takeshi; Shimazaki, Jun; Takamura, Etsuko; Yokoi, Norihiko; Watanabe, Hitoshi; Ohashi, Yuichi

2015-01-01

Purpose To evaluate the efficacy and safety of diquafosol (DQS) ophthalmic solution in dry eye (DE) patients wearing contact lenses (CLs) or with concomitant meibomian gland dysfunction (MGD) or conjunctivochalasis in a real-world setting. Patients and methods From a cohort of patients enrolled in a prospective observational study, DE patients who met the Japanese diagnostic criteria and who received DQS as a monotherapy were extracted and stratified according to the presence or absence of CL use, MGD, and conjunctivochalasis. Corneal and conjunctival fluorescein staining score, tear film break-up time, total symptom score (12 DE-related subjective symptoms), patient-reported outcomes, and adverse reactions were investigated. Results DQS treatment resulted in significant improvement in total symptom score, corneal and conjunctival fluorescein staining score, and tear film break-up time without significant differences between patient subgroups with versus without CL use, MGD, or conjunctivochalasis. Comparable proportions of patients perceived symptomatic improvements in all subgroups. There were no adverse reactions specifically associated with the CL use or any comorbidity of MGD or conjunctivochalasis. Conclusion DQS can be used effectively and safely as a monotherapy for the treatment of DE patients wearing CLs or with concomitant MGD or conjunctivochalasis. PMID:26664039

Fast determination of structurally cohesive subgroups in large networks

PubMed Central

Sinkovits, Robert S.; Moody, James; Oztan, B. Tolga; White, Douglas R.

2016-01-01

Structurally cohesive subgroups are a powerful and mathematically rigorous way to characterize network robustness. Their strength lies in the ability to detect strong connections among vertices that not only have no neighbors in common, but that may be distantly separated in the graph. Unfortunately, identifying cohesive subgroups is a computationally intensive problem, which has limited empirical assessments of cohesion to relatively small graphs of at most a few thousand vertices. We describe here an approach that exploits the properties of cliques, k-cores and vertex separators to iteratively reduce the complexity of the graph to the point where standard algorithms can be used to complete the analysis. As a proof of principle, we apply our method to the cohesion analysis of a 29,462-vertex biconnected component extracted from a 128,151-vertex co-authorship data set. PMID:28503215

Safety and efficacy of ipragliflozin in elderly versus non-elderly Japanese patients with type 2 diabetes mellitus: a subgroup analysis of the STELLA-LONG TERM study.

PubMed

Maegawa, Hiroshi; Tobe, Kazuyuki; Tabuchi, Hiromi; Nakamura, Ichiro; Uno, Satoshi

2018-03-01

This subgroup analysis of STELLA-LONG TERM interim data explored the long-term safety and efficacy of ipragliflozin in non-elderly vs. elderly Japanese type 2 diabetes mellitus (T2DM) patients. STELLA-LONG TERM is an ongoing 3-year prospective surveillance study of Japanese T2DM patients receiving ipragliflozin 50 mg once daily. In this subgroup analysis, patient characteristics, laboratory variables, and adverse drug reactions (ADRs) were compared between non-elderly (<65 years) and elderly (≥65 years) patients. Non-elderly patients had significantly higher body mass index and low-density lipoprotein cholesterol than elderly patients (P < 0.001). The proportion of patients with hemoglobin A1c (HbA1c) <8.0% was significantly higher among elderly patients (P < 0.001). HbA1c, fasting plasma glucose, and body weight significantly decreased from baseline to 3 and 12 months in both groups (all P < 0.05 vs. baseline). The ADR incidence was 10.83% vs. 10.42% in non-elderly and elderly patients. The incidence of skin complications was 0.98% vs. 1.65% and that of renal disorder was 0.47% vs. 0.95% in non-elderly and elderly patients (both P = 0.003). Ipragliflozin was effective in non-elderly and elderly Japanese T2DM patients in a real-world clinical setting. The incidence of renal disorder and skin complications was significantly higher in elderly vs. non-elderly patients.

Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study.

PubMed

Giovannoni, Gavin; Soelberg Sorensen, Per; Cook, Stuart; Rammohan, Kottil W; Rieckmann, Peter; Comi, Giancarlo; Dangond, Fernando; Hicking, Christine; Vermersch, Patrick

2018-04-01

In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis. Describe two clinically relevant definitions for patients with high disease activity (HDA) at baseline of the CLARITY study (utility verified in patients receiving placebo) and assess the treatment effects of Cladribine Tablets 3.5 mg/kg compared with the overall study population. Outcomes of patients randomised to Cladribine Tablets 3.5 mg/kg or placebo were analysed for subgroups using HDA definitions based on high relapse activity (HRA; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not) or HRA plus disease activity on treatment (HRA + DAT; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not, PLUS patients with ⩾1 relapse during the year prior to study entry while on therapy with other DMDs and ⩾1 T1 Gd+ or ⩾9 T2 lesions). In the overall population, Cladribine Tablets 3.5 mg/kg reduced the risk of 6-month-confirmed Expanded Disability Status Scale (EDSS) worsening by 47% vs placebo. A risk reduction of 82% vs placebo was seen in both the HRA and HRA + DAT subgroups (vs 19% for non-HRA and 18% for non-HRA + DAT), indicating greater responsiveness to Cladribine Tablets 3.5 mg/kg in patients with HDA. There were consistent results for other efficacy endpoints. The safety profile in HDA patients was consistent with the overall CLARITY population. Patients with HDA showed clinical and MRI responses to Cladribine Tablets 3.5 mg/kg that were generally better than, or at least comparable with, the outcomes seen in the overall CLARITY population.

Afatinib versus methotrexate in older patients with second-line recurrent and/or metastatic head and neck squamous cell carcinoma: subgroup analysis of the LUX-Head & Neck 1 trial.

PubMed

Clement, P M; Gauler, T; Machiels, J P; Haddad, R I; Fayette, J; Licitra, L F; Tahara, M; Cohen, E E W; Cupissol, D; Grau, J J; Guigay, J; Caponigro, F; de Castro, G; de Souza Viana, L; Keilholz, U; Del Campo, J M; Cong, X J; Ehrnrooth, E; Vermorken, J B

2016-08-01

In the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged ≥65 and <65 years. Patients were randomized (2:1) to 40 mg/day oral afatinib or 40 mg/m(2)/week intravenous methotrexate. PFS was the primary end point; overall survival (OS) was the key secondary end point. Other end points included: objective response rate (ORR), patient-reported outcomes, tumor shrinkage, and safety. Disease control rate (DCR) was also assessed. Of 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged ≥65 years (older) and 73% (239 afatinib; 116 methotrexate) <65 years (younger) at study entry. Similar PFS benefit with afatinib versus methotrexate was observed in older {median 2.8 versus 2.3 months, hazard ratio (HR) = 0.68 [95% confidence interval (CI) 0.45-1.03], P = 0.061} and younger patients [2.6 versus 1.6 months, HR = 0.79 (0.62-1.01), P = 0.052]. In older and younger patients, the median OS with afatinib versus methotrexate was 7.3 versus 6.4 months [HR = 0.84 (0.54-1.31)] and 6.7 versus 6.2 months [HR = 0.98 (0.76-1.28)]. ORRs with afatinib versus methotrexate were 10.8% versus 6.7% and 10.0% versus 5.2%; DCRs were 53.0% versus 37.8% and 47.7% versus 38.8% in older and younger patients, respectively. In both subgroups, the most frequent treatment-related adverse events were rash/acne (73%-77%) and diarrhea (70%-80%) with afatinib, and stomatitis (43%) and fatigue (31%-34%) with methotrexate. Fewer treatment-related discontinuations were observed with afatinib (each subgroup 7% versus 16%). A trend toward improved time to deterioration of global health status, pain, and swallowing with afatinib was observed in both subgroups. Advancing age (≥65 years) did not

OMERACT-based fibromyalgia symptom subgroups: an exploratory cluster analysis.

PubMed

Vincent, Ann; Hoskin, Tanya L; Whipple, Mary O; Clauw, Daniel J; Barton, Debra L; Benzo, Roberto P; Williams, David A

2014-10-16

The aim of this study was to identify subsets of patients with fibromyalgia with similar symptom profiles using the Outcome Measures in Rheumatology (OMERACT) core symptom domains. Female patients with a diagnosis of fibromyalgia and currently meeting fibromyalgia research survey criteria completed the Brief Pain Inventory, the 30-item Profile of Mood States, the Medical Outcomes Sleep Scale, the Multidimensional Fatigue Inventory, the Multiple Ability Self-Report Questionnaire, the Fibromyalgia Impact Questionnaire-Revised (FIQ-R) and the Short Form-36 between 1 June 2011 and 31 October 2011. Hierarchical agglomerative clustering was used to identify subgroups of patients with similar symptom profiles. To validate the results from this sample, hierarchical agglomerative clustering was repeated in an external sample of female patients with fibromyalgia with similar inclusion criteria. A total of 581 females with a mean age of 55.1 (range, 20.1 to 90.2) years were included. A four-cluster solution best fit the data, and each clustering variable differed significantly (P <0.0001) among the four clusters. The four clusters divided the sample into severity levels: Cluster 1 reflects the lowest average levels across all symptoms, and cluster 4 reflects the highest average levels. Clusters 2 and 3 capture moderate symptoms levels. Clusters 2 and 3 differed mainly in profiles of anxiety and depression, with Cluster 2 having lower levels of depression and anxiety than Cluster 3, despite higher levels of pain. The results of the cluster analysis of the external sample (n = 478) looked very similar to those found in the original cluster analysis, except for a slight difference in sleep problems. This was despite having patients in the validation sample who were significantly younger (P <0.0001) and had more severe symptoms (higher FIQ-R total scores (P = 0.0004)). In our study, we incorporated core OMERACT symptom domains, which allowed for clustering based on a

Combining moderators to identify clinical profiles of patients who will, and will not, benefit from aripiprazole augmentation for treatment resistant late-life major depressive disorder

PubMed Central

Smagula, Stephen F.; Wallace, Meredith L.; Anderson, Stewart J.; Karp, Jordan F.; Lenze, Eric J.; Mulsant, Benoit H.; Butters, Meryl A.; Blumberger, Daniel M.; Diniz, Breno S.; Lotrich, Francis; Dew, Mary Amanda; Reynolds, Charles F.

2016-01-01

Personalizing treatment for late-life depression requires identifying and integrating information from multiple factors that influence treatment efficacy (moderators). We performed exploratory moderator analyses using data from a multi-site, randomized, placebo-controlled, double-blind trial of aripiprazole augmentation. Patients (n=159) aged ≥60 years had major depressive disorder that failed to remit with venlafaxine monotherapy. We examined effect sizes of 39 potential moderators of aripiprazole (vs. placebo) augmentation efficacy using the outcome of percentage reduction in depressive symptom after 12 weeks. We then incorporated information from the individually relevant variables in combined moderators. A larger aripiprazole treatment effect was related to: white race, better physical function, better performance on Trail-Making, attention, immediate, and delayed memory tests, greater psychomotor agitation and suicidality symptoms, and a history of adequate antidepressant pharmacotherapy. A smaller aripiprazole treatment effect was observed in patients with: more pain and more work/activity impairment and libido symptoms. Combining information from race and Trail-Making test performance (base combined moderator (Mb*)) produced a larger effect size (Spearman effect size=0.29 (95% confidence interval (CI): 0.15, 0.42)) than any individual moderator. Adding other individually relevant moderators in the full combined moderator (Mf*) further improved effect size (Spearman effect size=0.39 (95% CI: 0.25, 0.52)) and identified a sub-group benefiting more from placebo plus continuation venlafaxine monotherapy than adjunctive aripiprazole. Combining moderators can help clinicians personalize depression treatment. We found the majority of our patients benefited from adjunctive aripiprazole, but a smaller subgroup that is identifiable using clinical measures appeared to benefit more from continuation venlafaxine plus placebo. PMID:27438687

Biopsychosocial influence on shoulder pain: risk subgroups translated across preclinical and clinical prospective cohorts

PubMed Central

George, Steven Z.; Wallace, Margaret R.; Wu, Samuel S.; Moser, Michael W.; Wright, Thomas W.; Farmer, Kevin W.; Borsa, Paul A.; Parr, Jeffrey J.; Greenfield, Warren H.; Dai, Yunfeng; Li, Hua; Fillingim, Roger B.

2016-01-01

Tailored treatment based on individual risk factors is an area with promise to improve options for pain relief. Musculoskeletal pain has a biopsychosocial nature, and multiple factors should be considered when determining risk for chronic pain. This study investigated whether subgroups comprised genetic and psychological factors predicted outcomes in preclinical and clinical models of shoulder pain. Classification and regression tree analysis was performed for an exercise-induced shoulder injury cohort (n = 190) to identify high-risk subgroups, and a surgical pain cohort (n = 150) was used for risk validation. Questionnaires for fear of pain and pain catastrophizing were administered before injury and preoperatively. DNA collected from saliva was genotyped for a priori selected genes involved with pain modulation (COMT and AVPR1A) and inflammation (IL1B and TNF/LTA). Recovery was operationalized as a brief pain inventory rating of 0/10 for current pain intensity and <2/10 for worst pain intensity. Follow-up for the preclinical cohort was in daily increments, whereas follow-up for the clinical cohort was at 3, 6, and 12 months postoperatively. Risk subgroups comprised the COMT high pain sensitivity variant and either pain catastrophizing or fear of pain were predictive of heightened shoulder pain responses in the preclinical model. Further analysis in the clinical model identified the COMT high pain sensitivity variant and pain catastrophizing subgroup as the better predictor. Future studies will determine whether these findings can be replicated in other anatomical regions and whether personalized medicine strategies can be developed for this risk subgroup. PMID:25599310

The direct assignment option as a modular design component: an example for the setting of two predefined subgroups.

PubMed

An, Ming-Wen; Lu, Xin; Sargent, Daniel J; Mandrekar, Sumithra J

2015-01-01

A phase II design with an option for direct assignment (stop randomization and assign all patients to experimental treatment based on interim analysis, IA) for a predefined subgroup was previously proposed. Here, we illustrate the modularity of the direct assignment option by applying it to the setting of two predefined subgroups and testing for separate subgroup main effects. We power the 2-subgroup direct assignment option design with 1 IA (DAD-1) to test for separate subgroup main effects, with assessment of power to detect an interaction in a post-hoc test. Simulations assessed the statistical properties of this design compared to the 2-subgroup balanced randomized design with 1 IA, BRD-1. Different response rates for treatment/control in subgroup 1 (0.4/0.2) and in subgroup 2 (0.1/0.2, 0.4/0.2) were considered. The 2-subgroup DAD-1 preserves power and type I error rate compared to the 2-subgroup BRD-1, while exhibiting reasonable power in a post-hoc test for interaction. The direct assignment option is a flexible design component that can be incorporated into broader design frameworks, while maintaining desirable statistical properties, clinical appeal, and logistical simplicity.

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…

Temporal relationship between cancer and myositis identifies two distinctive subgroups of cancers: impact on cancer risk and survival in patients with myositis.

PubMed

Kang, Eun Ha; Lee, Sang Jin; Ascherman, Dana P; Lee, Yun Jong; Lee, Eun Young; Lee, Eun Bong; Song, Yeong Wook

2016-09-01

The aim was to compare standardized incidence ratios (SIRs) of cancers temporally related and unrelated to active myositis in patients with myositis. Fifty-two cancer cases were identified in 281 myositis patients. SIRs of cancers having temporal overlap with the active phase of myositis [cancers concurrent with active myositis (CAM), n = 30] and cancers not having such temporal overlap [cancers non-concurrent with active myositis (CNM), n = 22] were compared in 281 patients. Patients with CAM were older at diagnosis of myositis, had a greater tendency to be male, more frequent dysphagia and less frequent interstitial lung disease than patients with CNM. CAM SIR (95% CI) was 1.78 (1.19, 2.56) and CNM SIR 1.23 (0.75, 1.90). The peak SIR was observed in the seventh decade of life for CAM and in the third decade for CNM. When stratified by myositis-cancer intervals, CAM SIR was 9.94 (6.43, 14.67) within 1 year of myositis diagnosis, whereas no temporal relationship was found for CNM. Elevated SIRs were observed for oesophageal cancer [57.77 (11.91, 168.82)], non-Hodgkin's lymphoma [41.43 (13.45, 96.69)], adenocarcinoma of unknown primary origin [67.6 (18.42, 173.07]), lung cancer [7.27 (1.98, 18.61)] and ovarian cancer [19.15 (2.32, 69.17)] within 3 years of CAM diagnosis. The cancer stage at the time of diagnosis was more advanced in CAM than CNM (P < 0.001), with a correspondingly increased hazard ratio of mortality [4.3 (1.5, 12.7)] in patients with CAM vs CNM. A significantly elevated SIR was found for CAM, whereas there was a comparable SIR for CNM relative to the general population. Multiple types of cancers showed elevated SIRs among CAM, but none among CNM. Given that cancer stages in CAM were far advanced at diagnosis, mortality risk was greater in patients with CAM. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Identifying mortality risks in patients with opioid use disorder using brief screening assessment: Secondary mental health clinical records analysis.

PubMed

Bogdanowicz, Karolina Magda; Stewart, Robert; Chang, Chin-Kuo; Downs, Johnny; Khondoker, Mizanur; Shetty, Hitesh; Strang, John; Hayes, Richard Derek

2016-07-01

Risk assessments are widely used, but their ability to predict outcomes in opioid use disorder (OUD) treatment remains unclear. Therefore, the aim was to investigate if addiction-specific brief risk screening is effective in identifying high mortality risk groups and if subsequent clinical actions following risk assessment impacts on mortality levels. Opioid use disorder (OUD) patients were identified in the South London and Maudsley Case Register. Deaths were identified through database linkage to the national mortality dataset. Cox and competing-risk regression were used to model associations between brief risk assessment domains and all-cause and overdose mortality in 4488 OUD patients, with up-to 6-year follow-up time where 227 deaths were registered. Data were stratified by admission to general mental health services. All-cause mortality was significantly associated with unsafe injecting (HR 1.53, 95% CI 1.10-2.11) and clinically appraised likelihood of accidental overdose (HR 1.48, 95% CI 1.00-2.19). Overdose-mortality was significantly associated with unsafe injecting (SHR 2.52, 95% CI 1.11-5.70) and clinically appraised suicidality (SHR 2.89, 95% CI 1.38-6.03). Suicidality was associated with a twofold increase in mortality risk among OUD patients who were not admitted to mental health services within 2 months of their risk assessment (HR 2.03, 95% CI 1.67-3.24). Diagnosis-specific brief risk screening can identify OUD patient subgroups at increased risk of all-cause and overdose mortality. OUD patients, where suicidality is evident, who are not admitted into services are particularly vulnerable. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.

A Subgroup Analysis of the Impact of Vortioxetine on Functional Capacity, as Measured by UPSA, in Patients with Major Depressive Disorder and Subjective Cognitive Dysfunction

PubMed Central

Keefe, Richard S E; Nomikos, George; Zhong, Wei; Christensen, Michael Cronquist; Jacobson, William

2018-01-01

Abstract Background We evaluated vortioxetine’s effects on functional capacity in demographic and clinical subgroups of patients with major depressive disorder. Methods This was an exploratory analysis of the CONNECT study (NCT01564862) that evaluated changes in functional capacity using University of California San Diego Performance-based Skills Assessment data, categorized by sex, age, education, employment status, and baseline disease severity (Montgomery-Åsberg Depression Rating Scale, Clinical Global Impressions–Severity of Illness). Results Greater changes in University of California San Diego Performance-based Skills Assessment composite scores were observed with vortioxetine vs placebo in specific subgroups: males (∆+3.2), females (∆+2.9), 45–54 or ≥55 years (∆+5.6, ∆+3.4), working (∆+2.8), high school or greater education (∆+2.7, ∆+2.8), disease severity (Montgomery-Åsberg Depression Rating Scale, <30, ∆+3.5; ≥30, ∆+2.5; Clinical Global Impressions–Severity of Illness ≤4, ∆+2.8; >4, ∆+3.0), major depressive episodes (≤2, >2 [∆+2.7,+3.3]), and episode duration (≤22, >22 weeks [∆+3.7,+2.4]). Conclusions Our findings support the need for additional studies to assess whether vortioxetine improves functional capacity within specific patient subgroups. Clinical Trial Registry clinicaltrials.gov: NCT01564862 PMID:29546401

Identifying Patients at Higher Risk of Prolonged Air Leak After Lung Resection.

PubMed

Gilbert, Sebastien; Maghera, Sonam; Seely, Andrew J; Maziak, Donna E; Shamji, Farid M; Sundaresan, Sudhir R; Villeneuve, Patrick J

2016-11-01

Predictive models of prolonged air leak have relied on information not always available preoperatively (eg, extent of resection, pleural adhesions). Our objective was to construct a model to identify patients at increased risk of prolonged air leak using preoperative factors exclusively. From 2012 to 2014, data on consecutive patients undergoing pulmonary resection were collected prospectively. Prolonged air leak was defined as lasting longer than 7 days and requiring hospitalization. Factors associated with the primary outcome (p < 0.2) were included in a multivariate model. Regression coefficients were used to develop a weighted risk score for prolonged air leak. Of 225 patients, 8% (18/225) experienced a prolonged air leak. Male gender (p = 0.08), smoking history (p = 0.03), body mass index (BMI) 25 or below (p < 0.01), Medical Research Council (MRC) dyspnea score above 1 (p = 0.06), and diffusion capacity for carbon monoxide below 80% (Dlco) (p = 0.01) were selected for inclusion in the final model. Weighted scores were male gender (1 point), BMI 25 or below (0.5 point), smoker (2 points), Dlco% below 80% (2 points), and MRC dyspnea score above 1 (1 point). The area under the receiver operating characteristic curve was 0.8 (95% confidence interval [CI] = 0.7 to 0.9]. An air leak score above 4 points offered the best combination of sensitivity (83% [95% CI = 58 to 96]) and specificity (65% [95% CI = 58 to 71]). A subgroup of lung resection patients at higher risk for a prolonged air leak can be effectively identified with the use of widely available, preoperative factors. The proposed scoring system is simple, is clinically relevant to the informed consent, and allows preoperative patient selection for interventions to reduce the risk of prolonged air leak. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Prognostic value of Ki-67 index in adult medulloblastoma after accounting for molecular subgroup: a retrospective clinical and molecular analysis.

PubMed

Zhao, Fu; Zhang, Jing; Li, Peng; Zhou, Qiangyi; Zhang, Shun; Zhao, Chi; Wang, Bo; Yang, Zhijun; Li, Chunde; Liu, Pinan

2018-04-23

Medulloblastoma (MB) is a rare primary brain tumor in adults. We previously evaluated that combining both clinical and molecular classification could improve current risk stratification for adult MB. In this study, we aimed to identify the prognostic value of Ki-67 index in adult MB. Ki-67 index of 51 primary adult MBs was reassessed using a computer-based image analysis (Image-Pro Plus). All patients were followed up ranging from 12 months up to 15 years. Gene expression profiling and immunochemistry were used to establish the molecular subgroups in adult MB. Combined risk stratification models were designed based on clinical characteristics, molecular classification and Ki-67 index, and identified by multivariable Cox proportional hazards analysis. In our cohort, the mean Ki-67 value was 30.0 ± 11.3% (range 6.56-63.55%). The average Ki-67 value was significantly higher in LC/AMB than in CMB and DNMB (P = .001). Among three molecular subgroups, Group 4-tumors had the highest average Ki-67 value compared with WNT- and SHH-tumors (P = .004). Patients with Ki-67 index large than 30% displayed poorer overall survival (OS) and progression free survival (PFS) than those with Ki-67 less than 30% (OS: P = .001; PFS: P = .006). Ki-67 index (i.e. > 30%, < 30%) was identified as an independent significant prognostic factor (OS: P = .017; PFS: P = .024) by using multivariate Cox proportional hazards model. In conclusion, Ki-67 index can be considered as a valuable independent prognostic biomarker for adult patients with MB.

Identifying Adolescent Patients at Risk for Sexually Transmitted Infections: Development of a Brief Sexual Health Screening Survey.

PubMed

Victor, Elizabeth C; Chung, Richard; Thompson, Robert J

2015-08-01

This study examined the association between survey responses to health behaviors, personality/psychosocial factors, and self-reported sexually transmitted infections (STIs) to create a brief survey to identify youth at risk for contracting STIs. Participants included 200 racially diverse 14- to 18-year-old patients from a pediatric primary care clinic. Two sexual behavior variables and one peer norm variable were used to differentiate subgroups of individuals at risk of contracting a STI based on reported history of STIs using probability (decision tree) analyses. These items, as well as sexual orientation and having ever had oral sex, were used to create a brief sexual health screening (BSHS) survey. Each point increase in total BSHS score was associated with exponential growth in the percentage of sexually active adolescents reporting STIs. Findings suggest that the BSHS could serve as a useful tool for clinicians to quickly and accurately detect sexual risk among adolescent patients. © The Author(s) 2014.

Efficacy and tolerability of vardenafil for treatment of erectile dysfunction in patient subgroups.

PubMed

Porst, Hartmut; Young, Jay M; Schmidt, Abraham C; Buvat, Jacques

2003-09-01

To assess whether vardenafil would improve erectile function irrespective of etiology, baseline severity, or patient age. The consistency of the response over time was also evaluated. A multicenter, randomized, double-blind, placebo-controlled at-home study of vardenafil treatment (5, 10, and 20 mg) was performed. This secondary analysis compared the mean International Index of Erectile Function (IIEF) erectile function domain scores of various subgroups at 12 weeks of treatment. These populations included organic, psychogenic, or mixed etiologies; mild, moderate, or severe baseline severity; and four age groups (younger than 45, 45 to 55, 56 to 65, and older than 65 years). In addition, all IIEF domains were compared at sequential 4-week periods, before and during treatment. In the 580 men of the intent-to-treat population, the mean erectile function domain scores were statistically greater than placebo, irrespective of etiology, baseline severity, or age. This was seen at all dosages. Compared with placebo, vardenafil statistically improved the IIEF domain scores of erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction after 4 weeks of treatment, and these improvements were maintained for 12 weeks. The rates of the most common adverse events (headache, flushing, and dyspepsia) were either constant or declined over time; they were generally mild to moderate and transient in nature. Vardenafil improved erectile function regardless of the general etiology, baseline severity of erectile dysfunction, or patient age. Improvements in erectile function and other key IIEF domains were consistently seen throughout the study.

Subgroup Economic Evaluation of Radiotherapy for Breast Cancer After Mastectomy.

PubMed

Wan, Xiaomin; Peng, Liubao; Ma, Jinan; Chen, Gannong; Li, Yuanjian

2015-11-01

A recent meta-analysis by the Early Breast Cancer Trialists' Collaborative Group found significant improvements achieved by postmastectomy radiotherapy (PMRT) for patients with breast cancer with 1 to 3 positive nodes (pN1-3). It is unclear whether PMRT is cost-effective for subgroups of patients with positive nodes. To determine the cost-effectiveness of PMRT for subgroups of patients with breast cancer with positive nodes. A semi-Markov model was constructed to estimate the expected lifetime costs, life expectancy, and quality-adjusted life-years for patients receiving or not receiving radiation therapy. Clinical and health utilities data were from meta-analyses by the Early Breast Cancer Trialists' Collaborative Group or randomized clinical trials. Costs were estimated from the perspective of the Chinese society. One-way and probabilistic sensitivity analyses were performed. The incremental cost-effective ratio was estimated as $7984, $4043, $3572, and $19,021 per quality-adjusted life-year for patients with positive nodes (pN+), patients with pN1-3, patients with pN1-3 who received systemic therapy, and patients with >4 positive nodes (pN4+), respectively. According to World Health Organization recommendations, these incremental cost-effective ratios were judged as cost-effective. However, the results of one-way sensitivity analyses suggested that the results were highly sensitive to the relative effectiveness of PMRT (rate ratio). We determined that the results were highly sensitive to the rate ratio. However, the addition of PMRT for patients with pN1-3 in China has a reasonable chance to be cost-effective and may be judged as an efficient deployment of limited health resource, and the risk and uncertainty of PMRT are relatively greater for patients with pN4+. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Methylation profiling of choroid plexus tumors reveals 3 clinically distinct subgroups.

PubMed

Thomas, Christian; Sill, Martin; Ruland, Vincent; Witten, Anika; Hartung, Stefan; Kordes, Uwe; Jeibmann, Astrid; Beschorner, Rudi; Keyvani, Kathy; Bergmann, Markus; Mittelbronn, Michel; Pietsch, Torsten; Felsberg, Jörg; Monoranu, Camelia M; Varlet, Pascale; Hauser, Peter; Olar, Adriana; Grundy, Richard G; Wolff, Johannes E; Korshunov, Andrey; Jones, David T; Bewerunge-Hudler, Melanie; Hovestadt, Volker; von Deimling, Andreas; Pfister, Stefan M; Paulus, Werner; Capper, David; Hasselblatt, Martin

2016-06-01

Choroid plexus tumors are intraventricular neoplasms derived from the choroid plexus epithelium. A better knowledge of molecular factors involved in choroid plexus tumor biology may aid in identifying patients at risk for recurrence. Methylation profiles were examined in 29 choroid plexus papillomas (CPPs, WHO grade I), 32 atypical choroid plexus papillomas (aCPPs, WHO grade II), and 31 choroid plexus carcinomas (CPCs, WHO grade III) by Illumina Infinium HumanMethylation450 Bead Chip Array. Unsupervised hierarchical clustering identified 3 subgroups: methylation cluster 1 (pediatric CPP and aCPP of mainly supratentorial location), methylation cluster 2 (adult CPP and aCPP of mainly infratentorial location), and methylation cluster 3 (pediatric CPP, aCPP, and CPC of supratentorial location). In methylation cluster 3, progression-free survival (PFS) accounted for a mean of 72 months (CI, 55-89 mo), whereas only 1 of 42 tumors of methylation clusters 1 and 2 progressed (P< .001). On stratification of outcome data according to WHO grade, all CPCs clustered within cluster 3 and were associated with shorter overall survival (mean, 105 mo [CI, 81-128 mo]) and PFS (mean, 55 mo [CI, 36-73 mo]). The aCPP of methylation cluster 3 also progressed frequently (mean, 69 mo [CI, 44-93 mo]), whereas no tumor progression was observed in aCPP of methylation clusters 1 and 2 (P< .05). Only 1 of 29 CPPs recurred. Methylation profiling of choroid plexus tumors reveals 3 distinct subgroups (ie, pediatric low-risk choroid plexus tumors [cluster 1], adult low-risk choroid plexus tumors [cluster 2], and pediatric high-risk choroid plexus tumors [cluster 3]) and may provide useful prognostic information in addition to histopathology. Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

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

[Subgroup Analysis of the Non-interventional REASON Study: PFS and OS According to Age, Smoking History, Gender, and Histology in NSCLC Patients Treated with Gefitinib or Chemotherapy].

PubMed

Schuette, W; Eberhardt, W E E; Waller, C; Schirmacher, P; Dietel, M; Zirrgiebel, U; Radke, S; Thomas, M

2016-09-01

Assessment of several clinical factors on progression-free (PFS) and overall survival (OS) in NSCLC patients (pts.) (stage IV) with mutated epidermal growth factor receptor (EGFRm+) treated with gefitinib (gef) or with chemotherapy (CT) under real-world conditions. 285 EGFRm+ pts. of the non-interventional REASON study treated with gef (n = 206) or CT (n = 79) as first-line therapy or with gef (n = 213) or CT (n = 61) in any line throughout the course of therapy were analyzed according to age, gender, smoking history and histology. Compared with CT, patients treated with gef showed prolongation of PFS and OS in all subgroups. PFS was significantly increased in women and non-smokers. OS was significantly increased in women, non-smokers, (ex)-smokers, patients with adenocarcinoma and elderly patients when treated with gef compared to CT. Female gender turned out to be an independent positive predictive factor for OS in patients treated with gef (HRmale: 1.74, p = 0.0009). A clinical benefit of gef was shown for all analyzed clinical subgroups of EGFRm+ pts. This was confirmed for the female gender in a multivariate analysis. © Georg Thieme Verlag KG Stuttgart · New York.

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.

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.

High Blood Pressure Increases the Risk of Poor Outcome at Discharge and 12-month Follow-up in Patients with Symptomatic Intracranial Large Artery Stenosis and Occlusions: Subgroup analysis of the CICAS Study.

PubMed

Yu, Dan-Dan; Pu, Yue-Hua; Pan, Yue-Song; Zou, Xin-Ying; Soo, Yannie; Leung, Thomas; Liu, Li-Ping; Wang, David Z; Wong, Ka-Sing; Wang, Yi-Long; Wang, Yong-Jun

2015-06-01

The purpose of this study was to discuss the relationship between blood pressure and prognosis of patients with symptomatic intracranial arterial stenosis. Data on 2426 patients with symptomatic intracranial large artery stenosis and occlusion who participated in the Chinese Intracranial Atherosclerosis (CICAS) study were analyzed. According to the JNC 7 criteria, blood pressure of all patients was classified into one of the four subgroups: normal, prehypertension, hypertension stage I, and hypertension stage II. Poor outcomes were defined as death and functional dependency (mRS 3-5) at discharge or at 1 year. For patients with intracranial stenosis of 70% to 99%, the rate of poor outcome at discharge was 19.3%, 23.5%, 26.8%, and 39.8% (P = 0.001) for each blood pressure subgroup. For patients with intracranial large artery occlusion, the rates were 17.6%, 22.1%, 29.5%, and 49.8%, respectively (P < 0.0001). The rate of poor outcome at 12-month follow-up was 12.6%, 15.3%, 28.5%, and 27.9% (P = 0.0038) in patients with stenosis of 70% to 99% for each blood pressure subgroup and 11.6%, 21.5%, 23.9%, 35.1% (P < 0.0001) in patients with occlusion. For patients with severe intracranial arterial stenosis or occlusion, higher hypertension stages are associated with an increased risk of poor outcome at discharge and 12-month follow-up. © 2015 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

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.

Sitagliptin on carotid intima-media thickness in type 2 diabetes patients receiving primary or secondary prevention of cardiovascular disease: A subgroup analysis of the PROLOGUE study.

PubMed

Tanaka, Atsushi; Yoshida, Hisako; Nanasato, Mamoru; Oyama, Jun-Ichi; Ishizu, Tomoko; Ajioka, Masayoshi; Ishiki, Ryoji; Saito, Makoto; Shibata, Yoshisato; Kaku, Kohei; Maemura, Koji; Higashi, Yukihito; Inoue, Teruo; Murohara, Toyoaki; Node, Koichi

2018-05-19

Whether a dipeptidyl peptidase-4 (DPP-4) inhibitor can attenuate atherosclerosis is still controversial. Some clinical trials reported that DPP-4 inhibitors in diabetes patients without a previous history of cardiovascular (CV) events could reduce carotid intima-media thickness (IMT). However, in the PROLOGUE study, which enrolled diabetes patients both with and without previous CV events, sitagliptin failed to slow the progression of carotid IMT relative to conventional therapy. We hypothesized that the effect of DPP-4 inhibitors on carotid atherosclerosis might be different between the primary and secondary prevention groups. We performed a post hoc analysis of the PROLOGUE study and compared the effects of sitagliptin and conventional therapy on changes in carotid IMT in subgroups with or without previous CV events. No significant difference in the IMT changes between the treatment groups was found in the secondary prevention subgroup (sitagliptin, N = 102; conventional, 111). However, in the primary prevention subgroup (sitagliptin, 120; conventional, 109), we found significant inhibitory effects of sitagliptin on mean and max internal carotid artery IMT [estimated group difference: -0.096 mm (95% CI -0.175 to -0.018, p = 0.017) and -0.162 mm (95% CI -0.272 to -0.052, p = 0.004), respectively], although there was no significant difference in the common carotid artery IMT. Our data suggest that there is a favorable effect of DPP-4 inhibitor treatment on carotid atherosclerosis in diabetes patients without previous CV events. Copyright © 2017 Elsevier B.V. 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

.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.

Identification of New World Quails Susceptible to Infection with Avian Leukosis Virus Subgroup J

PubMed Central

Plachý, Jiří; Reinišová, Markéta; Kučerová, Dana; Šenigl, Filip; Stepanets, Volodymyr; Hron, Tomáš; Trejbalová, Kateřina; Elleder, Daniel

2016-01-01

ABSTRACT The J subgroup of avian leukosis virus (ALV-J) infects domestic chickens, jungle fowl, and turkeys. This virus enters the host cell through a receptor encoded by the tvj locus and identified as Na+/H+ exchanger 1. The resistance to avian leukosis virus subgroup J in a great majority of galliform species has been explained by deletions or substitutions of the critical tryptophan 38 in the first extracellular loop of Na+/H+ exchanger 1. Because there are concerns of transspecies virus transmission, we studied natural polymorphisms and susceptibility/resistance in wild galliforms and found the presence of tryptophan 38 in four species of New World quails. The embryo fibroblasts of New World quails are susceptible to infection with avian leukosis virus subgroup J, and the cloned Na+/H+ exchanger 1 confers susceptibility on the otherwise resistant host. New World quails are also susceptible to new avian leukosis virus subgroup J variants but resistant to subgroups A and B and weakly susceptible to subgroups C and D of avian sarcoma/leukosis virus due to obvious defects of the respective receptors. Our results suggest that the avian leukosis virus subgroup J could be transmitted to New World quails and establish a natural reservoir of circulating virus with a potential for further evolution. IMPORTANCE Since its spread in broiler chickens in China and Southeast Asia in 2000, ALV-J remains a major enzootic challenge for the poultry industry. Although the virus diversifies rapidly in the poultry, its spillover and circulation in wild bird species has been prevented by the resistance of most species to ALV-J. It is, nevertheless, important to understand the evolution of the virus and its potential host range in wild birds. Because resistance to avian retroviruses is due particularly to receptor incompatibility, we studied Na+/H+ exchanger 1, the receptor for ALV-J. In New World quails, we found a receptor compatible with virus entry, and we confirmed the

Identification of New World Quails Susceptible to Infection with Avian Leukosis Virus Subgroup J.

PubMed

Plachý, Jiří; Reinišová, Markéta; Kučerová, Dana; Šenigl, Filip; Stepanets, Volodymyr; Hron, Tomáš; Trejbalová, Kateřina; Elleder, Daniel; Hejnar, Jiří

2017-02-01

The J subgroup of avian leukosis virus (ALV-J) infects domestic chickens, jungle fowl, and turkeys. This virus enters the host cell through a receptor encoded by the tvj locus and identified as Na + /H + exchanger 1. The resistance to avian leukosis virus subgroup J in a great majority of galliform species has been explained by deletions or substitutions of the critical tryptophan 38 in the first extracellular loop of Na + /H + exchanger 1. Because there are concerns of transspecies virus transmission, we studied natural polymorphisms and susceptibility/resistance in wild galliforms and found the presence of tryptophan 38 in four species of New World quails. The embryo fibroblasts of New World quails are susceptible to infection with avian leukosis virus subgroup J, and the cloned Na + /H + exchanger 1 confers susceptibility on the otherwise resistant host. New World quails are also susceptible to new avian leukosis virus subgroup J variants but resistant to subgroups A and B and weakly susceptible to subgroups C and D of avian sarcoma/leukosis virus due to obvious defects of the respective receptors. Our results suggest that the avian leukosis virus subgroup J could be transmitted to New World quails and establish a natural reservoir of circulating virus with a potential for further evolution. Since its spread in broiler chickens in China and Southeast Asia in 2000, ALV-J remains a major enzootic challenge for the poultry industry. Although the virus diversifies rapidly in the poultry, its spillover and circulation in wild bird species has been prevented by the resistance of most species to ALV-J. It is, nevertheless, important to understand the evolution of the virus and its potential host range in wild birds. Because resistance to avian retroviruses is due particularly to receptor incompatibility, we studied Na + /H + exchanger 1, the receptor for ALV-J. In New World quails, we found a receptor compatible with virus entry, and we confirmed the susceptibilities

Depression and Suicide in Schizophrenic Patients.

ERIC Educational Resources Information Center

Salama, Aziz A.

1988-01-01

Identified schizophrenic patients as distinctive subgroup of patients who can suffer from major depressive illness and can commit suicide. Found 22.4 percent of 620 schizophrenics in psychiatric facility showed symptoms of major depressive episode. Seven patients committed suicide during acute phase of illness, 9 attempted suicide while…

Discrimination of multilocus sequence typing-based Campylobacter jejuni subgroups by MALDI-TOF mass spectrometry.

PubMed

Zautner, Andreas Erich; Masanta, Wycliffe Omurwa; Tareen, Abdul Malik; Weig, Michael; Lugert, Raimond; Groß, Uwe; Bader, Oliver

2013-11-07

Campylobacter jejuni, the most common bacterial pathogen causing gastroenteritis, shows a wide genetic diversity. Previously, we demonstrated by the combination of multi locus sequence typing (MLST)-based UPGMA-clustering and analysis of 16 genetic markers that twelve different C. jejuni subgroups can be distinguished. Among these are two prominent subgroups. The first subgroup contains the majority of hyperinvasive strains and is characterized by a dimeric form of the chemotaxis-receptor Tlp7(m+c). The second has an extended amino acid metabolism and is characterized by the presence of a periplasmic asparaginase (ansB) and gamma-glutamyl-transpeptidase (ggt). Phyloproteomic principal component analysis (PCA) hierarchical clustering of MALDI-TOF based intact cell mass spectrometry (ICMS) spectra was able to group particular C. jejuni subgroups of phylogenetic related isolates in distinct clusters. Especially the aforementioned Tlp7(m+c)(+) and ansB+/ ggt+ subgroups could be discriminated by PCA. Overlay of ICMS spectra of all isolates led to the identification of characteristic biomarker ions for these specific C. jejuni subgroups. Thus, mass peak shifts can be used to identify the C. jejuni subgroup with an extended amino acid metabolism. Although the PCA hierarchical clustering of ICMS-spectra groups the tested isolates into a different order as compared to MLST-based UPGMA-clustering, the isolates of the indicator-groups form predominantly coherent clusters. These clusters reflect phenotypic aspects better than phylogenetic clustering, indicating that the genes corresponding to the biomarker ions are phylogenetically coupled to the tested marker genes. Thus, PCA clustering could be an additional tool for analyzing the relatedness of bacterial isolates.

Combining moderators to identify clinical profiles of patients who will, and will not, benefit from aripiprazole augmentation for treatment resistant late-life major depressive disorder.

PubMed

Smagula, Stephen F; Wallace, Meredith L; Anderson, Stewart J; Karp, Jordan F; Lenze, Eric J; Mulsant, Benoit H; Butters, Meryl A; Blumberger, Daniel M; Diniz, Breno S; Lotrich, Francis E; Dew, Mary Amanda; Reynolds, Charles F

2016-10-01

Personalizing treatment for late-life depression requires identifying and integrating information from multiple factors that influence treatment efficacy (moderators). We performed exploratory moderator analyses using data from a multi-site, randomized, placebo-controlled, double-blind trial of aripiprazole augmentation. Patients (n = 159) aged ≥60 years had major depressive disorder that failed to remit with venlafaxine monotherapy. We examined effect sizes of 39 potential moderators of aripiprazole (vs. placebo) augmentation efficacy using the outcome of percentage reduction in depressive symptom after 12 weeks. We then incorporated information from the individually relevant variables in combined moderators. A larger aripiprazole treatment effect was related to: white race, better physical function, better performance on Trail-Making, attention, immediate, and delayed memory tests, greater psychomotor agitation and suicidality symptoms, and a history of adequate antidepressant pharmacotherapy. A smaller aripiprazole treatment effect was observed in patients with: more pain and more work/activity impairment and libido symptoms. Combining information from race and Trail-Making test performance (base combined moderator (Mb*)) produced a larger effect size (Spearman effect size = 0.29 (95% confidence interval (CI): 0.15, 0.42)) than any individual moderator. Adding other individually relevant moderators in the full combined moderator (Mf*) further improved effect size (Spearman effect size = 0.39 (95% CI: 0.25, 0.52)) and identified a sub-group benefiting more from placebo plus continuation venlafaxine monotherapy than adjunctive aripiprazole. Combining moderators can help clinicians personalize depression treatment. We found the majority of our patients benefited from adjunctive aripiprazole, but a smaller subgroup that is identifiable using clinical measures appeared to benefit more from continuation venlafaxine plus placebo. Copyright © 2016 Elsevier Ltd

Identification of Subgroups of Women with Carpal Tunnel Syndrome with Central Sensitization.

PubMed

Fernández-de-Las-Peñas, César; Fernández-Muñoz, Juan J; Navarro-Pardo, Esperanza; da-Silva-Pocinho, Ricardo F; Ambite-Quesada, Silvia; Pareja, Juan A

2016-09-01

Identification of subjects with different sensitization mechanisms can help to identify better therapeutic strategies for carpal tunnel syndrome (CTS). The aim of the current study was to identify subgroups of women with CTS with different levels of sensitization. A total of 223 women with CTS were recruited. Self-reported variables included pain intensity, function, disability, and depression. Pressure pain thresholds (PPT) were assessed bilaterally over median, ulnar, and radial nerves, C5-C6 joint, carpal tunnel, and tibialis anterior to assess widespread pressure pain hyperalgesia. Heat (HPT) and cold (CPT) pain thresholds were also bilaterally assessed over the carpal tunnel and the thenar eminence to determine thermal pain hyperalgesia. Pinch grip force between the thumb and the remaining fingers was calculated to determine motor assessment. Subgroups were determined according to the status on a previous clinical prediction rule: PPT over the affected C5-C6 joint < 137 kPa, HPT on affected carpal tunnel <39.6ºC, and general health >66 points. The ANOVA showed that women within group 1 (positive rule, n = 60) exhibited bilateral widespread pressure hyperalgesia (P < 0.001) and bilateral thermal thresholds (P < 0.001) than those within group 2 (negative rule, n = 162). Women in group 1 also exhibited higher depression than those in group 2 (P = 0.023). No differences in self-reported variables were observed. This study showed that a clinical prediction rule originally developed for identifying women with CTS who are likely to respond favorably to manual physical therapy was able to identify women exhibiting higher widespread pressure hyper-sensitivity and thermal hyperalgesia. This subgroup of women with CTS exhibiting higher sensitization may need specific therapeutic programs. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The effectiveness and safety of amisulpride in Chinese patients with schizophrenia who switch from risperidone or olanzapine: a subgroup analysis of the ESCAPE study

PubMed Central

Liang, Ying; Yu, Xin

2017-01-01

Introduction Second-generation antipsychotics show significant interpatient variability in treatment response and side-effect profiles, and the majority of patients with schizophrenia require multiple treatment changes. This subgroup analysis of the ESCAPE study evaluated the efficacy and safety of amisulpride in Chinese patients with schizophrenia who switched from risperidone or olanzapine. Methods ESCAPE was a prospective, open-label, multicenter, single-arm Phase IV study in which Chinese patients with an ICD-10 diagnosis of schizophrenia received amisulpride for 8 weeks. This analysis included 109 patients who switched to amisulpride from risperidone (n=68) or olanzapine (n=41) and 59 treatment-naïve patients for reference. The primary effectiveness outcome was a ≥50% decrease in Positive and Negative Syndrome Scale (PANSS) Total score from Baseline to Week 8. The study was registered at ClinicalTrials.gov (NCT01795183). Results Of the patients who switched from risperidone and olanzapine, 77.9% and 56.1% achieved ≥50% reduction in PANSS Total score from Baseline to Week 8 and 57.4% and 46.3% achieved ≥20% reduction in PANSS score from Baseline to Week 2, respectively; these end points were achieved by 66.1% and 61.0% of treatment-naïve patients, respectively. No unexpected adverse events (AEs) were reported. Of the most common AEs, extrapyramidal side effects occurred in 32.4% and 14.6%, blood prolactin increase in 32.4% and 39.0%, and ≥7% increase in body weight in 4.4% and 12% of patients switching from risperidone and olanzapine, respectively. Conclusion The results of this subgroup analysis suggest that switching to amisulpride from risperidone and olanzapine is effective and generally well tolerated in Chinese patients with schizophrenia. PMID:28461752

Surveillance of the colorectal cancer disparities among demographic subgroups: a spatial analysis.

PubMed

Hsu, Chiehwen Ed; Mas, Francisco Soto; Hickey, Jessica M; Miller, Jerry A; Lai, Dejian

2006-09-01

The literature suggests that colorectal cancer mortality in Texas is distributed inhomogeneously among specific demographic subgroups and in certain geographic regions over an extended period. To understand the extent of the demographic and geographic disparities, the present study examined colorectal cancer mortality in 15 demographic groups in Texas counties between 1990 and 2001. The Spatial Scan Statistic was used to assess the standardized mortality ratio, duration and age-adjusted rates of excess mortality, and their respective p-values for testing the null hypothesis of homogeneity of geographic and temporal distribution. The study confirmed the excess mortality in some Texas counties found in the literature, identified 13 additional excess mortality regions, and found 4 health regions with persistent excess mortality involving several population subgroups. Health disparities of colorectal cancer mortality continue to exist in Texas demographic subpopulations. Health education and intervention programs should be directed to the at-risk subpopulations in the identified regions.

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.

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

Informant discrepancy defines discrete, clinically useful autism spectrum disorder subgroups.

PubMed

Lerner, Matthew D; De Los Reyes, Andres; Drabick, Deborah A G; Gerber, Alan H; Gadow, Kenneth D

2017-07-01

Discrepancy between informants (parents and teachers) in severity ratings of core symptoms commonly arise when assessing autism spectrum disorder (ASD). Whether such discrepancy yields unique information about the ASD phenotype and its clinical correlates has not been examined. We examined whether degree of discrepancy between parent and teacher ASD symptom ratings defines discrete, clinically meaningful subgroups of youth with ASD using an efficient, cost-effective procedure. Children with ASD (N = 283; 82% boys; M age  = 10.5 years) were drawn from a specialty ASD clinic. Parents and teachers provided ratings of the three core DSM-IV-TR domains of ASD symptoms (communication, social, and perseverative behavior) with the Child and Adolescent Symptom Inventory-4R (CASI-4R). External validators included child psychotropic medication status, frequency of ASD-relevant school-based services, and the Autism Diagnostic Observation Schedule (ADOS-2). Four distinct subgroups emerged that ranged from large between-informant discrepancy (informant-specific) to relative lack of discrepancy (i.e. informant agreement; cross-situational): Moderate Parent/Low Teacher or Low Parent/Moderate Teacher Severity (Discrepancy), and Moderate or High Symptom Severity (Agreement). Subgroups were highly distinct (mean probability of group assignment = 94%). Relative to Discrepancy subgroups, Agreement subgroups were more likely to receive psychotropic medication, school-based special education services, and an ADOS-2 diagnosis. These differential associations would not have been identified based solely on CASI-4R scores from one informant. The degree of parent-teacher discrepancy about ASD symptom severity appears to provide more clinically useful information than reliance on a specific symptom domain or informant, and thus yields an innovative, cost-effective approach to assessing functional impairment. This conclusion stands in contrast to existing symptom clustering approaches in

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

Attacking Heterogeneity in Schizophrenia by Deriving Clinical Subgroups From Widely Available Symptom Data.

PubMed

Dickinson, Dwight; Pratt, Danielle N; Giangrande, Evan J; Grunnagle, MeiLin; Orel, Jennifer; Weinberger, Daniel R; Callicott, Joseph H; Berman, Karen F

2018-01-13

Previous research has identified (1) a "deficit" subtype of schizophrenia characterized by enduring negative symptoms and diminished emotionality and (2) a "distress" subtype associated with high emotionality-including anxiety, depression, and stress sensitivity. Individuals in deficit and distress categories differ sharply in development, clinical course and behavior, and show distinct biological markers, perhaps signaling different etiologies. We tested whether deficit and distress subtypes would emerge from a simple but novel data-driven subgrouping analysis, based on Positive and Negative Syndrome Scale (PANSS) negative and distress symptom dimensions, and whether subgrouping was informative regarding other facets of behavior and brain function. PANSS data, and other assessments, were available for 549 people with schizophrenia diagnoses. Negative and distress symptom composite scores were used as indicators in 2-step cluster analyses, which divided the sample into low symptom (n = 301), distress (n = 121), and deficit (n = 127) subgroups. Relative to the low-symptom group, the deficit and distress subgroups had comparably higher total PANSS symptoms (Ps < .001) and were similarly functionally impaired (eg, global functioning [GAF] Ps < .001), but showed markedly different patterns on symptom, cognitive and personality variables, among others. Initial analyses of functional magnetic resonance imaging (fMRI) data from a 182-participant subset of the full sample also suggested distinct patterns of neural recruitment during working memory. The field seeks more neuroscience-based systems for classifying psychiatric conditions, but these are inescapably behavioral disorders. More effective parsing of clinical and behavioral traits could identify homogeneous target groups for further neural system and molecular studies, helping to integrate clinical and neuroscience approaches. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center

Investigative clinical study on prostate cancer part III: exploring total PSA and free testosterone distributions and linear correlations in groups and subgroups of operated prostate cancer patients according to the total PSA/FT ratio.

PubMed

Porcaro, Antonio B; Petrozziello, Aldo; Romano, Mario; Sava, Teodoro; Ghimenton, Claudio; Caruso, Beatrice; Migliorini, Filippo; Zecchini Antoniolli, Stefano; Rubilotta, Emanuele; Lacola, Vincenzo; Monaco, Carmelo; Comunale, Luigi

2010-01-01

Prostate cancer is an interesting tumor for endocrine investigation. The prostate-specific antigen/free testosterone (PSA/FT) ratio has been shown to be effective in clustering patients in prognostic groups as follows: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40) and high risk (PSA/FT >0.40 and ≤1.5). In the present study we explored the total PSA and FT distributions, and linear regression of FT predicting PSA in the different groups (PSA/FT, pT and pG) and subgroups (pT and pG) of patients according to the prognostic PSA/FT ratio. The study included 128 operated prostate cancer patients. Pretreatment simultaneous serum samples were obtained for measuring free testosterone (FT) and total PSA levels. Patients were grouped according to the total PSA/FT ratio prognostic clusters (≤0.20, >0.20 and ≤0.40, >0.40), pT (2, 3a and 3b+4) and pathological Gleason score (pG) (≤6, = 7 >3 + 4, ≥7 >4 + 3). The pT and pG sets were subgrouped according to the prognostic PSA/FT ratio. Linear regression analysis of FT predicting total PSA was computed according to the different PSA/FT prognostic clusters for the: (1) total sample population, (2) pT and pG groups, (3) intraprostatic (pT2) and extraprostatic disease (pT3a/3b/4), and (4) low-intermediate grade (pG ≤6) and high-grade (pG ≥7) prostate cancer. Analysis of variance always showed highly significant different PSA distributions for (1) the different PSA/FT, pT and pG groups; and (2) the pT and pG prognostic subgroups. Significant FT distributions were detected for the (1) PSA/FT and pT groups; and (2) the pT2, pT3a and pG ≤6 prognostic PSA/FT subgroups. Correlation, variance and linear regression analysis of FT predicting total PSA was significant for (1) the PSA/FT prognostic clusters, (2) all the pT2 and pT3a subgroups, and (3) the pT3b/4 subgroup with PSA/FT >0.20 and ≤0.40, and (4) all the pG subsets. Linear regression analysis showed that the slopes of the predicting variable

Individual, Cultural and Structural Predictors of Vaccine Safety Confidence and Influenza Vaccination Among Hispanic Female Subgroups.

PubMed

Moran, Meghan Bridgid; Chatterjee, Joyee S; Frank, Lauren B; Murphy, Sheila T; Zhao, Nan; Chen, Nancy; Ball-Rokeach, Sandra

2017-08-01

Rates of influenza vaccination among US Hispanics are lower than for non-Hispanic whites, yet little is known about factors affecting vaccination in this population. Additionally, although Hispanics are a diverse population with culturally distinct subgroups, they are often treated as a homogenous population. This study (1) examines how confidence in vaccine safety and influenza vaccine use vary by Hispanic subgroup and (2) identifies individual, cultural and structural correlates of these outcomes. This study analyzed survey data from 1565 Hispanic women who were recruited at clinic- and community-based sites in Los Angeles. Education, healthcare coverage, acculturation, fatalism, and religiosity were predictors of influenza vaccination behavior and predictors varied by subgroup. These findings provide guidance for how influenza vaccine promotion efforts can be developed for Hispanic subgroups. Confidence in the safety of a vaccine is a major predictor of flu vaccination and an important modifiable target for intervention.

(Epi)genotype-Phenotype Analysis in 69 Japanese Patients With Pseudohypoparathyroidism Type I

PubMed Central

Sano, Shinichiro; Nakamura, Akie; Matsubara, Keiko; Nagasaki, Keisuke; Fukami, Maki; Kagami, Masayo

2018-01-01

Context: Pseudohypoparathyroidism type I (PHP-I) is divided into PHP-Ia with Albright hereditary osteodystrophy and PHP-Ib, which usually shows no Albright hereditary osteodystrophy features. Although PHP-Ia and PHP-Ib are typically caused by genetic defects involving α subunit of the stimulatory G protein (Gsα)–coding GNAS exons and methylation defects of the GNAS differentially methylated regions (DMRs) on the maternal allele, respectively, detailed phenotypic characteristics still remains to be examined. Objective: To clarify phenotypic characteristics according to underlying (epi)genetic causes. Patients and Methods: We performed (epi)genotype-phenotype analysis in 69 Japanese patients with PHP-I; that is, 28 patients with genetic defects involving Gsα-coding GNAS exons (group 1) consisting of 12 patients with missense variants (subgroup A) and 16 patients with null variants (subgroup B), as well as 41 patients with methylation defects (group 2) consisting of 21 patients with broad methylation defects of the GNAS-DMRs (subgroup C) and 20 patients with an isolated A/B-DMR methylation defect accompanied by the common STX16 microdeletion (subgroup D). Results: Although (epi)genotype-phenotype findings were grossly similar to those reported previously, several important findings were identified, including younger age at hypocalcemic symptoms and higher frequencies of hyperphosphatemia in subgroup C than in subgroup D, development of brachydactyly in four patients of subgroup C, predominant manifestation of subcutaneous ossification in subgroup B, higher frequency of thyrotropin resistance in group 1 than in group 2, and relatively low thyrotropin values in four patients with low T4 values and relatively low luteinizing hormone/follicle-stimulating hormone values in five adult females with ovarian dysfunction. Conclusion: The results imply the presence of clinical findings characteristic of each underlying cause and provide useful information on the imprinting

Distinguishing between respiratory syncytial virus subgroups by protein profile analysis.

PubMed Central

Walpita, P; Mufson, M A; Stanek, R J; Pfeifer, D; Connor, J D

1992-01-01

We subgrouped 75 strains of respiratory syncytial virus by a protein profile method (PPM) which relies on different mobilities of the phosphoprotein in one-dimensional polyacrylamide gel electrophoresis and does not require monoclonal antibodies. When compared with enzyme immunoassay, PPM correctly subgrouped 54 of 56 subgroup A and all 19 subgroup B strains. Images PMID:1572961

Can we identify patients at risk of life-threatening allergic reactions to food?

PubMed

Turner, P J; Baumert, J L; Beyer, K; Boyle, R J; Chan, C-H; Clark, A T; Crevel, R W R; DunnGalvin, A; Fernández-Rivas, M; Gowland, M H; Grabenhenrich, L; Hardy, S; Houben, G F; O'B Hourihane, J; Muraro, A; Poulsen, L K; Pyrz, K; Remington, B C; Schnadt, S; van Ree, R; Venter, C; Worm, M; Mills, E N C; Roberts, G; Ballmer-Weber, B K

2016-09-01

Anaphylaxis has been defined as a 'severe, life-threatening generalized or systemic hypersensitivity reaction'. However, data indicate that the vast majority of food-triggered anaphylactic reactions are not life-threatening. Nonetheless, severe life-threatening reactions do occur and are unpredictable. We discuss the concepts surrounding perceptions of severe, life-threatening allergic reactions to food by different stakeholders, with particular reference to the inclusion of clinical severity as a factor in allergy and allergen risk management. We review the evidence regarding factors that might be used to identify those at most risk of severe allergic reactions to food, and the consequences of misinformation in this regard. For example, a significant proportion of food-allergic children also have asthma, yet almost none will experience a fatal food-allergic reaction; asthma is not, in itself, a strong predictor for fatal anaphylaxis. The relationship between dose of allergen exposure and symptom severity is unclear. While dose appears to be a risk factor in at least a subgroup of patients, studies report that individuals with prior anaphylaxis do not have a lower eliciting dose than those reporting previous mild reactions. It is therefore important to consider severity and sensitivity as separate factors, as a highly sensitive individual will not necessarily experience severe symptoms during an allergic reaction. We identify the knowledge gaps that need to be addressed to improve our ability to better identify those most at risk of severe food-induced allergic reactions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

ARID1B alterations identify aggressive tumors in neuroblastoma.

PubMed

Lee, Soo Hyun; Kim, Jung-Sun; Zheng, Siyuan; Huse, Jason T; Bae, Joon Seol; Lee, Ji Won; Yoo, Keon Hee; Koo, Hong Hoe; Kyung, Sungkyu; Park, Woong-Yang; Sung, Ki W

2017-07-11

Targeted panel sequencing was performed to determine molecular targets and biomarkers in 72 children with neuroblastoma. Frequent genetic alterations were detected in ALK (16.7%), BRCA1 (13.9%), ATM (12.5%), and PTCH1 (11.1%) in an 83-gene panel. Molecular targets for targeted therapy were identified in 16 of 72 patients (22.2%). Two-thirds of ALK mutations were known to increase sensitivity to ALK inhibitors. Sequence alterations in ARID1B were identified in 5 of 72 patients (6.9%). Four of five ARID1B alterations were detected in tumors of high-risk patients. Two of five patients with ARID1B alterations died of disease progression. Relapse-free survival was lower in patients with ARID1B alterations than in those without (p = 0.01). In analysis confined to high-risk patients, 3-year overall survival was lower in patients with an ARID1B alteration (33.3 ± 27.2%) or MYCN amplification (30.0 ± 23.9%) than in those with neither ARID1B alteration nor MYCN amplification (90.5 ± 6.4%, p = 0.05). These results provide possibilities for targeted therapy and a new biomarker identifying a subgroup of neuroblastoma patients with poor prognosis.

Efficacy of an autophagy-targeted DNA vaccine against avian leukosis virus subgroup J

USDA-ARS?s Scientific Manuscript database

Infection with the avian leukosis virus subgroup J (ALV-J) can lead to neoplastic disease in chickens, inflicting significant economic losses to the poultry industry. Recent reports have identified inhibitory effects of ALV-J on autophagy, a process involving in innate and adaptive immunity. Inspire...

Etiological Subgroups of Small-for-Gestational-Age: Differential Neurodevelopmental Outcomes

PubMed Central

Li, Xiuhong; Eiden, Rina D.; Epstein, Leonard H.; Shenassa, Edmond D.; Xie, Chuanbo; Wen, Xiaozhong

2016-01-01

Objectives It remains unclear why substantial variations in neurodevelopmental outcomes exist within small-for-gestational-age (SGA) children. We prospectively compared 5-y neurodevelopmental outcomes across SGA etiological subgroups. Methods Children born SGA (N = 1050) from U.S. Early Childhood Longitudinal Study-Birth Cohort (2001–2007) was divided into etiological subgroups by each of 7 well-established prenatal risk factors. We fit linear regression models to compare 5-y reading, math, gross motor and fine motor scores across SGA subgroups, adjusting for socio-demographic confounders. Results Compared to singleton SGA subgroup, multiple-birth SGA subgroup had lower mean reading (adjusted mean difference, -4.08 [95% confidence interval, -6.10, -2.06]) and math (-2.22 [-3.61, -0.84]) scores. These disadvantages in reading and math existed only among multiple-birth SGA subgroup without ovulation stimulation (reading, -4.50 [-6.64, -2.36]; math, -2.91 [-4.37, -1.44]), but not among those with ovulation stimulation (reading, -2.33 [-6.24, 1.57]; math 0.63 [-1.86, 3.12]). Compared to singleton SGA subgroup without maternal smoking and inadequate gestational weight gain, singleton SGA subgroup with co-occurrence of maternal smoking and inadequate gestational weight gain (GWG) had lower mean reading (-4.81 [-8.50, -1.12]) and math (-2.95 [-5.51, -0.38]) scores. These differences were not mediated by Apgar score. Conclusions Multiple-birth SGA subgroups (vs. singleton SGA) or singleton SGA subgroup with co-occurrence of smoking and inadequate GWG (vs. singleton SGA subgroup without maternal smoking and inadequate gestational weight gain) have poorer cognitive development up to 5 y. PMID:27501456

Subgroups of Adult Basic Education Learners with Different Profiles of Reading Skills

ERIC Educational Resources Information Center

MacArthur, Charles A.; Konold, Timothy R.; Glutting, Joseph J.; Alamprese, Judith A.

2012-01-01

The purpose of this study was to identify subgroups of adult basic education (ABE) learners with different profiles of skills in the core reading components of decoding, word recognition, spelling, fluency, and comprehension. The analysis uses factor scores of those 5 reading components from on a prior investigation of the reliability and…

Amoxicillin for acute lower respiratory tract infection in primary care: subgroup analysis of potential high-risk groups

PubMed Central

Moore, Michael; Stuart, Beth; Coenen, Samuel; Butler, Chris C; Goossens, Herman; Verheij, Theo JM; Little, Paul

2014-01-01

Background Antibiotics are of limited overall clinical benefit for uncomplicated lower respiratory tract infection (LRTI) but there is uncertainty about their effectiveness for patients with features associated with higher levels of antibiotic prescribing. Aim To estimate the benefits and harms of antibiotics for acute LRTI among those producing coloured sputum, smokers, those with fever or prior comorbidities, and longer duration of prior illness. Design and setting Secondary analysis of a randomised controlled trial of antibiotic placebo for acute LRTI in primary care. Method Two thousand and sixty-one adults with acute LRTI, where pneumonia was not suspected clinically, were given amoxicillin or matching placebo. The duration of symptoms, rated moderately bad or worse (primary outcome), symptom severity on days 2–4 (0–6 scale), and the development of new or worsening symptoms were analysed in pre-specified subgroups of interest. Evidence of differential treatment effectiveness was assessed in prespecified subgroups by interaction terms. Results No subgroups were identified that were significantly more likely to benefit from antibiotics in terms of symptom duration or the development of new or worsening symptoms. Those with a history of significant comorbidities experienced a significantly greater reduction in symptom severity between days 2 and 4 (interaction term −0.28, P = 0.003; estimated effect of antibiotics among those with a past history −0.28 [95% confidence interval = −0.44 to −0.11], P = 0.001), equivalent to three people in 10 rating symptoms as a slight rather than a moderately bad problem. For subgroups not specified in advance antibiotics provided a modest reduction in symptom severity for non-smokers and for those with short prior illness duration (<7 days), and a modest reduction in symptom duration for those with short prior illness duration. Conclusion There is no clear evidence of clinically meaningful benefit from antibiotics in

Subgroups Among Opiate Addicts

ERIC Educational Resources Information Center

Berzins, Juris I.; And Others

1974-01-01

The principal objective of the present investigation was to delineate homogeneous MMPI profile subgroups (types) through multivariate clustering procedures and to compare the derived (replicable) types on measures of the components of "sociopathy" as well as on other psychometric devices. (Author)

Quality of life and patient preferences: identification of subgroups of multiple sclerosis patients.

PubMed

Rosato, Rosalba; Testa, Silvia; Oggero, Alessandra; Molinengo, Giorgia; Bertolotto, Antonio

2015-09-01

The aim of this study was to estimate preferences related to quality of life attributes in people with multiple sclerosis, by keeping heterogeneity of patient preference in mind, using the latent class approach. A discrete choice experiment survey was developed using the following attributes: activities of daily living, instrumental activities of daily living, pain/fatigue, anxiety/depression and attention/concentration. Choice sets were presented as pairs of hypothetical health status, based upon a fractional factorial design. The latent class logit model estimated on 152 patients identified three subpopulations, which, respectively, attached more importance to: (1) the physical dimension; (2) pain/fatigue and anxiety/depression; and (3) instrumental activities of daily living impairments, anxiety/depression and attention/concentration. A posterior analysis suggests that the latent class membership may be related to an individual's age to some extent, or to diagnosis and treatment, while apart from energy dimension, no significant difference exists between latent groups, with regard to Multiple Sclerosis Quality of Life-54 scales. A quality of life preference-based utility measure for people with multiple sclerosis was developed. These utility values allow identification of a hierarchic priority among different aspects of quality of life and may allow physicians to develop a care programme tailored to patient needs.

Transcriptomes define distinct subgroups of salivary gland adenoid cystic carcinoma with different driver mutations and outcomes

PubMed Central

Frerich, Candace A.; Brayer, Kathryn J.; Painter, Brandon M.; Kang, Huining; Mitani, Yoshitsugu; El-Naggar, Adel K.; Ness, Scott A.

2018-01-01

The relative rarity of salivary gland adenoid cystic carcinoma (ACC) and its slow growing yet aggressive nature has complicated the development of molecular markers for patient stratification. To analyze molecular differences linked to the protracted disease course of ACC and metastases that form 5 or more years after diagnosis, detailed RNA-sequencing (RNA-seq) analysis was performed on 68 ACC tumor samples, starting with archived, formalin-fixed paraffin-embedded (FFPE) samples up to 25 years old, so that clinical outcomes were available. A statistical peak-finding approach was used to classify the tumors that expressed MYB or MYBL1, which had overlapping gene expression signatures, from a group that expressed neither oncogene and displayed a unique phenotype. Expression of MYB or MYBL1 was closely correlated to the expression of the SOX4 and EN1 genes, suggesting that they are direct targets of Myb proteins in ACC tumors. Unsupervised hierarchical clustering identified a subgroup of approximately 20% of patients with exceptionally poor overall survival (median less than 30 months) and a unique gene expression signature resembling embryonic stem cells. The results provide a strategy for stratifying ACC patients and identifying the high-risk, poor-outcome group that are candidates for personalized therapies. PMID:29484115

Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group.

PubMed

Lübbert, Michael; Suciu, Stefan; Hagemeijer, Anne; Rüter, Björn; Platzbecker, Uwe; Giagounidis, Aristoteles; Selleslag, Dominik; Labar, Boris; Germing, Ulrich; Salih, Helmut R; Muus, Petra; Pflüger, Karl-Heinz; Schaefer, Hans-Eckart; Bogatyreva, Lioudmila; Aul, Carlo; de Witte, Theo; Ganser, Arnold; Becker, Heiko; Huls, Gerwin; van der Helm, Lieke; Vellenga, Edo; Baron, Frédéric; Marie, Jean-Pierre; Wijermans, Pierre W

2016-01-01

In a study of elderly AML patients treated with the hypomethylating agent decitabine (DAC), we noted a surprisingly favorable outcome in the (usually very unfavorable) subgroup with two or more autosomal monosomies (MK2+) within a complex karyotype (Lübbert et al., Haematologica 97:393-401, 2012). We now analyzed 206 myelodysplastic syndrome (MDS) patients (88 % of 233 patients randomized in the EORTC/GMDSSG phase III trial 06011, 61 of them with RAEBt, i.e. AML by WHO) with cytogenetics informative for MK status.. Endpoints are the following: complete/partial (CR/PR) and overall response rate (ORR) and progression-free (PFS) and overall survival (OS). Cytogenetic subgroups are the following: 63 cytogenetically normal (CN) patients, 143 with cytogenetic abnormalities, 73 of them MK-negative (MK-), and 70 MK-positive (MK+). These MK+ patients could be divided into 17 with a single autosomal monosomy (MK1) and 53 with at least two monosomies (MK2+). ORR with DAC in CN patients: 36.1 %, in MK- patients: 16.7 %, in MK+ patients: 43.6 % (MK1: 44.4 %, MK2+ 43.3 %). PFS was prolonged by DAC compared to best supportive care (BSC) in the CN (hazard ratio (HR) 0.55, 99 % confidence interval (CI), 0.26; 1.15, p = 0.03) and MK2+ (HR 0.50; 99 % CI, 0.23; 1.06, p = 0.016) but not in the MK-, MK+, and MK1 subgroups. OS was not improved by DAC in any subgroup. In conclusion, we demonstrate for the first time in a randomized phase III trial that high-risk MDS patients with complex karyotypes harboring two or more autosomal monosomies attain encouraging responses and have improved PFS with DAC treatment compared to BSC.

Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups.

PubMed

Sumazin, Pavel; Chen, Yidong; Treviño, Lisa R; Sarabia, Stephen F; Hampton, Oliver A; Patel, Kayuri; Mistretta, Toni-Ann; Zorman, Barry; Thompson, Patrick; Heczey, Andras; Comerford, Sarah; Wheeler, David A; Chintagumpala, Murali; Meyers, Rebecka; Rakheja, Dinesh; Finegold, Milton J; Tomlinson, Gail; Parsons, D Williams; López-Terrada, Dolores

2017-01-01

Despite being the most common liver cancer in children, hepatoblastoma (HB) is a rare neoplasm. Consequently, few pretreatment tumors have been molecularly profiled, and there are no validated prognostic or therapeutic biomarkers for HB patients. We report on the first large-scale effort to profile pretreatment HBs at diagnosis. Our analysis of 88 clinically annotated HBs revealed three risk-stratifying molecular subtypes that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways: high-risk tumors were characterized by up-regulated nuclear factor, erythroid 2-like 2 activity; high lin-28 homolog B, high mobility group AT-hook 2, spalt-like transcription factor 4, and alpha-fetoprotein expression; and high coordinated expression of oncofetal proteins and stem-cell markers, while low-risk tumors had low lin-28 homolog B and lethal-7 expression and high hepatic nuclear factor 1 alpha activity. Analysis of immunohistochemical assays using antibodies targeting these genes in a prospective study of 35 HBs suggested that these candidate biomarkers have the potential to improve risk stratification and guide treatment decisions for HB patients at diagnosis; our results pave the way for clinical collaborative studies to validate candidate biomarkers and test their potential to improve outcome for HB patients. (Hepatology 2017;65:104-121). © 2016 by the American Association for the Study of Liver Diseases.

Urinary infection caused by Micrococcus subgroup 3

PubMed Central

Kerr, Helen

1973-01-01

The laboratory findings and clinical presentations in urinary infections in 23 nurses, 10 caused by Micrococcus subgroup 3 and 13 by Escherichia coli, were studied, and the symptoms and possible predisposing factors compared. There were no important differences between the two groups. The infections caused by Micrococcus subgroup 3 were symptomatically severe, as were those caused by Escherichia coli. PMID:4593863

Determination of patellofemoral pain sub-groups and development of a method for predicting treatment outcome using running gait kinematics.

PubMed

Watari, Ricky; Kobsar, Dylan; Phinyomark, Angkoon; Osis, Sean; Ferber, Reed

2016-10-01

Not all patients with patellofemoral pain exhibit successful outcomes following exercise therapy. Thus, the ability to identify patellofemoral pain subgroups related to treatment response is important for the development of optimal therapeutic strategies to improve rehabilitation outcomes. The purpose of this study was to use baseline running gait kinematic and clinical outcome variables to classify patellofemoral pain patients on treatment response retrospectively. Forty-one individuals with patellofemoral pain that underwent a 6-week exercise intervention program were sub-grouped as treatment Responders (n=28) and Non-responders (n=13) based on self-reported measures of pain and function. Baseline three-dimensional running kinematics, and self-reported measures underwent a linear discriminant analysis of the principal components of the variables to retrospectively classify participants based on treatment response. The significance of the discriminant function was verified with a Wilk's lambda test (α=0.05). The model selected 2 gait principal components and had a 78.1% classification accuracy. Overall, Non-responders exhibited greater ankle dorsiflexion, knee abduction and hip flexion during the swing phase and greater ankle inversion during the stance phase, compared to Responders. This is the first study to investigate an objective method to use baseline kinematic and self-report outcome variables to classify on patellofemoral pain treatment outcome. This study represents a significant first step towards a method to help clinicians make evidence-informed decisions regarding optimal treatment strategies for patients with patellofemoral pain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular subgroups of medulloblastoma identification using noninvasive magnetic resonance spectroscopy.

PubMed

Blüml, Stefan; Margol, Ashley S; Sposto, Richard; Kennedy, Rebekah J; Robison, Nathan J; Vali, Marzieh; Hung, Long T; Muthugounder, Sakunthala; Finlay, Jonathan L; Erdreich-Epstein, Anat; Gilles, Floyd H; Judkins, Alexander R; Krieger, Mark D; Dhall, Girish; Nelson, Marvin D; Asgharzadeh, Shahab

2016-01-01

Medulloblastomas in children can be categorized into 4 molecular subgroups with differing clinical characteristics, such that subgroup determination aids in prognostication and risk-adaptive treatment strategies. Magnetic resonance spectroscopy (MRS) is a widely available, noninvasive tool that is used to determine the metabolic characteristics of tumors and provide diagnostic information without the need for tumor tissue. In this study, we investigated the hypothesis that metabolite concentrations measured by MRS would differ between molecular subgroups of medulloblastoma and allow accurate subgroup determination. MRS was used to measure metabolites in medulloblastomas across molecular subgroups (SHH = 12, Groups 3/4 = 17, WNT = 1). Levels of 14 metabolites were analyzed to determine those that were the most discriminant for medulloblastoma subgroups in order to construct a multivariable classifier for distinguishing between combined Group 3/4 and SHH tumors. Medulloblastomas across molecular subgroups revealed distinct spectral features. Group 3 and Group 4 tumors demonstrated metabolic profiles with readily detectable taurine, lower levels of lipids, and high levels of creatine. SHH tumors showed prominent choline and lipid with low levels of creatine and little or no evidence of taurine. A 5-metabolite subgroup classifier inclusive of creatine, myo-inositol, taurine, aspartate, and lipid 13a was developed that could discriminate between Group 3/4 and SHH medulloblastomas with excellent accuracy (cross-validated area under the curve [AUC] = 0.88). The data show that medulloblastomas of Group 3/4 differ metabolically as measured using MRS when compared with SHH molecular subgroups. MRS is a useful and accurate tool to determine medulloblastoma molecular subgroups. © The Author(s) 2015. 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.

Distinctive ribonucleic acid patterns of human rotavirus subgroups 1 and 2.

PubMed Central

Kalica, A R; Greenberg, H B; Espejo, R T; Flores, J; Wyatt, R G; Kapikian, A Z; Chanock, R M

1981-01-01

The ribonucleic acid migration patterns of 7 subgroup 1 and 16 subgroup 2 human rotaviruses recovered from four geographic areas were compared. The subgroup 1 ribonucleic acid patterns had strikingly slower-moving segments 10 and 11, suggesting a correlation between the ribonucleic acid pattern and the subgroup specificity. Images PMID:6270002

A post-hoc subgroup analysis of outcomes in the first phase III clinical study of edaravone (MCI-186) in amyotrophic lateral sclerosis.

PubMed

2017-10-01

Our first phase III study failed to demonstrate efficacy of edaravone for amyotrophic lateral sclerosis (ALS) compared to placebo. Here, we performed post-hoc subgroup analysis to identify a subgroup in which edaravone might be expected to show efficacy. We focussed on two newly defined subgroups, EESP and dpEESP2y. The EESP was defined as the efficacy-expected subpopulation with % forced vital capacity of ≥80%, and ≥2 points for all item scores in the revised ALS functional rating scale (ALSFRS-R) score before treatment. The dpEESP2y was defined as the greater-efficacy-expected subpopulation within EESP having a diagnosis of 'definite' or 'probable' ALS according to the El Escorial revised Airlie House diagnostic criteria and onset of disease within two years. The primary endpoint of the post-hoc analysis was the change in the ALSFRS-R score during the 24-week treatment period. The intergroup differences of the least-squares mean change in the ALSFRS-R score ± standard error during treatment were 0.65 ± 0.78 (p = 0.4108) in the full analysis set, 2.20 ± 1.03 (p = 0.0360) in the EESP, and 3.01 ± 1.33 (p = 0.0270) in the dpEESP2y. Edaravone exhibited efficacy in the dpEESP2y subgroup. A further clinical study in patients meeting dpEESP2y criteria is warranted.

Physiotherapy movement based classification approaches to low back pain: comparison of subgroups through review and developer/expert survey.

PubMed

Karayannis, Nicholas V; Jull, Gwendolen A; Hodges, Paul W

2012-02-20

Several classification schemes, each with its own philosophy and categorizing method, subgroup low back pain (LBP) patients with the intent to guide treatment. Physiotherapy derived schemes usually have a movement impairment focus, but the extent to which other biological, psychological, and social factors of pain are encompassed requires exploration. Furthermore, within the prevailing 'biological' domain, the overlap of subgrouping strategies within the orthopaedic examination remains unexplored. The aim of this study was "to review and clarify through developer/expert survey, the theoretical basis and content of physical movement classification schemes, determine their relative reliability and similarities/differences, and to consider the extent of incorporation of the bio-psycho-social framework within the schemes". A database search for relevant articles related to LBP and subgrouping or classification was conducted. Five dominant movement-based schemes were identified: Mechanical Diagnosis and Treatment (MDT), Treatment Based Classification (TBC), Pathoanatomic Based Classification (PBC), Movement System Impairment Classification (MSI), and O'Sullivan Classification System (OCS) schemes. Data were extracted and a survey sent to the classification scheme developers/experts to clarify operational criteria, reliability, decision-making, and converging/diverging elements between schemes. Survey results were integrated into the review and approval obtained for accuracy. Considerable diversity exists between schemes in how movement informs subgrouping and in the consideration of broader neurosensory, cognitive, emotional, and behavioural dimensions of LBP. Despite differences in assessment philosophy, a common element lies in their objective to identify a movement pattern related to a pain reduction strategy. Two dominant movement paradigms emerge: (i) loading strategies (MDT, TBC, PBC) aimed at eliciting a phenomenon of centralisation of symptoms; and (ii) modified

What works best for whom? An exploratory, subgroup analysis in a randomized, controlled trial on the effectiveness of a workplace intervention in low back pain patients on return to work.

PubMed

Steenstra, Ivan A; Knol, Dirk L; Bongers, Paulien M; Anema, Johannes R; van Mechelen, Willem; de Vet, Henrica C W

2009-05-20

Exploratory subgroup analysis in a randomized controlled trial (RCT). To detect possible moderators in the effectiveness of a workplace intervention in a population of workers with sick leave due to sub acute nonspecific low back pain. In a recently published RCT, a workplace intervention was effective on return to work, compared to usual care. Examining the heterogeneity of effect sizes within the population in this RCT (n = 196) can lead to information on the effectiveness of the intervention in subgroups of patients. A subgroup analysis was performed by adding interaction terms to the statistical model. Before analysis the following possible moderators for treatment were identified: age, gender, pain, functional status, heavy work, and sick leave in the previous 12 months. Cox regression analyses were performed and survival curves were plotted. The interaction (P = 0.02) between age (dichotomized at the median value) and the workplace intervention indicates a modifying effect. The workplace intervention is more effective for workers > or =44 years (HR, 95% CI = 2.5, [1.6, 4.1] vs. 1.2 [0.8, 1.8] for workers <44 years old). The interaction between sick leave in the previous 12 months and the workplace intervention is significant (P = 0.02). The intervention is more effective for workers with previous sick leave (HR, 95% CI = 2.8 [1.7, 4.9] vs. 1.3 [0.8, 2.0]). A modifying effect of gender, heavy work, and pain score and functional status on the effectiveness of this intervention was not found. The findings from these exploratory analyses should be tested in future RCTs. This workplace intervention seems very suitable for return to work of older workers and workers with previous sick leave. Gender, perceived heavy work, and baseline scores in pain and functional status should not be a basis for assignment to this intervention.

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.

Characteristics of Patients with Chronic Obstructive Pulmonary Disease at the First Visit to a Pulmonary Medical Center in Korea: The KOrea COpd Subgroup Study Team Cohort

PubMed Central

2016-01-01

The Korea Chronic Obstructive Pulmonary Disorders Subgroup Study Team (Korea COPD Subgroup Study team, KOCOSS) is a multicenter observational study that includes 956 patients (mean age 69.9 ± 7.8 years) who were enrolled from 45 tertiary and university-affiliated hospitals from December 2011 to October 2014. The initial evaluation for all patients included pulmonary function tests (PFT), 6-minute walk distance (6MWD), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and the COPD-specific version of St. George’s Respiratory Questionnaire (SGRQ-C). Here, we report the comparison of baseline characteristics between patients with early- (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage I and II/groups A and B) and late-stage COPD (GOLD stage III and IV/groups C and D). Among all patients, the mean post-bronchodilator FEV1 was 55.8% ± 16.7% of the predicted value, and most of the patients were in GOLD stage II (520, 56.9%) and group B (399, 42.0%). The number of exacerbations during one year prior to the first visit was significantly lower in patients with early COPD (0.4 vs. 0.9/0.1 vs. 1.2), as were the CAT score (13.9 vs. 18.3/13.5 vs. 18.1), mMRC (1.4 vs. 2.0/1.3 vs.1.9), and SGRQ-C total score (30.4 vs. 42.9/29.1 vs. 42.6) compared to late-stage COPD (all P < 0.001). Common comorbidities among all patients were hypertension (323, 37.7%), diabetes mellitus (139, 14.8%), and depression (207, 23.6%). The data from patients with early COPD will provide important information towards early detection, proper initial management, and design of future studies. PMID:27051239

Characteristics of Patients with Chronic Obstructive Pulmonary Disease at the First Visit to a Pulmonary Medical Center in Korea: The KOrea COpd Subgroup Study Team Cohort.

PubMed

Lee, Jung Yeon; Chon, Gyu Rak; Rhee, Chin Kook; Kim, Deog Kyeom; Yoon, Hyoung Kyu; Lee, Jin Hwa; Yoo, Kwang Ha; Lee, Sang Haak; Lee, Sang Yeub; Kim, Tae-Eun; Kim, Tae-Hyung; Park, Yong Bum; Hwang, Yong Il; Kim, Young Sam; Jung, Ki Suck

2016-04-01

The Korea Chronic Obstructive Pulmonary Disorders Subgroup Study Team (Korea COPD Subgroup Study team, KOCOSS) is a multicenter observational study that includes 956 patients (mean age 69.9 ± 7.8 years) who were enrolled from 45 tertiary and university-affiliated hospitals from December 2011 to October 2014. The initial evaluation for all patients included pulmonary function tests (PFT), 6-minute walk distance (6MWD), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and the COPD-specific version of St. George's Respiratory Questionnaire (SGRQ-C). Here, we report the comparison of baseline characteristics between patients with early- (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage I and II/groups A and B) and late-stage COPD (GOLD stage III and IV/groups C and D). Among all patients, the mean post-bronchodilator FEV1 was 55.8% ± 16.7% of the predicted value, and most of the patients were in GOLD stage II (520, 56.9%) and group B (399, 42.0%). The number of exacerbations during one year prior to the first visit was significantly lower in patients with early COPD (0.4 vs. 0.9/0.1 vs. 1.2), as were the CAT score (13.9 vs. 18.3/13.5 vs. 18.1), mMRC (1.4 vs. 2.0/1.3 vs.1.9), and SGRQ-C total score (30.4 vs. 42.9/29.1 vs. 42.6) compared to late-stage COPD (all P < 0.001). Common comorbidities among all patients were hypertension (323, 37.7%), diabetes mellitus (139, 14.8%), and depression (207, 23.6%). The data from patients with early COPD will provide important information towards early detection, proper initial management, and design of future studies.

Clinical usefulness of ursodeoxycholic acid for Japanese patients with autoimmune hepatitis

PubMed Central

Torisu, Yuichi; Nakano, Masanori; Takano, Keiko; Nakagawa, Ryo; Saeki, Chisato; Hokari, Atsushi; Ishikawa, Tomohisa; Saruta, Masayuki; Zeniya, Mikio

2017-01-01

AIM To evaluate the therapeutic effects of ursodeoxycholic acid (UDCA) on autoimmune hepatitis (AIH). METHODS A total 136 patients who were diagnosed with AIH were included in our study. All of the patients underwent a liver biopsy, and had at least a probable diagnosis on the basis of either the revised scoring system or the simplified scores. Initial treatment included UDCA monotherapy (Group U, n = 48) and prednisolone (PSL) monotherapy (Group P, n = 88). Group U was further classified into two subgroups according to the effect of UDCA: Patients who had achieved remission induction with UDCA monotherapy and showed no sign of relapse (Subgroup U1, n = 34) and patients who additionally received PSL during follow-up (Subgroup U2, n = 14). We compared the clinical and histological findings between each groups, and investigated factors contributing to the response to UDCA monotherapy. RESULTS In Group U, 34 patients (71%) achieved and maintained remission over 49 (range: 8-90) mo (Subgroup U1) and 14 patients (29%) additionally received PSL (Subgroup U2) during follow-up. Two patients in Subgroup U2 achieved remission induction once but additionally required PSL administration because of relapse (15 and 35 mo after the start of treatment). The remaining 12 patients in Subgroup U2 failed to achieve remission induction during follow-up, and PSL was added during 7 (range: 2-18) mo. Compared with Subgroup U2, Subgroup U1 had significantly lower alanine aminotransferase (ALT) levels at onset (124 IU/L vs 262 IU/L, P = 0.023) and a significantly higher proportion of patients with mild inflammation (A1) on histological examination (70.6% vs 35.7%, P = 0.025). When multivariate analysis was performed to identify factors contributing to the response to UDCA monotherapy, only a serum ALT level of 200 IU/L or lower was found to be associated with a significant difference (P = 0.013). CONCLUSION To prevent adverse events related to corticosteroids, UDCA monotherapy for AIH needs

Toward a patient-centered ambulatory after-visit summary: Identifying primary care patients' information needs.

PubMed

Clarke, Martina A; Moore, Joi L; Steege, Linsey M; Koopman, Richelle J; Belden, Jeffery L; Canfield, Shannon M; Kim, Min S

2018-09-01

The purpose of this study was to determine the information needs of primary care patients as they review clinic visit notes to inform information that should be contained in an after-visit summary (AVS). We collected data from 15 patients with an acute illness and 14 patients with a chronic disease using semi-structured interviews. The acute patients reviewed seven major sections, and chronic patients reviewed eight major sections of a simulated, but realistic visit note to identify relevant information needs for their AVS. Patients in the acute illness group identified the Plan, Assessment and History of Present Illness the most as important note sections, while patients in the chronic care group identified Significant Lab Data, Plan, and Assessment the most as important note sections. This study was able to identify primary care patients' information needs after clinic visit. Primary care patients have information needs pertaining to diagnosis and treatment, which may be the reason why both patient groups identified Plan and Assessment as important note sections. Future research should also develop and assess an AVS based on the information gathered in this study and evaluate its usefulness among primary care patients. The results of this study can be used to inform the development of an after-visit summary that assists patients to fully understand their treatment plan, which may improve treatment adherence.

Divide and Conquer: Sub-Grouping of ASD Improves ASD Detection Based on Brain Morphometry.

PubMed

Katuwal, Gajendra J; Baum, Stefi A; Cahill, Nathan D; Michael, Andrew M

2016-01-01

Low success (<60%) in autism spectrum disorder (ASD) classification using brain morphometry from the large multi-site ABIDE dataset and inconsistent findings on brain morphometric abnormalities in ASD can be attributed to the ASD heterogeneity. In this study, we show that ASD brain morphometry is highly heterogeneous, and demonstrate that the heterogeneity can be mitigated and classification improved if autism severity (AS), verbal IQ (VIQ) and age are used with morphometric features. Morphometric features from structural MRIs (sMRIs) of 734 males (ASD: 361, controls: 373) of ABIDE were derived using FreeSurfer. Applying the Random Forest classifier, an AUC of 0.61 was achieved. Adding VIQ and age to morphometric features, AUC improved to 0.68. Sub-grouping the subjects by AS, VIQ and age improved the classification with the highest AUC of 0.8 in the moderate-AS sub-group (AS = 7-8). Matching subjects on age and/or VIQ in each sub-group further improved the classification with the highest AUC of 0.92 in the low AS sub-group (AS = 4-5). AUC decreased with AS and VIQ, and was the lowest in the mid-age sub-group (13-18 years). The important features were mainly from the frontal, temporal, ventricular, right hippocampal and left amygdala regions. However, they highly varied with AS, VIQ and age. The curvature and folding index features from frontal, temporal, lingual and insular regions were dominant in younger subjects suggesting their importance for early detection. When the experiments were repeated using the Gradient Boosting classifier similar results were obtained. Our findings suggest that identifying brain biomarkers in sub-groups of ASD can yield more robust and insightful results than searching across the whole spectrum. Further, it may allow identification of sub-group specific brain biomarkers that are optimized for early detection and monitoring, increasing the utility of sMRI as an important tool for early detection of ASD.

Divide and Conquer: Sub-Grouping of ASD Improves ASD Detection Based on Brain Morphometry

PubMed Central

Baum, Stefi A.; Cahill, Nathan D.; Michael, Andrew M.

2016-01-01

Low success (<60%) in autism spectrum disorder (ASD) classification using brain morphometry from the large multi-site ABIDE dataset and inconsistent findings on brain morphometric abnormalities in ASD can be attributed to the ASD heterogeneity. In this study, we show that ASD brain morphometry is highly heterogeneous, and demonstrate that the heterogeneity can be mitigated and classification improved if autism severity (AS), verbal IQ (VIQ) and age are used with morphometric features. Morphometric features from structural MRIs (sMRIs) of 734 males (ASD: 361, controls: 373) of ABIDE were derived using FreeSurfer. Applying the Random Forest classifier, an AUC of 0.61 was achieved. Adding VIQ and age to morphometric features, AUC improved to 0.68. Sub-grouping the subjects by AS, VIQ and age improved the classification with the highest AUC of 0.8 in the moderate-AS sub-group (AS = 7–8). Matching subjects on age and/or VIQ in each sub-group further improved the classification with the highest AUC of 0.92 in the low AS sub-group (AS = 4–5). AUC decreased with AS and VIQ, and was the lowest in the mid-age sub-group (13–18 years). The important features were mainly from the frontal, temporal, ventricular, right hippocampal and left amygdala regions. However, they highly varied with AS, VIQ and age. The curvature and folding index features from frontal, temporal, lingual and insular regions were dominant in younger subjects suggesting their importance for early detection. When the experiments were repeated using the Gradient Boosting classifier similar results were obtained. Our findings suggest that identifying brain biomarkers in sub-groups of ASD can yield more robust and insightful results than searching across the whole spectrum. Further, it may allow identification of sub-group specific brain biomarkers that are optimized for early detection and monitoring, increasing the utility of sMRI as an important tool for early detection of ASD. PMID:27065101

Posttraumatic Stress Disorder Post Iraq and Afghanistan: Prevalence Among Military Subgroups

PubMed Central

Hines, Lindsey A; Sundin, Josefin; Rona, Roberto J; FFPH; Wessely, Simon; FMedSci; Fear, Nicola T

2014-01-01

A large body of research has been produced in recent years investigating posttraumatic stress disorder (PTSD) among military personnel following deployment to Iraq and Afghanistan, resulting in apparent differences in PTSD prevalence. We compare prevalence estimates for current PTSD between military subgroups, providing insight into how groups may be differentially affected by deployment. Systematic literature searches using the terms PTSD, stress disorder, and acute stress, combined with terms relating to military personnel, identified 49 relevant papers. Studies with a sample size of less than 100 and studies based on data for treatment seeking or injured populations were excluded. Studies were categorized according to theatre of deployment (Iraq or Afghanistan), combat and noncombat deployed samples, sex, enlistment type (regular or reserve and [or] National Guard), and service branch (for example, army, navy, and air force). Meta-analysis was used to assess PTSD prevalence across subgroups. There was large variability in PTSD prevalence between studies, but, regardless of heterogeneity, prevalence rates of PTSD were higher among studies of Iraq-deployed personnel (12.9%; 95% CI 11.3% to 14.4%), compared with personnel deployed to Afghanistan (7.1%; 95% CI 4.6% to 9.6%), combat deployed personnel, and personnel serving in the Canadian, US, or UK army or the navy or marines (12.4%; 95% CI 10.9% to 13.4%), compared with the other services (4.9%; 95% CI 1.4% to 8.4%). Contrary to findings from within-study comparisons, we did not find a difference in PTSD prevalence for regular active-duty and reserve or National Guard personnel. Categorizing studies according to deployment location and branch of service identified differences among subgroups that provide further support for factors underlying the development of PTSD. PMID:25569079

Posttraumatic stress disorder post Iraq and Afghanistan: prevalence among military subgroups.

PubMed

Hines, Lindsey A; Sundin, Josefin; Rona, Roberto J; Wessely, Simon; Fear, Nicola T

2014-09-01

A large body of research has been produced in recent years investigating posttraumatic stress disorder (PTSD) among military personnel following deployment to Iraq and Afghanistan, resulting in apparent differences in PTSD prevalence. We compare prevalence estimates for current PTSD between military subgroups, providing insight into how groups may be differentially affected by deployment. Systematic literature searches using the terms PTSD, stress disorder, and acute stress, combined with terms relating to military personnel, identified 49 relevant papers. Studies with a sample size of less than 100 and studies based on data for treatment seeking or injured populations were excluded. Studies were categorized according to theatre of deployment (Iraq or Afghanistan), combat and noncombat deployed samples, sex, enlistment type (regular or reserve and [or] National Guard), and service branch (for example, army, navy, and air force). Meta-analysis was used to assess PTSD prevalence across subgroups. There was large variability in PTSD prevalence between studies, but, regardless of heterogeneity, prevalence rates of PTSD were higher among studies of Iraq-deployed personnel (12.9%; 95% CI 11.3% to 14.4%), compared with personnel deployed to Afghanistan (7.1%; 95% CI 4.6% to 9.6%), combat deployed personnel, and personnel serving in the Canadian, US, or UK army or the navy or marines (12.4%; 95% CI 10.9% to 13.4%), compared with the other services (4.9%; 95% CI 1.4% to 8.4%). Contrary to findings from within-study comparisons, we did not find a difference in PTSD prevalence for regular active-duty and reserve or National Guard personnel. Categorizing studies according to deployment location and branch of service identified differences among subgroups that provide further support for factors underlying the development of PTSD.

Psychological Features and Their Relationship to Movement-Based Subgroups in People Living With Low Back Pain.

PubMed

Karayannis, Nicholas V; Jull, Gwendolen A; Nicholas, Michael K; Hodges, Paul W

2018-01-01

To determine the distribution of higher psychological risk features within movement-based subgroups for people with low back pain (LBP). Cross-sectional observational study. Participants were recruited from physiotherapy clinics and community advertisements. Measures were collected at a university outpatient-based physiotherapy clinic. People (N=102) seeking treatment for LBP. Participants were subgrouped according to 3 classification schemes: Mechanical Diagnosis and Treatment (MDT), Treatment-Based Classification (TBC), and O'Sullivan Classification (OSC). Questionnaires were used to categorize low-, medium-, and high-risk features based on depression, anxiety, and stress (Depression, Anxiety, and Stress Scale-21 Items); fear avoidance (Fear-Avoidance Beliefs Questionnaire); catastrophizing and coping (Pain-Related Self-Symptoms Scale); and self-efficacy (Pain Self-Efficacy Questionnaire). Psychological risk profiles were compared between movement-based subgroups within each scheme. Scores across all questionnaires revealed that most patients had low psychological risk profiles, but there were instances of higher (range, 1%-25%) risk profiles within questionnaire components. The small proportion of individuals with higher psychological risk scores were distributed between subgroups across TBC, MDT, and OSC schemes. Movement-based subgrouping alone cannot inform on individuals with higher psychological risk features. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

PubMed

Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

2017-02-01

Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas

Effects of internet-based cognitive behavioural therapy and physical exercise on sick leave and employment in primary care patients with depression: two subgroup analyses.

PubMed

Kaldo, Viktor; Lundin, Andreas; Hallgren, Mats; Kraepelien, Martin; Strid, Catharina; Ekblom, Örjan; Lavebratt, Catharina; Lindefors, Nils; Öjehagen, Agneta; Forsell, Yvonne

2018-01-01

Depression can negatively impact work capacity, but treatment effects on sick leave and employment are unclear. This study evaluates if internet-based cognitive behavioural therapy (ICBT) or physical exercise (PE), with already reported positive effects on clinical outcome and short-term work ability, has better effects on employment, sick leave and long-term work ability compared with treatment as usual (TAU) for depressed primary care patients (German clinical trials: DRKS00008745). After randomisation and exclusion of patients not relevant for work-related analysis, patients were divided into two subgroups: initially unemployed (total n=118) evaluated on employment, and employed (total n=703) evaluated on long-term sick leave. Secondary outcomes were self-rated work ability and average number of sick days per month evaluated for both subgroups. Assessments (self-reports) were made at baseline and follow-up at 3 and 12 months. For the initially unemployed subgroup, 52.6% were employed after 1 year (response rate 82%). Both PE (risk ratio (RR)=0.44; 95% CI 0.23 to 0.87) and ICBT (RR=0.37; 95% CI 0.16 to 0.84) showed lower rates compared with TAU after 3 months, but no difference was found after 1 year (PE: RR=0.97; 95% CI 0.69 to 1.57; ICBT: RR=1.23; 95% CI 0.72 to 2.13). For those with initial employment, long-term sick leave (response rate 75%) decreased from 7.8% to 6.5%, but neither PE (RR=1.4; 95% CI 0.52 to 3.74) nor ICBT (RR=0.99; 95% CI 0.39 to 2.46) decreased more than TAU, although a temporary positive effect for PE was found. All groups increased self-rated work ability with no differences found. No long-term effects were found for the initially unemployed on employment status or for the initially employed on sick leave. New types of interventions need to be explored. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly

Exploring the cost-utility of stratified primary care management for low back pain compared with current best practice within risk-defined subgroups.

PubMed

Whitehurst, David G T; Bryan, Stirling; Lewis, Martyn; Hill, Jonathan; Hay, Elaine M

2012-11-01

Stratified management for low back pain according to patients' prognosis and matched care pathways has been shown to be an effective treatment approach in primary care. The aim of this within-trial study was to determine the economic implications of providing such an intervention, compared with non-stratified current best practice, within specific risk-defined subgroups (low-risk, medium-risk and high-risk). Within a cost-utility framework, the base-case analysis estimated the incremental healthcare cost per additional quality-adjusted life year (QALY), using the EQ-5D to generate QALYs, for each risk-defined subgroup. Uncertainty was explored with cost-utility planes and acceptability curves. Sensitivity analyses were performed to consider alternative costing methodologies, including the assessment of societal loss relating to work absence and the incorporation of generic (ie, non-back pain) healthcare utilisation. The stratified management approach was a cost-effective treatment strategy compared with current best practice within each risk-defined subgroup, exhibiting dominance (greater benefit and lower costs) for medium-risk patients and acceptable incremental cost to utility ratios for low-risk and high-risk patients. The likelihood that stratified care provides a cost-effective use of resources exceeds 90% at willingness-to-pay thresholds of £4000 (≈ 4500; $6500) per additional QALY for the medium-risk and high-risk groups. Patients receiving stratified care also reported fewer back pain-related days off work in all three subgroups. Compared with current best practice, stratified primary care management for low back pain provides a highly cost-effective use of resources across all risk-defined subgroups.

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.

Serological analysis of the subgroup protein of rotavirus, using monoclonal antibodies.

PubMed Central

Greenberg, H; McAuliffe, V; Valdesuso, J; Wyatt, R; Flores, J; Kalica, A; Hoshino, Y; Singh, N

1983-01-01

Ten monoclones directed to the 42,000-dalton inner structural protein of rotavirus were analyzed. Eight monoclones reacted broadly with antigenic domains common to virtually all mammalian rotaviruses. Two monoclones had specificities similar or identical to previously characterized subgroup specificities. These subgroup monoclones were more efficient in detecting subgroup antigen than either hyperimmune or postinfection antisera. Using the subgroup monoclones, we determined that some animal as well as human rotavirus strains carry subgroup 2 specificity and that epizootic diarrhea of infant mice virus and turkey rotavirus are antigenically distinct from other mammalian rotavirus strains. Images PMID:6185436

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

A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole

PubMed Central

2010-01-01

Background Aromatase (CYP19A1) regulates estrogen biosynthesis. Polymorphisms in CYP19A1 have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of CYP19A1 and their effect on response to neoadjuvant letrozole in early BC. Methods We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4th month by World Health Organization (WHO) criteria. Three polymorphisms of CYP19A1, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood. Results Thirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009). Conclusions Our study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients. PMID:20144226

Is Pain Intensity Really That Important to Assess in Chronic Pain Patients? A Study Based on the Swedish Quality Registry for Pain Rehabilitation (SQRP)

PubMed Central

Bromley Milton, Maria; Börsbo, Björn; Rovner, Graciela; Lundgren-Nilsson, Åsa; Stibrant-Sunnerhagen, Katharina; Gerdle, Björn

2013-01-01

Background Incorporating the patient's view on care and treatment has become increasingly important for health care. Patients describe the variety of consequences of their chronic pain conditions as significant pain intensity, depression, and anxiety. We hypothesised that intensities of common symptoms in chronic pain conditions carry important information that can be used to identify clinically relevant subgroups. This study has three aims: 1) to determine the importance of different symptoms with respect to participation and ill-health; 2) to identify subgroups based on data concerning important symptoms; and 3) to determine the secondary consequences for the identified subgroups with respect to participation and health factors. Methods and Subjects This study is based on a cohort of patients referred to a multidisciplinary pain centre at a university hospital (n = 4645, participation rate 88%) in Sweden. The patients answered a number of questionnaires concerning symptoms, participation, and health aspects as a part of the Swedish Quality Registry for Pain Rehabilitation (SQRP). Results Common symptoms (such as pain intensity, depression, and anxiety) in patients with chronic pain showed great variability across subjects and 60% of the cohort had normal values with respect to depressive and anxiety symptoms. Pain intensity more than psychological symptoms showed stronger relationships with participation and health. It was possible to identify subgroups based on pain intensity, depression, and anxiety. With respect to participation and health, high depressive symptomatology had greater negative consequences than high anxiety. Conclusions Common symptoms (such as pain intensity and depressive and anxiety symptoms) in chronic pain conditions carry important information that can be used to identify clinically relevant subgroups. PMID:23805183

Cytokine profiling identifies an interaction of IL-6 and IL-1α to drive PSMA-PSA prostate clones.

PubMed

Jemaa, Awatef Ben; Bouraoui, Yosra; Rais, Nawfel Ben; Nouira, Yassine; Oueslati, Ridha

2016-12-01

Several PSMA-PSA prostate clones have been identified during prostate cancer progression; however, until now, their in situ inflammatory characteristics have remained unclear. We therefore investigated the interplay between proinflammatory cytokines and (PSMA,PSA) sub-groups. 27 benign prostate hyperplasia (BPH) and 18 prostate cancers (PC) were enrolled in this study. Immunohistochemical analysis was performed. Serum levels of PSA were assayed by Immulite autoanalyser. In BPH and PC patients with elevated serum PSA levels, IL-1α was the most proinflammatory cytokine expressed in (PSMA+,PSA-) subgroup. However, most samples of (PSMA+,PSA+) subgroup had positive immunoreaction to IL-6. In samples of PC with PSA serum levels of 4-20ng/mL or >20ng/mL, immunoreaction to TNF-α was seen only in (PSMA+,PSA+) subgroup. Interestingly, several combinations of proinflammatory cytokines (IL-6, IL-1α and TNF-α) showed that coexpression of tissue PSMA and PSA was concomitant with high immunoreactions to (IL-6+,TNF-α-), (IL-6+,IL-1α+) and (IL-1α+,TNFα-) in BPH and PC patients. (PSMA,PSA) subgroup lacking tissue PSA expression showed a high immunoexpression of the profile (IL-6+,TNF-α-). The combinations of (IL-6-, TNF-α-) and (IL-6-, IL-1α-) were absent in (PSMA+,PSA-) and (PSMA+,PSA+) BPH sub-groups. Collectively, these findings underscore the importance of TNF-α and highlight the interaction between IL-6 and IL-1α to generate an inflammatory microenvironment in driving (PSMA,PSA) prostate clones. Copyright © 2016 Elsevier GmbH. All rights reserved.

Evaluation of anterior third of superior sagittal sinus in normal population: Identifying the subgroup with dominant drainage.

PubMed

Sahoo, Sushanta K; Ghuman, Mandeep S; Salunke, Pravin; Vyas, Sameer; Bhar, Rahat; Khandelwal, N K

2016-01-01

The ligation and transection of anterior third of superior sagittal sinus (AT-SSS) is an important step to approach anterior skull base lesions. Some clinical studies have shown frontal lobe venous infarct following such surgical procedures questioning the safety of its ligation. We have studied the variations in venous drainage patterns to AT-SSS in the normal population using postcontrast magnetic resonance venogram (MRV). A novel scoring system to recognize the subgroup with dominant venous drainage from frontal lobes has been described. In this study, 60 three-dimensional contrast-enhanced (CE) MRVs were obtained from those cases being evaluated for a headache not harboring any intracranial mass lesion. The AT-SSS with all its draining veins was studied in detail. Morphology of individual veins such as length, caliber, tributaries, and angulation with AT-SSS was studied, and a numerical value of 0 or 1 was assigned for each of the above parameters. Summing up these scores derived from the individual cortical veins quantified the drainage of AT-SSS. There are 3-4 veins on either side draining to AT-SSS. Barely, 3% of the veins had > 3 tributaries. Only 6.6% of veins had a caliber >3 mm, and 16.5% drained at acute angles to AT-SSS. About 26% of the veins did cross at least half of the lateral frontal lobe. We found in 26 individuals the AT-SSS score was 0-2, in 22 it was 3-5 and, in only in 12 (20%) the score was 6 or more (dominant drainage). There are anatomical variations in venous drainage of frontal lobes into AT-SSS. Those with dominant drainage are likely to develop venous congestion and complications if sacrificed. It is possible to identify these individuals on the basis of venous drainage pattern as shown in CE-MRV.

[The psychosocial status of patients with endogenous eczema. A study using cluster analysis for the correlation of psychological factors with somatic findings].

PubMed

Gieler, U; Ehlers, A; Höhler, T; Burkard, G

1990-08-01

The present study was performed to investigate whether patients with atopic dermatitis differ as a group from controls on psychological measures of mood and personality or whether psychologically deviant and normal patient subgroups can be distinguished. Furthermore, we were interested in what clinical characteristics might co-vary with psychological disability in patients with atopic dermatitis. In all, 93 patients filled in a standardized mood scale (Hamburg-Erlanger-Stimmungsbarometer) and a personality scale (Kurztest zur Erfassung der Persönlichkeitsstruktur). Compared with matched controls, patients described themselves as being more anxious, more aroused, more depressed and less energetic, and they reached higher neuroticism scores. A cluster analysis identified four patient subgroups. Only one of the subgroups (n = 17) was psychologically disabled according to the questionnaire scores. In contrast to a psychologically stabile patient group, the psychologically disabled patients showed an earlier age of onset of dermatitis, but less intense itching and scratching. They reported more somatic complaints and a higher level of familial stress, were more dissatisfied with their life situation and work, had fewer friends and experienced more losses of significant others. Furthermore, they more frequently rated their disorder as being determined by psychological factors and were more intelligent. Thus, the questionnaires identified a subgroup of patients who may need psychotherapeutic interventions.

Subgroup conflicts? Try the psychodramatic "double triad method".

PubMed

Verhofstadt-Denève, Leni M F

2012-04-01

The present article suggests the application of a psychodramatic action method for tackling subgroup conflicts in which the direct dialogue between representatives of two opposing subgroups is prepared step by step through an indirect dialogue strategy within two triads, a strategy known as the Double Triad Method (DTM). In order to achieve integration in the group as a whole, it is important that all the members of both subgroups participate actively during the entire process. The first part of the article briefly explores the theoretical background, with a special emphasis on the Phenomenological-Dialectical Personality Model (Phe-Di PModel). In the second part, the DTM procedure is systematically described through its five action stages, each accompanied with 1) a spatial representation of the consecutive actions, 2) some illustrative statements for each stage, and 3) a theoretical interpretation of the dialectically involved personality dimensions in both protagonists. The article concludes with a discussion and suggestions for more extensive applications of the DTM method, including the question of its relationships to Agazarian's functional subgrouping, psychodrama, and sociodrama.

Subgroup Achievement and Gap Trends: New Hampshire, 2010

ERIC Educational Resources Information Center

Center on Education Policy, 2010

2010-01-01

This paper profiles the student subgroup achievement and gap trends in New Hampshire for 2010. New Hampshire's demographic profile is such that, with the exception of Latino students at the elementary level, there are fewer than 500 students in the racial/ethnic subgroups at the various grade levels, and therefore these groups are too small to…

Variability in the impairment of recognition memory in patients with frontal lobe lesions.

PubMed

Bastin, Christine; Van der Linden, Martial; Lekeu, Françoise; Andrés, Pilar; Salmon, Eric

2006-10-01

Fourteen patients with frontal lobe lesions and 14 normal subjects were tested on a recognition memory task that required discriminating between target words, new words that are synonyms of the targets and unrelated distractors. A deficit was found in 12 of the patients. Moreover, three different patterns of recognition impairment were identified: (I) poor memory for targets, (II) normal hits but increased false recognitions for both types of distractors, (III) normal hit rates, but increased false recognitions for synonyms only. Differences in terms of location of the damage and behavioral characteristics between these subgroups were examined. An encoding deficit was proposed to explain the performance of patients in subgroup I. The behavioral patterns of the patients in subgroups II and III could be interpreted as deficient post-retrieval verification processes and an inability to recollect item-specific information, respectively.

Association between obesity and cardiometabolic health risk in Asian-Canadian sub-groups.

PubMed

Nie, Jason X; Ardern, Chris I

2014-01-01

To quantify and compare the association between the World Health Organizations' Asian-specific trigger points for public health action ['increased risk': body mass index (BMI) ≥23 kg/m2, and; 'high risk': BMI ≥27.5 kg/m2] with self-reported cardiovascular-related conditions in Asian-Canadian sub-groups. Six cycles of the Canadian Community Health Survey (2001-2009) were pooled to examine BMI and health in Asian sub-groups (South Asians, Chinese, Filipino, Southeast Asians, Arabs, West Asians, Japanese and Korean; N = 18 794 participants, ages 18-64 y). Multivariable logistic regression, adjusting for demographic, lifestyle characteristics and acculturation measures, was used to estimate the odds of cardiovascular-related health (high blood pressure, heart disease, diabetes, 'at least one cardiometabolic condition') outcomes across all eight Asian sub-groups. Compared to South Asians (OR = 1.00), Filipinos had higher odds of having 'at least one cardiometabolic condition' (OR = 1.29, 95% CI: 1.04-1.62), whereas Chinese (0.63, 0.474-0.9) and Arab-Canadians had lower odds (0.38, 0.28-0.51). In ethnic-specific analyses (with 'acceptable' risk weight as the referent), 'increased' and 'high' risk weight categories were the most highly associated with 'at least one cardiometabolic condition' in Chinese ('increased': 3.6, 2.34-5.63; 'high': 8.9, 3.6-22.01). Compared to normal weight South Asians, being in the 'high' risk weight category in all but the Southeast Asian, Arab, and Japanese ethnic groups was associated with approximately 3-times the likelihood of having 'at least one cardiometabolic condition'. Differences in the association between obesity and cardiometabolic health risks were seen among Asian sub-groups in Canada. The use of WHO's lowered Asian-specific BMI cut-offs identified obesity-related risks in South Asian, Filipino and Chinese sub-groups that would have been masked by traditional BMI categories. These findings have implications for

Gait disorders in the elderly and dual task gait analysis: a new approach for identifying motor phenotypes.

PubMed

Auvinet, Bernard; Touzard, Claude; Montestruc, François; Delafond, Arnaud; Goeb, Vincent

2017-01-31

Gait disorders and gait analysis under single and dual-task conditions are topics of great interest, but very few studies have looked for the relevance of gait analysis under dual-task conditions in elderly people on the basis of a clinical approach. An observational study including 103 patients (mean age 76.3 ± 7.2, women 56%) suffering from gait disorders or memory impairment was conducted. Gait analysis under dual-task conditions was carried out for all patients. Brain MRI was performed in the absence of contra-indications. Three main gait variables were measured: walking speed, stride frequency, and stride regularity. For each gait variable, the dual task cost was computed and a quartile analysis was obtained. Nonparametric tests were used for all the comparisons (Wilcoxon, Kruskal-Wallis, Fisher or Chi 2 tests). Four clinical subgroups were identified: gait instability (45%), recurrent falls (29%), memory impairment (18%), and cautious gait (8%). The biomechanical severity of these subgroups was ordered according to walking speed and stride regularity under both conditions, from least to most serious as follows: memory impairment, gait instability, recurrent falls, cautious gait (p < 0.01 for walking speed, p = 0.05 for stride regularity). According to the established diagnoses of gait disorders, 5 main pathological subgroups were identified (musculoskeletal diseases (n = 11), vestibular diseases (n = 6), mild cognitive impairment (n = 24), central nervous system pathologies, (n = 51), and without diagnosis (n = 8)). The dual task cost for walking speed, stride frequency and stride regularity were different among these subgroups (p < 0.01). The subgroups mild cognitive impairment and central nervous system pathologies both showed together a higher dual task cost for each variable compared to the other subgroups combined (p = 0.01). The quartile analysis of dual task cost for stride frequency and stride regularity

Criteria for phytoplasma 16Sr group/subgroup delineation and the need of a platform for proper registration of new groups and subgroups

USDA-ARS?s Scientific Manuscript database

As more phytoplasmas are discovered in emerging and re-emerging plant diseases worldwide, the scheme for classification of phytoplasmas into 16S rRNA gene RFLP (16Sr) groups and subgroups is experiencing an ongoing rapid expansion. Improper delineation or designation of new groups and subgroups can...

Data mining model using simple and readily available factors could identify patients at high risk for hepatocellular carcinoma in chronic hepatitis C.

PubMed

Kurosaki, Masayuki; Hiramatsu, Naoki; Sakamoto, Minoru; Suzuki, Yoshiyuki; Iwasaki, Manabu; Tamori, Akihiro; Matsuura, Kentaro; Kakinuma, Sei; Sugauchi, Fuminaka; Sakamoto, Naoya; Nakagawa, Mina; Izumi, Namiki

2012-03-01

Assessment of the risk of hepatocellular carcinoma (HCC) development is essential for formulating personalized surveillance or antiviral treatment plan for chronic hepatitis C. We aimed to build a simple model for the identification of patients at high risk of developing HCC. Chronic hepatitis C patients followed for at least 5 years (n=1003) were analyzed by data mining to build a predictive model for HCC development. The model was externally validated using a cohort of 1072 patients (472 with sustained virological response (SVR) and 600 with nonSVR to PEG-interferon plus ribavirin therapy). On the basis of factors such as age, platelet, albumin, and aspartate aminotransferase, the HCC risk prediction model identified subgroups with high-, intermediate-, and low-risk of HCC with a 5-year HCC development rate of 20.9%, 6.3-7.3%, and 0-1.5%, respectively. The reproducibility of the model was confirmed through external validation (r(2)=0.981). The 10-year HCC development rate was also significantly higher in the high-and intermediate-risk group than in the low-risk group (24.5% vs. 4.8%; p<0.0001). In the high-and intermediate-risk group, the incidence of HCC development was significantly reduced in patients with SVR compared to those with nonSVR (5-year rate, 9.5% vs. 4.5%; p=0.040). The HCC risk prediction model uses simple and readily available factors and identifies patients at a high risk of HCC development. The model allows physicians to identify patients requiring HCC surveillance and those who benefit from IFN therapy to prevent HCC. Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Autoimmune-autoinflammatory rheumatoid arthritis overlaps: a rare but potentially important subgroup of diseases.

PubMed

Savic, Sinisa; Mistry, Anoop; Wilson, Anthony G; Barcenas-Morales, Gabriela; Doffinger, Rainer; Emery, Paul; McGonagle, Dennis

2017-01-01

At the population level, rheumatoid arthritis (RA) is generally viewed as autoimmune in nature with a small subgroup of cases having a palindromic form or systemic autoinflammatory disorder (SAID) phenotype. Herein, we describe resistant cases of classical autoantibody associated RA that had clinical, genetic and therapeutic responses indicative of coexistent autoinflammatory disease. Five patients with clinically overlapping features between RA and SAID including polysynovitis and autoantibody/shared epitope positivity, and who had abrupt severe self-limiting attacks including fevers and serositis, are described. Mutations or single nucleotide polymorphisms in recognised autoinflammatory pathways were evident. Generally, these cases responded poorly to conventional Disease-modifying anti-rheumatic drugs (DMARD) treatment with some excellent responses to colchicine or interleukin 1 pathway blockade. A subgroup of RA cases have a mixed autoimmune-autoinflammatory phenotype and genotype with therapeutic implications.

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.

Progression-free survival results in postmenopausal Asian women: subgroup analysis from a phase III randomized trial of fulvestrant 500 mg vs anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON).

PubMed

Noguchi, Shinzaburo; Ellis, Matthew J; Robertson, John F R; Thirlwell, Jackie; Fazal, Mehdi; Shao, Zhimin

2018-05-01

The international, phase III FALCON study (NCT01602380) in postmenopausal patients with hormone receptor-positive, locally advanced/metastatic breast cancer (LA/MBC) who had not received prior endocrine therapy, demonstrated statistically significant improvement in progression-free survival (PFS) for patients who received fulvestrant 500 mg vs anastrozole 1 mg. This subgroup analysis evaluated PFS in Asian (randomized in China, Japan, or Taiwan) and non-Asian patients from the FALCON study. Eligible patients (estrogen receptor- and/or progesterone receptor-positive LA/MBC; World Health Organization performance status 0-2; ≥ 1 measurable/non-measurable lesion[s]) were randomized. PFS was assessed via Response Evaluation Criteria in Solid Tumours version 1.1, surgery/radiotherapy for disease worsening, or death (any cause). Secondary endpoints included: objective response rate, clinical benefit rate, duration of response, and duration of clinical benefit. Consistency of effect across subgroups was assessed via hazard ratios and 95% confidence intervals (CIs) using a log-rank test. Adverse events (AEs) were evaluated. Of the 462 randomized patients, the Asian and non-Asian subgroups comprised 67 and 395 patients, respectively. In the Asian subgroup, median PFS was 16.6 and 15.9 months with fulvestrant and anastrozole, respectively (hazard ratio 0.81; 95% CI 0.44-1.50). In the non-Asian subgroup, median PFS was 16.5 and 13.8 months, respectively (hazard ratio 0.79; 95% CI 0.62-1.01). Secondary outcomes were numerically improved with fulvestrant vs anastrozole in both subgroups. AE profiles were generally consistent between Asian and non-Asian subgroups. Results of this subgroup analysis suggest that treatment effects in the Asian patient subgroup are broadly consistent with the non-Asian population.

Healthcare costs in psoriasis and psoriasis sub-groups over time following psoriasis diagnosis.

PubMed

Al Sawah, Sarah; Foster, Shonda A; Goldblum, Orin M; Malatestinic, William N; Zhu, Baojin; Shi, Nianwen; Song, Xue; Feldman, Steven R

2017-09-01

To quantify healthcare costs in patients with psoriasis overall and in psoriasis patient sub-groups, by level of disease severity, presence or absence of psoriatic arthritis, or use of biologics. Administrative data from Truven Health Analytics MarketScan Research Database were used to select adult patients with psoriasis from January 2009 to January 2014. The first psoriasis diagnosis was set as the index date. Patients were required to have ≥6 months of continuous enrollment with medical and pharmacy benefits pre-index and ≥12 months post-index. Patients were followed from index until the earliest of loss to follow-up or study end. All-cause healthcare costs and outpatient pharmacy costs were calculated for the overall psoriasis cohort and for the six different psoriasis patient sub-groups: (a) patients with moderate-to-severe disease and mild disease, (b) patients with psoriatic arthritis and those without, and (c) patients on biologics and those who are not. Costs are presented per-patient-per-year (PPPY) and by years 1, 2, 3, 4, and 5 of follow-up, expressed in 2014 US dollars. A total of 108,790 psoriasis patients were selected, with a mean age of 46.0 years (52.7% females). Average follow-up was 962 days. All-cause healthcare costs were $12,523 PPPY. Outpatient pharmacy costs accounted for 38.6% of total costs. All-cause healthcare costs were highest for patients on biologics ($29,832), then for patients with psoriatic arthritis ($23,427) and those with moderate-to-severe disease ($21,481). Overall, all-cause healthcare costs and outpatient pharmacy costs presented an upward trend over a 5-year period. Psoriasis is associated with significant economic burden, which increases over time as the disease progresses. Patients with moderate-to-severe psoriasis, those with psoriatic arthritis, or use of biologics contributes to higher healthcare costs. Psoriasis-related pharmacy expenditure is the largest driver of healthcare costs in patients with psoriasis.

Relating plaque morphology to respiratory syncytial virus subgroup, viral load, and disease severity in children.

PubMed

Kim, Young-In; Murphy, Ryan; Majumdar, Sirshendu; Harrison, Lisa G; Aitken, Jody; DeVincenzo, John P

2015-10-01

Viral culture plaque morphology in human cell lines are markers for growth capability and cytopathic effect, and have been used to assess viral fitness and select preattenuation candidates for live viral vaccines. We classified respiratory syncytial virus (RSV) plaque morphology and analyzed the relationship between plaque morphology as compared to subgroup, viral load and clinical severity of infection in infants and children. We obtained respiratory secretions from 149 RSV-infected children. Plaque morphology and viral load was assessed within the first culture passage in HEp-2 cells. Viral load was measured by polymerase chain reaction (PCR), as was RSV subgroup. Disease severity was determined by hospitalization, length of stay, intensive care requirement, and respiratory failure. Plaque morphology varied between individual subjects; however, similar results were observed among viruses collected from upper and lower respiratory tracts of the same subject. Significant differences in plaque morphology were observed between RSV subgroups. No correlations were found among plaque morphology and viral load. Plaque morphology did not correlate with disease severity. Plaque morphology measures parameters that are viral-specific and independent of the human host. Morphologies vary between patients and are related to RSV subgroup. In HEp-2 cells, RSV plaque morphology appears unrelated to disease severity in RSV-infected children.

Against the odds: what to expect in rehabilitation of chronic spinal cord injury with a neurologically controlled Hybrid Assistive Limb exoskeleton. A subgroup analysis of 55 patients according to age and lesion level.

PubMed

Grasmücke, Dennis; Zieriacks, Amrei; Jansen, Oliver; Fisahn, Christian; Sczesny-Kaiser, Matthias; Wessling, Martin; Meindl, Renate C; Schildhauer, Thomas A; Aach, Mirko

2017-05-01

Objective Age and lesion level are believed to represent outcome predictors in rehabilitation of patients with chronic spinal cord injury (SCI). The Hybrid Assistive Limb (HAL) exoskeleton enables patients to perform a voluntary controlled gait pattern via an electromyography-triggered neuromuscular feedback system, and has been introduced as a temporary gait training tool in patients with SCI. The aim of this prospective pre- and postintervention study was to examine functional outcomes as a function of age and lesion level in patients with chronic incomplete SCI (iSCI) or chronic complete SCI (cSCI) with zones of partial preservation (ZPP) by using the HAL as a temporary training tool. Methods Fifty-five participants with chronic iSCI or cSCI (mean time since injury 6.85 ± 5.12 years) were classified according to the American Spinal Injury Association (ASIA) Impairment Scale (AIS) and divided by age (< 50 or ≥ 50 years), independent of lesion level, and also into 4 homogeneous groups according to lesion level. The subgroups were as follows: Subgroup 1, tetraplegic iSCI (n = 13) (C2-8, AIS C [n = 8] and AIS D [n = 5]); Subgroup 2, paraplegic iSCI with spastic motor behavior (n = 15) (T2-12, AIS C [n = 8] and AIS D [n = 7]); Subgroup 3, paraplegic cSCI with complete motor paraplegia and absence of spastic motor behavior (n = 18) (T11-L4 [AIS A], and ZPP from L-3 to S-1); and Subgroup 4, paraplegic iSCI with absence of spastic motor behavior (n = 9) (T12-L3, AIS C [n = 8] and AIS D [n = 1]). The training paradigm consisted of 12 weeks of HAL-assisted treadmill training (5 times/week). Baseline status was documented prior to intervention by using the AIS grade, Walking Index for SCI II (WISCI II) score, the 10-meter walk test (10MWT), and the 6-minute walk test (6MinWT). Training effects were assessed after 6 and 12 weeks of therapy, without HAL assistance. Results Overall, a time reduction of 47% in the 10MWT, self-selected speed (10MWTsss) (< 50 years = 56% vs �

When Is the Story in the Subgroups? Strategies for Interpreting and Reporting Intervention Effects on Subgroups. MDRC Working Papers on Research Methodology

ERIC Educational Resources Information Center

Bloom, Howard S.; Michalopoulos, Charles

2010-01-01

This paper examines strategies for interpreting and reporting estimates of intervention effects for subgroups of a study sample. Specifically, the paper considers: why and how subgroup findings are important for applied research, the importance of pre-specifying sub- groups before analyses are conducted, the importance of using existing theory and…

[Comparative data of prokinetics in treatment of gastroesophageal reflux disease in patients with diabetes].

PubMed

Fedorchenko, Iu L

2013-01-01

The purpose is to evaluate the effectiveness of itopride (IP) and domperidone (DP) in the treatment of patients with gastroesophageal reflux disease (GERD), in combination with diabetes mellitus (DM) type 1 and 2. 40 patients were examined with GERD and type 1 diabetes and 50 patients with GERD and type 2 diabetes. Each group of patients with GERD, DM 1 and 2 has been divided into: the basic subgroup receiving IG 50 mg 3 tid and control--DP 10 mg tid. Patients were also administered omeprazole. Both subgroups were strictly randomized to key indicators, except for therapy. Baseline and after 2 and 4 weeks, all patients were examined to identify complaints, endoscopy and pH-metric changes, gastric motility was studied by electrogastroenterographic method (PEGEG). In the subgroups of patients with GERD + DM 1 and GERD + DM 2, received treatment with IG complaints on heartburn, regurgitation, odynophagia relieved significantly earlier then in the subgroups treated with DP. After 4 weeks of therapy, decreasing in the number of gastroesophageal refluxes, number of patients with erosive esophagitis B level, and normalization of the motility of the stomach were significantly higher in the groups of GERD + DM 1 and GERD + DM 2 received treatment with IG when compared with the subgroup of PD. There were no side effects of prokinetics. IG was more effective then DP in the treatment of GERD in patients with diabetes, and may be recommended for inclusion in the scheme of treatment of this comorbidity.

Anatomic and Physiologic Heterogeneity of Subgroup-A Auditory Sensory Neurons in Fruit Flies.

PubMed

Ishikawa, Yuki; Okamoto, Natsuki; Nakamura, Mizuki; Kim, Hyunsoo; Kamikouchi, Azusa

2017-01-01

The antennal ear of the fruit fly detects acoustic signals in intraspecific communication, such as the courtship song and agonistic sounds. Among the five subgroups of mechanosensory neurons in the fly ear, subgroup-A neurons respond maximally to vibrations over a wide frequency range between 100 and 1,200 Hz. The functional organization of the neural circuit comprised of subgroup-A neurons, however, remains largely unknown. In the present study, we used 11 GAL4 strains that selectively label subgroup-A neurons and explored the diversity of subgroup-A neurons by combining single-cell anatomic analysis and Ca 2+ imaging. Our findings indicate that the subgroup-A neurons that project into various combinations of subareas in the brain are more anatomically diverse than previously described. Subgroup-A neurons were also physiologically diverse, and some types were tuned to a narrow frequency range, suggesting that the response of subgroup-A neurons to sounds of a wide frequency range is due to the existence of several types of subgroup-A neurons. Further, we found that an auditory behavioral response to the courtship song of flies was attenuated when most subgroup-A neurons were silenced. Together, these findings characterize the heterogeneous functional organization of subgroup-A neurons, which might facilitate species-specific acoustic signal detection.

Anatomic and Physiologic Heterogeneity of Subgroup-A Auditory Sensory Neurons in Fruit Flies

PubMed Central

Ishikawa, Yuki; Okamoto, Natsuki; Nakamura, Mizuki; Kim, Hyunsoo; Kamikouchi, Azusa

2017-01-01

The antennal ear of the fruit fly detects acoustic signals in intraspecific communication, such as the courtship song and agonistic sounds. Among the five subgroups of mechanosensory neurons in the fly ear, subgroup-A neurons respond maximally to vibrations over a wide frequency range between 100 and 1,200 Hz. The functional organization of the neural circuit comprised of subgroup-A neurons, however, remains largely unknown. In the present study, we used 11 GAL4 strains that selectively label subgroup-A neurons and explored the diversity of subgroup-A neurons by combining single-cell anatomic analysis and Ca2+ imaging. Our findings indicate that the subgroup-A neurons that project into various combinations of subareas in the brain are more anatomically diverse than previously described. Subgroup-A neurons were also physiologically diverse, and some types were tuned to a narrow frequency range, suggesting that the response of subgroup-A neurons to sounds of a wide frequency range is due to the existence of several types of subgroup-A neurons. Further, we found that an auditory behavioral response to the courtship song of flies was attenuated when most subgroup-A neurons were silenced. Together, these findings characterize the heterogeneous functional organization of subgroup-A neurons, which might facilitate species-specific acoustic signal detection. PMID:28701929

Pain Sensitivity Subgroups in Individuals With Spine Pain: Potential Relevance to Short-Term Clinical Outcome

PubMed Central

Bialosky, Joel E.; Robinson, Michael E.

2014-01-01

Background Cluster analysis can be used to identify individuals similar in profile based on response to multiple pain sensitivity measures. There are limited investigations into how empirically derived pain sensitivity subgroups influence clinical outcomes for individuals with spine pain. Objective The purposes of this study were: (1) to investigate empirically derived subgroups based on pressure and thermal pain sensitivity in individuals with spine pain and (2) to examine subgroup influence on 2-week clinical pain intensity and disability outcomes. Design A secondary analysis of data from 2 randomized trials was conducted. Methods Baseline and 2-week outcome data from 157 participants with low back pain (n=110) and neck pain (n=47) were examined. Participants completed demographic, psychological, and clinical information and were assessed using pain sensitivity protocols, including pressure (suprathreshold pressure pain) and thermal pain sensitivity (thermal heat threshold and tolerance, suprathreshold heat pain, temporal summation). A hierarchical agglomerative cluster analysis was used to create subgroups based on pain sensitivity responses. Differences in data for baseline variables, clinical pain intensity, and disability were examined. Results Three pain sensitivity cluster groups were derived: low pain sensitivity, high thermal static sensitivity, and high pressure and thermal dynamic sensitivity. There were differences in the proportion of individuals meeting a 30% change in pain intensity, where fewer individuals within the high pressure and thermal dynamic sensitivity group (adjusted odds ratio=0.3; 95% confidence interval=0.1, 0.8) achieved successful outcomes. Limitations Only 2-week outcomes are reported. Conclusions Distinct pain sensitivity cluster groups for individuals with spine pain were identified, with the high pressure and thermal dynamic sensitivity group showing worse clinical outcome for pain intensity. Future studies should aim to confirm

Association of Inflammatory Cytokines With the Symptom Cluster of Pain, Fatigue, Depression, and Sleep Disturbance in Chinese Patients With Cancer.

PubMed

Ji, Yan-Bo; Bo, Chun-Lu; Xue, Xiu-Juan; Weng, En-Ming; Gao, Guang-Chao; Dai, Bei-Bei; Ding, Kai-Wen; Xu, Cui-Ping

2017-12-01

Pain, fatigue, depression, and sleep disturbance are common in patients with cancer and usually co-occur as a symptom cluster. However, the mechanism underlying this symptom cluster is unclear. This study aimed to identify subgroups of cluster symptoms, compare demographic and clinical characteristics between subgroups, and examine the associations between inflammatory cytokines and cluster symptoms. Participants were 170 Chinese inpatients with cancer from two tertiary hospitals. Inflammatory markers including interleukin-6 (IL-6), interleukin-1 receptor antagonist, and tumor necrosis factor alpha were measured. Intergroup differences and associations of inflammatory cytokines with the cluster symptoms were examined with one-way analyses of variance and logistic regression. Based on cluster analysis, participants were categorized into Subgroup 1 (all low symptoms), Subgroup 2 (low pain and moderate fatigue), or Subgroup 3 (moderate-to-high on all symptoms). The three subgroups differed significantly in Eastern Cooperative Oncology Group (ECOG) performance status, sex, residence, current treatment, education, economic status, and inflammatory cytokines levels (all P < 0.05). Compared with Subgroup 1, Subgroup 3 had a significantly poorer ECOG physical performance status and higher IL-6 levels, were more often treated with combined chemoradiotherapy, and were more likely to be rural residents. IL-6 and ECOG physical performance status were significantly associated with 1.246-fold (95% CI 1.114-1.396) and 31.831-fold (95% CI 6.017-168.385) increased risk of Subgroup 3. Our findings suggest that IL-6 levels are associated with cluster symptoms in cancer patients. Clinicians should identify patients at risk for more severe symptoms and formulate novel target interventions to improve symptom management. Copyright © 2017. Published by Elsevier Inc.

Dysexecutive versus amnestic Alzheimer disease subgroups: analysis of demographic, genetic, and vascular factors.

PubMed

Mez, Jesse; Cosentino, Stephanie; Brickman, Adam M; Huey, Edward D; Manly, Jennifer J; Mayeux, Richard

2013-01-01

The objective of this study was to compare the demographic and vascular characteristics and APOE genotypes of a dysexecutive subgroup of Alzheimer disease (AD) with an amnestic subgroup of AD early in the disease course. A total of 2224 participants from the National Alzheimer's Coordinating Center database who carried a diagnosis of mild cognitive impairment (n=1188) or mild AD (clinical dementia rating ≤1) (n=1036) were included in this study. A subset of the mild cognitive impairment (n=61) and mild AD (n=79) participants underwent an autopsy. A dysexecutive subgroup (n=587) was defined as having executive performance >1 SD worse than memory performance, and an amnestic subgroup (n=549) was defined conversely. Among the autopsy subset, the odds of an AD pathologic diagnosis were compared in the 2 subgroups. The demographics, APOE[Latin Small Letter Open E]4 status, and vascular risk factors were compared in the 2 subgroups. Among the autopsy subset, the odds of having an AD pathologic diagnosis did not differ between the dysexecutive and amnestic subgroups. Under an additive model, participants in the dysexecutive subgroup possessed the APOE[Latin Small Letter Open E]4 allele less frequently compared with those in the amnestic subgroup. The dysexecutive subgroup had a history of hypertension less frequently compared with the amnestic subgroup. These distinct characteristics add to accumulating evidence that a dysexecutive subgroup of AD may have a unique underlying pathophysiology.

Identifying cut points for biomarker defined subset effects in clinical trials with survival endpoints.

PubMed

He, Pei

2014-07-01

The advancements in biotechnology and genetics lead to an increasing research interest in personalized medicine, where a patient's genetic profile or biological traits contribute to choosing the most effective treatment for the patient. The process starts with finding a specific biomarker among all possible candidates that can best predict the treatment effect. After a biomarker is chosen, identifying a cut point of the biomarker value that splits the patients into treatment effective and non-effective subgroups becomes an important scientific problem. Numerous methods have been proposed to validate the predictive marker and select the appropriate cut points either prospectively or retrospectively using clinical trial data. In trials with survival outcomes, the current practice applies an interaction testing procedure and chooses the cut point that minimizes the p-values for the tests. Such method assumes independence between the baseline hazard and biomarker value. In reality, however, this assumption is often violated, as the chosen biomarker might also be prognostic in addition to its predictive nature for treatment effect. In this paper we propose a block-wise estimation and a sequential testing approach to identify the cut point in biomarkers that can group the patients into subsets based on their distinct treatment outcomes without assuming independence between the biomarker and baseline hazard. Numerical results based on simulated survival data show that the proposed method could pinpoint accurately the cut points in biomarker values that separate the patient subpopulations into subgroups with distinctive treatment outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant

PubMed Central

Agnihothram, Sudhakar; Yount, Boyd L.; Donaldson, Eric F.; Huynh, Jeremy; Menachery, Vineet D.; Gralinski, Lisa E.; Graham, Rachel L.; Becker, Michelle M.; Tomar, Sakshi; Scobey, Trevor D.; Osswald, Heather L.; Whitmore, Alan; Gopal, Robin; Ghosh, Arun K.; Mesecar, Andrew; Zambon, Maria; Heise, Mark; Denison, Mark R.; Baric, Ralph S.

2014-01-01

ABSTRACT Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and Pipistrellus bat coronavirus (BtCoV) strain HKU5 of Betacoronavirus (β-CoV) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine targets. BtCoV HKU5 has been described in silico but has not been shown to replicate in culture, thus hampering drug and vaccine studies against subgroup 2c β-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5 containing the severe acute respiratory syndrome (SARS)-CoV spike (S) glycoprotein ectodomain (BtCoV HKU5-SE). This virus replicates efficiently in cell culture and in young and aged mice, where the virus targets airway and alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence, causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14, open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs. Synthetic-genome platforms capable of reconstituting emerging zoonotic viral pathogens or their phylogenetic relatives provide new strategies for identifying broad-based therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis. PMID:24667706

Suicidal ideation and suicide attempts among Hispanic subgroups in the United States: 1991–1992 and 2001–2002

PubMed Central

Baca-Garcia, Enrique; Perez-Rodriguez, M. Mercedes; Keyes, Katherine M.; Oquendo, Maria A.; Hasin, Deborah S.; Grant, Bridget F.; Blanco, Carlos

2010-01-01

Objective To compare the prevalence of suicidal ideation/attempts among Hispanic subgroups in the US in 1991–1992 and 2001–2002, and identify high-risk groups. Method Data were drawn from the 1991–1992 National Longitudinal Alcohol Epidemiologic Survey (NLAES, n=42,862) and the 2001–2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC,n=43,093), two nationally representative surveys of individuals aged 18 years and older. Results 1) Puerto Ricans are the Hispanic ethnic subgroup with the highest rates of suicide attempts; 2) 45- to 64-year-old Puerto Rican women are a high- risk group for suicide attempts; 3) Over the 10 year period between the two surveys, the lifetime prevalence of suicide attempts significantly increased among 18- to 24-year-old Puerto Rican women and Cuban men, and among 45- to 64-year-old Puerto Rican men. Conclusion Hispanics in the US are not a homogeneous group. We identify high-risk groups among Hispanics. Specific interventions for subgroups of Hispanics at high risk for suicidal behaviors may be required. PMID:20937507

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.

Autoimmune-autoinflammatory rheumatoid arthritis overlaps: a rare but potentially important subgroup of diseases

PubMed Central

Savic, Sinisa; Mistry, Anoop; Wilson, Anthony G; Barcenas-Morales, Gabriela; Doffinger, Rainer; Emery, Paul; McGonagle, Dennis

2017-01-01

At the population level, rheumatoid arthritis (RA) is generally viewed as autoimmune in nature with a small subgroup of cases having a palindromic form or systemic autoinflammatory disorder (SAID) phenotype. Herein, we describe resistant cases of classical autoantibody associated RA that had clinical, genetic and therapeutic responses indicative of coexistent autoinflammatory disease. Five patients with clinically overlapping features between RA and SAID including polysynovitis and autoantibody/shared epitope positivity, and who had abrupt severe self-limiting attacks including fevers and serositis, are described. Mutations or single nucleotide polymorphisms in recognised autoinflammatory pathways were evident. Generally, these cases responded poorly to conventional Disease-modifying anti-rheumatic drugs (DMARD) treatment with some excellent responses to colchicine or interleukin 1 pathway blockade. A subgroup of RA cases have a mixed autoimmune-autoinflammatory phenotype and genotype with therapeutic implications. PMID:29177082

Memory profiles in parents of patients with schizophrenia.

PubMed

Sitskoorn, Margriet M; Ebisch, Sjoerd J H; Appels, Melanie; Nuyen, Jasper; Kahn, René S

2004-08-30

Recent research shows that categorizing patients with schizophrenia based on frontal-striatal and frontal-temporal memory profiles may yield neurobiologically meaningful disease subtypes. We hypothesize that parents of patients exhibit similar memory profiles. Both parents of 36 patients with schizophrenia (N = 72) and 26 healthy married control couples (N = 52) participated in this study. All subjects were physically healthy and had no history of neurological illness or alcohol/drug abuse. The presence of a psychiatric and/or personality disorder was assessed with the Comprehensive Assessment of Symptoms and History (CASH) interview, the Schedule for Affective Disorders and Schizophrenia-lifetime (SADS-L) interview and the Structured Interview for DSM-IV Personality Disorders (SIDP-IV), respectively. Cluster analysis of selected measures from the Dutch version of the California Verbal Learning Test (CVLT) delineated parents into two subgroups with distinct memory deficits and a third subgroup without impairments. Specific frontal-striatal and frontal-temporal subgroups, however, were not found. In addition, our results indicated that mothers seem to be more protected against the negative effects of genetic liability to schizophrenia than fathers. Furthermore, relatives with a higher level of intelligence may have more cognitive reserve to compensate for the negative impact of implied brain dysfunction on verbal memory than relatives with a low level of intelligence. Although the parents of patients with schizophrenia could be delineated into subgroups with primary memory deficits, frontal-striatal and frontal-temporal subgroups could not be unambiguously identified. The association that emerged between level of intelligence, gender and severity of memory impairment deserves further exploration.

Nonparametric Subgroup Identification by PRIM and CART: A Simulation and Application Study

PubMed Central

2017-01-01

Two nonparametric methods for the identification of subgroups with outstanding outcome values are described and compared to each other in a simulation study and an application to clinical data. The Patient Rule Induction Method (PRIM) searches for box-shaped areas in the given data which exceed a minimal size and average outcome. This is achieved via a combination of iterative peeling and pasting steps, where small fractions of the data are removed or added to the current box. As an alternative, Classification and Regression Trees (CART) prediction models perform sequential binary splits of the data to produce subsets which can be interpreted as subgroups of heterogeneous outcome. PRIM and CART were compared in a simulation study to investigate their strengths and weaknesses under various data settings, taking different performance measures into account. PRIM was shown to be superior in rather complex settings such as those with few observations, a smaller signal-to-noise ratio, and more than one subgroup. CART showed the best performance in simpler situations. A practical application of the two methods was illustrated using a clinical data set. For this application, both methods produced similar results but the higher amount of user involvement of PRIM became apparent. PRIM can be flexibly tuned by the user, whereas CART, although simpler to implement, is rather static. PMID:28611849

Nonparametric Subgroup Identification by PRIM and CART: A Simulation and Application Study.

PubMed

Ott, Armin; Hapfelmeier, Alexander

2017-01-01

Two nonparametric methods for the identification of subgroups with outstanding outcome values are described and compared to each other in a simulation study and an application to clinical data. The Patient Rule Induction Method (PRIM) searches for box-shaped areas in the given data which exceed a minimal size and average outcome. This is achieved via a combination of iterative peeling and pasting steps, where small fractions of the data are removed or added to the current box. As an alternative, Classification and Regression Trees (CART) prediction models perform sequential binary splits of the data to produce subsets which can be interpreted as subgroups of heterogeneous outcome. PRIM and CART were compared in a simulation study to investigate their strengths and weaknesses under various data settings, taking different performance measures into account. PRIM was shown to be superior in rather complex settings such as those with few observations, a smaller signal-to-noise ratio, and more than one subgroup. CART showed the best performance in simpler situations. A practical application of the two methods was illustrated using a clinical data set. For this application, both methods produced similar results but the higher amount of user involvement of PRIM became apparent. PRIM can be flexibly tuned by the user, whereas CART, although simpler to implement, is rather static.

Can dialysis patients be accurately identified using healthcare claims data?

PubMed

Taneja, Charu; Berger, Ariel; Inglese, Gary W; Lamerato, Lois; Sloand, James A; Wolff, Greg G; Sheehan, Michael; Oster, Gerry

2014-01-01

While health insurance claims data are often used to estimate the costs of renal replacement therapy in patients with end-stage renal disease (ESRD), the accuracy of methods used to identify patients receiving dialysis - especially peritoneal dialysis (PD) and hemodialysis (HD) - in these data is unknown. The study population consisted of all persons aged 18 - 63 years in a large US integrated health plan with ESRD and dialysis-related billing codes (i.e., diagnosis, procedures) on healthcare encounters between January 1, 2005, and December 31, 2008. Using billing codes for all healthcare encounters within 30 days of each patient's first dialysis-related claim ("index encounter"), we attempted to designate each study subject as either a "PD patient" or "HD patient." Using alternative windows of ± 30 days, ± 90 days, and ± 180 days around the index encounter, we reviewed patients' medical records to determine the dialysis modality actually received. We calculated the positive predictive value (PPV) for each dialysis-related billing code, using information in patients' medical records as the "gold standard." We identified a total of 233 patients with evidence of ESRD and receipt of dialysis in healthcare claims data. Based on examination of billing codes, 43 and 173 study subjects were designated PD patients and HD patients, respectively (14 patients had evidence of PD and HD, and modality could not be ascertained for 31 patients). The PPV of codes used to identify PD patients was low based on a ± 30-day medical record review window (34.9%), and increased with use of ± 90-day and ± 180-day windows (both 67.4%). The PPV for codes used to identify HD patients was uniformly high - 86.7% based on ± 30-day review, 90.8% based on ± 90-day review, and 93.1% based on ± 180-day review. While HD patients could be accurately identified using billing codes in healthcare claims data, case identification was much more problematic for patients receiving PD. Copyright �

Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a predefined subgroup analysis from AVERROES, a randomised trial.

PubMed

Diener, Hans-Christoph; Eikelboom, John; Connolly, Stuart J; Joyner, Campbell D; Hart, Robert G; Lip, Gregory Y H; O'Donnell, Martin; Hohnloser, Stefan H; Hankey, Graeme J; Shestakovska, Olga; Yusuf, Salim

2012-03-01

In the AVERROES study, apixaban, a novel factor Xa inhibitor, reduced the risk of stroke or systemic embolism in patients with atrial fibrillation who were at high risk of stroke but unsuitable for vitamin K antagonist therapy. We aimed to investigate whether the subgroup of patients with previous stroke or transient ischaemic attack (TIA) would show a greater benefit from apixaban compared with aspirin than would patients without previous cerebrovascular events. In AVERROES, 5599 patients (mean age 70 years) with atrial fibrillation who were at increased risk of stroke and unsuitable for vitamin K antagonist therapy were randomly assigned to receive apixaban (5 mg twice daily) or aspirin (81-324 mg per day). The mean follow-up was 1·1 years. The primary efficacy outcome was stroke or systemic embolism; the primary safety outcome was major bleeding. Patients and investigators were masked to study treatment. In this prespecified subgroup analysis, we used Kaplan-Meier estimates of 1-year event risk and Cox proportional hazards regression models to compare the effects of apixaban in patients with and without previous stroke or TIA. AVERROES is registered at ClinicalTrials.gov, number NCT00496769. In patients with previous stroke or TIA, ten events of stroke or systemic embolism occurred in the apixaban group (n=390, cumulative hazard 2·39% per year) compared with 33 in the aspirin group (n=374, 9·16% per year; hazard ratio [HR] 0·29, 95% CI 0·15-0·60). In those without previous stroke or TIA, 41 events occurred in the apixaban group (n=2417, 1·68% per year) compared with 80 in the aspirin group (n=2415, 3·06% per year; HR 0·51, 95% CI 0·35-0·74). The p value for interaction of the effects of aspirin and apixaban with previous cerebrovascular events was 0·17. Major bleeding was more frequent in patients with history of stroke or TIA than in patients without (HR 2·88, 95% CI 1·77-4·55) but risk of this event did not differ between treatment groups. In

Methoxyflurane Analgesia in Adult Patients in the Emergency Department: A Subgroup Analysis of a Randomized, Double-blind, Placebo-controlled Study (STOP!).

PubMed

Coffey, Frank; Dissmann, Patrick; Mirza, Kazim; Lomax, Mark

2016-11-01

Acute pain remains highly prevalent in the Emergency Department (ED) setting. This double-blind, randomized, placebo-controlled UK study investigated the efficacy and safety of low-dose methoxyflurane analgesia for the treatment of acute pain in the ED in the adult population of the STOP! trial. Patients presenting to the ED requiring analgesia for acute pain (pain score of 4-7 on the Numerical Rating Scale) due to minor trauma were randomized in a 1:1 ratio to receive methoxyflurane (up to 6 mL) or placebo (normal saline), both via a Penthrox ® (Medical Developments International Limited, Scoresby, Australia) inhaler. Rescue medication (paracetamol/opioids) was available immediately upon request. Change from baseline in visual analog scale (VAS) pain intensity was the primary endpoint. 300 adult and adolescent patients were randomized; data are presented for the adult subgroup (N = 204). Mean baseline VAS pain score was ~66 mm in both groups. The mean change from baseline to 5, 10, 15 and 20 min was greater for methoxyflurane (-20.7, -27.4, -33.3 and -34.8 mm, respectively) than placebo (-8.0, -11.1, -12.3 and -15.2 mm, respectively). The primary analysis showed a highly significant treatment effect overall across all four time points (-17.4 mm; 95% confidence interval: -22.3 to -12.5 mm; p < 0.0001). Median time to first pain relief was 5 min with methoxyflurane [versus 20 min with placebo; (hazard ratio: 2.32; 95% CI: 1.63, 3.30; p < 0.0001)]; 79.4% of methoxyflurane-treated patients experienced pain relief within 1-10 inhalations. 22.8% of placebo-treated patients requested rescue medication within 20 min compared with 2.0% of methoxyflurane-treated patients (p = 0.0003). Methoxyflurane treatment was rated 'Excellent', 'Very Good' or 'Good' by 77.6% of patients, 74.5% of physicians and 72.5% of nurses. Treatment-related adverse events (mostly dizziness/headache) were reported by 42.2% of patients receiving methoxyflurane and 14.9% of patients

Subgroup analyses of the effectiveness of oral glucosamine for knee and hip osteoarthritis: a systematic review and individual patient data meta-analysis from the OA trial bank.

PubMed

Runhaar, Jos; Rozendaal, Rianne M; van Middelkoop, Marienke; Bijlsma, Hans J W; Doherty, Michael; Dziedzic, Krysia S; Lohmander, L Stefan; McAlindon, Timothy; Zhang, Weiya; Bierma Zeinstra, Sita

2017-11-01

To evaluate the effectiveness of oral glucosamine in subgroups of people with hip or knee osteoarthritis (OA) based on baseline pain severity, body mass index (BMI), sex, structural abnormalities and presence of inflammation using individual patient data. After a systematic search of the literature and clinical trial registries, all randomised controlled trials (RCTs) evaluating the effect of any oral glucosamine substance in patients with clinically or radiographically defined hip or knee OA were contacted. As a minimum, pain, age, sex and BMI at baseline and pain as an outcome measure needed to be assessed. Of 21 eligible studies, six (n=1663) shared their trial data with the OA Trial Bank. Five trials (all independent of industry, n=1625) compared glucosamine with placebo, representing 55% of the total number of participants in all published placebo-controlled RCTs. Glucosamine was no better than placebo for pain or function at short (3 months) and long-term (24 months) follow-up. Glucosamine was also no better than placebo among the predefined subgroups. Stratification for knee OA and type of glucosamine did not alter these results. Although proposed and debated for several years, open trial data are not widely made available for studies of glucosamine for OA, especially those sponsored by industry. Currently, there is no good evidence to support the use of glucosamine for hip or knee OA and an absence of evidence to support specific consideration of glucosamine for any clinically relevant OA subgroup according to baseline pain severity, BMI, sex, structural abnormalities or presence of inflammation. © 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.

Rivaroxaban for Thromboprophylaxis among Patients Recently Hospitalized for Acute Infectious Diseases: A Subgroup Analysis of the MAGELLAN Study.

PubMed

Cohoon, Kevin P; De Sanctis, Yoriko; Haskell, Lloyd; McBane, Robert D; Spiro, Theodore E

2018-05-12

Despite the well-established association between infection and venous thromboembolism (VTE), there are few data specifically assessing the efficacy and safety of the VTE prophylaxis strategies for patients hospitalized for acute infectious diseases. Estimate incidence of VTE and bleeding outcomes comparing prolonged prophylaxis with rivaroxaban 10 mg daily for 35 days with enoxaparin 40 mg daily for 10 days. A subgroup analysis of patients hospitalized for acute infectious diseases in the MAGELLAN trial was performed. The primary efficacy outcome was the composite of asymptomatic proximal or symptomatic VTE at days 10 and 35. The principal safety outcome was the composite of major or clinically relevant non-major bleeding. 3173 patients with acute infectious diseases leading to hospitalization were randomized to either rivaroxaban (n=1585) or enoxaparin/placebo (n=1588) and received at least one dose of study medication. At day 10, primary composite efficacy outcomes did not differ between prophylaxis strategies (rivaroxaban 2.7% and enoxaparin 3.7%). At day 35, VTE events were lower for rivaroxaban (4.2%) compared to enoxaparin (6.6%) (Relative risk [RR] 0.64; 95%CI, 0.45, 0.92). Patients with pulmonary infections randomized to rivaroxaban had lower incidence of VTE both at 10 days (RR 0.50, 95%CI 0.28, 0.90) and 35 days (RR 0.54, 95%CI 0.33, 0.87). Primary safety outcome events were higher for those receiving rivaroxaban (RR 2.42, 95%CI 1.60, 3.66). Prolonged rivaroxaban prophylaxis reduced VTE in patients hospitalized for acute infectious diseases particularly involving the lungs. Efficacy benefits were, in part, offset by bleeding outcomes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Delineation of Two Clinically and Molecularly Distinct Subgroups of Posterior Fossa Ependymoma

PubMed Central

Witt, Hendrik; Mack, Stephen C.; Ryzhova, Marina; Bender, Sebastian; Sill, Martin; Isserlin, Ruth; Benner, Axel; Hielscher, Thomas; Milde, Till; Remke, Marc; Jones, David T.W.; Northcott, Paul A.; Garzia, Livia; Bertrand, Kelsey C.; Wittmann, Andrea; Yao, Yuan; Roberts, Stephen S.; Massimi, Luca; Van Meter, Tim; Weiss, William A.; Gupta, Nalin; Grajkowska, Wiesia; Lach, Boleslaw; Cho, Yoon-Jae; von Deimling, Andreas; Kulozik, Andreas E.; Witt, Olaf; Bader, Gary D.; Hawkins, Cynthia E.; Tabori, Uri; Guha, Abhijit; Rutka, James T.; Lichter, Peter; Korshunov, Andrey

2014-01-01

Summary Despite the histological similarity of ependymomas from throughout the neuroaxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymoma reveals the existence of two demographically, transcriptionally, genetically, and clinically distinct groups of posterior fossa (PF) ependymomas. Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastasis at recurrence, and death compared with Group B patients. Identification and optimization of immunohistochemical (IHC) markers for PF ependymoma subgroups allowed validation of our findings on a third independent cohort, using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients. PMID:21840481

Distinct neuropsychological subgroups in typically developing youth inform heterogeneity in children with ADHD

PubMed Central

Fair, Damien A.; Bathula, Deepti; Nikolas, Molly A.; Nigg, Joel T.

2012-01-01

Research and clinical investigations in psychiatry largely rely on the de facto assumption that the diagnostic categories identified in the Diagnostic and Statistical Manual (DSM) represent homogeneous syndromes. However, the mechanistic heterogeneity that potentially underlies the existing classification scheme might limit discovery of etiology for most developmental psychiatric disorders. Another, perhaps less palpable, reality may also be interfering with progress—heterogeneity in typically developing populations. In this report we attempt to clarify neuropsychological heterogeneity in a large dataset of typically developing youth and youth with attention deficit/hyperactivity disorder (ADHD), using graph theory and community detection. We sought to determine whether data-driven neuropsychological subtypes could be discerned in children with and without the disorder. Because individual classification is the sine qua non for eventual clinical translation, we also apply support vector machine-based multivariate pattern analysis to identify how well ADHD status in individual children can be identified as defined by the community detection delineated subtypes. The analysis yielded several unique, but similar subtypes across both populations. Just as importantly, comparing typically developing children with ADHD children within each of these distinct subgroups increased diagnostic accuracy. Two important principles were identified that have the potential to advance our understanding of typical development and developmental neuropsychiatric disorders. The first tenet suggests that typically developing children can be classified into distinct neuropsychological subgroups with high precision. The second tenet proposes that some of the heterogeneity in individuals with ADHD might be “nested” in this normal variation. PMID:22474392

Association between Obesity and Cardiometabolic Health Risk in Asian-Canadian Sub-Groups

PubMed Central

Nie, Jason X.; Ardern, Chris I.

2014-01-01

Objectives To quantify and compare the association between the World Health Organizations’ Asian-specific trigger points for public health action [‘increased risk’: body mass index (BMI) ≥23 kg/m2, and; ‘high risk’: BMI ≥27.5 kg/m2] with self-reported cardiovascular-related conditions in Asian-Canadian sub-groups. Methods Six cycles of the Canadian Community Health Survey (2001–2009) were pooled to examine BMI and health in Asian sub-groups (South Asians, Chinese, Filipino, Southeast Asians, Arabs, West Asians, Japanese and Korean; N = 18 794 participants, ages 18–64 y). Multivariable logistic regression, adjusting for demographic, lifestyle characteristics and acculturation measures, was used to estimate the odds of cardiovascular-related health (high blood pressure, heart disease, diabetes, ‘at least one cardiometabolic condition’) outcomes across all eight Asian sub-groups. Results Compared to South Asians (OR = 1.00), Filipinos had higher odds of having ‘at least one cardiometabolic condition’ (OR = 1.29, 95% CI: 1.04–1.62), whereas Chinese (0.63, 0.474–0.9) and Arab-Canadians had lower odds (0.38, 0.28–0.51). In ethnic-specific analyses (with ‘acceptable’ risk weight as the referent), ‘increased’ and ‘high’ risk weight categories were the most highly associated with ‘at least one cardiometabolic condition’ in Chinese (‘increased’: 3.6, 2.34–5.63; ‘high’: 8.9, 3.6–22.01). Compared to normal weight South Asians, being in the ‘high’ risk weight category in all but the Southeast Asian, Arab, and Japanese ethnic groups was associated with approximately 3-times the likelihood of having ‘at least one cardiometabolic condition’. Conclusion Differences in the association between obesity and cardiometabolic health risks were seen among Asian sub-groups in Canada. The use of WHO’s lowered Asian-specific BMI cut-offs identified obesity-related risks in South Asian, Filipino and Chinese sub-groups

A new treatment regimen with high-dose and fractioned immunoglobulin in a special subgroup of severe and dependent CIDP patients.

PubMed

Debs, Rabab; Reach, Pauline; Cret, Corina; Demeret, Sophie; Saheb, Samir; Maisonobe, Thierry; Viala, Karine

2017-10-01

Chronic inflammatory demyelinating polyneuropathy (CIDP) is treated with intravenous immunoglobulins (IVIg), corticosteroids or plasma exchange (PE). IVIg dosage is not universal and markers for treatment management are needed. We report the response to high-dose and fractioned IVIg in a subgroup of definite CIDP patients, resistant to corticosteroids and PE, responders to IVIg but with an efficacy window <15 d. Four patients were included with similar predominantly clinical motor form and conduction abnormalities. Treatment management consisted of fractioning IVIg and increasing the monthly cumulated dose (mean: 3 g/kg/month). Serum IgG concentration was measured and correlated to the clinical state. Monitoring of serum IgG helped to guide IVIg administration dosage and frequency. A mean of 10 months was required to improve symptoms; therapy was then switched to subcutaneous (SC) route (maintenance dose: 3.5 g/kg/month). The mean Overall Neuropathy Limitations Scale was improved from 11 to 3.2 and the mean Medical Research Council scale from 26 to 90. It is important to distinguish patients with short IVIg efficacy window from those with classical resistance since the former may benefit from fractioning and increasing the IVIg dose. The monitoring of serum IgG level and its correlation to the clinical response could be of help in monitoring each individual's dosage.

Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial

PubMed Central

Coghlan, John Gerry; Galiè, Nazzareno; Barberà, Joan Albert; Frost, Adaani E; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M; Kuwana, Masataka; McLaughlin, Vallerie V; Peacock, Andrew J; Simonneau, Gérald; Vachiéry, Jean-Luc; Blair, Christiana; Gillies, Hunter; Miller, Karen L; Harris, Julia H N; Langley, Jonathan; Rubin, Lewis J

2017-01-01

Background Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. Objective To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial. Methods This was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response). Results In the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups. Conclusions This post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy. Trial registration number NCT01178073, post results. PMID:28039187

Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial.

PubMed

Coghlan, John Gerry; Galiè, Nazzareno; Barberà, Joan Albert; Frost, Adaani E; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M; Kuwana, Masataka; McLaughlin, Vallerie V; Peacock, Andrew J; Simonneau, Gérald; Vachiéry, Jean-Luc; Blair, Christiana; Gillies, Hunter; Miller, Karen L; Harris, Julia H N; Langley, Jonathan; Rubin, Lewis J

2017-07-01

Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial. This was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response). In the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups. This post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy. NCT01178073, post results. 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/.

Differences of Sagittal Lumbosacral Parameters between Patients with Lumbar Spondylolysis and Normal Adults

PubMed Central

Yin, Jin; Peng, Bao-Gan; Li, Yong-Chao; Zhang, Nai-Yang; Yang, Liang; Li, Duan-Ming

2016-01-01

Background: Recent studies have suggested an association between elevated pelvic incidence (PI) and the development of lumbar spondylolysis. However, there is still lack of investigation for Han Chinese people concerning the normal range of spinopelvic parameters and relationship between abnormal sagittal parameters and lumbar diseases. The objective of the study was to investigate sagittal lumbosacral parameters of adult lumbar spondylolysis patients in Han Chinese population. Methods: A total of 52 adult patients with symptomatic lumbar spondylolysis treated in the General Hospital of Armed Police Force (Beijing, China) were identified as the spondylolysis group. All the 52 patients were divided into two subgroups, Subgroup A: 36 patients with simple lumbar spondylolysis, and Subgroup B: 16 patients with lumbar spondylolysis accompanying with mild lumbar spondylolisthesis (slip percentage <30%). Altogether 207 healthy adults were chosen as the control group. All patients and the control group took lumbosacral lateral radiographs. Seven sagittal lumbosacral parameters, including PI, pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), L5 incidence, L5 slope, and sacral table angle (STA), were measured in the lateral radiographs. All the parameters aforementioned were compared between the two subgroups and between the spondylolysis group and the control group with independent-sample t-test. Results: There were no statistically significant differences of all seven sagittal lumbosacral parameters between Subgroup A and Subgroup B. PI, PT, SS, and LL were higher (P < 0.05) in the spondylolysis group than those in the control group, but STA was lower (P < 0.001) in the spondylolysis group. Conclusions: Current study results suggest that increased PI and decreased STA may play important roles in the pathology of lumbar spondylolysis in Han Chinese population. PMID:27174324

Differences of Sagittal Lumbosacral Parameters between Patients with Lumbar Spondylolysis and Normal Adults.

PubMed

Yin, Jin; Peng, Bao-Gan; Li, Yong-Chao; Zhang, Nai-Yang; Yang, Liang; Li, Duan-Ming

2016-05-20

Recent studies have suggested an association between elevated pelvic incidence (PI) and the development of lumbar spondylolysis. However, there is still lack of investigation for Han Chinese people concerning the normal range of spinopelvic parameters and relationship between abnormal sagittal parameters and lumbar diseases. The objective of the study was to investigate sagittal lumbosacral parameters of adult lumbar spondylolysis patients in Han Chinese population. A total of 52 adult patients with symptomatic lumbar spondylolysis treated in the General Hospital of Armed Police Force (Beijing, China) were identified as the spondylolysis group. All the 52 patients were divided into two subgroups, Subgroup A: 36 patients with simple lumbar spondylolysis, and Subgroup B: 16 patients with lumbar spondylolysis accompanying with mild lumbar spondylolisthesis (slip percentage <30%). Altogether 207 healthy adults were chosen as the control group. All patients and the control group took lumbosacral lateral radiographs. Seven sagittal lumbosacral parameters, including PI, pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), L5 incidence, L5 slope, and sacral table angle (STA), were measured in the lateral radiographs. All the parameters aforementioned were compared between the two subgroups and between the spondylolysis group and the control group with independent-sample t- test. There were no statistically significant differences of all seven sagittal lumbosacral parameters between Subgroup A and Subgroup B. PI, PT, SS, and LL were higher (P < 0.05) in the spondylolysis group than those in the control group, but STA was lower (P < 0.001) in the spondylolysis group. Current study results suggest that increased PI and decreased STA may play important roles in the pathology of lumbar spondylolysis in Han Chinese population.

Meta-analysis of Clear Cell Renal Cell Carcinoma Gene Expression Defines a Variant Subgroup and Identifies Gender Influences on Tumor Biology

PubMed Central

Brannon, A. Rose; Haake, Scott M.; Hacker, Kathryn E.; Pruthi, Raj S.; Wallen, Eric M.; Nielsen, Matthew E.; Rathmell, W. Kimryn

2011-01-01

Background Clear cell renal cell carcinoma (ccRCC) displays molecular and histologic heterogeneity. Previously described subsets of this disease, ccA and ccB, were defined based on multigene expression profiles, but it is unclear whether these subgroupings reflect the full spectrum of disease or how these molecular subtypes relate to histologic descriptions or gender. Objective Determine whether additional subtypes of ccRCC exist and whether these subtypes are related to von Hippel-Lindau (VHL) inactivation, hypoxia-inducible factor (HIF) 1 and 2 expression, tumor histology, or gender. Design, setting, and participants Six large, publicly available ccRCC gene expression databases were identified that cumulatively provided data for 480 tumors for meta-analysis via meta-array compilation. Measurements Unsupervised consensus clustering was performed on the meta-arrays. Tumors were examined for the relationship of multigene-defined consensus subtypes and expression signatures of VHL mutation and HIF status, tumor histology, and gender. Results and limitations Two dominant subsets of ccRCC were observed. However, a minor third cluster was revealed that correlated strongly with a wild type (WT) VHL expression profile and indications of variant histologies. When variant histologies were removed, ccA tumors naturally divided by gender. This technique is limited by the potential for persistent batch effect, tumor sampling bias, and restrictions of annotated information. Conclusions The ccA and ccB subsets of ccRCC are robust in meta-analysis among histologically conventional ccRCC tumors. A third group of tumors was identified that may represent a new variant of ccRCC. Within definitively clear cell tumors, gender may delineate tumors in such a way that it could have implications regarding current treatments and future drug development. PMID:22030119

A multicenter, randomized, double-blind, retrospective comparison of 5- and 10-day regimens of levofloxacin in a subgroup of patients aged > or =65 years with community-acquired pneumonia.

PubMed

Shorr, Andrew F; Zadeikis, Neringa; Xiang, Jim X; Tennenberg, Alan M; Wes Ely, E

2005-08-01

This subgroup analysis sought to determine the efficacy and tolerability of a 5-day regimen of levofloxacin 750 mg/d compared with a 10-day regimen of levofloxacin 500 mg/d in the treatment of community-acquired pneumonia (CAP) in elderly patients (aged > or =65 years). This subgroup analysis was based on the outcomes in patients aged > or =65 years from a randomized, double-blind, controlled trial conducted at 70 US centers. Patients in Pneumonia Severity Index (PSI) class I/II and III/IV were randomized to receive levofloxacin 750 mg/d for 5 days or levofloxacin 500 mg/d for 10 days. Study investigators assessed clinical and microbiologic outcomes 7 to 14 days after administration of the last dose of medication and collected adverse events for 30 days after the last dose. This analysis included 177 elderly patients, 80 receiving levofloxacin 750 mg/d for 5 days and 97 receiving levofloxacin 500 mg/d for 10 days. Although most demographic and baseline clinical characteristics were comparable between the 2 groups, the group that received levofloxacin 500 mg/d was older than the group that received levofloxacin 750 mg/d (median age, 76.0 vs 72.5 years, respectively; P = 0.029) and had a higher mean PSI score (90.7 vs 83.1; P = 0.017). Despite the halved duration of therapy, unadjusted clinical success rates were comparable between the 2 groups (89.0% and 91.9% in the 750- and 500-mg arms, respectively; 95% CI, -7.1 to 12.7). Microbiologic eradication rates were 90.3% (28/31) in the 750-mg arm and 87.5% (14/16) in the 500-mg arm (P = NS). Multivariate analysis adjusting for baseline PSI score indicated that treatment assignment was not statistically associated with clinical success (adjusted odds ratio for clinical success with 500-mg dose, 1.92; 95% CI, 0.62 to 5.99). The incidence of treatment-emergent adverse events did not differ between the 2 study treatments. The most common adverse events in both groups were insomnia, constipation, and headache. This subgroup

Adenoma Prevalence and Distribution Among US Latino Subgroups Undergoing Screening Colonoscopy.

PubMed

Chablani, Sumedha V; Jandorf, Lina; DuHamel, Katherine; Lee, Kristen K; Sriphanlop, Pathu; Villagra, Cristina; Itzkowitz, Steven H

2017-06-01

Colorectal cancer (CRC) is the second leading malignancy diagnosed among US Latinos. Latinos in the USA represent a heterogeneous amalgam of subgroups varying in genetic background, culture, and socioeconomic status. Little is known about the frequency of CRC precursor lesions found at screening colonoscopy among Latino subgroups. The aim was to determine the prevalence and distribution of histologically confirmed adenomas found at screening colonoscopy among average-risk, asymptomatic US Latinos according to their subgroup and socio-demographic background. Cross-sectional analysis of pathological findings resulting from screening colonoscopy among average-risk, asymptomatic US Latinos aged ≥50 in two prospective randomized controlled trials at an academic medical center. Among the 561 Latinos who completed screening colonoscopy, the two largest subgroups were Puerto Ricans and Dominicans. The findings among both subgroups were: adenomas 30.6%, proximal adenomas 23.5%, advanced adenomas 12.0%, and proximal advanced adenomas 8.9%. These rates are at least as high as those found at screening colonoscopy among US whites. While Puerto Ricans were more likely than Dominicans to be born in the USA, speak English, be acculturated, have a smoking history, and be obese, there were no significant differences in adenoma rates between these subgroups. The prevalence of adenomas, advanced adenomas, and proximal neoplasia was high among both subgroups. These findings have implications for CRC screening and surveillance among the increasingly growing Latino population in the USA.

Long-term course of negative symptom subdomains and relationship with outcome in patients with a psychotic disorder.

PubMed

Stiekema, Annemarie P M; Islam, Md Atiqul; Liemburg, Edith J; Castelein, Stynke; van den Heuvel, Edwin R; van Weeghel, Jaap; Aleman, André; Bruggeman, Richard; van der Meer, Lisette

2018-03-01

The longitudinal course of the negative symptoms subdomains social amotivation (SA) and expressive deficits (ED) remains largely unknown. We investigated i) the longitudinal course of SA and ED subdomain scores, ii) whether subgroups based on the course of SA and ED subdomain scores could be identified, iii) whether baseline SA and ED subdomain scores were related to functioning and quality of life six years later and iv) the longitudinal relationship between subgroups and outcomes. Measurements at baseline, three and six years from 1067 patients participating in the Genetic Risk and Outcome of Psychosis (GROUP) project were used. We applied mixed models analysis, regression analysis and trajectory analyses. SA and ED subdomain scores decreased over time. Within both subdomains, four subgroups were identified: for both SA and ED a steady low course (±60%), increased (±15%) and decreased course (±15%). Within SA only, a higher level decreased course (±6%) and within ED only, a course with relatively stable high ED scores (±6%) was found. Lower symptom levels at baseline were related to better functioning (SA & ED) and quality of life (SA) at six years. Overall, low SA and low ED subgroups showed better outcomes than the other subgroups. In many patients the course of negative symptoms is unstable and related to the course of outcome. Patients who do show steady low negative symptom levels (60%) may complicate the interpretation of treatment evaluation studies, as they may average out possible effects in subgroups with fluctuating symptom levels. Copyright © 2017 Elsevier B.V. All rights reserved.

Validation of an International Classification of Diseases, Ninth Revision Code Algorithm for Identifying Chiari Malformation Type 1 Surgery in Adults.

PubMed

Greenberg, Jacob K; Ladner, Travis R; Olsen, Margaret A; Shannon, Chevis N; Liu, Jingxia; Yarbrough, Chester K; Piccirillo, Jay F; Wellons, John C; Smyth, Matthew D; Park, Tae Sung; Limbrick, David D

2015-08-01

The use of administrative billing data may enable large-scale assessments of treatment outcomes for Chiari Malformation type I (CM-1). However, to utilize such data sets, validated International Classification of Diseases, Ninth Revision (ICD-9-CM) code algorithms for identifying CM-1 surgery are needed. To validate 2 ICD-9-CM code algorithms identifying patients undergoing CM-1 decompression surgery. We retrospectively analyzed the validity of 2 ICD-9-CM code algorithms for identifying adult CM-1 decompression surgery performed at 2 academic medical centers between 2001 and 2013. Algorithm 1 included any discharge diagnosis code of 348.4 (CM-1), as well as a procedure code of 01.24 (cranial decompression) or 03.09 (spinal decompression, or laminectomy). Algorithm 2 restricted this group to patients with a primary diagnosis of 348.4. The positive predictive value (PPV) and sensitivity of each algorithm were calculated. Among 340 first-time admissions identified by Algorithm 1, the overall PPV for CM-1 decompression was 65%. Among the 214 admissions identified by Algorithm 2, the overall PPV was 99.5%. The PPV for Algorithm 1 was lower in the Vanderbilt (59%) cohort, males (40%), and patients treated between 2009 and 2013 (57%), whereas the PPV of Algorithm 2 remained high (≥99%) across subgroups. The sensitivity of Algorithms 1 (86%) and 2 (83%) were above 75% in all subgroups. ICD-9-CM code Algorithm 2 has excellent PPV and good sensitivity to identify adult CM-1 decompression surgery. These results lay the foundation for studying CM-1 treatment outcomes by using large administrative databases.

Can physicians recognize their own patients in de-identified notes?

PubMed

Meystre, Stéphane; Shen, Shuying; Hofmann, Deborah; Gundlapalli, Adi

2014-01-01

The adoption of Electronic Health Records is growing at a fast pace, and this growth results in very large quantities of patient clinical information becoming available in electronic format, with tremendous potentials, but also equally growing concern for patient confidentiality breaches. De-identification of patient information has been proposed as a solution to both facilitate secondary uses of clinical information, and protect patient information confidentiality. Automated approaches based on Natural Language Processing have been implemented and evaluated, allowing for much faster text de-identification than manual approaches. A U.S. Veterans Affairs clinical text de-identification project focused on investigating the current state of the art of automatic clinical text de-identification, on developing a best-of-breed de-identification application for clinical documents, and on evaluating its impact on subsequent text uses and the risk for re-identification. To evaluate this risk, we de-identified discharge summaries from 86 patients using our 'best-of-breed' text de-identification application with resynthesis of the identifiers detected. We then asked physicians working in the ward the patients were hospitalized in if they could recognize these patients when reading the de-identified documents. Each document was examined by at least one resident and one attending physician, and with 4.65% of the documents, physicians thought they recognized the patient because of specific clinical information, but after verification, none was correctly re-identified.

The association of pagophagia with Helicobacter pylori infection in patients with iron-deficiency anemia.

PubMed

Asma, Suheyl; Boga, Can; Ozdogu, Hakan; Serin, Ender

2009-07-01

This study aimed to determine the relationship between pagophagia (compulsive ice eating) and H. pylori infection in patients with iron-deficiency anemia. We identified H. pylori infection using the (13)C-urea breath test in 45 patients with iron-deficiency anemia (group 1) and 55 patients with iron-deficiency anemia and pagophagia (group 2). Subgroups for testing oral intestinal iron absorption were randomly assigned from both groups. These subgroups consisted of (a) 10 patients with iron-deficiency anemia, (b) 10 patients with iron-deficiency anemia and pagophagia, (c) 10 patients with iron-deficiency anemia, pagophagia, and H. pylori infection before the eradication of H. pylori and (d) subgroup c after eradication therapy. There was no difference in the rate of H. pylori infection in the iron-deficiency anemia groups, with or without pagophagia. Furthermore, oral intestinal iron absorption was not influenced by pagophagia and/or H. pylori infection. Pagophagia did not increase the risk of H. pylori infection in patients with iron-deficiency anemia. Pagophagia and H. pylori infection do not synergistically affect the development of intestinal iron absorption abnormalities.

Analysis of the complete genome of subgroup A' hepatitis B virus isolates from South Africa.

PubMed

Kramvis, Anna; Weitzmann, Louise; Owiredu, William K B A; Kew, Michael C

2002-04-01

A phylogenetic analysis is presented of six complete and seven pre-S1/S2/S gene sequences of hepatitis B virus (HBV) isolates from South Africa. Five of the full-length sequences and all of the pre-S2/S sequences have been previously reported. Four of the six complete genomes and three of the five incomplete sequences clustered with subgroup A', a unique segment of genotype A of HBV previously identified in 60% of South African isolates using analysis of the pre-S2/S region alone. This separation was also evident when the polymerase open reading frame was analysed, but not on analysis of either the X or pre-core/core genes. Amino acids were identified in the pre-S1 and polymerase regions specific to subgroup A'. In common with genotype D, 10 of 11 genotype A South African isolates had an 11 amino acid deletion in the amino end of the pre-S1 region. This deletion is also found in hepadnaviruses from non-human primates.

Detection of FAM172A expressed in circulating tumor cells is a feasible method to predict high-risk subgroups of colorectal cancer.

PubMed

Cui, Chun-Hui; Chen, Ri-Hong; Zhai, Duan-Yang; Xie, Lang; Qi, Jia; Yu, Jin-Long

2017-06-01

Previous studies used to enumerate circulating tumor cells to predict prognosis and therapeutic effect of colorectal cancer. However, increasing studies have shown that only circulating tumor cells enumeration was not enough to reflect the heterogeneous condition of tumor. In this study, we classified different metastatic-potential circulating tumor cells from colorectal cancer patients and measured FAM172A expression in circulating tumor cells to improve accuracy of clinical diagnosis and treatment of colorectal cancer. Blood samples were collected from 45 primary colorectal cancer patients. Circulating tumor cells were enriched by blood filtration using isolation by size of epithelial tumor cells, and in situ hybridization with RNA method was used to identify and discriminate subgroups of circulating tumor cells. Afterwards, FAM172A expression in individual circulating tumor cells was measured. Three circulating tumor cell subgroups (epithelial/biophenotypic/mesenchymal circulating tumor cells) were identified using epithelial-mesenchymal transition markers. In our research, mesenchymal circulating tumor cells significantly increased along with tumor progression, development of distant metastasis, and vascular invasion. Furthermore, FAM172A expression rate in mesenchymal circulating tumor cells was significantly higher than that in epithelial circulating tumor cells, which suggested that FAM172A may correlate with malignant degree of tumor. This hypothesis was further verified by FAM172A expression in mesenchymal circulating tumor cells, which was strictly related to tumor aggressiveness factors. Mesenchymal circulating tumor cells and FAM172A detection may predict highrisk stage II colorectal cancer. Our research proved that circulating tumor cells were feasible surrogate samples to detect gene expression and could serve as a predictive biomarker for tumor evaluation.

Discriminant Value of Rome III Questionnaire in Dyspeptic Patients

PubMed Central

Abid, Shahab; Siddiqui, Shaheryar; Jafri, Wasim

2011-01-01

Background/Aim: Rome III criteria has modified the description of functional dyspepsia (FD) and divided this into subgroups. However, the discriminative value of Rome III questionnaire-based diagnosis of FD is yet to be determined. Objectives: To evaluate the Rome III questionnaire for the diagnosis of FD and whether it can discriminate between postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) in patients with dyspeptic symptoms. Patients and Methods: Consecutive patients, who were not on proton pump inhibitors (PPI), were asked to participate. Patients who have previously established acid peptic disease or predominantly reflux symptoms or having alarm symptoms such as weight loss and hematemesis were excluded. Rome III questionnaire for FD was used to identify the patients as having FD and divide into its subgroups; PDS or EPS. Gastro-duodenal biopsies, liver function tests and ultrasound were done to establish the diagnosis of FD. Results: Out of 272 patients with upper gastrointestinal (GI) symptoms without alarm features, who were enrolled in the study, a total of 191 (70%) fulfilled the criteria of FD based upon Rome III questionnaire. EPS subgroup was found in 109 (57%), PDS in 17 (9%) patients, overlap between EPS and PDS was present in 56 (29%) patients. Nine (5%) patients remained indeterminate. Diagnosis of FD was established in 136/191 (71%) patients only. Gastritis was present in 116 patients (85%), Duodenitis in 44 (32%) and Helicobacter pylori infection in 70 (51%) patients. Among 55 patients (29%) who had organic diseases, EPS was seen in 35 (64%), PDS in 5 (9%) and overlap in 15 (27%) patients. Underlying organic causes were gastric or duodenal ulcers in 14 patients, Barrett esophagus in five, chronic liver disease in seven, gall stones in five, Giardiasis and celiac disease in three each. Gastric carcinoma, Crohns disease and gastric polyps were seen in one patient each. Conclusion: This study indicates that 30% of patients

The effect of active video games by ethnicity, sex and fitness: subgroup analysis from a randomised controlled trial.

PubMed

Foley, Louise; Jiang, Yannan; Ni Mhurchu, Cliona; Jull, Andrew; Prapavessis, Harry; Rodgers, Anthony; Maddison, Ralph

2014-04-03

The prevention and treatment of childhood obesity is a key public health challenge. However, certain groups within populations have markedly different risk profiles for obesity and related health behaviours. Well-designed subgroup analysis can identify potential differential effects of obesity interventions, which may be important for reducing health inequalities. The study aim was to evaluate the consistency of the effects of active video games across important subgroups in a randomised controlled trial (RCT). A two-arm, parallel RCT was conducted in overweight or obese children (n=322; aged 10-14 years) to determine the effect of active video games on body composition. Statistically significant overall treatment effects favouring the intervention group were found for body mass index, body mass index z-score and percentage body fat at 24 weeks. For these outcomes, pre-specified subgroup analyses were conducted among important baseline demographic (ethnicity, sex) and prognostic (cardiovascular fitness) groups. No statistically significant interaction effects were found between the treatment and subgroup terms in the main regression model (p=0.36 to 0.93), indicating a consistent treatment effect across these groups. Preliminary evidence suggests an active video games intervention had a consistent positive effect on body composition among important subgroups. This may support the use of these games as a pragmatic public health intervention to displace sedentary behaviour with physical activity in young people.

Determinants of pain treatment response and nonresponse: identification of TMD patient subgroups.

PubMed

Litt, Mark D; Porto, Felipe B

2013-11-01

The purpose of the present study was to determine if we could identify a specific subtype of temporomandibular disorder (TMD) pain patients that does not respond to treatment. Patients were 101 men and women with chronic TMD pain recruited from the community and randomly assigned to 1 of 2 treatment conditions: a standard conservative care (STD) condition or a standard care plus cognitive-behavioral therapy condition (STD + CBT) in which patients received all elements of STD but also received cognitive-behavioral coping skills training. Growth mixture modeling, incorporating a series of treatment-related predictors, was used to distinguish several distinct classes of responders or nonresponders to treatment based on reported pain over a 1-year follow-up period. Results indicated that treatment nonresponders accounted for 16% of the sample and did not differ from treatment responders on demographics or temporomandibular joint pathology, but that they reported more psychiatric symptoms, poorer coping, and higher levels of catastrophizing. Treatment-related predictors of membership in treatment responder groups versus the nonresponder group included the addition of CBT to STD, treatment attendance, and decreasing catastrophization. It was concluded that CBT may be made more efficacious for TMD patients by placing further emphasis on decreasing catastrophization and on individualizing care. This article provides evidence that the TMD chronic pain population is heterogeneous and that a subsample of patients will be unresponsive to standard or psychosocial approaches. The addition of CBT to treatment may be helpful for this group, but new individualized approaches will be needed to treat all patients effectively. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Subgroups of Paediatric Acute Lymphoblastic Leukaemia Might Differ Significantly in Genetic Predisposition to Asparaginase Hypersensitivity

PubMed Central

Kutszegi, Nóra; Semsei, Ágnes F.; Gézsi, András; Sági, Judit C.; Nagy, Viktória; Csordás, Katalin; Jakab, Zsuzsanna; Lautner-Csorba, Orsolya; Gábor, Krisztina Míta; Kovács, Gábor T.; Erdélyi, Dániel J.; Szalai, Csaba

2015-01-01

L-asparaginase (ASP) is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL). However, hypersensitivity reactions (HSRs) to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin—Frankfurt—Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs) in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01–0.26); p = 4.70E-04), while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176) were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09–0.53); p = 8.48E-04 and OR = 3.02 (1.36–6.73); p = 6.76E-03, respectively). Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect. PMID:26457809

Identity Management Systems in Healthcare: The Issue of Patient Identifiers

NASA Astrophysics Data System (ADS)

Soenens, Els

According to a recent recommendation of the European Commission, now is the time for Europe to enhance interoperability in eHealth. Although interoperability of patient identifiers seems promising for matters of patient mobility, patient empowerment and effective access to care, we see that today there is indeed a considerable lack of interoperability in the field of patient identification. Looking from a socio-technical rather than a merely technical point of view, one can understand the fact that the development and implementation of an identity management system in a specific healthcare context is influenced by particular social practices, affected by socio-economical history and the political climate and regulated by specific data protection legislations. Consequently, the process of making patient identification in Europe more interoperable is a development beyond semantic and syntactic levels. In this paper, we gives some examples of today’s patient identifier systems in Europe, discuss the issue of interoperability of (unique) patient identifiers from a socio-technical point of view and try not to ignore the ‘privacy side’ of the story.

Latino Male Ethnic Subgroups: Patterns in College Enrollment and Degree Completion

ERIC Educational Resources Information Center

Ponjuan, Luis; Palomin, Leticia; Calise, Angela

2015-01-01

This chapter examines Latino male ethnic subgroups and their college enrollment and degree completion patterns. The chapter also offers recommendations to improve Latino male ethnic subgroups' educational achievement.

Suicide Risk across Latent Class Subgroups: A Test of the Generalizability of the Interpersonal Psychological Theory of Suicide.

PubMed

Ma, Jennifer S; Batterham, Philip J; Calear, Alison L; Han, Jin

2018-01-06

It remains unclear whether the Interpersonal Psychological Theory of Suicide (IPTS; Joiner, ) is generalizable to the population or holds more explanatory power for certain subgroups compared to others. The aim of this study was to (1) identify subgroups of individuals who endorsed suicide ideation in the past month based on a range of mental health and demographic variables, (2) compare levels of the IPTS constructs within these subgroups, and (3) test the IPTS predictions for suicide ideation and suicide attempt for each group. Latent class, negative binomial, linear, and logistic regression analyses were conducted on population-based data obtained from 1,321 adults recruited from Facebook. Among participants reporting suicide ideation, four distinct patterns of risk factors emerged based on age and severity of mental health symptoms. Groups with highly elevated mental health symptoms reported the highest levels of thwarted belongingness and perceived burdensomeness. Tests of the IPTS interactions provided partial support for the theory, primarily in young adults with elevated mental health symptoms. Lack of support found for the IPTS predictions across the subgroups and full sample in this study raise some questions around the broad applicability of the theory. © 2018 The American Association of Suicidology.

The Simulium nigritarse subgroup (Diptera: Simuliidae) in Uganda: New species and country records.

PubMed

Krüger, Andreas

2016-06-07

Amongst blackfly samples from western Uganda three different morphospecies of the Simulium (Nevermannia) nigritarse Coquillett subgroup were identified. Of these, S. perforatum Fain & Dujardin showed the widest distribution and is reported from Uganda for the first time. In addition, two new species are described: S. bwambanum sp. nov. and S. itwariense sp. nov. Diagnostic characters are the different structures of the pupal cocoon, the configurations of the gill filaments and adult colour features.

Contribution of Dietary Supplements to Nutritional Adequacy by Socioeconomic Subgroups in Adults of the United States.

PubMed

Blumberg, Jeffrey B; Frei, Balz; Fulgoni, Victor L; Weaver, Connie M; Zeisel, Steven H

2017-12-22

Many Americans have inadequate intakes of several nutrients, and the Dietary Guidelines for Americans 2015-2020 identified vitamins A, C, D, and E, in addition to calcium, magnesium, iron, potassium, choline, and fiber as "underconsumed nutrients". Based on nationally representative data on 10,698 adults from National Health and Nutrition Examination Surveys (NHANES), 2009-2012, assessments were made of socioeconomic differences, based on the Poverty Income Ratio (PIR), in terms of the association of dietary supplement use on nutrient intake and nutrient inadequacies. Compared to food alone, the use of any dietary supplement plus food was associated with significantly ( p < 0.01) higher intakes of 15-16 of 19 nutrients examined in all socioeconomic groups; and significantly reduced rates of inadequacy for 10/17 nutrients in the subgroup PIR > 1.85 (not poor), but only 4-5/17 nutrients (calcium and vitamins A, C, D, E) for the poor and nearly poor subgroups (PIR < 1.35 and PIR 1.35 to ≤1.85, respectively). An increased prevalence of intakes above the Tolerable Upper Intake Level (UL) was seen for 3-9/13 nutrients, but all were less than 5% in the PIR subgroups. In conclusion, dietary supplement use was associated with an increased micronutrient intake, decreased inadequacies, and a slight increase in the prevalence of intakes above the UL, with greater benefits seen in the PIR > 1.85 subgroup.

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

Commognitive analysis of undergraduate mathematics students' first encounter with the subgroup test

NASA Astrophysics Data System (ADS)

Ioannou, Marios

2018-06-01

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 conflicts. In the data analysis, one can identify three types of difficulties, relevant to object-level learning: namely regarding the frequently observed confusion between groups and sets, the object-level rules of visual mediators, and the object-level rules of contextual notions, such as permutations, exponentials, sets and matrices. In addition, data analysis suggests two types of difficulties, relevant to metalevel learning. The first refers to the actual proof that the three conditions of subgroup test hold, and the second is related to syntactic inaccuracies, incomplete argumentation and problematic use of visual mediators. Finally, this study suggests that there are clear links between object-level and metalevel learning, mainly due to the fact that objectification of the various relevant mathematical notions influences the endorsement of the governing metarules.

Cluster subgroups based on overall pressure pain sensitivity and psychosocial factors in chronic musculoskeletal pain: Differences in clinical outcomes.

PubMed

Almeida, Suzana C; George, Steven Z; Leite, Raquel D V; Oliveira, Anamaria S; Chaves, Thais C

2018-05-17

We aimed to empirically derive psychosocial and pain sensitivity subgroups using cluster analysis within a sample of individuals with chronic musculoskeletal pain (CMP) and to investigate derived subgroups for differences in pain and disability outcomes. Eighty female participants with CMP answered psychosocial and disability scales and were assessed for pressure pain sensitivity. A cluster analysis was used to derive subgroups, and analysis of variance (ANOVA) was used to investigate differences between subgroups. Psychosocial factors (kinesiophobia, pain catastrophizing, anxiety, and depression) and overall pressure pain threshold (PPT) were entered into the cluster analysis. Three subgroups were empirically derived: cluster 1 (high pain sensitivity and high psychosocial distress; n = 12) characterized by low overall PPT and high psychosocial scores; cluster 2 (high pain sensitivity and intermediate psychosocial distress; n = 39) characterized by low overall PPT and intermediate psychosocial scores; and cluster 3 (low pain sensitivity and low psychosocial distress; n = 29) characterized by high overall PPT and low psychosocial scores compared to the other subgroups. Cluster 1 showed higher values for mean pain intensity (F (2,77)  = 10.58, p < 0.001) compared with cluster 3, and cluster 1 showed higher values for disability (F (2,77)  = 3.81, p = 0.03) compared with both clusters 2 and 3. Only cluster 1 was distinct from cluster 3 according to both pain and disability outcomes. Pain catastrophizing, depression, and anxiety were the psychosocial variables that best differentiated the subgroups. Overall, these results call attention to the importance of considering pain sensitivity and psychosocial variables to obtain a more comprehensive characterization of CMP patients' subtypes.

Clinical Outcomes among Diagnostic Subgroups of Infants with Severe Bronchopulmonary Dysplasia through 2 Years of Age.

PubMed

Akangire, Gangaram; Manimtim, Winston; Nyp, Michael F; Noel-MacDonnell, Janelle; Kays, Allyssa N; Truog, William E; Taylor, Jane B

2018-05-31

 This article aimed to identify readmission risk factors through 2 years of life for infants with severe bronchopulmonary dysplasia (BPD) who do not require tracheostomy and ventilatory support after neonatal intensive care unit (NICU) discharge. It also aimed to identify if clinical differences exist between the subcategories of severe BPD.  A retrospective chart review was performed on 182 infants with severe BPD born between 2010 and 2015. A total of 130 infants met the inclusion criteria and were stratified into three groups based on their respiratory status at 36 weeks of gestational age: group A-oxygen (O 2 ), group B-assisted ventilation (AV), group C-both O 2 and AV. NICU clinical risk factors for readmission were assessed at set time points (6/12/18/24 months). Reasons for readmission were assessed for the entire cohort and severe BPD subgroups.  An NICU diagnosis of neurologic abnormality, necrotizing enterocolitis, invasive NICU infection, dysphagia, and O 2 at NICU discharge differed between the three subgroups of severe BPD. The most common cause of readmission was viral respiratory tract infection. Inhaled steroid use remained stable over time, while oxygen use and diuretic use declined over time. Risk factors for readmission in the entire cohort included g-tube, O 2 use, and diuretic use at 12 months. There was no significant difference in readmission rates between the three BPD subgroups. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Clebsch-Gordan coefficients of discrete groups in subgroup bases

NASA Astrophysics Data System (ADS)

Chen, Gaoli

2018-04-01

We express each Clebsch-Gordan (CG) coefficient of a discrete group as a product of a CG coefficient of its subgroup and a factor, which we call an embedding factor. With an appropriate definition, such factors are fixed up to phase ambiguities. Particularly, they are invariant under basis transformations of irreducible representations of both the group and its subgroup. We then impose on the embedding factors constraints, which relate them to their counterparts under complex conjugate and therefore restrict the phases of embedding factors. In some cases, the phase ambiguities are reduced to sign ambiguities. We describe the procedure of obtaining embedding factors and then calculate CG coefficients of the group 𝒫𝒮ℒ2(7) in terms of embedding factors of its subgroups S4 and 𝒯7.

Identifying patients likely to have atopic dermatitis: development of a pilot algorithm.

PubMed

Farage, Miranda A; Bowtell, Philip; Katsarou, Alexandra

2010-01-01